Favorable Preoperative Exocrine Function Evaluated by 13C Trioctanoin Breath Test is a Significant Physiological Predictor of Pancreatic Fistula After Pancreaticoduodenectomy

Favorable Preoperative Exocrine Function Evaluated by 13C Trioctanoin Breath Test is a Significant Physiological Predictor of Pancreatic Fistula After Pancreaticoduodenectomy | 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 Favorable Preoperative Exocrine Function Evaluated by 13 C Trioctanoin Breath Test is a Significant Physiological Predictor of Pancreatic Fistula After Pancreaticoduodenectomy Hiroyuki Kato, Yukio Asano, Masahiro Ito, Norihiko Kawabe, Satoshi Arakawa, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-668860/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Aim The association between the pancreatic fistula (PF) after pancreaticoduodenectomy (PD) and preoperative exocrine function has yet to be elucidated. The aim of this study is to evaluate the association between the preoperative results of 13 C-trioctanoin breath test and occurrence of PF, showing the clinical relevancy of the breath test to predict the PF. Method In the present study, the subject were 80 patients who underwent 13 C trioctanoin breath test prior to PD from 2006 to 2018. We conducted the uni- and multivariate analyses to reveal the preoperative predictor of PF, showing the association of the 13 C trioctanoin absorption and incidence of PF. Results: Among 80 patients (Age:68.0+/-11.9, male/female:46/34, pancreatic ductal adenocarcinoma: PDAC/non-PDAC: 30/50), the incidence of PF is 12.5% (10/80). When we compared the levels of 13 C trioctanoin absorption between PF and non-PF group, preoperative fat absorption level is significantly higher than in the PF group than in the non-PF group (41.2+/-5.9 vs. 33.9+/-8.1, p = 0.019). Moreover, optimal cut-off value of the preoperative fat absorption level to predict PF was 38.0 (sensitivity:90%, specificity:74%, AUC:0.78, p = 0.005). Indeed, the incidence of PF was extremely higher in the patients whose value of breath test was greater than 38.0 (33%, 9/27) compared to the patients with those less than 38.0 (1.8%, 1/53). Conclusion Favorable preoperative fat absorption evaluated by 13 C trioctanoin breath test is a feasible and objective predictor of PF after PD. Surgery General Surgery 13C trioctanoin breath test pancreatic fistula postoperative fat absorption Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction The postoperative mortality after pancreatoduodenectomy (PD) has been reducing especially in high-volume centers because of the advancement of surgical skill and perioperative administration. 30-day and in-hospital mortality rates were reported to be 1.2 and 2.8%, respectively, by national clinical database from Japan 1 . However, postoperative pancreatic fistula (PF) is still a large threat to both patients and pancreatic surgeons, because it sometimes causes the postoperative fatal intraabdominal bleeding 2 , 3 and abscess 4 , 5 , and its incidence is still reported to be high (11-29.4%) in patients with soft pancreas 6 – 8 . Therefore, it is urgent to elucidate the global preoperative risk factor of PF and there has been several articles showing the preoperative risk factors such as obesity, fatty pancreas, narrow pancreatic duct, male and surgical technics et al 9 – 11 . However, most of these predictors might affect the incidence of PF in an indirect fashion. In contrast, we conjectured that preoperative favorable exocrine function, which could be associated with normal pancreas, directly affect the incidence of PF, because excessive secretion of pancreatic juice after PD might cause the disruption of the anastomotic site. However, this assumption remains unclear because it has been still clinically challenging to address the preoperative exocrine function, which is mainly represented by fat absorption. In terms of evaluating pancreatic exocrine functions, several articles have already reported the relevancy of various pancreatic function tests 12 – 17 . Indeed, BT- PABA (N-benzoyl-L-trypsyl-p-aminobenzoic acid), fecal chymotrypsin, fecal elastase-1testing (FE-1), fecal fat excretion test, and 13 C-trioctanoin breath test has been clinically employed for the evaluation of it. Among these usable testing, 13 C-trioctanoin breath test does not have a necessity of urine or stool collection, and also is not affected by hepato-renal function of subjected patients; thus, we consider possibly more acceptable for evaluating a perioperative pancreatic exocrine function. The aim of this study is to evaluate the association between the results of 13 C-trioctanoin breath test and occurrence of PF, showing the clinical relevancy of the breath test to predict the PF. Patients And Methods Among the 133 patients who underwent 13 C-labeled trioctanoin breath test before and after pancreatectomies in our institution from 2006 to 2018, the subjects were 80 patients who underwent PD and perioperative course and factors associating PF could be precisely evaluated. 