Method and efficacy of cryoablation combined with hyperthermia for the treatment of unresectable pancreatic cancer

Method and efficacy of cryoablation combined with hyperthermia for the treatment of unresectable pancreatic cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Method and efficacy of cryoablation combined with hyperthermia for the treatment of unresectable pancreatic cancer Kaiyu Wang, Tianyu Guo, Wenheng Zheng, Wenhui Zhang, Xin Wang, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4154317/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective: To explore the method and short-term efficacy of cryoablation combined with hyperthermia (CCH) for patients with unresectable pancreatic cancer. Methods: The study recruited 22 patients with unresectable pancreatic cancer diagnosed by a multidisciplinary team (MDT) at the Liaoning Cancer Hospital from February 2023 to December 2023. We explored the treatment procedure and evaluated the efficacy of the CCH therapy. The method of examination and characteristics before and after surgery were compared, and the effectiveness of open surgery versus a laparoscopic approach was evaluated. Results: All patients underwent an MDT-centered surgery to receive CCH. Patients were categorized based on the surgery into simple CCH (n=12, 55%), CCH with bilioenterostomy (n=4, 18%), and CCH with bilioenterostomy and gastroenterostomy (n=6, 27%). The average intraoperative blood loss volume was 114.1±81.1 mL; the average number of cryoprobes used was 1.3±0.5. The average time was 11.6±2.9 min for the first CCH cycle and 12.5±5.3 min for the second cycle. The average postoperative fasting time was 3.1±0.6 days, and the average postoperative hospital stay was 9.2±2.4 days. The rate of postoperative pancreatic fistula was 9.1% (n=2), with severe complications. Pathology of the puncture biopsy tumor tissue showed malignancy in 77.3% of cases. There were no significant differences in tumor markers and CT values before and after surgery. The average maximum diameter of the tumor before and after surgery was statistically significant (P=0.001), but there was no difference in tumor volume change (P=0.67). The surgical approaches included open surgery (n=15, 68%) and laparoscopy (n=7, 32%), with only a difference in surgical categories (P=0.006). Five patients (29%) underwent genetic testing, and all had identified potentially clinically significant mutations, but none had BRCA1/2 germline mutations. Conclusions: CCH therapy through MDT is suggested as the primary treatment approach for unresectable pancreatic cancer. This approach is applied with the aim to demonstrate high safety and low complication rate associated with CCH treatment for unresectable pancreatic cancer. Unresectable pancreatic cancer Cryoablation Combined with Hyperthermia MDT efficacy evaluation Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction The global threat of pancreatic cancer continues to rise, with a sustained increase in incidence rates [ 1 ] . The mortality rate closely parallels the incidence rate [ 2 , 3 ] . Due to the diagnostic challenges at the early stages of pancreatic cancer, over 80% of patients have already lost the opportunity of curative surgery [ 3 , 4 ] . The prognosis is extremely poor for patients with unresectable pancreatic cancer, with a median survival time of 3 to 6 months [ 4 ] . Currently, systemic chemotherapy or radiotherapy as the primary treatment for unresectable pancreatic cancer does not yield satisfactory patient outcomes [ 5 , 6 ] . There is an urgent need for innovative and effective treatment methods. Recent reports suggest that cryoablation combined with hyperthermia (CCH) demonstrates promising efficacy in unresectable pancreatic cancer [ 7 ] . CCH is an improvement and upgrade of single cryoablation therapy, which achieves an organic combination of deep cryoablation and hyperthermic therapy [ 7 ] . However, the medical centers offering this treatment are currently limited, further challenged by insufficient numbers of related cases and a lack of standardized treatment procedures. This study aims to summarize the clinical practice experience of CCH therapy for unresectable pancreatic cancer conducted at our center, explore the treatment procedure centered around a multidisciplinary team (MDT), and comprehensively assess the safety and efficacy of the treatment. Patients and methods Patient selection This study included 22 patients with unresectable pancreatic cancer who underwent CCH during surgery at the Department of Hepatopancreatobiliary Surgery, Liaoning Cancer Hospital. All patients’ data and history were discussed comprehensively by a multidisciplinary team (MDT) before surgery. Inclusion criteria were confirmed unresectable locally advanced pancreatic cancer and distant metastases and diagnoses confirmed through tumor markers, imaging examinations, and MDT consultations before surgery. Locally advanced pancreatic cancer refers to tumor contact of > 180° with the superior mesenteric artery (SMA) or celiac artery (CA), tumor contact with the CA and aortic involvement, or unreconstructible superior mesenteric vein or portal vein due to tumor involvement or occlusion. Exclusion criteria were patients with severe cardiopulmonary, hepatic, or renal dysfunction and those unable to tolerate general anesthesia and or undergo surgery due to other underlying diseases. The Medical Ethics Committee of Liaoning Cancer Hospital approved this (Approval Number: 20200802yg). Informed consent was obtained from all patients and their families as needed. Treatment procedure The patients underwent routine examinations, tumor marker tests (CA19-9/CEA/CA125), and imaging studies (contrast-enhanced computed tomography [CT] and magnetic resonance imaging [MRI] of the entire abdomen), leading to a preliminary diagnosis of pancreatic cancer. The resection ability was evaluated through MDT discussion. Patient tumors were categorized as resectable, borderline resectable, and unresectable. The resection status was further evaluated intraoperatively based on tumor invasion into surrounding vessels for distinguishing between resectable and unresectable cases. For patients with locally advanced unresectable pancreatic cancer, a pathological examination was performed on the punctured tumor tissue. In case of metastasis to the liver, one of the metastatic liver lesions was pathologically examined, whereas the pancreatic tumor was not subjected to biopsy. CCH was administered to the tumor intraoperatively. Postoperatively, the MDT re-evaluated the patient based on pathological examination results, genetic testing, and the patient's physical recovery. An individualized comprehensive treatment plan termed as Multidisciplinary Team to Health Information Management (MDT to HIM; Fig. 1 ) was formulated for each patient. Evaluation of treatment outcomes Postoperative complications were assessed according to the Clavien-Dindo classification [ 8 ] and included acute pancreatitis, pseudocyst formation, pancreatic fistula, bleeding, delayed gastric emptying, infection, or abscess. Parameters, including total bilirubin (TB), albumin (ALB), visual analogue scale (VAS) scores [ 7 , 9 ] , fasting blood glucose, and tumor markers (CA19-9, CA125, CEA), were evaluated at one week before surgery and one week after surgery. Abdominal contrast-enhanced CT scans were performed one week before surgery and three weeks after surgery before subsequent chemotherapy. The maximum diameter of the tumor was measured, and CT values during the plain phase, arterial phase, and venous phase were assessed. CT images were independently reviewed by two experienced radiologists and one experienced hepatobiliary surgeon who were blinded to the pathological results. While measuring CT values, the region with the most uniform density and the most significant changes in the lesion was identified, and average CT values were calculated after measuring values in three consecutive adjacent layers. The differences in CT values between arterial phase and portal venous phase, arterial phase and plain phase, and portal venous phase and plain phase were calculated independently. In the portal venous phase, the difference between the CT values of normal pancreatic tissue and the tumor tissue was measured, which was represented as ΔCT. Preoperative MDT consultations Based on the clinical history, laboratory tests, and imaging examinations of patients, the MDT organized a consultation to assess the resection ability. The preoperative MDT consultation included the Pancreatic Surgery, Imaging, Anesthesiology, Interventional Radiology and Radiotherapy departments. Tumor locations were generally categorized into the pancreatic head or neck and the body or tail. The Imaging department focused on studying the relationship between the tumor and structures, such as the celiac trunk, SMA, hepatic artery, portal vein, splenic vein, and their association with the abdominal aorta. The presence of regional lymph node metastasis or distant metastasis, including non-regional lymph node involvement, was evaluated. Resection ability criteria were based on the guidelines of the eighth edition of American Joint Committee on Cancer staging criteria and National Comprehensive Cancer Network for pancreatic cancer. The Anesthesiology department was responsible for ruling out any contraindications to anesthesia. The Interventional Radiology and Pancreatic Surgery departments collaborated during the intraoperative procedures, including biopsy sampling and CCH. Three-dimensional (3D) reconstruction technology In this study, the Myrian V1.12 software was utilized to import enhanced complete abdominal CT scans with a slice thickness of 1.0 mm. Within the “Liver Surgery Planning” module of the software, an automatic generation of vessels, skin, and skeletal structures was performed. Any deficiencies in the generated structures could be manually enhanced. The pancreas and tumor were manually outlined, and the software automatically calculated the tumor volume. Additionally, diameters and various oblique diameters were subject to manual measurements. In the “Ablation Planning” module, simulation of puncture ablation was carried out allowing for preoperative measurements of simulated puncture depth (Fig. 2 ). CCH surgery and palliative surgery Laparoscopy and open surgery were the selected surgical approaches. Preoperative MDT discussions based on imaging and 3D reconstruction helped assess the relationship between the tumor and the surrounding vessels to determine the surgical risk. If the surgical risk was low, a laparoscopic surgery was considered (Fig. 3 ); if the risk was high, open surgery was considered (Fig. 4 ). After exposing the pancreas, tumor size and impact on the surrounding organs were assessed through manual palpation or an intraoperative ultrasound. A tumor biopsy was performed under an ultrasound guidance at the same puncture site in 2–3 different directions. Following the pathological results, intraoperative CCH treatment was initiated, and any obstruction due to the tumor in the bile duct or duodenum was relieved. A 2.6 mm-diameter cryoprobe was precisely inserted into the farthest end of the tumor under direct vision or intraoperative ultrasound guidance. Using liquid nitrogen, the target tissue was frozen to approximately − 196°C, and the temperature was maintained until an ice ball was formed. The process was then repeated using the thermal effect of alcohol vapor, and the tumor was reheated to approximately 80°C. This was considered one cycle. This procedure was completed for a total of two cycles (Fig. 5 ). Throughout the process, an ultrasound was used to monitor the morphology, size, and complete coverage of the tumor by the ice ball. The freezing duration was adjusted based on complete coverage, and the melting degree of the ice ball was monitored. After removing the probe, hemostatic gel materials were used to seal the puncture hole to prevent uncontrollable bleeding or pancreatic fistula. If necessary, 4 − 0 PROLENE™ sutures were used for closure. One probe was used if the tumor's maximum diameter was < 3 cm, and two probes were used if it was larger than 3 cm. Real-time adjustment and observation using ultrasound were performed to avoid frostbite, and the probe was positioned to minimize contact with the main pancreatic duct. For patients with concurrent biliary obstruction or those expected to develop biliary obstruction, bilioenterostomy was performed. For those with duodenal obstruction, gastroenterostomy was performed. In patients without current duodenal obstruction but with an expected survival of ≥ 3 months, the decision to perform gastroenterostomy was made based on clinical indications and intraoperative considerations with respect to the tumor's relationship with the duodenum. Genetic testing and postoperative MDT to HIM Before initiating internal medicine drug therapy for locally advanced and metastatic pancreatic cancer, genetic testing was conducted to identify mutations, including but not limited to, BRCA1/2, NTRK1/2/3, PALB2, ATM/ATR, and RAS, encompassing genomic mutation and immune-related assessments. Tumor samples were collected from malignant pancreatic lesions confirmed through pathology. For patients in late-stage pancreatic cancer with BRCA1/2 germline mutations, sensitivity to platinum-based drugs was considered. Treatment options including cisplatin or oxaliplatin were preferred, with the final choice dependent on the patient's physical condition. Postoperative MDT to HIM involved establishing a multidisciplinary integrated diagnostic and therapeutic model. This model tailored to individualized and integrated diagnostic and therapeutic plans, ultimately achieving optimized integrated medical outcomes. This extended beyond the preoperative MDT departments to include radiation oncology, pathology, and medical oncology. The integration of pathology and genetic testing guided the selection of the most appropriate drug treatment plan for