Treatment and Prognosis for Pancreatic Duct Disruption Associated with Pancreatic Cancer: a case series of 16 patients

Treatment and Prognosis for Pancreatic Duct Disruption Associated with Pancreatic Cancer: a case series of 16 patients | 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 Article Treatment and Prognosis for Pancreatic Duct Disruption Associated with Pancreatic Cancer: a case series of 16 patients Yuki Oka, Takeshi Tanaka, Takashi Kobayashi, Atsuhiro Masuda, and 18 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3978666/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 Pancreatic duct (PD) disruption can be attributed to pancreatic cancer. This study investigated the therapeutic modalities and prognostic implications of PD disruption in pancreatic cancer. This retrospective study included 16 patients with PD disruption concomitant with pancreatic cancer between April 2011 and March 2023. Of the 16 cases of PD disruption, 12, nine, and two included pseudocysts, infected cysts, and walled–off necrosis, respectively. Five patients underwent endoscopic pancreatic stenting, nine were managed endoscopic ultrasonography-guided pancreatic fluid collection drainage, and two were treated with lumen-apposing metal stent placement. All patients achieved both technical and clinical success without complications. The clinical stage of pancreatic cancer spanned from carcinoma in situ to the metastatic phase. For the treatment of pancreatic cancer, six patients underwent surgical resection, and eight underwent chemotherapy. No cases of peritoneal dissemination were observed. The median overall survival from the diagnosis of pancreatic cancer in the resected and non-resected cases was 2222 and 289 days, respectively. Endoscopic intervention was effective in all cases of PD disruption due to pancreatic cancer. Furthermore, even in cases of pancreatic cancer after PD disruption, survival rates were similar to those in cases without PD disruption and were achieved through surgical resection or chemotherapy. Biological sciences/Cancer/Gastrointestinal cancer/Pancreatic cancer Biological sciences/Biological techniques/Imaging/Endoscopy Pancreatic ductal disruption Pancreatic fluid collection Walled–off necrosis Pancreatic cancer Endoscopic treatment Figures Figure 1 Introduction Pancreatic ductal (PD) disruption occurs because of injuries to the pancreatic duct, including acute pancreatitis, chronic pancreatitis, surgical interventions, trauma, and pancreatic tumors [ 1 – 5 ]. PD disruption results in leakage of pancreatic juice, leading to numerous complications, including pancreatic ascites, a pancreatic pleural effusion, a fistula, a pancreatic pseudocyst (PPC), and the formation of abscesses, potentially necessitating surgical intervention [ 1 , 2 , 6 ]. Endoscopic retrograde pancreatography (ERP) is useful in identifying a PD injury and treating PD disruptions caused by endoscopic pancreatic stenting (EPS) [ 6 ]. In cases of symptomatic PPC, endoscopic ultrasonography-guided pancreatic fluid collection drainage (EUS–PFD) is an efficacious approach. Moreover, it has been demonstrated that direct endoscopic necrosectomy (DEN) offers a safer and more efficacious option for patients with walled-off necrosis (WON) when compared to surgical or percutaneous drainage methods [ 7 ]. These complications, PPC and WON, can also arise because of malignant tumors. There have been several reports on PD disruption and PPC caused by pancreatic cancer [ 8 – 16 ]. When pancreatic cancer coexists, it is necessary to address not only PD disruption and the accompanying PPC/WON but also devise a therapeutic strategy for the pancreatic malignancy itself. However, an efficacious treatment for pancreatic cancer-associated PD disruption remains unclear. Furthermore, the prognosis of patients with pancreatic cancer concomitant with PD disruption and whether pancreatic juice leakage poses a risk for peritoneal dissemination have not been clarified. In this case series, we aimed to investigate the effectiveness of interventions for PD disruption associated with pancreatic cancer and the treatment modalities and prognosis of pancreatic cancer. Methods Patients Database Sixteen patients who underwent endoscopic treatment for PD disruption due to pancreatic cancer at the Kobe University Graduate School of Medicine between April 2011 and March 2023 were retrospectively analyzed. The clinical information collected included sex, age, body mass index (BMI), lifestyle history, medical history, symptoms, blood test results, imaging findings, endoscopic treatment details, and tumor treatment history. The study protocol was approved by The Kobe University School of Medicine Ethics Committee (No. B232030). All authors had access to the study data and reviewed and approved the final manuscript. Endoscopic treatment Computed tomography (CT) was performed before the initiation of endoscopic treatment for PD disruption. EPS was performed in cases where cyst formation was absent or inaccessible via the gastrointestinal tract. Using a TJF Q290V or 260V endoscope (Olympus Optical, Tokyo, Japan), a 5 or 7 French pancreatic plastic stent (PS) was inserted to bridge the PD disruption. In cases where direct placement across the disruption site was unattainable, the stent was positioned as close as possible to the disruption site. EUS-PFD was performed when the cysts displayed distinct encapsulation and were accessible via the gastrointestinal tract. Using a GF–UCT260 linear echoendoscope (Olympus Optical, Tokyo, Japan), several 7 French, 4 to 7 cm double pigtail PS were inserted into patients with pseudocysts, with the addition of a nasocystic drainage catheter in select cases. In cases of WON, lumen- apposing metal stents (LAMS) were placed, and repeated DEN was performed as required. After verification of WON reduction using CT, the LAMS was removed. Definitions of pancreatic duct disruption and outcomes PD disruption was defined as leakage of the contrast agent outside the PD during ERP or loss of continuity in the PD, accompanied by fluid accumulation in its vicinity, as visualized on CT. Technical success was