13 C-labeled trioctanoin breath test, which directly and objectively reflects the ability of fat absorption, was performed one to three before the surgery. All of the patients were fasted overnight prior to the breath test. Breath samples were collected in 100ml bags with a one-way check valve. Samples were obtained 15 minutes prior to the test, and 0, 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 105, 120, 135, 150, 165, 180, 210 and 240 minutes after oral administration of 13 C-labeled trioctanoin including diet (Lacol 200kcal/200ml + fat component:20g). Fat absorption was evaluated by Aa (Aa=AUC ∞ Kel*Vd) [Kel:0.35, Vd:distribution volume], using a POCone→ which is the specific analyzer of 13 CO2 concentration in exhaled air. In the present study, we retrospectively compared pre-and postoperative fat absorption levels and their change rate during pancreatectomies between the groups with PF and non-PF. The medical ethics committee approved the study protocol of Fujita Health University School of Medicine (HM17165). In terms of surgical procedure of PD, we employed the inferior pancreaticoduodenal artery (IPDA) first approach to reduce the intraoperative blood loss 18 . A drain was removed until postoperative day (POD) 5 to 7 as long as drain discharge was clear and drain amylase level was not as three times high as the upper limit of serum amylase level (132U/ml). In all patients, amylase level of abdominal drainage fluid were measured until day 7 after PD. Pancreatic fistula was defined and graded according to the International Study Group on Pancreatic Fistula classification 19 . In the present study, we divided the subject into the patients with clinically relevant PF of Grade B or C and those with non-PF or biochemical leak. To identify pre- and intra-operative risk factors of pancreatic fistula, we compared various factors between these two groups. In terms of surgical procedure of PD, we employed the IPDA (inferior pancreatoduodenal artery)-first approach from 2007 18 . Briefly, IPDA is encircled and ligated before pancreatic resection, aiming the reduction of intraoperative blood loss ( Fig. 1 ) . For pancreatojejunostomy, the first-layer anastomosis was done by duct-to-mucosa anastomosis with 6–8 interrupted sutures by 5–0 PDS II (Ethicon, Inc.Somerville, NJ, USA). The second-layer anastomosis was done by the 6 to modified Kakita procedure using 3 − 0 proline 20 . A 5F external pancreatic stent tube were inserted in the remnant main pancreatic duct in all 80 patients. All statistical analyses were done by the statistical software package SPSS for Macintosh (version 24.0, IBM, Armonk, NY, USA). The results of the continuous variables were expressed as median and range, and statistical significance was evaluated by the Mann-Whitney U test. Discrete variables were evaluated by χ2 analysis or Fisher's exact test, as appropriate. Pre- and intraoperative risk factors associated with POPF were analyzed using univariate and multivariate analysis (logistic regression analysis). Only variables with p-values less than 0.05, as determined by univariate analysis, were included in the multivariate analysis. Results were considered significant when P values were less than 0.05. Receiver operating characteristic (ROC) curve analysis were employed to estimate the best cut-off points for the 13 C-trioctanoin breath test to predict PF. In the present study, the pancreatic configuration based on the imaging study, pancreatic texture and diameter of pancreatic duct intraoperatively evaluated were excluded by the items of univariate analysis because these factor might be strong confounding factors and the aim of this study is to find the objective, quantitative and physiological predictor of PF. Results Preoperative background of the 80 patients is shown in Table 1. In these 80 patients, the median age (range) was 69.5 (26-88) year-old, and males/females were 46/34. Primary disease was PDAC in 30, and non-PDAC in 50. In terms of preoperative lab data, the detail of blood cell counts, and several nutritional markers were described also in Table.1. The median operation time (min) and intraoperative blood loss (ml) were 469 (296-842) minutes and, 325 (23-4900) g, respectively. Regarding the Incidence of PF, clinically relevant PF (more than grade B according to ISGPF criteria) was found in 10 out of 80 (12.5%). With regard to the results of breath test, the values of Aa before PD were 34.4 (16.4-69.7) dose/hour. Pre- and intraoperative risk factors of POPF As shown in Table 2, univariate analysis by comparing preoperative risk factors between the PF group and non-PF group identified the pancreatic ductal adenocarcinoma (PDAC) (p=0.009) and