patients. Statistical Analysis Statistical analysis was performed using SPSS 26.0; continuous quantitative variables were presented as mean ± standard deviation (SD). Between-group comparisons were conducted using Fisher's exact probability test. If both preoperative and postoperative indicators followed a normal distribution, paired t-tests were employed for analysis; otherwise, the Wilcoxon signed-rank test was applied. When the Youden Index reached its maximum value, a cut-off threshold was determined. A significance level of P < 0.05 was considered statistically significant for differences. Results Patient clinical and surgical characteristics Baseline demographic data of patients are presented in Table 1 . There were 12 males (55%) and 10 females (45%). Nine (41%) patients were aged 60 years or younger, and 13 (59%) were older than 60 years, with a mean age of 63.6 ± 10.6 years. Lesions were located in the pancreatic head/neck region (n = 14, 64%) or body/tail region (n = 8, 36%). Reasons for unresectable tumors were simple local invasion (n = 14, 64%), simple distant metastasis (n = 3, 13%), or simultaneous local invasion and distant metastasis (n = 5, 23%), with distant metastases predominantly in the liver. Surgical categories included simple CCH (n = 12, 55%), CCH with bilioenterostomy (n = 4, 18%), or CCH with bilioenterostomy and gastroenterostomy (n = 6, 27%). Surgical approaches were open surgery (n = 15, 68%) or laparoscopy (n = 7, 32%). Intraoperative blood loss was 114.1 ± 81.1 mL. Vascular invasion included simple arterial invasion (n = 11, 51%), simple venous invasion (n = 3, 13%), or simultaneous arterial and venous invasion (n = 8, 36%). The number of ablation probes used was 1.3 ± 0.5. The average time was 11.6 ± 2.9 min for the first CCH cycle and 12.5 ± 5.3 min for the second cycle. The average postoperative fasting time was 3.1 ± 0.6 days, and the average postoperative hospital stay was 9.2 ± 2.4 days. The rate of postoperative pancreatic fistula was 9.1% (n = 2). Seventeen (77.3%) patients showed malignant biopsy results. Table 1 Patient Clinical and Surgical Characteristics Characteristics N(%) Open surgery(n = 15) Laparoscopy Surgery(n = 7) P Sex 1.000 Male 12(55%) 8 4 Female 10(45%) 7 3 Year(y) 0.074 ≤ 60 9(41%) 4 5 >60 13(59%) 11 2 Tumor location 1.000 Head/Neck region 14(64%) 10 4 Body/Tail region 8(36%) 5 3 Reasons for unresectability 0.099 Simple local invasion 15(69%) 11 4 Simple distant metastasis 3(13%) 3 0 Simultaneous local invasion and distant metastasis 4(18%) 1 3 Surgical categories 0.006* Simple CCH 12(55%) 4 8 CCH combined bilioenterostomy 4(18%) 4 0 CCH combined bilioenterostomy and gastroenterostomy 6(27%) 6 0 Intraoperative blood loss(mL) 114.1 ± 81.1 114.0 ± 84.6 114.3 ± 80.2 0.970 Vascular invasion 0.338 None 3(13%) 3 0 Simple arterial invasion 9(41%) 4 5 Simple venous invasion 1(5%) 1 0 Simultaneous arterial and venous invasion 9(41%) 7 2 The number of ablation probes 1.3 ± 0.5 1.3 ± 0.5 1.3 ± 0.5 0.833 The average time of CCH cycle The average time of first cycle(min) 11.6 ± 2.9 10.9 ± 2.7 13.3 ± 3.0 0.050 The average time of second cycle(min) 12.5 ± 5.3 12.1 ± 5.9 13.4 ± 4.0 0.594 The average postoperative fasting time(d) 3.1 ± 0.6 3.1 ± 0.6 3.0 ± 0.6 0.797 The average postoperative hospital stay(d) 9.2 ± 2.4 9.3 ± 2.4 8.9 ± 2.3 0.527 The number of postoperative pancreatic fistula 2(9.1%) 1 1 1.000 Pathological results 1.000 Nonmalignancy 5(23%) 3 2 Malignancy 17(77%) 12 5 CCH: Cryoablation Combined with Hyperthermia Evaluation of preoperative and postoperative examination characteristics Preoperative and postoperative measurements were conducted for TB; ALB; tumor markers such as CA199, CA125, and CEA; and VAS scores (Table 2 ). The results indicated no significant differences in TB, fasting blood glucose, CA199, and CEA between preoperative and postoperative measurements. However, statistical significance was observed in ALB, VAS scores, and CA125. Postoperative CA125 levels were higher than the preoperative levels (P = 0.018). Table 2 Preoperative and Postoperative Examination and Imaging Characteristics Characteristics Preoperative Postoperative P TB(umol/L) 38.5 ± 86.3 19.2 ± 19.4 0.520 ALB(umol/L) 43.9 ± 5.2 38.1 ± 2.7 0.001* VAS scores 4.2 ± 1.7 1.5 ± 1.1 0.001* Fasting blood glucose(mmol/L) 6.4 ± 2.6 6.7 ± 1.3 0.562 CA199(U/mL) 434.3 ± 401.9 482.1 ± 444.7 0.442 CA125(U/mL) 50.9 ± 102.6 93.9 ± 156.2 0.011* CEA(ng/mL) 7.7 ± 9.2 9.8 ± 14.5 0.320 Tumor's maximum diameter(mm) 34.9 ± 17.2 38.6 ± 18.6 0.001* Tumor volume(ml) 31.5 ± 25.9 32.5 ± 29.2 0.599 Tumor CT values of the plain phase(HU) 38.3 ± 11.6 37.0 ± 10.3 0.673 Tumor CT values of the arterial phase(HU) 47.2 ± 17.5 43.2 ± 12.9 0.331 Tumor CT values of the venous phase(HU) 59.2 ± 22.1 49.9 ± 20.9 0.137 (arterial phase-venous phase) CT values(HU) -12.0 ± 9.4 -6.8 ± 12.9 0.116 (venous phase-plain phase) CT values(HU) 20.8 ± 13.7 12.9 ± 14.5 0.134 (arterial phase-plain phase) CT values(HU) 8.8 ± 11.3 6.2 ± 5.6 0.492 ΔCT(HU) 44.2 ± 21.2 52.4 ± 19.1 0.133 TB: total bilirubin; ALB: albumin; VAS: visual analogue scale; CA199: Carbohydrate antigen 199; CA125: Carbohydrate antigen 199; CEA: Carcinoembryonic antigen Evaluation of preoperative and postoperative imaging characteristics Preoperative and postoperative contrast-enhanced CT scans of the entire abdomen were generated, and tumor volumes were calculated using the 3D reconstruction technology. The results showed no statistically significant differences in the tumor CT values of the plain phase, arterial phase, venous phase, (arterial phase-venous phase) CT values, (venous phase-plain phase) CT values, and (arterial phase-plain phase) CT values. Further, ΔCT values between preoperative and postoperative measurements were not statistically significant. The maximum diameter of the tumor exhibited statistical significance (P = 0.001), whereas the tumor volume showed no statistical significance (P = 0.67; Table 2 ). Efficacy evaluation of different surgical approaches Fifteen patients (68%) underwent open surgery and seven (32%) underwent laparoscopic surgery. There were no significant differences in gender, age, tumor location, and reasons for inoperability between the two surgical groups. However, there was a significant difference between the groups in terms of surgical category (P = 0.006); no bilioenterostomy and gastroenterostomy was done in the laparoscopic group. In terms of intraoperative blood loss, vascular invasion, the average number of ablation probes used, average time of CCH cycles, postoperative fasting time, postoperative hospital stay, postoperative pancreatic fistula, and positive pathological results, there were no significant differences between the two surgical groups (Table 1 ). Statistical analysis of laboratory and imaging indicators revealed a significant difference only in preoperative CA125 levels (P = 0.034), whereas the other markers showed no significant differences (Table 3 ). Table 3 Efficacy Evaluation of Different Surgical Approaches Characteristics Open surgery(n = 15) Laparoscopy Surgery(n = 7) P Preoperative TB(umol/L) 68.3 ± 118.3 11.4 ± 5.6 0.217 Postoperative TB(umol/L) 17.3 ± 9.7 22.9 ± 32.0 0.456 Preoperative ALB(umol/L) 44.3 ± 4.2 44.7 ± 6.3 0.850 Postoperative ALB(umol/L) 37.7 ± 2.4 39.0 ± 3.3 0.302 Preoperative VAS scores 4.3 ± 1.9 4.0 ± 1.0 0.733 Postoperative VAS scores 1.7 ± 1.2 1.0 ± 0.6 0.210 Preoperative Fasting blood glucose(mmol/L) 6.7 ± 3.0 5.5 ± 0.9 0.359 Postoperative Fasting blood glucose(mmol/L) 6.7 ± 1.3 6.4 ± 1.3 0.549 Preoperative CA199(U/mL) 464.3 ± 372.9 252.0 ± 348.6 0.219 Postoperative CA199(U/mL) 573.6 ± 422.5 276.4 ± 483.2 0.315 Preoperative CA125(U/mL) 23.5 ± 16.4 99.2 ± 128.5 0.034* Postoperative CA125(U/mL) 55.1 ± 37.5 210.3 ± 318.4 0.782 Preoperative CEA(ng/mL) 5.5 ± 6.0 18.2 ± 30.5 0.805 Postoperative CEA(ng/mL) 7.6 ± 7.4 14.8 ± 25.5 0.355 Preoperative Tumor's maximum diameter(mm) 33.6 ± 18.5 37.1 ± 16.7 0.677 Postoperative Tumor's maximum diameter(mm) 37.6 ± 19.6 40.3 ± 18.1 0.771 Preoperative Tumor volume(ml) 33.7 ± 26.8 24.0 ± 17.3 0.393 Postoperative Tumor volume(ml) 35.7 ± 33.8 26.0 ± 17.2 0.815 Preoperative Tumor CT values of the plain phase(HU) 37.4 ± 13.7 39.2 ± 6.5 0.788 Postoperative Tumor CT values of the plain phase(HU) 37.9 ± 9.5 32.5 ± 12.4 0.406 Preoperative Tumor CT values of the arterial phase(HU) 45.6 ± 19.1 49.2 ± 13.9 0.725 Postoperative Tumor CT values of the arterial phase(HU) 44.1 ± 12.1 39.0 ± 15.0 0.524 Preoperative Tumor CT values of the venous phase(HU) 55.6 ± 22.7 63.2 ± 20.4 0.556 Postoperative Tumor CT values of the venous phase(HU) 49.0 ± 21.7 45.7 ± 23.3 0.811 Preoperative (arterial phase-venous phase) CT values(HU) -10.0 ± 9.9 -14.0 ± 8.1 0.466 Postoperative (arterial phase-venous phase) CT values(HU) -4.9 ± 14.7 -6.8 ± 11.0 0.826 Preoperative (venous phase-plain phase) CT values(HU) 18.3 ± 12.4 24.0 ± 15.0 0.468 Postoperative (venous phase-plain phase) CT values(HU) 11.1 ± 15.7 13.3 ± 13.1 0.818 Preoperative (arterial phase-plain phase) CT values(HU) 8.3 ± 12.7 10.0 ± 8.2 0.790 Postoperative (arterial phase-plain phase) CT values(HU) 6.2 ± 6.4 6.5 ± 2.6 0.936 Preoperative ΔCT(HU) 42.1 ± 27.0 46.2 ± 7.0 0.751 Postoperative ΔCT(HU) 52.0 ± 22.7 53.1 ± 9.8 0.919 TB: total bilirubin; ALB: albumin; VAS: visual analogue scale; CA199: Carbohydrate antigen 199; CA125: Carbohydrate antigen 199; CEA: Carcinoembryonic antigen Genetic testing and subsequent medication plans Among the 22 patients, 5 cases were without pathologically confirmed malignancy. Among the remaining 17 patients, 5 (29%) underwent genetic testing (Table 4 ). Mutations with clear/potential clinical significance were found in all five patients, including KRAS, ARID1A and SMAD4. Only 1 patient was identified with genetic susceptibility genes causing/possibly causing mutations, namely DIS3L2 p.Q792X. No BRCA1/2 germline mutations were detected in the identified mutations. Regarding immunotherapy test results, the tumor mutation burden (TMB) was low in all cases, and microsatellite instability (MSI) was assessed as microsatellite stable. Based on the MDT to HIM results, treatment plans were determined sequentially. Two patients received gemcitabine combined with tegafur chemotherapy; two patients received tegafur chemotherapy; and one patient did not receive any adjuvant chemotherapy due to incomplete recovery of physical strength. The remaining 12 patients who did not undergo genetic testing received diverse treatments based on MDT to HIM recommendations. The treatments included gemcitabine combined with ALB paclitaxel chemotherapy for 1 patient, gemcitabine combined with tegafur chemotherapy for 8 patients, and tegafur for 2 patients. One patient did not undergo any treatment due to the short postoperative time. Table 4 The results of genetic testing and subsequent medication plans No Year(y) Sex Tumor location Surgical categories Genomic variation test results Immunotherapy test results Medication plans 1 60 Male Body/Tail region CCH Clear/potentially clinically significant variation: KRAS p.G12V Genetic susceptibility genes causing/possibly causing mutations: DIS3L2 p.Q792X Tumor mutation load(TMB) : 0.00 muts/Mb Microsatellite instability assessment(MSI) : Microsatellite stable type(MSS) Gemcitabine combined with Tegafur 2 63 Female Head/Neck region CCH + bilioenterostomy + gastroenterostomy Clear/potentially clinically significant variation: KRAS p.G12D/p.G12V Genetic susceptibility genes causing/possibly causing mutations: None Tumor mutation load(TMB) : 1.28 muts/Mb Microsatellite instability assessment(MSI) : Microsatellite stable type(MSS) Tegafur 3 76 Female Body/Tail region CCH Clear/potentially clinically significant variation: ARID1A p.Q944X; KRAS p.G12D; SMAD4 c.1308_1308 + 3del Genetic susceptibility genes causing/possibly causing mutations: None Tumor mutation load(TMB) : 0.00 muts/Mb Microsatellite instability assessment(MSI) : Microsatellite stable type(MSS) None 4 46 Male Body/Tail region CCH Clear/potentially clinically significant variation: KRAS p.G12C; TP53 c.560-1G > A; p. C401Y Genetic susceptibility genes causing/possibly causing mutations: None Tumor mutation load(TMB) : 0.00 muts/Mb Microsatellite instability assessment(MSI) : Microsatellite stable type(MSS) Tegafur 5 57 Male Head/Neck region CCH + bilioenterostomy Clear/potentially clinically significant variation: KRAS p.G12R Genetic susceptibility genes causing/possibly causing mutations: None Tumor mutation load(TMB) : 0.00 muts/Mb Microsatellite instability assessment(MSI) : Microsatellite stable type(MSS) Gemcitabine combined with Tegafur CCH: Cryoablation Combined with Hyperthermia Discussion Surgical resection is the only effective method that can provide long-term survival outcomes in pancreatic cancer [ 10 ] . However, over 80% of patients become ineligible for surgery due to delayed diagnosis and progression to late-stage disease [ 11 ] . Based on imaging results, tumors can be classified into resectable, borderline resectable, and unresectable [ 12 ] . Currently, the treatment of unresectable pancreatic cancer primarily relies on single-agent or combination chemotherapy, with gemcitabine as the mainstay [ 10 , 13 – 15 ] . Studies have shown that combination chemotherapy regimens can improve survival rates, but the median survival time remains less than 1 year [ 10 ] . Therefore, the current treatment options for unresectable pancreatic cancer are limited, and the outcomes are poor overall [ 16 , 17 ] . Our study explored CCH therapy for unresectable pancreatic cancer and discussed the treatment process and short-term efficacy. By leveraging the advantages of an MDT, the study conducted preoperative assessments to understand the resection ability of tumors in patients. If deemed unresectable intraoperatively, a biopsy was performed using direct visualization and ultrasound. This was followed by tumor ablation using CCH. Postoperatively, genetic testing was conducted based on biopsy results and was followed by MDT discussions. Individualized