defined as the successful placement of a plastic stent or LAMS using a TJF endoscope or GF a UCT260 linear echoendoscope. Clinical success was defined as an improvement in PD disruption, enabling the patient's discharge from the hospital. Pseudopancreatic cysts were categorized according to the revised Atlanta classification [17]. Results Patient characteristics The characteristics of the 16 patients are shown in Table 1 . The median age was 64.5 (range, 45–79), and among the 16 patients, 11 were male. The median C-reactive protein level was 5.95 mg/dL (range; 0.07–18.5), and the median total protein was 6.6 g/dl (range; 6.2–7.4). Thirteen of the 16 patients exhibited symptomatic presentations, with 12 reporting abdominal pain and four presenting with fever. Carcinoembryonic Antigen and Carbohydrate Antigen 19 − 9 levels exceeded the normal threshold in 5 (31.3%) and 12 (75.0%) cases, respectively. Table 1 patient’s characteristics Characteristic All patients (n = 16) Age, yr, median (range) 64.5 (45–79) BMI, g/m 2 , median (range) 18.6 (13.6–26.7) Sex, Male, n (%) 11 (68.8%) Alcohol consumption < 50 g/day, n (%) 6 (37.5%) History of smoking, presence, n (%) 9 (56.3%) Family history of PDAC, presence, n (%) 2 (12.5%) Diabetes mellitus, presence, n (%) 1 (6.3%) Chronic pancreatitis, presence, n (%) 1 (6.3%) Symptoms 13 (81.3%) Abdominal pain, presence, n (%) 12 (75.0%) Fever, presence, n (%) 4 (25.0%) CRP, mg/dl, median (range) 5.9 (0.07–18.5) TP, g/dl, median (range) 6.6 (6.2–7.4) CEA 5.0 ng/ml<, n (%) 5 (31.3%) CA19-9 37 U/ml<, n (%) 12 (75.0%) BMI, Body mass index; CA19-9, Carbohydrate Antigen 19 − 9; CEA; Carcinoembryonic Antigen; CRP, C-reactive protein; PDAC, Pancreatic ductal adenocarcinoma; TP, total protein. Features of pancreatic duct disruption and endoscopic treatment The details of PD disruption and endoscopic treatment are presented in Table 2 . The site of rupture in PD was identified as the head, body, and tail of the pancreas in two, seven, and seven cases, respectively. Disruption was observed proximal to the tumor in seven cases, while nine cases exhibited caudal disruption from the tumor. Two cases exhibited pancreatic juice leakage devoid of a pseudocyst, two cases presented with WON, and 12 cases manifested as PPC. The median cyst diameter was 75 mm (range; 16–174), and among the 12 cases, nine showed features of infection. Additionally, one patient presented with a concurrent mediastinal pancreatic fistula. No cases of disconnected pancreatic duct syndrome were observed. Table 2 Pancreatic duct disruption and treatment All patients (n = 16) Disruption site, n (%) Pancreatic head 2 (12.5%) Pancreatic body 7 (43.8%) Pancreatic tail 7 (43.8%) Tumor and disruption site, n (%) Proximal site to tumor 7 (43.8%) Caudal site from tumor 9 (56.2%) Phenotype of PD disruption Leakage of pancreatic juice without pseudocyst 2 (12.5%) PPC 12 (75.0%) WON 2 (12.5%) Long diameter of cyst, mm, median (range) 74.5 (16–174) Endoscopic treatment, n (%) EPS 5 (31.3%) PFD with only PS 9 (56.3%) PFD with LAMS 2 (12.5%) Technical success 16 (100%) Clinical success 16 (100%) Complications by endoscopic treatment 0 (0.0%) Median time to clinical success, days, median (range) 12.5 (2–46) EPS; Endoscopic pancreatic stenting, LAMS; Lumen-apposing metal stent, PD; Pancreatic duct, PFD; Pancreatic fluid collection drainage, PPC; Pancreatic pseudocyst, PS; Plastic stent, WON; Walled–off necrosis. Technical and clinical success were achieved without complications in all 16 patients. EPS was performed in five cases. Of the five cases treated with EPS, bridging of the ruptured site could not be performed in two cases. However, placing the EPS close to the disruption site yields a sufficient therapeutic effect. Nine patients with EUS-PFD underwent PS. Among them, an additional nasocystic drainage catheter was placed in eight cases. For the two patients with WON, a LAMS was inserted. In one case employing LAMS, an attempt at DEN was hindered owing to the lack of space to insert the endoscope, and the PS was placed after the LAMS was removed. The median time to clinical success after endoscopic treatment was 12.5 days (range, 2–46 days). Diagnosis of pancreatic cancer Diagnoses of pancreatic cancer are presented in Table 3 . Six cases of PD disruption developed during chemotherapy, 8 cases manifested pancreatic cancer diagnosis within one month of PD disruption onset, while in two cases, pancreatic cancer were diagnosed 200 days and four years subsequent to PD disruption. Table 3 Diagnosis and treatments for pancreatic cancer (n = 16) All patients (n = 16) Diagnosis of pancreatic cancer, n (%) Before PD disruption 6 (37.5%) At the same time of PD disruption 8 (50.0%) After PD disruption 2 (12.5%) Histological diagnosis, n (%) Pancreatic juice cytology 6 (37.5%) EUS-FNA 9 (56.2%) None 1 (6.3%) Diagnosis of pancreatic cancer PDAC 14 (87.5%) IPMC 2 (12.5%) Clinical stage (UICC 8th), n (%) 0 2 (12.5%) I 3 (18.7%) II 1 (6.3%) III 4 (25.0%) IV 6 (37.5%) Treatment for pancreatic cancer, n (%) Surgical resection 6 (37.5%) Chemotherapy 8 (50.0%) Best supportive care 2 (12.5%) EUS-FNA, Endoscopic ultrasonography-fine needle aspiration; IPMC, Intraductal papillary mucinous carcinoma; PD, Pancreatic duct; PDAC, Pancreatic ductal adenocarcinoma; All 6 cases receiving chemotherapy had already been diagnosed with pancreatic ductal adenocarcinoma (PDAC) by EUS-fine needle aspiration (FNA). Among the 8 cases diagnosed with pancreatic cancer within one month of PD disruption, 5 received a conclusive diagnosis through ERP, while 2 cases underwent diagnostic confirmation via EUS-FNA. In 1 case, diagnosis was difficult through ERP; however, a conclusive diagnosis of pancreatic cancer was successfully attained through surgical resection. One required approximately 200 days from the occurrence of PD disruption to the diagnosis of pancreatic cancer because of treatment for WON. Furthermore, in one case, pancreatic cancer could not be diagnosed by detailed imaging tests and cytology of the pancreatic juice at the time of PD disruption, and the patient was followed up. Four years later, a discernible mass emerged proximal to the site of the PD rupture, which was diagnosed as pancreatic cancer and surgical resection was performed. Among the cohort of 16 cases of pancreatic cancer, two cases were intraductal papillary mucinous carcinoma (IPMC), while the remaining cases were PDAC. At the time of pancreatic cancer diagnosis, the staging was as follows: two cases at stage 0, three cases at stage I, one case at stage II, four cases at stage III, and six cases at stage IV.there was a carcinoma in situ (Figure. 