favorable results of 13 C-trioctanoin breath test (p=0.005) as the significant risk factor of PF. Indeed, when we compared the levels of 13 C trioctanoin absorption between PF and non-PF group, preoperative fat absorption level is significantly higher than in the PF group than in the non-PF group (40.2 vs. 34.4, p=0.05). Moreover, optimal cut-off value of the preoperative fat absorption level to predict PF was 38.0 (sensitivity:90%, specificity:74%, AUC:0.78, p=0.005). Indeed, the incidence of PF was extremely higher in the patients whose value of breath test was greater than 38.0 (33%, 9/27) compared to the patients with those less than 38.0 (1.8%, 1/53). By multivariate analysis as shown in Table.3, preoperative 13 C trioctanoin breath test >38.0% dose/h were selected as the most independent risk factors for PF (p=0.001, Odd’s ratio:16.7). Next, we focused on the association between the incidence of PF and the level of 13 C trioctanoin breath test >38.0% dose/h in only non-PDAC patients because we considered that the prediction of PF in non-PDAC cases, that is mostly soft pancreas, is urgent issue to be solved. As the same manner of figure 2A, ROC curve revealed that the cut-off value was 37.9% dose/h (Area under the curve:AUC:0.78) (Figure 3A). As shown in figure3B, the incidence of PF was markedly high (39.0%, 9/23) in the patients with preoperative favorable fat absorption, whereas it was 3.7% (1/27) in the patients with unfavorable absorption (Figure 3b). Discussion In the present study, we newly elucidated the insight in which 13 C trioctanoin absorption (> 38.0% dose/h) were strong preoperative physiological predictor of PF after PD in not only total cohort, but also in non-PDAC patients whose pancreatic parenchyma could be soft. 13 C trioctanoin breath tests have been employed on the clinical settings to evaluate the pancreatic exocrine deficiency by detecting fat malabsorption through the gut after pancreatectomies 21 , 22 . Until now, however, there has been few studies evaluating whether preoperative exocrine function test affect the incidence of PF after PD 12 , 23 . To predict the development of PF preoperatively, a lot of researchers seek to find the relevant risk factors such as high BMI 24 , 25 , fatty pancreas 10 , 24 , 26 , male 27 , 28 and untreated jaundice 29 , and also developed the way of its prediction using various imaging modalities such as CT configurations (narrow main pancreatic duct 10 , thick pancreatic parenchyma 10 , pancreatic border 6 , CT attenuation value 30 ), MRI findings 31 , and pancreatic ultrasound elastography 32 , 33 et al. Even though these predictors might be clinically useful, most of these factors are strongly associated with the soft parenchymal condition, which cause a technical difficulty of anastomosis. Therefore, whether these risk factors are reproducible or not is also depending on the type of pancreato-enteral anastomosis and maturity of those procedures. On the other hands, the data obtained from 13 C trioctanoin breath test is more objective and quantitative, and especially in patients with Aa > 38.0 %dose/h, the PF incidence is extremely high regardless of parenchymal condition. Previous article mentioned the recovery of the 13 C-labeled trioctanoin absorption after PD positively associated with output of pancreatic enzymes such as lipase, amylase, and chymotrypsin 15 . Thus, we speculated the active production of pancreatic juice might be one of the major causes of PF after PD, and considered that outcome of the present study represented this aspect. In fact, our speculation is supported by the result showing that postoperative maximum drain amylase level (U/L) is significantly higher in patients with Aa > 38.0% dose/h than that in those with Aa < 38.0 (Fig. 4 ). According to the previous reports regarding the association between PF and results of pancreatic exocrine function test, several reports revealing that higher preoperative level of FE-1 was positively associated with the developments of postoperative PF 12 , 30 . However, there has been no study revealing the association between the result of 13 C-labeled trioctanoin and occurrence of PF. Therefore, to the best of our knowledge, Aa > 38.0% dose/h is considered to be first physiological quantitative predictor of PF. Clinical application of this study is challenging, because prevention of PF is quite difficult even if risky patients were identified preoperatively. the administration of octreotide or somatostatin analogs is well-accepted pharmacological treatment with PF targeting the secretion of pancreatic juice 34 , 35 . The effect of somatostatin analogs is to reduce the volume of fistula output, thereby potentially alleviating the PF 36 . Octreotide also has been considered to reduce the volume and potency of both pancreatic exocrine secretions and hormone production 37 . Since our