treatment plans were then formulated based on the patient's postoperative recovery status and genetic testing results. This concept was referred to as MDT to HIM. In recent years, localized treatments, such as high-intensity focused ultrasound therapy, irreversible electroporation, cryotherapy, and radiofrequency ablation, have been gradually employed for unresectable pancreatic cancer. These treatments have been reported to show relative safety, procedure efficiency, and convenience with significant efficacy in local tumor control and pain relief [ 18 – 20 ] . An ideal combination therapy aims to improve the quality of life and increase survival rates without increasing complications. However, currently, there is no standardized combination treatment plan, necessitating further clinical research. Qian et al had pioneered the CCH technology, which is an upgrade modified based on the existing single intraoperative cryoablation therapy [ 21 ] . This innovation marks the first successful integration of deep cryoablation and high-temperature hyperthermia for unresectable pancreatic cancer, both at the local and global level [ 21 ] . During surgery, the switch from freezing to heating induces intense and rapid warming, generating severe heat stress and high-temperature destructive effects within the tissue, thereby enhancing tumor damage [ 21 ] . CCH achieves complementary advantages of both cold and hot ablation. Hyperthermia accelerates the rewarming after cryotherapy, subjecting tumor tissues to rapid temperature changes and promoting the tumor cell death, whereas cryotherapy reduces blood flow perfusion in advance and decreases heat loss during hyperthermia, thereby enhancing the efficacy of hyperthermia [ 21 , 22 ] . The thermal effect during CCH is limited to the ice ball and only the target tissues get heated [ 21 ] . Combined with real-time ultrasound monitoring, the thermal effect is halted after complete melting of the ice ball, effectively preventing heat-induced damage and ensuring the safety of thermal ablation [ 7 , 21 ] . This study references the methods from another study [ 21 ] . The impact of CCH therapy was assessed through pre- and post-operative examinations and imaging studies. The maximum temperature attained during hyperthermia was 80°C, and the minimum temperature during cryotherapy was − 196°C. Intraoperative real-time ultrasound monitors the coverage range of the ice ball, ensuring full coverage of the tumor. All patients underwent two cycles of cryo-thermal ablation, with the first cycle averaging for 11.6 ± 2.9 minutes and the second cycle for 12.5 ± 5.3 minutes. Whether performed via laparotomy or laparoscopy, the surgery can be safely conducted under direct visualization. There were no serious postoperative complications. The incidence of pancreatic fistula was 9.1% and all were classified as biochemical fistulas. Both cryotherapy and hyperthermia can deactivate nerves around the puncture site, and their combined effect in CCH may better alleviate pain. VAS significantly decreased postoperatively compared to preoperative scores (P = 0.001). Due to the small volume of pancreatic tumors, up to two cryo-thermal ablation probes were used in this study, with a calculated threshold for the number of probes based on tumor volume set at 35.9 mL. This study advocates for the use of CCH as a novel treatment approach for patients with unresectable pancreatic cancer and explores an MDT-oriented diagnostic and treatment plan. The results indicate that the short-term efficacy of CCH for unresectable pancreatic cancer was successful to a certain extent. When pre- and post-operative laboratory indicators were compared, there were no significant differences in TB, fasting blood glucose, CA199, and CEA, but statistically significant differences were observed in ALB, VAS score, and CA125 (P = 0.018). Imaging indicators showed a significant improvement in the maximum diameter of tumors after surgery, whereas the tumor volume did not show statistically significant differences. The tumor volume is a better representative of overall tumor changes compared to tumor diameter. These results indicate that CCH can only delay the progression of pancreatic cancer and does not achieve a curative effect. There was no significant change in the tumor volume before and after CCH, indicating that it is less likely to cause obstruction to the duodenum. In this study, 4 patients (18%) underwent CCH and bilioenterostomy and did not develop duodenal obstruction. Among 6 patients (27%) who underwent CCH bilioenterostomy and gastroenterostomy, 3 developed duodenal obstruction and underwent gastroenterostomy, and the remaining 3 underwent preventive gastroenterostomy due to concerns of inflammation and edema caused by CCH compressing the duodenum. However, the lack of an impact of CCH on tumor volume changes suggests that preventive gastroenterostomy may not be necessary. Therefore, whether preventive gastroenterostomy with CCH is needed for the treatment of malignant tumors in the pancreatic head requires further investigation. We evaluated the changes in the radiographic density of tumors by measuring pre- and post-operative CT values during the plain phase, arterial phase, and venous phase, (arterial phase - venous phase) CT value, (arterial phase - plain phase) CT value, and ΔCT. However, none of these parameters showed statistical significance, indicating the need for further extraction of radiographic indicators to assess the degree of tumor necrosis. The impact of different surgical approaches on treatment outcomes is limited. The choice between open surgery and laparoscopic surgery did not show significant differences in intraoperative blood loss, the number of cryo-thermal probes needed, postoperative fasting time, and hospital stay. The only significant difference observed was in the category of surgery (P = 0.006), possibly due to the introduction of new techniques. From a safety standpoint, laparoscopic surgery is equally suitable for performing this technique. Before the surgery, we recommend routine 3D reconstruction based on patient imaging to gain a deeper understanding of the relationship between the tumor and surrounding vessels and tissues. In addition, the spatial diameter and tumor volume can be calculated, the direction and location of cryo-thermal probe insertion into the tumor on 3D images can be planned, and the needle depth can pre-planned. Integrating pre-planned parameters with intraoperative ultrasound measurements of the tumor diameter allows for comprehensive preparedness and guidance during the procedure. This preoperative planning approach enhances the precision and efficiency of CCH procedures. Since CCH can only delay the progression of pancreatic cancer to a certain extent with minimal curative effect, postoperative supplementary treatment is essential. The prerequisite for supplementary treatment is obtaining precise pathological information of the tumor to allow a definite diagnosis and genetic testing. Obtaining pancreatic cancer pathology is challenging, with a low success rate and high associated risks. We achieved a positivity rate of 77% in pathological diagnosis through direct visualization and ultrasound-guided biopsy, demonstrating effective and safe implementation. However, there is a need to further improve the positivity rate. Genetic testing has become crucial for formulating treatment plans. Five patients underwent genetic testing, and multiple gene mutations were identified, including frequent mutations in genes, such as KRAS, ARID1A, and TP53. This provides robust support for subsequent personalized treatment, namely MDT to HIM, enabling physicians to select more precise drug treatment plans based on the genetic characteristics. Cisplatin- or oxaliplatin-containing regimens were not selected due to absence of BRCA1/2 germline mutations because only a limited number of genetic tests were conducted. Currently, there is a lack of concrete and effective treatment options for unresectable pancreatic cancer. We explored the treatment process of CCH and evaluated its short-term efficacy. CCH can be considered safe and effective in pancreatic cancer. It not only relieves obstruction of the bile duct and gastrointestinal tract caused by tumors but also provides a pathological diagnosis. After genetic testing, an MDT consultation should be conducted to formulate personalized postoperative treatment plans. However, long-term efficacy requires further evaluation. The optimal parameters for the CCH, such as treatment time, number of probes, and ablation range, need further exploration. Future research should focus on expanding sample sizes and optimizing treatment protocols to provide more effective therapeutic approaches for patients with unresectable pancreatic cancer. Declarations Conflict of interest The authors declare that they have no confict of interest. Funding No funding for the present study. Author Contribution Kaiyu Wang and Yefu Liu wrote the main manuscript text. Kaiyu Wang, Tianyu Guo, Wenheng Zheng, Wenhui Zhang, Xin Wang, and Yefu Liu finished the surgery of cryoablation combined with hyperthermia for the treatment of unresectable pancreatic cancer. Wenheng Zheng, Yue Dong, Jinghui Bai, Dexin Jiao and Yefu Liu finished the MDT discussion. All authors reviewed the manuscript. Acknowledgement We thank Bullet Edits Limited for the linguistic editing and proofreading of the manuscript. Data Availability declaration The datasets generated or analyzed during this study are available from the corresponding author on reasonable request. References Pourshams A, Sepanlou SG, Ikuta KS, Bisignano C, Safiri S, Roshandel G, et al. The global, regional, and national burden of pancreatic cancer and its attributable risk factors in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2019;4(12):934–47. Siegel RL, Miller KD, Jemal A, Cancer. statistics, 2020. Ca-a Cancer Journal for Clinicians, 2020,70(1):7–30. Narayanan G, Daye D, Wilson NM, Noman R, Mahendra AM, Doshi MH. Ablation Pancreat Cancer: Past Present Future Cancers, 2021,13(11). Yousaf MN, Ehsan H, Muneeb A, Wahab A, Sana MK, Neupane K et al. Role of Radiofrequency Ablation in the Management of Unresectable Pancreatic Cancer. Front Med, 2021,7. Suker M, Beumer BR, Sadot E, Marthey L, Faris JE, Mellon EA, et al. FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol. 2016;17(6):801–10. Mizrahi JD, Surana R, Valle JW, Shroff RT. Pancreatic cancer. Lancet. 2020;395(10242):2008–20. Wu Y, Gu Y, Zhang B, Zhou X, Li Y, Qian Z. Laparoscopic ultrasonography-guided cryoablation of locally advanced pancreatic cancer: a preliminary report. Japanese J Radiol. 2022;40(1):86–93. Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, et al. Ann Surg. 2009;250(2):187–96. The Clavien-Dindo Classification of Surgical Complications Five- Year Experience Knop C, Oeser M, Bastian L, Lange U, Zdichavsky M, Blauth M. Development and validation of the visual analogue scale (VAS) spine score. Unfallchirurg. 2001;104(6):488–97. Wilkowski R, Thoma M, Bruns C, Wagner A, Heinemann V. Chemoradiotherapy with gemcitabine and continuous 5-FU in patients with primary inoperable pancreatic cancer. JOP: J pancreas. 2006;7(4):349–60. Esposito A, Balduzzi A, De Pastena M, Fontana M, Casetti L, Ramera M, et al. Minimally invasive surgery for pancreatic cancer. Expert Rev Anticancer Ther. 2019;19(11):947–58. Truty MJ, Kendrick ML, Nagorney DM, Smoot RL, Cleary SP, Graham RP, et al. Factors Predicting Response, Perioperative Outcomes, and Survival Following Total Neoadjuvant Therapy for Borderline/Locally Advanced Pancreatic Cancer. Ann Surg. 2021;273(2):341–9. Li Y-J, Wu J-Y, Wang J-M, Hu X-B, Cai J-X, Xiang D-X. Gemcitabine loaded autologous exosomes for effective and safe chemotherapy of pancreatic cancer. Acta Biomater. 2020;101:519–30. Philip PA, Lacy J, Portales F, Sobrero A, Pazo-Cid R, Manzano Mozo JL, et al. Nab-paclitaxel plus gemcitabine in patients with locally advanced pancreatic cancer (LAPACT): a multicentre, open-label phase 2 study. Lancet Gastroenterol Hepatol. 2020;5(3):285–94. Zhou C, Yi C, Yi Y, Qin W, Yan Y, Dong X et al. LncRNA PVT1 promotes gemcitabine resistance of pancreatic cancer via activating Wnt/β-catenin and autophagy pathway through modulating the miR-619-5p/Pygo2 and miR-619-5p/ATG14 axes. Mol Cancer, 2020,19(1). Oba A, Ho FL, Bao QR, Al-Musawi MH, Schulick RD, Del Chiaro M. Neoadjuvant Treatment in Pancreatic Cancer. Front Oncol, 2020,10. Jaoude JA, Kouzy R, Nguyen ND, Lin D, Noticewala SS, Ludmir EB et al. Radiation therapy for patients with locally advanced pancreatic cancer: Evolving techniques and treatment strategies. Curr Probl Cancer, 2020,44(6). Liu S, Qin Z, Xu J, Zeng J, Chen J, Niu L, et al. Irreversible electroporation combined with chemotherapy for unresectable pancreatic carcinoma: a prospective cohort study. Oncotargets Therapy. 2019;12:1341–50. Gu Y, Zhang B, Yang X, Yang G, Xu X, Qian Z. Intraoperative cryoablation of locally advanced pancreatic cancer: report of two cases. Int J Clin Exp Med. 2018;11(6):6302–8. D'Haese JG, Hartel M, Demir IE, Hinz U, Bergmann F, Buechler MW, et al. Pain sensation in pancreatic diseases is not uniform: The different facets of pancreatic pain. World J Gastroenterol. 2014;20(27):9154–61. Qian Z, Zhang B, Chen Y, Wu Y, Gu Y, Zhu Y. The clinical study of intraoperative cryoablation therapy and intraoperative combined cryoablation and hyperthermia in the treatment of unresectable pancreatic cancer. J Nanjing Med Univ Nat Sci Ed. 2021;41(8):1203–7. Luo X-M, Niu L-Z, Chen J-B, Xu K-C. Advances in cryoablation for pancreatic cancer. World J Gastroenterol. 2016;22(2):790–800. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4154317","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":285238193,"identity":"e160e372-bbb3-4876-a9e1-3bcda4d4aae0","order_by":0,"name":"Kaiyu Wang","email":"","orcid":"","institution":"Department of Hepatopancreatobiliary Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital \u0026 Institute","correspondingAuthor":false,"prefix":"","firstName":"Kaiyu","middleName":"","lastName":"Wang","suffix":""},{"id":285238194,"identity":"b629343f-8b5d-4168-bdc7-c0d2bab04f91","order_by":1,"name":"Tianyu Guo","email":"","orcid":"","institution":"Department of Hepatopancreatobiliary Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital \u0026 Institute","correspondingAuthor":false,"prefix":"","firstName":"Tianyu","middleName":"","lastName":"Guo","suffix":""},{"id":285238195,"identity":"3cacffbb-01fe-4d6e-a5ba-86d2f1062ecb","order_by":2,"name":"Wenheng Zheng","email":"","orcid":"","institution":"Department of Interventional Radiology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital \u0026 Institute","correspondingAuthor":false,"prefix":"","firstName":"Wenheng","middleName":"","lastName":"Zheng","suffix":""},{"id":285238196,"identity":"78db3450-81e6-4103-b5af-5728e0352a99","order_by":3,"name":"Wenhui Zhang","email":"","orcid":"","institution":"Department of Hepatopancreatobiliary Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital \u0026 Institute","correspondingAuthor":false,"prefix":"","firstName":"Wenhui","middleName":"","lastName":"Zhang","suffix":""},{"id":285238197,"identity":"05c4039f-1ee2-4865-8847-e41d7b1ba0b8","order_by":4,"name":"Xin Wang","email":"","orcid":"","institution":"Department of Hepatopancreatobiliary Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital \u0026 Institute","correspondingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Wang","suffix":""},{"id":285238198,"identity":"7e095781-247a-4203-8616-c7c8f71de1b7","order_by":5,"name":"Yue Dong","email":"","orcid":"","institution":"Department of Imaging, Cancer Hospital of China Medical University, Liaoning Cancer Hospital \u0026 Institute","correspondingAuthor":false,"prefix":"","firstName":"Yue","middleName":"","lastName":"Dong","suffix":""},{"id":285238199,"identity":"bef52023-92a2-44c9-99bc-29fe50585d4a","order_by":6,"name":"Jinghui Bai","email":"","orcid":"","institution":"Department of General internal medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital \u0026 Institute","correspondingAuthor":false,"prefix":"","firstName":"Jinghui","middleName":"","lastName":"Bai","suffix":""},{"id":285238200,"identity":"96686b33-7e4b-4eda-af96-faeb02af876a","order_by":7,"name":"Dexin Jiao","email":"","orcid":"","institution":"Department of Radiotherapy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital \u0026 Institute","correspondingAuthor":false,"prefix":"","firstName":"Dexin","middleName":"","lastName":"Jiao","suffix":""},{"id":285238201,"identity":"622fe0ae-6ff0-47f0-96e9-121d56674d81","order_by":8,"name":"Yefu Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5ElEQVRIie3PsQrCMBCA4ZSILtU6XgfxFQ4CRVB8lgahLipO4uCQqY6ufQxF6HxS0MG4O7iI4NwHEFFxcrCtm0M+yBC4n1wYM4w/5DQvRCneu877zvMTVwXyHI2p56qiCdJACDsla0nFE+2BjScudvsA2LQtVeVA2YttwgkAXmueHsbAdF8qe+RnJrWEx4DIuXesxmCFiVTPR7M32zIPfOTWOnol9wJJXZcEEibWEl6JKpC4UVmeFQY90MN1y9/2RWgPshMHOCW3W6frzA+rYzprNxYVnfOXD/7zlH+YNwzDML54AABCR4oi7yMnAAAAAElFTkSuQmCC","orcid":"","institution":"Department of Hepatopancreatobiliary Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital \u0026 Institute","correspondingAuthor":true,"prefix":"","firstName":"Yefu","middleName":"","lastName":"Liu","suffix":""}],"badges":[],"createdAt":"2024-03-23 12:14:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4154317/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4154317/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":54029012,"identity":"289db2ff-1ede-4339-8bb8-7d30fd9176ae","added_by":"auto","created_at":"2024-04-03 15:31:45","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":223799,"visible":true,"origin":"","legend":"\u003cp\u003eTreatment Protocol. MDT: multidisciplinary team; CCH: cryoablation combined with hyperthermia; MDT to HIM: Multidisciplinary Team to Health Information Management\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4154317/v1/c608994b81d44f7b11b4ca9c.jpeg"},{"id":54029016,"identity":"4097e8f4-e9da-4efd-99c1-4a1f03d78ec9","added_by":"auto","created_at":"2024-04-03 15:31:46","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":358276,"visible":true,"origin":"","legend":"\u003cp\u003eThree-dimensional(3D) Reconstruction Technology\u003cstrong\u003e \u003c/strong\u003eA: Preoperative enhanced CT showed tumor in the body of pancreas. The white dotted line area was tumor; B: Preoperative enhanced CT showed the simulated ablation needle puncture tumor, and the white arrow showed the ablation needle; C: Preoperative 3D showed the simulated puncture ablation needle puncture tumor, and the white arrow showed the ablation needle; D: The position and direction of the ablation needle were shown during the actual operation.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4154317/v1/20f189d7429c427dc396d601.jpeg"},{"id":54029014,"identity":"0bef0392-3287-40f0-bffc-cbca5f47db75","added_by":"auto","created_at":"2024-04-03 15:31:46","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":377204,"visible":true,"origin":"","legend":"\u003cp\u003eCCH of laparoscopic surgery. A: The pancreatic tumor was fully exposed during the operation, and the white dotted line area was the tumor; B: CCH of tumor was performed under real-time monitoring of laparoscopic ultrasound; C: Ice ball formed after the tumor was frozen; D: Laparoscopic ultrasound showed the ablation process of the puncture needle, and the ice ball showed low echo on the ultrasound. The white arrow was the ablation probe, and the dotted white area was the ice ball.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4154317/v1/5e4f6b92a67aee8347f5be07.jpeg"},{"id":54029013,"identity":"8cb4496c-4bd2-4415-8f39-ee4898e160e7","added_by":"auto","created_at":"2024-04-03 15:31:45","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":570490,"visible":true,"origin":"","legend":"\u003cp\u003eCCH of open surgery A: The pancreatic tumor was fully exposed during the operation, and the white dotted line area was the tumor; B: Pancreatic tumor biopsy; C: The ablation probe with a diameter of 2.6 mm was punctured to the farthest end of the tumor; D: After the tumor was frozen, ice ball was formed, and the white dotted line was ice ball; E: After tumor rewarming, the white dotted line area was puncture needle hole; F: Hemostatic gel materials closed the pinhole to prevent pancreatic fistula, and the white dotted line area was hemostatic gel materials.\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4154317/v1/4393e592fd863860511b03ec.jpeg"},{"id":54029015,"identity":"c2331939-6af7-4754-9591-c64ec0d2520b","added_by":"auto","created_at":"2024-04-03 15:31:46","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":82046,"visible":true,"origin":"","legend":"\u003cp\u003eThe procedure of CCH is repeated for a total of two cycles. Every cycle includes cooling, freezing and rewarming process.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-4154317/v1/f949e993c65b7fb3596fc5bd.png"},{"id":91164249,"identity":"b2727e8e-a0fc-495d-b4e4-19d6f4d3955e","added_by":"auto","created_at":"2025-09-12 10:01:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2663607,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4154317/v1/2caa5dc9-dfba-49a4-a215-3f153aa82738.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Method and efficacy of cryoablation combined with hyperthermia for the treatment of unresectable pancreatic cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe global threat of pancreatic cancer continues to rise, with a sustained increase in incidence rates\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. The mortality rate closely parallels the incidence rate\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Due to the diagnostic challenges at the early stages of pancreatic cancer, over 80% of patients have already lost the opportunity of curative surgery\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. The prognosis is extremely poor for patients with unresectable pancreatic cancer, with a median survival time of 3 to 6 months\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Currently, systemic chemotherapy or radiotherapy as the primary treatment for unresectable pancreatic cancer does not yield satisfactory patient outcomes\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. There is an urgent need for innovative and effective treatment methods.\u003c/p\u003e \u003cp\u003eRecent reports suggest that cryoablation combined with hyperthermia (CCH) demonstrates promising efficacy in unresectable pancreatic cancer\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. CCH is an improvement and upgrade of single cryoablation therapy, which achieves an organic combination of deep cryoablation and hyperthermic therapy\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. However, the medical centers offering this treatment are currently limited, further challenged by insufficient numbers of related cases and a lack of standardized treatment procedures. This study aims to summarize the clinical practice experience of CCH therapy for unresectable pancreatic cancer conducted at our center, explore the treatment procedure centered around a multidisciplinary team (MDT), and comprehensively assess the safety and efficacy of the treatment.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient selection\u003c/h2\u003e \u003cp\u003eThis study included 22 patients with unresectable pancreatic cancer who underwent CCH during surgery at the Department of Hepatopancreatobiliary Surgery, Liaoning Cancer Hospital. All patients\u0026rsquo; data and history were discussed comprehensively by a multidisciplinary team (MDT) before surgery. Inclusion criteria were confirmed unresectable locally advanced pancreatic cancer and distant metastases and diagnoses confirmed through tumor markers, imaging examinations, and MDT consultations before surgery. Locally advanced pancreatic cancer refers to tumor contact of \u0026gt;\u0026thinsp;180\u0026deg; with the superior mesenteric artery (SMA) or celiac artery (CA), tumor contact with the CA and aortic involvement, or unreconstructible superior mesenteric vein or portal vein due to tumor involvement or occlusion. Exclusion criteria were patients with severe cardiopulmonary, hepatic, or renal dysfunction and those unable to tolerate general anesthesia and or undergo surgery due to other underlying diseases. The Medical Ethics Committee of Liaoning Cancer Hospital approved this (Approval Number: 20200802yg). Informed consent was obtained from all patients and their families as needed.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eTreatment procedure\u003c/h2\u003e \u003cp\u003eThe patients underwent routine examinations, tumor marker tests (CA19-9/CEA/CA125), and imaging studies (contrast-enhanced computed tomography [CT] and magnetic resonance imaging [MRI] of the entire abdomen), leading to a preliminary diagnosis of pancreatic cancer. The resection ability was evaluated through MDT discussion. Patient tumors were categorized as resectable, borderline resectable, and unresectable. The resection status was further evaluated intraoperatively based on tumor invasion into surrounding vessels for distinguishing between resectable and unresectable cases. For patients with locally advanced unresectable pancreatic cancer, a pathological examination was performed on the punctured tumor tissue. In case of metastasis to the liver, one of the metastatic liver lesions was pathologically examined, whereas the pancreatic tumor was not subjected to biopsy. CCH was administered to the tumor intraoperatively. Postoperatively, the MDT re-evaluated the patient based on pathological examination results, genetic testing, and the patient's physical recovery. An individualized comprehensive treatment plan termed as Multidisciplinary Team to Health Information Management (MDT to HIM; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) was formulated for each patient.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eEvaluation of treatment outcomes\u003c/h2\u003e \u003cp\u003ePostoperative complications were assessed according to the Clavien-Dindo classification\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e and included acute pancreatitis, pseudocyst formation, pancreatic fistula, bleeding, delayed gastric emptying, infection, or abscess. Parameters, including total bilirubin (TB), albumin (ALB), visual analogue scale (VAS) scores\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e, fasting blood glucose, and tumor markers (CA19-9, CA125, CEA), were evaluated at one week before surgery and one week after surgery. Abdominal contrast-enhanced CT scans were performed one week before surgery and three weeks after surgery before subsequent chemotherapy. The maximum diameter of the tumor was measured, and CT values during the plain phase, arterial phase, and venous phase were assessed. CT images were independently reviewed by two experienced radiologists and one experienced hepatobiliary surgeon who were blinded to the pathological results. While measuring CT values, the region with the most uniform density and the most significant changes in the lesion was identified, and average CT values were calculated after measuring values in three consecutive adjacent layers. The differences in CT values between arterial phase and portal venous phase, arterial phase and plain phase, and portal venous phase and plain phase were calculated independently. In the portal venous phase, the difference between the CT values of normal pancreatic tissue and the tumor tissue was measured, which was represented as ΔCT.