1) and one case of microscopic pancreatic cancer smaller than 10 mm that could not be detected on CT. Treatment for pancreatic cancer and overall survival The treatment options for pancreatic cancer are presented in Table 3 . According to the National Comprehensive Cancer Network guidelines [ 18 ], after the diagnosis and treatment of PD disruption, six cases underwent surgical resection, eight underwent chemotherapy, and two received best supportive care (BSC). The median time from the first endoscopic treatment to surgery was 48.5 days (range, 19–1520). Among the six cases who underwent surgical resection, one was resected after treatment for WON, and none experienced complications graded as 2 or higher within the initial 30-day postoperative period according to the Clavien-Dindo classification [ 18 ]. Of the six surgically resected cases, three had pancreatic recurrence, one had liver metastasis, and one had lung metastasis. However, peritoneal dissemination did not recur. The median time from the first endoscopic treatment to chemotherapy in the eight chemotherapy-treated patients was 28 days (range, 16–166 days). The median duration of continued chemotherapy was 214 days (range, 71–886). Two patients opted for BSC after treatment for PD disruption without the desire for chemotherapy. The median overall survival from the diagnosis of pancreatic cancer in the resected and non-resected cases was 2222 and 289 days, respectively. Discussion PD disruptions associated with pancreatic cancer and the need for therapeutic intervention are rare; only a few cases have been reported [ 8 – 15 ]. Given their infrequency, the effectiveness and safety of endoscopic treatments have not been sufficiently investigated. In this case study, we showed that pancreatic cancer can be effectively addressed with the appropriate management of PD disruption, and the prognosis is the same as that reported previously. Pancreatic duct rupture due to pancreatic cancer is thought to be caused by an increase in intrapancreatic duct pressure [ 12 ]. One of the factors contributing to the infrequency of pancreatic cancer-related PD disruption is the gradual advancement of pancreatic duct obstruction. As the tumor diameter increases, caudal pancreatic atrophy ensues, leading to a reduction in pancreatic juice production [ 16 ]. In the management of PD disruption, it is important not to neglect the acquisition of a cytological diagnosis, considering the potential coexistence of pancreatic cancer. Although the tumor could not be identified during PD disruption in one case, pancreatic cancer was identified four years later. Therefore, in cases involving PD disruption of an indeterminate etiology that cannot be diagnosed at the time of onset, careful follow-up, including imaging tests, is required to account for the possibility of early pancreatic cancer development. Tyberg et al. reported that PD disruption could be safely and effectively treated using various endoscopic procedures [ 8 ]. In this study, both technical and clinical success of endoscopic treatment was achieved in all cases. Shrode et al. reported that the disruption of the main pancreatic duct should be managed using bridging stenting [ 19 ]. Although bridging stenting was prioritized in two of the five cases treated with EPS, bridging stent placement could not be achieved. Therefore, the stent was placed proximal to the PD rupture, and the rupture could be effectively treated. Decreasing the duodenal pressure gradient of the pancreatic duct by placing the EPS near the disruption site may be sufficient therapy. For the majority of PPC EUS-drainage has been reported to allow for safer access and a decrease in complications [ 8 ]. Although metallic stents may be better than plastic stents, combining a nasocystic catheter and a PS is effective. LAMS for WON was as effective as that in previous studies. In this study, the patients could receive appropriate surgery or chemotherapy through endoscopic treatment for PD disruption. Adverse effects of surgery are feared due to intra-abdominal adhesions associated with PD disruption [ 20 ]. However, all patients who underwent resection could leave the hospital early without postoperative complications. Chemotherapy was continued in eight patients. Although there was a case in which the pancreatic fistula spread to the mediastinum and thoracic cavity, resulting in postoperative pulmonary metastasis, there were no cases of peritoneal dissemination recurrence. The median overall survival in this study was comparable to that previously reported for pancreatic cancer in Japan [ 21 ]. It has been reported that clinically relevant postoperative pancreatic fistulae after resection for pancreatic cancer are significantly associated with worse overall and disease-free survival [ 22 ]. However, future case studies are needed to determine whether preoperative pancreatic pleural effusion or pancreatic ascites affect recurrence. A limitation of this study is that it was a single-center retrospective study, the number of cases was small, and a multicenter clinical study is warranted. In this study, endoscopic treatment was effective and safe in all cases of pancreatic cancer-associated PD disruption. Even in the presence of cyst infection or WON along with PD disruption, pancreatic cancer can be treated through appropriate management with endoscopic therapy. Furthermore, the prognosis of pancreatic cancer was comparable to that of pancreatic cancer without PD disruption. Declarations Competing interests: The authors declare no competing interests. Author Contribution All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by