study demonstrate that the favorable preoperative exocrine function, which in turn high output of pancreatic juice, is regarded as the risk factor of PF, administration of these drugs might become a key treatment of PF in these risky patients. However, prospective or randomized control study should be needed to show this hypothesis. The present research has several limitations. The first is that this study included only small number of patients. The second limitation is that the present analysis was a retrospective analysis, and we could not identify the precise mechanism how favorable pancreatic exocrine function cause the PF postoperatively. Therefore, the study is regarded as only an exploratory research. Nonetheless, our study could draw significant attention to the association between PF and preoperative pancreatic exocrine function. In conclusion, favorable pancreatic exocrine function evaluated by 13 C trioctanoin breath test preoperatively, is a feasible and objective predictor of PF after PD, paying attention to the development of PF in such high-risk patients. Abbreviations pancreatic fistula (PF), pancreaticoduodenectomy (PD), pancreatic ductal adenocarcinoma (PDAC), fecal elastase-1testing (FE-1), the inferior pancreaticoduodenal artery (IPDA), postoperative day (POD), Receiver operating characteristic (ROC), Area under the curve (AUC) Declarations Availability of data and materials The datasets analyzed during the current study available from the corresponding author on reasonable request. Authors’ contributions HK analyzed and drafted the manuscript. UA and AH participated data collection and assisted with data interpretation. MI, NK, SA, MS, DK, C, KK, TK, TO, HY, TH, DT, UK, HN TU, and AH reviewed and revised the manuscript. All authors read and approved the final manuscript. Competing interests The authors declare that they have no competing interests. Consent for publication Not applicable. Ethics approval and consent to participate This retrospective study was approved by the ethics committee of Fujita Health University School of Medicine (HM17165). and was conducted in accordance with the principles of the Declaration of Helsinki. Informed consent was obtained from all patients before treatment. Data availability statement: All the data generated or analyzed during this study are included within the article. Funding No funding was obtained for this study References Kimura W, Miyata H, Gotoh M, et al. A pancreaticoduodenectomy risk model derived from 8575 cases from a national single-race population (Japanese) using a web-based data entry system: the 30-day and in-hospital mortality rates for pancreaticoduodenectomy. Annals of surgery . 2014;259(4):773–780. Chipaila J, Kato H, Iizawa Y, et al. 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Background of 80 patients who underwentpancreaticoduodenectomy PD (n=80) Pre-operative variables Age (years) 69.5 (26-88) Gender (male / female) 46/34 Body weight (kg) 51.5 (33.0-96.0) Diagnosis PDAC/ non PDAC 30/50 Hemoglobin (g/dl) 12.7 (8.7-15.9) White blood cell counts (/mm2) 5200 (620-11300) Neutrophil (/mm2) 3200 (1365-8512) Lymphocyte (/mm2) 1470 (400-2940) Total protein (mg/dl) 6.9 (5.7-8.3) Albumin (mg/dl) 4.0 (2.5-5.0) Serum amylase (U/l) 90 (12-604) Total cholesterol 182 (120-282) Breath test (%dose/h) 34.4 (16.4-69.7) Intra-operative variables Operation time (min) 469.0 (296-842) Blood loss (g) 325 (23-4900) Post-operative variables Pancreatic fistula (yes/no) 10/70 Table. 2 Univariate analysis for identifying risk factor of PF non-PF (n=70) PF (n=10) P-value Pre-operative variables Age (years) 69.0 (43-88) 71.0 (26-79) 0.961 Gender (male / female) 38/32 8/2 0.114 Body weight (kg) 50.6 (33.0-83.5) 63.9 (44.3-96.0) 0.075 Diagnosis PDAC/ non PDAC 30/40 0/10 *0.009 Hemoglobin (g/dl) 12.8 (8.9-15.6) 12.1 (9.1-15.9) 0.708 White blood cell counts (/mm2) 5100 (3300-11300) 4950 (2100-8000) 0.782 Neutrophil (/mm2) 3245 (2046-8512) 2718 (1365-4880) 0.106 Lymphocyte (/mm2) 1428 (630-2438) 1760 (400-2940) 0.135 Total protein (mg/dl) 6.9 (4.7-8.3) 6.6 (6.7-7.8) 0.923 Albumin (mg/dl) 4.0 (2.5-4.7) 4.0 (2.7-5.0) 0.857 Serum amylase (U/l) 90 (12-604) 94.5 (45-218) 0.903 Total cholesterol 179 (120 -282) 195 (120-282) 0.295 Breath test (%dose/h) 33.4 (16.3-69.6) 40.2 (29.1-51.4) *0.005 Intra-operative variables Operation time (min) 466.5 (296-842) 489.0 (338-607) 0.813 Blood loss (g) 325.5 (23-4900) 321.0 (205-1545) 0.745 Table. 3 Results of multivariate analysis for identifying risk factor of PF There is no patients with PF in PDAC group PDAC:pancreatic ductal adenocarcinoma Variables Odd’s ratio 95% CI P-value PDAC Not applicant* 0.00-0.00 0.998 Preoperative breath test (>38) 16.7 0.007-0.522 0.001 Additional Declarations No competing interests reported. 