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003ePreoperative MDT consultations\u003c/h2\u003e \u003cp\u003eBased on the clinical history, laboratory tests, and imaging examinations of patients, the MDT organized a consultation to assess the resection ability. The preoperative MDT consultation included the Pancreatic Surgery, Imaging, Anesthesiology, Interventional Radiology and Radiotherapy departments. Tumor locations were generally categorized into the pancreatic head or neck and the body or tail. The Imaging department focused on studying the relationship between the tumor and structures, such as the celiac trunk, SMA, hepatic artery, portal vein, splenic vein, and their association with the abdominal aorta. The presence of regional lymph node metastasis or distant metastasis, including non-regional lymph node involvement, was evaluated. Resection ability criteria were based on the guidelines of the eighth edition of American Joint Committee on Cancer staging criteria and National Comprehensive Cancer Network for pancreatic cancer. The Anesthesiology department was responsible for ruling out any contraindications to anesthesia. The Interventional Radiology and Pancreatic Surgery departments collaborated during the intraoperative procedures, including biopsy sampling and CCH.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eThree-dimensional (3D) reconstruction technology\u003c/h2\u003e \u003cp\u003eIn this study, the Myrian V1.12 software was utilized to import enhanced complete abdominal CT scans with a slice thickness of 1.0 mm. Within the \u0026ldquo;Liver Surgery Planning\u0026rdquo; module of the software, an automatic generation of vessels, skin, and skeletal structures was performed. Any deficiencies in the generated structures could be manually enhanced. The pancreas and tumor were manually outlined, and the software automatically calculated the tumor volume. Additionally, diameters and various oblique diameters were subject to manual measurements. In the \u0026ldquo;Ablation Planning\u0026rdquo; module, simulation of puncture ablation was carried out allowing for preoperative measurements of simulated puncture depth (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eCCH surgery and palliative surgery\u003c/h2\u003e \u003cp\u003eLaparoscopy and open surgery were the selected surgical approaches. Preoperative MDT discussions based on imaging and 3D reconstruction helped assess the relationship between the tumor and the surrounding vessels to determine the surgical risk. If the surgical risk was low, a laparoscopic surgery was considered (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e); if the risk was high, open surgery was considered (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). After exposing the pancreas, tumor size and impact on the surrounding organs were assessed through manual palpation or an intraoperative ultrasound. A tumor biopsy was performed under an ultrasound guidance at the same puncture site in 2\u0026ndash;3 different directions. Following the pathological results, intraoperative CCH treatment was initiated, and any obstruction due to the tumor in the bile duct or duodenum was relieved. A 2.6 mm-diameter cryoprobe was precisely inserted into the farthest end of the tumor under direct vision or intraoperative ultrasound guidance. Using liquid nitrogen, the target tissue was frozen to approximately \u0026minus;\u0026thinsp;196\u0026deg;C, and the temperature was maintained until an ice ball was formed. The process was then repeated using the thermal effect of alcohol vapor, and the tumor was reheated to approximately 80\u0026deg;C. This was considered one cycle. This procedure was completed for a total of two cycles (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Throughout the process, an ultrasound was used to monitor the morphology, size, and complete coverage of the tumor by the ice ball. The freezing duration was adjusted based on complete coverage, and the melting degree of the ice ball was monitored. After removing the probe, hemostatic gel materials were used to seal the puncture hole to prevent uncontrollable bleeding or pancreatic fistula. If necessary, 4\u0026thinsp;\u0026minus;\u0026thinsp;0 PROLENE\u0026trade; sutures were used for closure. One probe was used if the tumor's maximum diameter was \u0026lt;\u0026thinsp;3 cm, and two probes were used if it was larger than 3 cm. Real-time adjustment and observation using ultrasound were performed to avoid frostbite, and the probe was positioned to minimize contact with the main pancreatic duct. For patients with concurrent biliary obstruction or those expected to develop biliary obstruction, bilioenterostomy was performed. For those with duodenal obstruction, gastroenterostomy was performed. In patients without current duodenal obstruction but with an expected survival of \u0026ge;\u0026thinsp;3 months, the decision to perform gastroenterostomy was made based on clinical indications and intraoperative considerations with respect to the tumor's relationship with the duodenum.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eGenetic testing and postoperative MDT to HIM\u003c/h2\u003e \u003cp\u003eBefore initiating internal medicine drug therapy for locally advanced and metastatic pancreatic cancer, genetic testing was conducted to identify mutations, including but not limited to, BRCA1/2, NTRK1/2/3, PALB2, ATM/ATR, and RAS, encompassing genomic mutation and immune-related assessments. Tumor samples were collected from malignant pancreatic lesions confirmed through pathology. For patients in late-stage pancreatic cancer with BRCA1/2 germline mutations, sensitivity to platinum-based drugs was considered. Treatment options including cisplatin or oxaliplatin were preferred, with the final choice dependent on the patient's physical condition. Postoperative MDT to HIM involved establishing a multidisciplinary integrated diagnostic and therapeutic model. This model tailored to individualized and integrated diagnostic and therapeutic plans, ultimately achieving optimized integrated medical outcomes. This extended beyond the preoperative MDT departments to include radiation oncology, pathology, and medical oncology. The integration of pathology and genetic testing guided the selection of the most appropriate drug treatment plan for patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using SPSS 26.0; continuous quantitative variables were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD). Between-group comparisons were conducted using Fisher's exact probability test. If both preoperative and postoperative indicators followed a normal distribution, paired t-tests were employed for analysis; otherwise, the Wilcoxon signed-rank test was applied. When the Youden Index reached its maximum value, a cut-off threshold was determined. A significance level of P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant for differences.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003ePatient clinical and surgical characteristics\u003c/h2\u003e \u003cp\u003eBaseline demographic data of patients are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. There were 12 males (55%) and 10 females (45%). Nine (41%) patients were aged 60 years or younger, and 13 (59%) were older than 60 years, with a mean age of 63.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.6 years. Lesions were located in the pancreatic head/neck region (n\u0026thinsp;=\u0026thinsp;14, 64%) or body/tail region (n\u0026thinsp;=\u0026thinsp;8, 36%). Reasons for unresectable tumors were simple local invasion (n\u0026thinsp;=\u0026thinsp;14, 64%), simple distant metastasis (n\u0026thinsp;=\u0026thinsp;3, 13%), or simultaneous local invasion and distant metastasis (n\u0026thinsp;=\u0026thinsp;5, 23%), with distant metastases predominantly in the liver. Surgical categories included simple CCH (n\u0026thinsp;=\u0026thinsp;12, 55%), CCH with bilioenterostomy (n\u0026thinsp;=\u0026thinsp;4, 18%), or CCH with bilioenterostomy and gastroenterostomy (n\u0026thinsp;=\u0026thinsp;6, 27%). Surgical approaches were open surgery (n\u0026thinsp;=\u0026thinsp;15, 68%) or laparoscopy (n\u0026thinsp;=\u0026thinsp;7, 32%). Intraoperative blood loss was 114.1\u0026thinsp;\u0026plusmn;\u0026thinsp;81.1 mL. Vascular invasion included simple arterial invasion (n\u0026thinsp;=\u0026thinsp;11, 51%), simple venous invasion (n\u0026thinsp;=\u0026thinsp;3, 13%), or simultaneous arterial and venous invasion (n\u0026thinsp;=\u0026thinsp;8, 36%). The number of ablation probes used was 1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5. The average time was 11.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9 min for the first CCH cycle and 12.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3 min for the second cycle. The average postoperative fasting time was 3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6 days, and the average postoperative hospital stay was 9.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4 days. The rate of postoperative pancreatic fistula was 9.1% (n\u0026thinsp;=\u0026thinsp;2). Seventeen (77.3%) patients showed malignant biopsy results.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient Clinical and Surgical Characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOpen surgery(n\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLaparoscopy Surgery(n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12(55%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10(45%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYear(y)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.074\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(41%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13(59%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor location\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHead/Neck region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14(64%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody/Tail region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(36%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReasons for unresectability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.099\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSimple local invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(69%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSimple distant metastasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSimultaneous local invasion and distant metastasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(18%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical categories\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.006*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSimple CCH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12(55%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCCH combined bilioenterostomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(18%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCCH combined bilioenterostomy and gastroenterostomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(27%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraoperative blood loss(mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e114.1\u0026thinsp;\u0026plusmn;\u0026thinsp;81.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e114.0\u0026thinsp;\u0026plusmn;\u0026thinsp;84.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e114.3\u0026thinsp;\u0026plusmn;\u0026thinsp;80.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.970\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVascular invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.338\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSimple arterial invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(41%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSimple venous invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSimultaneous arterial and venous invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(41%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe number of ablation probes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.833\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe average time of CCH cycle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe average time of first cycle(min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.050\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe average time of second cycle(min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.594\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe average postoperative fasting time(d)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.797\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe average postoperative hospital stay(d)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.527\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe number of postoperative pancreatic fistula\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(9.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathological results\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNonmalignancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(23%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalignancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17(77%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eCCH: Cryoablation Combined with Hyperthermia\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eEvaluation of preoperative and postoperative examination characteristics\u003c/h2\u003e \u003cp\u003ePreoperative and postoperative measurements were conducted for TB; ALB; tumor markers such as CA199, CA125, and CEA; and VAS scores (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The results indicated no significant differences in TB, fasting blood glucose, CA199, and CEA between preoperative and postoperative measurements. However, statistical significance was observed in ALB, VAS scores, and CA125. Postoperative CA125 levels were higher than the preoperative levels (P\u0026thinsp;=\u0026thinsp;0.018).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e Preoperative and Postoperative Examination and Imaging Characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePreoperative\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePostoperative\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTB(umol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.5\u0026thinsp;\u0026plusmn;\u0026thinsp;86.