YO, TT, MT, SA, MG, SM, HU, SK, NI, KN, YH, MM, YI, NJ and YY. The first draft of the manuscript was writtenby YO, and TT designed the study concept, analyzed data, and wrote the manuscript. TK, AS, AM, HT, TF and YK were involved in study supervision and revised the manuscript. Acknowledgments We would like to thank Editage (www.edita ge.jp) for the English language editing. Availability of materials and data: The datasets generated during and analysed during the current study are available from the corresponding author on reasonable request. Financial Support ; This work was supported by JSPS KAKENHI (Grants-in-Aid for Scientific Research), Grant no. 23K19618 (T.T.) References Varadarajulu, S., Noone, T. C., Tutuian, R., Hawes, R. H. & Cotton, P. B. Predictors of outcome in pancreatic duct disruption managed by endoscopic transpapillary stent placement. Gastrointest Endosc 61, 568–575, doi: 10.1016/s0016-5107(04)02832-9 (2005). Testoni, P. A. Endoscopic stenting in benign pancreatic diseases. JOP 8, 141–150 (2007). Kozarek, R. A. et al. Endoscopic transpapillary therapy for disrupted pancreatic duct and peripancreatic fluid collections. Gastroenterology 100, 1362–1370 (1991). Huibregtse, K., Schneider, B., Vrij, A. A. & Tytgat, G. N. J. 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University","correspondingAuthor":false,"prefix":"","firstName":"Testuhisa","middleName":"","lastName":"Ko","suffix":""},{"id":276222129,"identity":"0f32a71e-ae2f-4473-be87-799d1eee3074","order_by":18,"name":"Yusuke Yokotani","email":"","orcid":"","institution":"Kobe University","correspondingAuthor":false,"prefix":"","firstName":"Yusuke","middleName":"","lastName":"Yokotani","suffix":""},{"id":276222130,"identity":"0f190157-8889-4959-bb4e-8adbca90d274","order_by":19,"name":"Hirochika Toyama","email":"","orcid":"","institution":"Kobe University","correspondingAuthor":false,"prefix":"","firstName":"Hirochika","middleName":"","lastName":"Toyama","suffix":""},{"id":276222131,"identity":"f3833933-1497-421b-986b-793b1def8680","order_by":20,"name":"Takumi Fukumoto","email":"","orcid":"","institution":"Kobe University","correspondingAuthor":false,"prefix":"","firstName":"Takumi","middleName":"","lastName":"Fukumoto","suffix":""},{"id":276222132,"identity":"a23927d5-ba3e-42b0-9d2f-8c43b3b1fb4e","order_by":21,"name":"Yuzo Kodama","email":"","orcid":"","institution":"Kobe University","correspondingAuthor":false,"prefix":"","firstName":"Yuzo","middleName":"","lastName":"Kodama","suffix":""}],"badges":[],"createdAt":"2024-02-22 13:14:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3978666/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3978666/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":52035227,"identity":"7509b071-814d-44d3-8f1f-0a24b7b5f597","added_by":"auto","created_at":"2024-03-05 16:56:50","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1296842,"visible":true,"origin":"","legend":"\u003cp\u003eCIS with PD disruption. a) CE-CT image showing loss of continuity of the pancreatic duct (arrowhead). b) MRCP resonance cholangiopancreatography showing MPD stricture (arrowhead) and dilation of the caudal MPD (arrow). c) ERP showing leakage of the contrast agent outside the MPD (arrowhead). d) EUS image showing no mass in the MPD stricture (arrowhead). e) Pancreatic juice cytology revealed atypical cell clusters with enlarged, irregularly sized, and unevenly distributed nuclei; adenocarcinoma was suspected. f) The surgical specimen showed enlarged, irregular nuclei and disturbed cell polarity and was diagnosed as CIS (H\u0026amp;E, x40 ). Scale bars, 200 μm.\u003c/p\u003e\n\u003cp\u003eCE-CT, Contrast-enhanced computed tomography; CIS: Carcinoma in situ; ERP, Endoscopic retrograde pancreatography; EUS, Endoscopic Ultrasonography; H\u0026amp;E, Hematoxylin, and eosin; MRCP, Magnetic resonance cholangiopancreatography; MPD, Main pancreatic duct; PD, Pancreatic duct.\u003c/p\u003e","description":"","filename":"Figure0219.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3978666/v1/7280deb4e6bfb33b35b01af5.jpg"},{"id":55264683,"identity":"e96257ba-84e5-4c0a-bb85-9dddcec0f0ce","added_by":"auto","created_at":"2024-04-25 01:46:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":633105,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3978666/v1/29028c25-cd02-4f8a-8882-10c7fdfffb76.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Treatment and Prognosis for Pancreatic Duct Disruption Associated with Pancreatic Cancer: a case series of 16 patients","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePancreatic ductal (PD) disruption occurs because of injuries to the pancreatic duct, including acute pancreatitis, chronic pancreatitis, surgical interventions, trauma, and pancreatic tumors [\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. PD disruption results in leakage of pancreatic juice, leading to numerous complications, including pancreatic ascites, a pancreatic pleural effusion, a fistula, a pancreatic pseudocyst (PPC), and the formation of abscesses, potentially necessitating surgical intervention [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEndoscopic retrograde pancreatography (ERP) is useful in identifying a PD injury and treating PD disruptions caused by endoscopic pancreatic stenting (EPS) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In cases of symptomatic PPC, endoscopic ultrasonography-guided pancreatic fluid collection drainage (EUS\u0026ndash;PFD) is an efficacious approach. Moreover, it has been demonstrated that direct endoscopic necrosectomy (DEN) offers a safer and more efficacious option for patients with walled-off necrosis (WON) when compared to surgical or percutaneous drainage methods [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. These complications, PPC and WON, can also arise because of malignant tumors.