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Kato","email":"data:image/png;base64,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","orcid":"","institution":"Fujita Health University School of Medicine, Bantane Hospital","correspondingAuthor":true,"prefix":"","firstName":"Hiroyuki","middleName":"","lastName":"Kato","suffix":""},{"id":44337584,"identity":"59cb74bb-fa80-4aba-a4e4-846dce4f5c6c","order_by":1,"name":"Yukio Asano","email":"","orcid":"","institution":"Fujita Health University School of Medicine, Bantane Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yukio","middleName":"","lastName":"Asano","suffix":""},{"id":44337585,"identity":"30b268c0-6725-47a8-8232-5b7db66507e7","order_by":2,"name":"Masahiro Ito","email":"","orcid":"","institution":"Fujita Health University School of Medicine, Bantane Hospital","correspondingAuthor":false,"prefix":"","firstName":"Masahiro","middleName":"","lastName":"Ito","suffix":""},{"id":44337586,"identity":"01137c38-5105-46b5-af47-d79a0d530ab9","order_by":3,"name":"Norihiko Kawabe","email":"","orcid":"","institution":"Fujita Health University School of Medicine, Bantane Hospital","correspondingAuthor":false,"prefix":"","firstName":"Norihiko","middleName":"","lastName":"Kawabe","suffix":""},{"id":44337587,"identity":"518250cb-1a06-42d3-8a0f-8d17cad08d8a","order_by":4,"name":"Satoshi Arakawa","email":"","orcid":"","institution":"Fujita Health University School of Medicine, Bantane Hospital","correspondingAuthor":false,"prefix":"","firstName":"Satoshi","middleName":"","lastName":"Arakawa","suffix":""},{"id":44337588,"identity":"ed0e2f74-676c-48e3-a0a7-8949afa53820","order_by":5,"name":"Masahiro Shimura","email":"","orcid":"","institution":"Fujita Health University School of Medicine, Bantane Hospital","correspondingAuthor":false,"prefix":"","firstName":"Masahiro","middleName":"","lastName":"Shimura","suffix":""},{"id":44337589,"identity":"15d8de19-c417-481d-a974-d4e5daedb0df","order_by":6,"name":"Daisuke Koike","email":"","orcid":"","institution":"Fujita Health University School of Medicine, Bantane Hospital","correspondingAuthor":false,"prefix":"","firstName":"Daisuke","middleName":"","lastName":"Koike","suffix":""},{"id":44337590,"identity":"4bb0e416-dd1a-4598-9977-1ee0aa18e879","order_by":7,"name":"Chihiro Hayashi","email":"","orcid":"","institution":"Fujita Health University School of Medicine, Bantane Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chihiro","middleName":"","lastName":"Hayashi","suffix":""},{"id":44337591,"identity":"7ead1b8e-8853-406f-9a23-f9f677c646ee","order_by":8,"name":"Kenshiro Kamio","email":"","orcid":"","institution":"Fujita Health University School of Medicine, Bantane Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kenshiro","middleName":"","lastName":"Kamio","suffix":""},{"id":44337592,"identity":"efe7c3c1-baba-4a6d-b50e-37a7815701d2","order_by":9,"name":"Toki Kawai","email":"","orcid":"","institution":"Fujita Health University School of Medicine, Bantane Hospital","correspondingAuthor":false,"prefix":"","firstName":"Toki","middleName":"","lastName":"Kawai","suffix":""},{"id":44337593,"identity":"3e168616-4fae-4936-9738-7047839b5b46","order_by":10,"name":"Takayuki Ochi","email":"","orcid":"","institution":"Fujita Health University School of Medicine, Bantane Hospital","correspondingAuthor":false,"prefix":"","firstName":"Takayuki","middleName":"","lastName":"Ochi","suffix":""},{"id":44337595,"identity":"6b7795ae-e833-4d80-bb9e-6a2a23443c4e","order_by":11,"name":"Hironobu Yasuoka","email":"","orcid":"","institution":"Fujita Health University School of Medicine, Bantane Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hironobu","middleName":"","lastName":"Yasuoka","suffix":""},{"id":44337598,"identity":"c361d6cb-0e99-413a-9e4f-105621275268","order_by":12,"name":"Takahiko Higashiguchi","email":"","orcid":"","institution":"Fujita Health University School of Medicine, Bantane Hospital","correspondingAuthor":false,"prefix":"","firstName":"Takahiko","middleName":"","lastName":"Higashiguchi","suffix":""},{"id":44337600,"identity":"3c8e0e66-d0e3-4ee4-992e-c162eeb46806","order_by":13,"name":"Daisuke Tochii","email":"","orcid":"","institution":"Fujita Health University School of Medicine, Bantane Hospital","correspondingAuthor":false,"prefix":"","firstName":"Daisuke","middleName":"","lastName":"Tochii","suffix":""},{"id":44337601,"identity":"35ece9e9-1f67-4d3b-9c35-34fb400ea2d8","order_by":14,"name":"Yuka Kondo","email":"","orcid":"","institution":"Fujita Health University School of Medicine, Bantane Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuka","middleName":"","lastName":"Kondo","suffix":""},{"id":44337602,"identity":"76378128-ca2e-465d-804c-1b2d300fb140","order_by":15,"name":"Hidetoshi Nagata","email":"","orcid":"","institution":"Fujita Health University School of Medicine, Bantane Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hidetoshi","middleName":"","lastName":"Nagata","suffix":""},{"id":44337604,"identity":"2cfb2c67-045e-4ae0-8a53-3a20f19d2bd2","order_by":16,"name":"Toshiaki