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.2\u0026thinsp;\u0026plusmn;\u0026thinsp;19.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.520\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALB(umol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVAS scores\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFasting blood glucose(mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.562\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCA199(U/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e434.3\u0026thinsp;\u0026plusmn;\u0026thinsp;401.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e482.1\u0026thinsp;\u0026plusmn;\u0026thinsp;444.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.442\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCA125(U/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50.9\u0026thinsp;\u0026plusmn;\u0026thinsp;102.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93.9\u0026thinsp;\u0026plusmn;\u0026thinsp;156.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.011*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCEA(ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.7\u0026thinsp;\u0026plusmn;\u0026thinsp;9.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.8\u0026thinsp;\u0026plusmn;\u0026thinsp;14.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.320\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor's maximum diameter(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34.9\u0026thinsp;\u0026plusmn;\u0026thinsp;17.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.6\u0026thinsp;\u0026plusmn;\u0026thinsp;18.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor volume(ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31.5\u0026thinsp;\u0026plusmn;\u0026thinsp;25.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.5\u0026thinsp;\u0026plusmn;\u0026thinsp;29.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.599\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor CT values of the plain phase(HU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.3\u0026thinsp;\u0026plusmn;\u0026thinsp;11.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.0\u0026thinsp;\u0026plusmn;\u0026thinsp;10.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.673\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor CT values of the arterial phase(HU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47.2\u0026thinsp;\u0026plusmn;\u0026thinsp;17.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43.2\u0026thinsp;\u0026plusmn;\u0026thinsp;12.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.331\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor CT values of the venous phase(HU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.2\u0026thinsp;\u0026plusmn;\u0026thinsp;22.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.9\u0026thinsp;\u0026plusmn;\u0026thinsp;20.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.137\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(arterial phase-venous phase) CT values(HU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-12.0\u0026thinsp;\u0026plusmn;\u0026thinsp;9.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-6.8\u0026thinsp;\u0026plusmn;\u0026thinsp;12.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.116\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(venous phase-plain phase) CT values(HU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.8\u0026thinsp;\u0026plusmn;\u0026thinsp;13.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.9\u0026thinsp;\u0026plusmn;\u0026thinsp;14.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.134\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(arterial phase-plain phase) CT values(HU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.8\u0026thinsp;\u0026plusmn;\u0026thinsp;11.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.492\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eΔCT(HU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44.2\u0026thinsp;\u0026plusmn;\u0026thinsp;21.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52.4\u0026thinsp;\u0026plusmn;\u0026thinsp;19.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.133\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eTB: total bilirubin; ALB: albumin; VAS: visual analogue scale; CA199: Carbohydrate antigen 199; CA125: Carbohydrate antigen 199; CEA: Carcinoembryonic antigen\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eEvaluation of preoperative and postoperative imaging characteristics\u003c/h2\u003e \u003cp\u003ePreoperative and postoperative contrast-enhanced CT scans of the entire abdomen were generated, and tumor volumes were calculated using the 3D reconstruction technology. The results showed no statistically significant differences in the tumor CT values of the plain phase, arterial phase, venous phase, (arterial phase-venous phase) CT values, (venous phase-plain phase) CT values, and (arterial phase-plain phase) CT values. Further, ΔCT values between preoperative and postoperative measurements were not statistically significant. The maximum diameter of the tumor exhibited statistical significance (P\u0026thinsp;=\u0026thinsp;0.001), whereas the tumor volume showed no statistical significance (P\u0026thinsp;=\u0026thinsp;0.67; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eEfficacy evaluation of different surgical approaches\u003c/h2\u003e \u003cp\u003eFifteen patients (68%) underwent open surgery and seven (32%) underwent laparoscopic surgery. There were no significant differences in gender, age, tumor location, and reasons for inoperability between the two surgical groups. However, there was a significant difference between the groups in terms of surgical category (P\u0026thinsp;=\u0026thinsp;0.006); no bilioenterostomy and gastroenterostomy was done in the laparoscopic group. In terms of intraoperative blood loss, vascular invasion, the average number of ablation probes used, average time of CCH cycles, postoperative fasting time, postoperative hospital stay, postoperative pancreatic fistula, and positive pathological results, there were no significant differences between the two surgical groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Statistical analysis of laboratory and imaging indicators revealed a significant difference only in preoperative CA125 levels (P\u0026thinsp;=\u0026thinsp;0.034), whereas the other markers showed no significant differences (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e Efficacy Evaluation of Different Surgical Approaches\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOpen surgery(n\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLaparoscopy Surgery(n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative TB(umol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68.3\u0026thinsp;\u0026plusmn;\u0026thinsp;118.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.217\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative TB(umol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.3\u0026thinsp;\u0026plusmn;\u0026thinsp;9.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.9\u0026thinsp;\u0026plusmn;\u0026thinsp;32.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.456\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative ALB(umol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.850\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative ALB(umol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.302\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative VAS scores\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.733\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative VAS scores\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.210\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative Fasting blood glucose(mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.359\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative Fasting blood glucose(mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.549\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative CA199(U/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e464.3\u0026thinsp;\u0026plusmn;\u0026thinsp;372.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e252.0\u0026thinsp;\u0026plusmn;\u0026thinsp;348.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.219\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative CA199(U/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e573.6\u0026thinsp;\u0026plusmn;\u0026thinsp;422.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e276.4\u0026thinsp;\u0026plusmn;\u0026thinsp;483.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.315\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative CA125(U/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.5\u0026thinsp;\u0026plusmn;\u0026thinsp;16.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e99.2\u0026thinsp;\u0026plusmn;\u0026thinsp;128.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.034*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative CA125(U/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55.1\u0026thinsp;\u0026plusmn;\u0026thinsp;37.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e210.3\u0026thinsp;\u0026plusmn;\u0026thinsp;318.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.782\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative CEA(ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.2\u0026thinsp;\u0026plusmn;\u0026thinsp;30.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.805\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative CEA(ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.8\u0026thinsp;\u0026plusmn;\u0026thinsp;25.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.355\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative Tumor's maximum diameter(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.6\u0026thinsp;\u0026plusmn;\u0026thinsp;18.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.1\u0026thinsp;\u0026plusmn;\u0026thinsp;16.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.677\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative Tumor's maximum diameter(mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.6\u0026thinsp;\u0026plusmn;\u0026thinsp;19.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.3\u0026thinsp;\u0026plusmn;\u0026thinsp;18.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.771\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative Tumor volume(ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.7\u0026thinsp;\u0026plusmn;\u0026thinsp;26.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.0\u0026thinsp;\u0026plusmn;\u0026thinsp;17.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.393\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative Tumor volume(ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35.7\u0026thinsp;\u0026plusmn;\u0026thinsp;33.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.0\u0026thinsp;\u0026plusmn;\u0026thinsp;17.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.815\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative Tumor CT values of the plain phase(HU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.4\u0026thinsp;\u0026plusmn;\u0026thinsp;13.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.788\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative Tumor CT values of the plain phase(HU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.9\u0026thinsp;\u0026plusmn;\u0026thinsp;9.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.5\u0026thinsp;\u0026plusmn;\u0026thinsp;12.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.406\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative Tumor CT values of the arterial phase(HU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45.6\u0026thinsp;\u0026plusmn;\u0026thinsp;19.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.2\u0026thinsp;\u0026plusmn;\u0026thinsp;13.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.725\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative Tumor CT values of the arterial phase(HU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44.1\u0026thinsp;\u0026plusmn;\u0026thinsp;12.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39.0\u0026thinsp;\u0026plusmn;\u0026thinsp;15.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.524\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative Tumor CT values of the venous phase(HU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55.6\u0026thinsp;\u0026plusmn;\u0026thinsp;22.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63.2\u0026thinsp;\u0026plusmn;\u0026thinsp;20.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.556\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative Tumor CT values of the venous phase(HU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49.0\u0026thinsp;\u0026plusmn;\u0026thinsp;21.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45.7\u0026thinsp;\u0026plusmn;\u0026thinsp;23.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.811\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative (arterial phase-venous phase) CT values(HU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-10.0\u0026thinsp;\u0026plusmn;\u0026thinsp;9.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-14.0\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.466\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative (arterial phase-venous phase) CT values(HU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;14.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-6.8\u0026thinsp;\u0026plusmn;\u0026thinsp;11.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.826\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative (venous phase-plain phase) CT values(HU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.3\u0026thinsp;\u0026plusmn;\u0026thinsp;12.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.0\u0026thinsp;\u0026plusmn;\u0026thinsp;15.