\u003c/p\u003e \u003cp\u003eThere have been several reports on PD disruption and PPC caused by pancreatic cancer [\u003cspan additionalcitationids=\"CR9 CR10 CR11 CR12 CR13 CR14 CR15\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. When pancreatic cancer coexists, it is necessary to address not only PD disruption and the accompanying PPC/WON but also devise a therapeutic strategy for the pancreatic malignancy itself. However, an efficacious treatment for pancreatic cancer-associated PD disruption remains unclear. Furthermore, the prognosis of patients with pancreatic cancer concomitant with PD disruption and whether pancreatic juice leakage poses a risk for peritoneal dissemination have not been clarified. In this case series, we aimed to investigate the effectiveness of interventions for PD disruption associated with pancreatic cancer and the treatment modalities and prognosis of pancreatic cancer.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003ePatients Database\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSixteen patients who underwent endoscopic treatment for PD disruption due to pancreatic cancer at the Kobe University Graduate School of Medicine between April 2011 and March 2023 were retrospectively analyzed. The clinical information collected included sex, age, body mass index (BMI), lifestyle history, medical history, symptoms, blood test results, imaging findings, endoscopic treatment details, and tumor treatment history. The study protocol was approved by The Kobe University School of Medicine Ethics Committee (No. B232030). All authors had access to the study data and reviewed and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEndoscopic treatment\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eComputed tomography (CT) was performed before the initiation of endoscopic treatment for PD disruption. EPS was performed in cases where cyst formation was absent or inaccessible via the gastrointestinal tract. Using a TJF Q290V or 260V endoscope (Olympus Optical, Tokyo, Japan), a 5 or 7 French pancreatic plastic stent (PS) was inserted to bridge the PD disruption. In cases where direct placement across the disruption site was unattainable, the stent was positioned as close as possible to the disruption site.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEUS-PFD was performed when the cysts displayed distinct encapsulation and were accessible via the gastrointestinal tract. Using a GF–UCT260 linear echoendoscope (Olympus Optical, Tokyo, Japan), several 7 French, 4 to 7 cm double pigtail PS were inserted into patients with pseudocysts, with the addition of a nasocystic drainage catheter in select cases. In cases of WON, lumen- apposing metal stents (LAMS) were placed, and repeated DEN was performed as required. After verification of WON reduction using CT, the LAMS was removed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDefinitions of pancreatic duct disruption and outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePD disruption was defined as leakage of the contrast agent outside the PD during ERP or loss of continuity in the PD, accompanied by fluid accumulation in its vicinity, as visualized on CT. Technical success was defined as the successful placement of a plastic stent or LAMS using a TJF endoscope or GF a UCT260 linear echoendoscope. Clinical success was defined as an improvement in PD disruption, enabling the patient's discharge from the hospital. Pseudopancreatic cysts were categorized according to the revised Atlanta classification [17].\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003eThe characteristics of the 16 patients are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The median age was 64.5 (range, 45\u0026ndash;79), and among the 16 patients, 11 were male. The median C-reactive protein level was 5.95 mg/dL (range; 0.07\u0026ndash;18.5), and the median total protein was 6.6 g/dl (range; 6.2\u0026ndash;7.4). Thirteen of the 16 patients exhibited symptomatic presentations, with 12 reporting abdominal pain and four presenting with fever. Carcinoembryonic Antigen and Carbohydrate Antigen 19\u0026thinsp;\u0026minus;\u0026thinsp;9 levels exceeded the normal threshold in 5 (31.3%) and 12 (75.0%) cases, respectively.\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\u0026rsquo;s characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll patients (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, yr, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e64.5 (45\u0026ndash;79)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI, g/m\u003csup\u003e2\u003c/sup\u003e, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18.6 (13.6\u0026ndash;26.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex, Male, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11 (68.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcohol consumption\u0026thinsp;\u0026lt;\u0026thinsp;50 g/day, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (37.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of smoking, presence, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (56.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFamily history of PDAC, presence, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus, presence, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic pancreatitis, presence, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSymptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13 (81.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbdominal pain, presence, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (75.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever, presence, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (25.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP, mg/dl, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.9 (0.07\u0026ndash;18.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTP, g/dl, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.6 (6.2\u0026ndash;7.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCEA 5.0 ng/ml\u0026lt;, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (31.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCA19-9 37 U/ml\u0026lt;, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (75.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eBMI, Body mass index; CA19-9, Carbohydrate Antigen 19\u0026thinsp;\u0026minus;\u0026thinsp;9; CEA; Carcinoembryonic Antigen; CRP, C-reactive protein; PDAC, Pancreatic ductal adenocarcinoma; TP, total protein.