Utsumi","email":"","orcid":"","institution":"Fujita Health University School of Medicine, Bantane Hospital","correspondingAuthor":false,"prefix":"","firstName":"Toshiaki","middleName":"","lastName":"Utsumi","suffix":""},{"id":44337605,"identity":"18cbf054-ea0d-4c66-9ca1-753d8db950f6","order_by":17,"name":"Akihiko Horiguchi","email":"","orcid":"","institution":"Fujita Health University School of Medicine, Bantane Hospital","correspondingAuthor":false,"prefix":"","firstName":"Akihiko","middleName":"","lastName":"Horiguchi","suffix":""}],"badges":[],"createdAt":"2021-06-29 14:29:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-668860/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-668860/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":12257144,"identity":"44664a31-42da-4ae9-b598-96979e03e7d4","added_by":"auto","created_at":"2021-08-09 17:51:25","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":593647,"visible":true,"origin":"","legend":"See image above for figure legend","description":"","filename":"Figure1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-668860/v1/503ce45c140308c8127b7f8a.jpeg"},{"id":12257146,"identity":"5630bebe-1747-4888-9717-b1b64290a3fa","added_by":"auto","created_at":"2021-08-09 17:51:25","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":156809,"visible":true,"origin":"","legend":"See image above for figure legend","description":"","filename":"Figure2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-668860/v1/7acd840485cebfa1b4a6f3cd.jpeg"},{"id":12257313,"identity":"168173a3-0913-4592-b586-dea187034f53","added_by":"auto","created_at":"2021-08-09 17:54:25","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":183000,"visible":true,"origin":"","legend":"See image above for figure legend","description":"","filename":"Figure3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-668860/v1/ca65e611a1753e44eb2f44cc.jpeg"},{"id":12257143,"identity":"2af2b529-8d2a-49da-b7c9-9c561b322e3f","added_by":"auto","created_at":"2021-08-09 17:51:25","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":117826,"visible":true,"origin":"","legend":"See image above for figure legend","description":"","filename":"Figure4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-668860/v1/532299f442a5d242be6531e5.jpeg"},{"id":15674539,"identity":"fe71be5f-e114-4504-bad4-9d6d4eb039ee","added_by":"auto","created_at":"2021-11-18 14:23:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":681403,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-668860/v1/c737e063-7301-4970-88a8-baa8a12b9181.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eFavorable Preoperative Exocrine Function Evaluated by \u003csup\u003e13\u003c/sup\u003eC Trioctanoin Breath Test is a Significant Physiological Predictor of Pancreatic Fistula After Pancreaticoduodenectomy\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe postoperative mortality after pancreatoduodenectomy (PD) has been reducing especially in high-volume centers because of the advancement of surgical skill and perioperative administration. 30-day and in-hospital mortality rates were reported to be 1.2 and 2.8%, respectively, by national clinical database from Japan\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. However, postoperative pancreatic fistula (PF) is still a large threat to both patients and pancreatic surgeons, because it sometimes causes the postoperative fatal intraabdominal bleeding\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e and abscess\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e, and its incidence is still reported to be high (11-29.4%) in patients with soft pancreas\u003csup\u003e\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Therefore, it is urgent to elucidate the global preoperative risk factor of PF and there has been several articles showing the preoperative risk factors such as obesity, fatty pancreas, narrow pancreatic duct, male and surgical technics et al\u003csup\u003e\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. However, most of these predictors might affect the incidence of PF in an indirect fashion. In contrast, we conjectured that preoperative favorable exocrine function, which could be associated with normal pancreas, directly affect the incidence of PF, because excessive secretion of pancreatic juice after PD might cause the disruption of the anastomotic site. However, this assumption remains unclear because it has been still clinically challenging to address the preoperative exocrine function, which is mainly represented by fat absorption.