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.468\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative (venous phase-plain phase) CT values(HU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.1\u0026thinsp;\u0026plusmn;\u0026thinsp;15.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.3\u0026thinsp;\u0026plusmn;\u0026thinsp;13.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.818\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative (arterial phase-plain phase) CT values(HU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.3\u0026thinsp;\u0026plusmn;\u0026thinsp;12.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.0\u0026thinsp;\u0026plusmn;\u0026thinsp;8.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.790\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative (arterial phase-plain phase) CT values(HU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.936\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative ΔCT(HU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42.1\u0026thinsp;\u0026plusmn;\u0026thinsp;27.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46.2\u0026thinsp;\u0026plusmn;\u0026thinsp;7.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.751\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative ΔCT(HU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52.0\u0026thinsp;\u0026plusmn;\u0026thinsp;22.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.1\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.919\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eTB: total bilirubin; ALB: albumin; VAS: visual analogue scale; CA199: Carbohydrate antigen 199; CA125: Carbohydrate antigen 199; CEA: Carcinoembryonic antigen\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eGenetic testing and subsequent medication plans\u003c/h2\u003e \u003cp\u003eAmong the 22 patients, 5 cases were without pathologically confirmed malignancy. Among the remaining 17 patients, 5 (29%) underwent genetic testing (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Mutations with clear/potential clinical significance were found in all five patients, including KRAS, ARID1A and SMAD4. Only 1 patient was identified with genetic susceptibility genes causing/possibly causing mutations, namely DIS3L2 p.Q792X. No BRCA1/2 germline mutations were detected in the identified mutations. Regarding immunotherapy test results, the tumor mutation burden (TMB) was low in all cases, and microsatellite instability (MSI) was assessed as microsatellite stable. Based on the MDT to HIM results, treatment plans were determined sequentially. Two patients received gemcitabine combined with tegafur chemotherapy; two patients received tegafur chemotherapy; and one patient did not receive any adjuvant chemotherapy due to incomplete recovery of physical strength. The remaining 12 patients who did not undergo genetic testing received diverse treatments based on MDT to HIM recommendations. The treatments included gemcitabine combined with ALB paclitaxel chemotherapy for 1 patient, gemcitabine combined with tegafur chemotherapy for 8 patients, and tegafur for 2 patients. One patient did not undergo any treatment due to the short postoperative time.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe results of genetic testing and subsequent medication plans\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYear(y)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTumor location\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSurgical categories\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eGenomic variation test results\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003eImmunotherapy test results\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eMedication plans\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBody/Tail region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eCCH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eClear/potentially clinically significant variation: KRAS p.G12V\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eGenetic susceptibility genes causing/possibly causing mutations: DIS3L2 p.Q792X\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eTumor mutation load(TMB) : 0.00 muts/Mb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eMicrosatellite instability assessment(MSI) : Microsatellite stable type(MSS)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eGemcitabine combined with Tegafur\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHead/Neck region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eCCH\u0026thinsp;+\u0026thinsp;bilioenterostomy\u0026thinsp;+\u0026thinsp;gastroenterostomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eClear/potentially clinically significant variation: KRAS p.G12D/p.G12V\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eGenetic susceptibility genes causing/possibly causing mutations: None\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eTumor mutation load(TMB) : 1.28 muts/Mb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eMicrosatellite instability assessment(MSI) : Microsatellite stable type(MSS)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eTegafur\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBody/Tail region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eCCH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eClear/potentially clinically significant variation: ARID1A p.Q944X; KRAS p.G12D; SMAD4 c.1308_1308\u0026thinsp;+\u0026thinsp;3del\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eGenetic susceptibility genes causing/possibly causing mutations: None\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eTumor mutation load(TMB) : 0.00 muts/Mb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eMicrosatellite instability assessment(MSI) : Microsatellite stable type(MSS)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBody/Tail region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eCCH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eClear/potentially clinically significant variation: KRAS p.G12C; TP53 c.560-1G\u0026thinsp;\u0026gt;\u0026thinsp;A; p. C401Y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eGenetic susceptibility genes causing/possibly causing mutations: None\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eTumor mutation load(TMB) : 0.00 muts/Mb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eMicrosatellite instability assessment(MSI) : Microsatellite stable type(MSS)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eTegafur\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHead/Neck region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eCCH\u0026thinsp;+\u0026thinsp;bilioenterostomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eClear/potentially clinically significant variation: KRAS p.G12R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eGenetic susceptibility genes causing/possibly causing mutations: None\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eTumor mutation load(TMB) : 0.00 muts/Mb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eMicrosatellite instability assessment(MSI) : Microsatellite stable type(MSS)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eGemcitabine combined with Tegafur\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003eCCH: Cryoablation Combined with Hyperthermia\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eSurgical resection is the only effective method that can provide long-term survival outcomes in pancreatic cancer \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. However, over 80% of patients become ineligible for surgery due to delayed diagnosis and progression to late-stage disease\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Based on imaging results, tumors can be classified into resectable, borderline resectable, and unresectable\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Currently, the treatment of unresectable pancreatic cancer primarily relies on single-agent or combination chemotherapy, with gemcitabine as the mainstay\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. Studies have shown that combination chemotherapy regimens can improve survival rates, but the median survival time remains less than 1 year\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Therefore, the current treatment options for unresectable pancreatic cancer are limited, and the outcomes are poor overall\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. Our study explored CCH therapy for unresectable pancreatic cancer and discussed the treatment process and short-term efficacy. By leveraging the advantages of an MDT, the study conducted preoperative assessments to understand the resection ability of tumors in patients. If deemed unresectable intraoperatively, a biopsy was performed using direct visualization and ultrasound. This was followed by tumor ablation using CCH. Postoperatively, genetic testing was conducted based on biopsy results and was followed by MDT discussions. Individualized treatment plans were then formulated based on the patient's postoperative recovery status and genetic testing results. This concept was referred to as MDT to HIM.\u003c/p\u003e \u003cp\u003e In recent years, localized treatments, such as high-intensity focused ultrasound therapy, irreversible electroporation, cryotherapy, and radiofrequency ablation, have been gradually employed for unresectable pancreatic cancer. These treatments have been reported to show relative safety, procedure efficiency, and convenience with significant efficacy in local tumor control and pain relief\u003csup\u003e[\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. An ideal combination therapy aims to improve the quality of life and increase survival rates without increasing complications. However, currently, there is no standardized combination treatment plan, necessitating further clinical research. Qian et al had pioneered the CCH technology, which is an upgrade modified based on the existing single intraoperative cryoablation therapy\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. This innovation marks the first successful integration of deep cryoablation and high-temperature hyperthermia for unresectable pancreatic cancer, both at the local and global level\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. During surgery, the switch from freezing to heating induces intense and rapid warming, generating severe heat stress and high-temperature destructive effects within the tissue, thereby enhancing tumor damage\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. CCH achieves complementary advantages of both cold and hot ablation. Hyperthermia accelerates the rewarming after cryotherapy, subjecting tumor tissues to rapid temperature changes and promoting the tumor cell death, whereas cryotherapy reduces blood flow perfusion in advance and decreases heat loss during hyperthermia, thereby enhancing the efficacy of hyperthermia\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. The thermal effect during CCH is limited to the ice ball and only the target tissues get heated\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. Combined with real-time ultrasound monitoring, the thermal effect is halted after complete melting of the ice ball, effectively preventing heat-induced damage and ensuring the safety of thermal ablation\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThis study references the methods from another study\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. The impact of CCH therapy was assessed through pre- and post-operative examinations and imaging studies. The maximum temperature attained during hyperthermia was 80\u0026deg;C, and the minimum temperature during cryotherapy was \u0026minus;\u0026thinsp;196\u0026deg;C. Intraoperative real-time ultrasound monitors the coverage range of the ice ball, ensuring full coverage of the tumor. All patients underwent two cycles of cryo-thermal ablation, with the first cycle averaging for 11.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9 minutes and the second cycle for 12.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3 minutes. Whether performed via laparotomy or laparoscopy, the surgery can be safely conducted under direct visualization. There were no serious postoperative complications. The incidence of pancreatic fistula was 9.1% and all were classified as biochemical fistulas. Both cryotherapy and hyperthermia can deactivate nerves around the puncture site, and their combined effect in CCH may better alleviate pain. VAS significantly decreased postoperatively compared to preoperative scores (P\u0026thinsp;=\u0026thinsp;0.001). Due to the small volume of pancreatic tumors, up to two cryo-thermal ablation probes were used in this study, with a calculated threshold for the number of probes based on tumor volume set at 35.9 mL.\u003c/p\u003e \u003cp\u003eThis study advocates for the use of CCH as a novel treatment approach for patients with unresectable pancreatic cancer and explores an MDT-oriented diagnostic and treatment plan. The results indicate that the short-term efficacy of CCH for unresectable pancreatic cancer was successful to a certain extent. When pre- and post-operative laboratory indicators were compared, there were no significant differences in TB, fasting blood glucose, CA199, and CEA, but statistically significant differences were observed in ALB, VAS score, and CA125 (P\u0026thinsp;=\u0026thinsp;0.018). Imaging indicators showed a significant improvement in the maximum diameter of tumors after surgery, whereas the tumor volume did not show statistically significant differences. The tumor volume is a better representative of overall tumor changes compared to tumor diameter. These results indicate that CCH can only delay the progression of pancreatic cancer and does not achieve a curative effect. There was no significant change in the tumor volume before and after CCH, indicating that it is less likely to cause obstruction to the duodenum. In this study, 4 patients (18%) underwent CCH and bilioenterostomy and did not develop duodenal obstruction. Among 6 patients (27%) who underwent CCH bilioenterostomy and gastroenterostomy, 3 developed duodenal obstruction and underwent gastroenterostomy, and the remaining 3 underwent preventive gastroenterostomy due to concerns of inflammation and edema caused by CCH compressing the duodenum. However, the lack of an impact of CCH on tumor volume changes suggests that preventive gastroenterostomy may not be necessary. Therefore, whether preventive gastroenterostomy with CCH is needed for the treatment of malignant tumors in the pancreatic head requires further investigation. We evaluated the changes in the radiographic density of tumors by measuring pre- and post-operative CT values during the plain phase, arterial phase, and venous phase, (arterial phase - venous phase) CT value, (arterial phase - plain phase) CT value, and ΔCT. However, none of these parameters showed statistical significance, indicating the need for further extraction of radiographic indicators to assess the degree of tumor necrosis.