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eFeatures of pancreatic duct disruption and endoscopic treatment\u003c/h2\u003e \u003cp\u003eThe details of PD disruption and endoscopic treatment are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The site of rupture in PD was identified as the head, body, and tail of the pancreas in two, seven, and seven cases, respectively. Disruption was observed proximal to the tumor in seven cases, while nine cases exhibited caudal disruption from the tumor. Two cases exhibited pancreatic juice leakage devoid of a pseudocyst, two cases presented with WON, and 12 cases manifested as PPC. The median cyst diameter was 75 mm (range; 16\u0026ndash;174), and among the 12 cases, nine showed features of infection. Additionally, one patient presented with a concurrent mediastinal pancreatic fistula. No cases of disconnected pancreatic duct syndrome were observed.\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\u003ePancreatic duct disruption and treatment\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll patients (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisruption site, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePancreatic head\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePancreatic body\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (43.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePancreatic tail\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (43.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor and disruption site, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProximal site to tumor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (43.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCaudal site from tumor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (56.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhenotype of PD disruption\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeakage of pancreatic juice without pseudocyst\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePPC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (75.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWON\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLong diameter of cyst, mm, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74.5 (16\u0026ndash;174)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndoscopic treatment, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEPS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (31.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePFD with only PS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (56.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePFD with LAMS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTechnical success\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical success\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComplications by endoscopic treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian time to clinical success, days, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.5 (2\u0026ndash;46)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eEPS; Endoscopic pancreatic stenting, LAMS; Lumen-apposing metal stent, PD; Pancreatic duct, PFD; Pancreatic fluid collection drainage, PPC; Pancreatic pseudocyst, PS; Plastic stent, WON; Walled\u0026ndash;off necrosis.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTechnical and clinical success were achieved without complications in all 16 patients. EPS was performed in five cases. Of the five cases treated with EPS, bridging of the ruptured site could not be performed in two cases. However, placing the EPS close to the disruption site yields a sufficient therapeutic effect. Nine patients with EUS-PFD underwent PS. Among them, an additional nasocystic drainage catheter was placed in eight cases. For the two patients with WON, a LAMS was inserted. In one case employing LAMS, an attempt at DEN was hindered owing to the lack of space to insert the endoscope, and the PS was placed after the LAMS was removed. The median time to clinical success after endoscopic treatment was 12.5 days (range, 2\u0026ndash;46 days).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eDiagnosis of pancreatic cancer\u003c/h2\u003e \u003cp\u003eDiagnoses of pancreatic cancer are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Six cases of PD disruption developed during chemotherapy, 8 cases manifested pancreatic cancer diagnosis within one month of PD disruption onset, while in two cases, pancreatic cancer were diagnosed 200 days and four years subsequent to PD disruption.\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\u003eDiagnosis and treatments for pancreatic cancer (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll patients (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosis of pancreatic cancer, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBefore PD disruption\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (37.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAt the same time of PD disruption\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfter PD disruption\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistological diagnosis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePancreatic juice cytology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (37.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEUS-FNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (56.2%)\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=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosis of pancreatic cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePDAC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14 (87.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIPMC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical stage (UICC 8th), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (18.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (25.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (37.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment for pancreatic cancer, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (37.