\u003c/p\u003e \u003cp\u003eIn terms of evaluating pancreatic exocrine functions, several articles have already reported the relevancy of various pancreatic function tests\u003csup\u003e\u003cspan additionalcitationids=\"CR13 CR14 CR15 CR16\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. Indeed, BT- PABA (N-benzoyl-L-trypsyl-p-aminobenzoic acid), fecal chymotrypsin, fecal elastase-1testing (FE-1), fecal fat excretion test, and \u003csup\u003e13\u003c/sup\u003eC-trioctanoin breath test has been clinically employed for the evaluation of it. Among these usable testing, \u003csup\u003e13\u003c/sup\u003eC-trioctanoin breath test does not have a necessity of urine or stool collection, and also is not affected by hepato-renal function of subjected patients; thus, we consider possibly more acceptable for evaluating a perioperative pancreatic exocrine function. The aim of this study is to evaluate the association between the results of \u003csup\u003e13\u003c/sup\u003eC-trioctanoin breath test and occurrence of PF, showing the clinical relevancy of the breath test to predict the PF.\u003c/p\u003e"},{"header":"Patients And Methods","content":"\u003cp\u003eAmong the 133 patients who underwent \u003csup\u003e13\u003c/sup\u003eC-labeled trioctanoin breath test before and after pancreatectomies in our institution from 2006 to 2018, the subjects were 80 patients who underwent PD and perioperative course and factors associating PF could be precisely evaluated. \u003csup\u003e13\u003c/sup\u003eC-labeled trioctanoin breath test, which directly and objectively reflects the ability of fat absorption, was performed one to three before the surgery.\u003c/p\u003e \u003cp\u003eAll of the patients were fasted overnight prior to the breath test. Breath samples were collected in 100ml bags with a one-way check valve. Samples were obtained 15 minutes prior to the test, and 0, 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 105, 120, 135, 150, 165, 180, 210 and 240 minutes after oral administration of \u003csup\u003e13\u003c/sup\u003eC-labeled trioctanoin including diet (Lacol 200kcal/200ml\u0026thinsp;+\u0026thinsp;fat component:20g). Fat absorption was evaluated by Aa (Aa=AUC\u0026thinsp;\u0026infin;\u0026thinsp;Kel*Vd) [Kel:0.35, Vd:distribution volume], using a POCone\u0026rarr; which is the specific analyzer of \u003csup\u003e13\u003c/sup\u003eCO2 concentration in exhaled air. In the present study, we retrospectively compared pre-and postoperative fat absorption levels and their change rate during pancreatectomies between the groups with PF and non-PF. The medical ethics committee approved the study protocol of Fujita Health University School of Medicine (HM17165). In terms of surgical procedure of PD, we employed the inferior pancreaticoduodenal artery (IPDA) first approach to reduce the intraoperative blood loss\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. A drain was removed until postoperative day (POD) 5 to 7 as long as drain discharge was clear and drain amylase level was not as three times high as the upper limit of serum amylase level (132U/ml).\u003c/p\u003e \u003cp\u003eIn all patients, amylase level of abdominal drainage fluid were measured until day 7 after PD. Pancreatic fistula was defined and graded according to the International Study Group on Pancreatic Fistula classification\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. In the present study, we divided the subject into the patients with clinically relevant PF of Grade B or C and those with non-PF or biochemical leak. To identify pre- and intra-operative risk factors of pancreatic fistula, we compared various factors between these two groups.\u003c/p\u003e \u003cp\u003eIn terms of surgical procedure of PD, we employed the IPDA (inferior pancreatoduodenal artery)-first approach from 2007\u003csup\u003e18\u003c/sup\u003e. Briefly, IPDA is encircled and ligated before pancreatic resection, aiming the reduction of intraoperative blood loss \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. For pancreatojejunostomy, the first-layer anastomosis was done by duct-to-mucosa anastomosis with 6\u0026ndash;8 interrupted sutures by 5\u0026ndash;0 PDS II (Ethicon, Inc.Somerville, NJ, USA). The second-layer anastomosis was done by the 6 to modified Kakita procedure using 3\u0026thinsp;\u0026minus;\u0026thinsp;0 proline\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. A 5F external pancreatic stent tube were inserted in the remnant main pancreatic duct in all 80 patients.