\u003c/p\u003e \u003cp\u003eThe impact of different surgical approaches on treatment outcomes is limited. The choice between open surgery and laparoscopic surgery did not show significant differences in intraoperative blood loss, the number of cryo-thermal probes needed, postoperative fasting time, and hospital stay. The only significant difference observed was in the category of surgery (P\u0026thinsp;=\u0026thinsp;0.006), possibly due to the introduction of new techniques. From a safety standpoint, laparoscopic surgery is equally suitable for performing this technique. Before the surgery, we recommend routine 3D reconstruction based on patient imaging to gain a deeper understanding of the relationship between the tumor and surrounding vessels and tissues. In addition, the spatial diameter and tumor volume can be calculated, the direction and location of cryo-thermal probe insertion into the tumor on 3D images can be planned, and the needle depth can pre-planned. Integrating pre-planned parameters with intraoperative ultrasound measurements of the tumor diameter allows for comprehensive preparedness and guidance during the procedure. This preoperative planning approach enhances the precision and efficiency of CCH procedures.\u003c/p\u003e \u003cp\u003eSince CCH can only delay the progression of pancreatic cancer to a certain extent with minimal curative effect, postoperative supplementary treatment is essential. The prerequisite for supplementary treatment is obtaining precise pathological information of the tumor to allow a definite diagnosis and genetic testing. Obtaining pancreatic cancer pathology is challenging, with a low success rate and high associated risks. We achieved a positivity rate of 77% in pathological diagnosis through direct visualization and ultrasound-guided biopsy, demonstrating effective and safe implementation. However, there is a need to further improve the positivity rate. Genetic testing has become crucial for formulating treatment plans. Five patients underwent genetic testing, and multiple gene mutations were identified, including frequent mutations in genes, such as KRAS, ARID1A, and TP53. This provides robust support for subsequent personalized treatment, namely MDT to HIM, enabling physicians to select more precise drug treatment plans based on the genetic characteristics. Cisplatin- or oxaliplatin-containing regimens were not selected due to absence of BRCA1/2 germline mutations because only a limited number of genetic tests were conducted.\u003c/p\u003e \u003cp\u003eCurrently, there is a lack of concrete and effective treatment options for unresectable pancreatic cancer. We explored the treatment process of CCH and evaluated its short-term efficacy. CCH can be considered safe and effective in pancreatic cancer. It not only relieves obstruction of the bile duct and gastrointestinal tract caused by tumors but also provides a pathological diagnosis. After genetic testing, an MDT consultation should be conducted to formulate personalized postoperative treatment plans. However, long-term efficacy requires further evaluation. The optimal parameters for the CCH, such as treatment time, number of probes, and ablation range, need further exploration. Future research should focus on expanding sample sizes and optimizing treatment protocols to provide more effective therapeutic approaches for patients with unresectable pancreatic cancer.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflict of interest\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no confict of interest.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNo funding for the present study.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eKaiyu Wang and Yefu Liu wrote the main manuscript text. Kaiyu Wang, Tianyu Guo, Wenheng Zheng, Wenhui Zhang, Xin Wang, and Yefu Liu finished the surgery of cryoablation combined with hyperthermia for the treatment of unresectable pancreatic cancer. Wenheng Zheng, Yue Dong, Jinghui Bai, Dexin Jiao and Yefu Liu finished the MDT discussion. All authors reviewed the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe thank Bullet Edits Limited for the linguistic editing and proofreading of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated or analyzed during this study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePourshams A, Sepanlou SG, Ikuta KS, Bisignano C, Safiri S, Roshandel G, et al. The global, regional, and national burden of pancreatic cancer and its attributable risk factors in 195 countries and territories, 1990\u0026ndash;2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2019;4(12):934\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSiegel RL, Miller KD, Jemal A, Cancer. statistics, 2020. Ca-a Cancer Journal for Clinicians, 2020,70(1):7\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNarayanan G, Daye D, Wilson NM, Noman R, Mahendra AM, Doshi MH. Ablation Pancreat Cancer: Past Present Future Cancers, 2021,13(11).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYousaf MN, Ehsan H, Muneeb A, Wahab A, Sana MK, Neupane K et al. Role of Radiofrequency Ablation in the Management of Unresectable Pancreatic Cancer. Front Med, 2021,7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSuker M, Beumer BR, Sadot E, Marthey L, Faris JE, Mellon EA, et al. FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol. 2016;17(6):801\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMizrahi JD, Surana R, Valle JW, Shroff RT. Pancreatic cancer. Lancet. 2020;395(10242):2008\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu Y, Gu Y, Zhang B, Zhou X, Li Y, Qian Z. Laparoscopic ultrasonography-guided cryoablation of locally advanced pancreatic cancer: a preliminary report. Japanese J Radiol. 2022;40(1):86\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eClavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, et al. Ann Surg. 2009;250(2):187\u0026ndash;96. The Clavien-Dindo Classification of Surgical Complications\u0026thinsp;\u0026lt;\u0026thinsp;i\u0026thinsp;\u0026gt;\u0026thinsp;Five-\u0026thinsp;\u003cem\u003eYear Experience\u003c/em\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKnop C, Oeser M, Bastian L, Lange U, Zdichavsky M, Blauth M. Development and validation of the visual analogue scale (VAS) spine score. Unfallchirurg. 2001;104(6):488\u0026ndash;97.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWilkowski R, Thoma M, Bruns C, Wagner A, Heinemann V. Chemoradiotherapy with gemcitabine and continuous 5-FU in patients with primary inoperable pancreatic cancer. JOP: J pancreas. 2006;7(4):349\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEsposito A, Balduzzi A, De Pastena M, Fontana M, Casetti L, Ramera M, et al. Minimally invasive surgery for pancreatic cancer. Expert Rev Anticancer Ther. 2019;19(11):947\u0026ndash;58.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTruty MJ, Kendrick ML, Nagorney DM, Smoot RL, Cleary SP, Graham RP, et al. Factors Predicting Response, Perioperative Outcomes, and Survival Following Total Neoadjuvant Therapy for Borderline/Locally Advanced Pancreatic Cancer. Ann Surg. 2021;273(2):341\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Y-J, Wu J-Y, Wang J-M, Hu X-B, Cai J-X, Xiang D-X. Gemcitabine loaded autologous exosomes for effective and safe chemotherapy of pancreatic cancer. Acta Biomater. 2020;101:519\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePhilip PA, Lacy J, Portales F, Sobrero A, Pazo-Cid R, Manzano Mozo JL, et al. Nab-paclitaxel plus gemcitabine in patients with locally advanced pancreatic cancer (LAPACT): a multicentre, open-label phase 2 study. Lancet Gastroenterol Hepatol. 2020;5(3):285\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou C, Yi C, Yi Y, Qin W, Yan Y, Dong X et al. LncRNA PVT1 promotes gemcitabine resistance of pancreatic cancer via activating Wnt/β-catenin and autophagy pathway through modulating the miR-619-5p/Pygo2 and miR-619-5p/ATG14 axes. Mol Cancer, 2020,19(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOba A, Ho FL, Bao QR, Al-Musawi MH, Schulick RD, Del Chiaro M. Neoadjuvant Treatment in Pancreatic Cancer. Front Oncol, 2020,10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJaoude JA, Kouzy R, Nguyen ND, Lin D, Noticewala SS, Ludmir EB et al. Radiation therapy for patients with locally advanced pancreatic cancer: Evolving techniques and treatment strategies. Curr Probl Cancer, 2020,44(6).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu S, Qin Z, Xu J, Zeng J, Chen J, Niu L, et al. Irreversible electroporation combined with chemotherapy for unresectable pancreatic carcinoma: a prospective cohort study. Oncotargets Therapy. 2019;12:1341\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGu Y, Zhang B, Yang X, Yang G, Xu X, Qian Z. Intraoperative cryoablation of locally advanced pancreatic cancer: report of two cases. Int J Clin Exp Med. 2018;11(6):6302\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eD'Haese JG, Hartel M, Demir IE, Hinz U, Bergmann F, Buechler MW, et al. Pain sensation in pancreatic diseases is not uniform: The different facets of pancreatic pain. World J Gastroenterol. 2014;20(27):9154\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQian Z, Zhang B, Chen Y, Wu Y, Gu Y, Zhu Y. The clinical study of intraoperative cryoablation therapy and intraoperative combined cryoablation and hyperthermia in the treatment of unresectable pancreatic cancer. J Nanjing Med Univ Nat Sci Ed. 2021;41(8):1203\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuo X-M, Niu L-Z, Chen J-B, Xu K-C. Advances in cryoablation for pancreatic cancer. World J Gastroenterol. 2016;22(2):790\u0026ndash;800.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Unresectable pancreatic cancer, Cryoablation Combined with Hyperthermia, MDT, efficacy evaluation","lastPublishedDoi":"10.21203/rs.3.rs-4154317/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4154317/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e To explore the method and short-term efficacy of cryoablation combined with hyperthermia (CCH) for patients with unresectable pancreatic cancer.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e The study recruited 22 patients with unresectable pancreatic cancer diagnosed by a multidisciplinary team (MDT) at the Liaoning Cancer Hospital from February 2023 to December 2023. We explored the treatment procedure and evaluated the efficacy of the CCH therapy. The method of examination and characteristics before and after surgery were compared, and the effectiveness of open surgery versus a laparoscopic approach was evaluated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e All patients underwent an MDT-centered surgery to receive CCH. Patients were categorized based on the surgery into simple CCH (n=12, 55%), CCH with bilioenterostomy (n=4, 18%), and CCH with bilioenterostomy and gastroenterostomy (n=6, 27%). The average intraoperative blood loss volume was 114.1±81.1 mL; the average number of cryoprobes used was 1.3±0.5. The average time was 11.6±2.9 min for the first CCH cycle and 12.5±5.3 min for the second cycle. The average postoperative fasting time was 3.1±0.6 days, and the average postoperative hospital stay was 9.2±2.4 days. The rate of postoperative pancreatic fistula was 9.1% (n=2), with severe complications. Pathology of the puncture biopsy tumor tissue showed malignancy in 77.3% of cases. There were no significant differences in tumor markers and CT values before and after surgery. The average maximum diameter of the tumor before and after surgery was statistically significant (P=0.001), but there was no difference in tumor volume change (P=0.67). The surgical approaches included open surgery (n=15, 68%) and laparoscopy (n=7, 32%), with only a difference in surgical categories (P=0.006). Five patients (29%) underwent genetic testing, and all had identified potentially clinically significant mutations, but none had BRCA1/2 germline mutations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eCCH therapy through MDT is suggested as the primary treatment approach for unresectable pancreatic cancer. This approach is applied with the aim to demonstrate high safety and low complication rate associated with CCH treatment for unresectable pancreatic cancer.\u003c/p\u003e","manuscriptTitle":"Method and efficacy of cryoablation combined with hyperthermia for the treatment of unresectable pancreatic cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-03 15:31:37","doi":"10.21203/rs.3.rs-4154317/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d902f406-c324-403a-9e69-7183f519f01e","owner":[],"postedDate":"April 3rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-12T09:53:45+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-03 15:31:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4154317","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4154317","identity":"rs-4154317","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}