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBest supportive care\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eEUS-FNA, Endoscopic ultrasonography-fine needle aspiration; IPMC, Intraductal papillary mucinous carcinoma; PD, Pancreatic duct; PDAC, Pancreatic ductal adenocarcinoma;\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAll 6 cases receiving chemotherapy had already been diagnosed with pancreatic ductal adenocarcinoma (PDAC) by EUS-fine needle aspiration (FNA). Among the 8 cases diagnosed with pancreatic cancer within one month of PD disruption, 5 received a conclusive diagnosis through ERP, while 2 cases underwent diagnostic confirmation via EUS-FNA. In 1 case, diagnosis was difficult through ERP; however, a conclusive diagnosis of pancreatic cancer was successfully attained through surgical resection. One required approximately 200 days from the occurrence of PD disruption to the diagnosis of pancreatic cancer because of treatment for WON. Furthermore, in one case, pancreatic cancer could not be diagnosed by detailed imaging tests and cytology of the pancreatic juice at the time of PD disruption, and the patient was followed up. Four years later, a discernible mass emerged proximal to the site of the PD rupture, which was diagnosed as pancreatic cancer and surgical resection was performed.\u003c/p\u003e \u003cp\u003eAmong the cohort of 16 cases of pancreatic cancer, two cases were intraductal papillary mucinous carcinoma (IPMC), while the remaining cases were PDAC. At the time of pancreatic cancer diagnosis, the staging was as follows: two cases at stage 0, three cases at stage I, one case at stage II, four cases at stage III, and six cases at stage IV.there was a carcinoma in situ (Figure. 1) and one case of microscopic pancreatic cancer smaller than 10 mm that could not be detected on CT.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eTreatment for pancreatic cancer and overall survival\u003c/h2\u003e \u003cp\u003eThe treatment options for pancreatic cancer are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. According to the National Comprehensive Cancer Network guidelines [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], after the diagnosis and treatment of PD disruption, six cases underwent surgical resection, eight underwent chemotherapy, and two received best supportive care (BSC). The median time from the first endoscopic treatment to surgery was 48.5 days (range, 19\u0026ndash;1520). Among the six cases who underwent surgical resection, one was resected after treatment for WON, and none experienced complications graded as 2 or higher within the initial 30-day postoperative period according to the Clavien-Dindo classification [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Of the six surgically resected cases, three had pancreatic recurrence, one had liver metastasis, and one had lung metastasis. However, peritoneal dissemination did not recur.\u003c/p\u003e \u003cp\u003eThe median time from the first endoscopic treatment to chemotherapy in the eight chemotherapy-treated patients was 28 days (range, 16\u0026ndash;166 days). The median duration of continued chemotherapy was 214 days (range, 71\u0026ndash;886). Two patients opted for BSC after treatment for PD disruption without the desire for chemotherapy.\u003c/p\u003e \u003cp\u003eThe median overall survival from the diagnosis of pancreatic cancer in the resected and non-resected cases was 2222 and 289 days, respectively.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003ePD disruptions associated with pancreatic cancer and the need for therapeutic intervention are rare; only a few cases have been reported [\u003cspan additionalcitationids=\"CR9 CR10 CR11 CR12 CR13 CR14\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Given their infrequency, the effectiveness and safety of endoscopic treatments have not been sufficiently investigated. In this case study, we showed that pancreatic cancer can be effectively addressed with the appropriate management of PD disruption, and the prognosis is the same as that reported previously.\u003c/p\u003e \u003cp\u003ePancreatic duct rupture due to pancreatic cancer is thought to be caused by an increase in intrapancreatic duct pressure [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. One of the factors contributing to the infrequency of pancreatic cancer-related PD disruption is the gradual advancement of pancreatic duct obstruction. As the tumor diameter increases, caudal pancreatic atrophy ensues, leading to a reduction in pancreatic juice production [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In the management of PD disruption, it is important not to neglect the acquisition of a cytological diagnosis, considering the potential coexistence of pancreatic cancer. Although the tumor could not be identified during PD disruption in one case, pancreatic cancer was identified four years later. Therefore, in cases involving PD disruption of an indeterminate etiology that cannot be diagnosed at the time of onset, careful follow-up, including imaging tests, is required to account for the possibility of early pancreatic cancer development.\u003c/p\u003e \u003cp\u003eTyberg et al. reported that PD disruption could be safely and effectively treated using various endoscopic procedures [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In this study, both technical and clinical success of endoscopic treatment was achieved in all cases. Shrode et al. reported that the disruption of the main pancreatic duct should be managed using bridging stenting [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Although bridging stenting was prioritized in two of the five cases treated with EPS, bridging stent placement could not be achieved. Therefore, the stent was placed proximal to the PD rupture, and the rupture could be effectively treated. Decreasing the duodenal pressure gradient of the pancreatic duct by placing the EPS near the disruption site may be sufficient therapy. For the majority of PPC EUS-drainage has been reported to allow for safer access and a decrease in complications [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Although metallic stents may be better than plastic stents, combining a nasocystic catheter and a PS is effective. LAMS for WON was as effective as that in previous studies.\u003c/p\u003e \u003cp\u003eIn this study, the patients could receive appropriate surgery or chemotherapy through endoscopic treatment for PD disruption. Adverse effects of surgery are feared due to intra-abdominal adhesions associated with PD disruption [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. However, all patients who underwent resection could leave the hospital early without postoperative complications. Chemotherapy was continued in eight patients. Although there was a case in which the pancreatic fistula spread to the mediastinum and thoracic cavity, resulting in postoperative pulmonary metastasis, there were no cases of peritoneal dissemination recurrence. The median overall survival in this study was comparable to that previously reported for pancreatic cancer in Japan [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. It has been reported that clinically relevant postoperative pancreatic fistulae after resection for pancreatic cancer are significantly associated with worse overall and disease-free survival [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. However, future case studies are needed to determine whether preoperative pancreatic pleural effusion or pancreatic ascites affect recurrence.\u003c/p\u003e \u003cp\u003eA limitation of this study is that it was a single-center retrospective study, the number of cases was small, and a multicenter clinical study is warranted.\u003c/p\u003e \u003cp\u003eIn this study, endoscopic treatment was effective and safe in all cases of pancreatic cancer-associated PD disruption. Even in the presence of cyst infection or WON along with PD disruption, pancreatic cancer can be treated through appropriate management with endoscopic therapy. Furthermore, the prognosis of pancreatic cancer was comparable to that of pancreatic cancer without PD disruption.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eCompeting interests:\u003c/h2\u003e \u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by YO, TT, MT, SA, MG, SM, HU, SK, NI, KN, YH, MM, YI, NJ and YY. The first draft of the manuscript was writtenby YO, and TT designed the study concept, analyzed data, and wrote the manuscript. TK, AS, AM, HT, TF and YK were involved in study supervision and revised the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e\u003cp\u003eWe would like to thank Editage (www.edita ge.jp) for the English language editing.\u003c/p\u003e\u003ch2\u003eAvailability of materials and data:\u003c/h2\u003e \u003cp\u003eThe datasets generated during and analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eFinancial Support\u003c/strong\u003e; This work was supported by JSPS KAKENHI (Grants-in-Aid for Scientific Research), Grant no. 23K19618 (T.T.)\u0026emsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eVaradarajulu, S., Noone, T. C., Tutuian, R., Hawes, R. H. \u0026amp; Cotton, P. B. Predictors of outcome in pancreatic duct disruption managed by endoscopic transpapillary stent placement. 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A Systematic Review and Meta-Analysis. Cancers (Basel) 13, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/cancers13225803\u003c/span\u003e\u003cspan address=\"10.3390/cancers13225803\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2021).\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":"Pancreatic ductal disruption, Pancreatic fluid collection, Walled–off necrosis, Pancreatic cancer, Endoscopic treatment","lastPublishedDoi":"10.21203/rs.3.rs-3978666/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3978666/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePancreatic duct (PD) disruption can be attributed to pancreatic cancer. This study investigated the therapeutic modalities and prognostic implications of PD disruption in pancreatic cancer. This retrospective study included 16 patients with PD disruption concomitant with pancreatic cancer between April 2011 and March 2023. Of the 16 cases of PD disruption, 12, nine, and two included pseudocysts, infected cysts, and walled–off necrosis, respectively. Five patients underwent endoscopic pancreatic stenting, nine were managed endoscopic ultrasonography-guided pancreatic fluid collection drainage, and two were treated with lumen-apposing metal stent placement. All patients achieved both technical and clinical success without complications. The clinical stage of pancreatic cancer spanned from carcinoma in situ to the metastatic phase. For the treatment of pancreatic cancer, six patients underwent surgical resection, and eight underwent chemotherapy. No cases of peritoneal dissemination were observed. The median overall survival from the diagnosis of pancreatic cancer in the resected and non-resected cases was 2222 and 289 days, respectively. Endoscopic intervention was effective in all cases of PD disruption due to pancreatic cancer. Furthermore, even in cases of pancreatic cancer after PD disruption, survival rates were similar to those in cases without PD disruption and were achieved through surgical resection or chemotherapy.\u003c/p\u003e","manuscriptTitle":"Treatment and Prognosis for Pancreatic Duct Disruption Associated with Pancreatic Cancer: a case series of 16 patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-05 16:56:45","doi":"10.21203/rs.3.rs-3978666/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":"de94e1ba-6cb6-470d-8ae4-31d6f589208c","owner":[],"postedDate":"March 5th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":29117277,"name":"Biological sciences/Cancer/Gastrointestinal cancer/Pancreatic cancer"},{"id":29117278,"name":"Biological sciences/Biological techniques/Imaging/Endoscopy"}],"tags":[],"updatedAt":"2024-04-22T05:10:58+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-05 16:56:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3978666","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3978666","identity":"rs-3978666","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}