\u003c/p\u003e\u003cp\u003eAll statistical analyses were done by the statistical software package SPSS for Macintosh (version 24.0, IBM, Armonk, NY, USA). The results of the continuous variables were expressed as median and range, and statistical significance was evaluated by the Mann-Whitney U test. Discrete variables were evaluated by χ2 analysis or Fisher's exact test, as appropriate. Pre- and intraoperative risk factors associated with POPF were analyzed using univariate and multivariate analysis (logistic regression analysis). Only variables with p-values less than 0.05, as determined by univariate analysis, were included in the multivariate analysis. Results were considered significant when P values were less than 0.05. Receiver operating characteristic (ROC) curve analysis were employed to estimate the best cut-off points for the \u003csup\u003e13\u003c/sup\u003eC-trioctanoin breath test to predict PF. In the present study, the pancreatic configuration based on the imaging study, pancreatic texture and diameter of pancreatic duct intraoperatively evaluated were excluded by the items of univariate analysis because these factor might be strong confounding factors and the aim of this study is to find the objective, quantitative and physiological predictor of PF.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003ePreoperative background of the 80 patients is shown in Table 1. In these 80 patients, the median age (range) was 69.5 (26-88) year-old, and males/females were 46/34. Primary disease was PDAC in 30, and non-PDAC in 50.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn terms of preoperative lab data, the detail of blood cell counts, and several nutritional markers were described also in Table.1. The median operation time (min) and intraoperative blood loss (ml) were 469 (296-842) minutes and, 325 (23-4900) g, respectively. Regarding the Incidence of PF, clinically relevant PF (more than grade B according to ISGPF criteria) was found in 10 out of 80 (12.5%). With regard to the results of breath test, the values of Aa before PD were 34.4 (16.4-69.7) dose/hour.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePre- and intraoperative risk factors of POPF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs shown in Table 2, univariate analysis by comparing preoperative risk factors between the PF group and non-PF group identified the pancreatic ductal adenocarcinoma (PDAC) (p=0.009) and favorable results of \u003csup\u003e13\u003c/sup\u003eC-trioctanoin breath test (p=0.005) as the significant risk factor of PF. Indeed, when we compared the levels of \u003csup\u003e13\u003c/sup\u003eC trioctanoin absorption between PF and non-PF group, preoperative fat absorption level is significantly higher than in the PF group than in the non-PF group (40.2 vs. 34.4, p=0.05). Moreover, optimal cut-off value of the preoperative fat absorption level to predict PF was 38.0 (sensitivity:90%, specificity:74%, AUC:0.78, p=0.005). Indeed, the incidence of PF was extremely higher in the patients whose value of breath test was greater than 38.0 (33%, 9/27) compared to the patients with those less than 38.0 (1.8%, 1/53). By multivariate analysis as shown in Table.3, preoperative \u003csup\u003e13\u003c/sup\u003eC trioctanoin breath test \u0026gt;38.0% dose/h were selected as the most independent risk factors for PF (p=0.001, Odd\u0026rsquo;s ratio:16.7).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNext, we focused on the association between the incidence of PF and \u0026nbsp;the level of \u003csup\u003e13\u003c/sup\u003eC trioctanoin breath test \u0026gt;38.0% dose/h in only non-PDAC patients because we considered that the prediction of PF in non-PDAC cases, that is mostly soft pancreas, is urgent issue to be solved.\u003c/p\u003e\n\u003cp\u003eAs the same manner of figure 2A, ROC curve revealed that the cut-off value was 37.9% dose/h (Area under the curve:AUC:0.78) (Figure 3A). As shown in figure3B, the incidence of PF was markedly high (39.0%, 9/23) in the patients with preoperative favorable fat absorption, whereas it was 3.7% (1/27) in the patients with unfavorable absorption (Figure 3b).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the present study, we newly elucidated the insight in which \u003csup\u003e13\u003c/sup\u003eC trioctanoin absorption (\u0026gt;\u0026thinsp;38.0% dose/h) were strong preoperative physiological predictor of PF after PD in not only total cohort, but also in non-PDAC patients whose pancreatic parenchyma could be soft.\u003c/p\u003e \u003cp\u003e \u003csup\u003e13\u003c/sup\u003eC trioctanoin breath tests have been employed on the clinical settings to evaluate the pancreatic exocrine deficiency by detecting fat malabsorption through the gut after pancreatectomies\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Until now, however, there has been few studies evaluating whether preoperative exocrine function test affect the incidence of PF after PD\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTo predict the development of PF preoperatively, a lot of researchers seek to find the relevant risk factors such as high BMI\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e, fatty pancreas\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e, male\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e and untreated jaundice\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e, and also developed the way of its prediction using various imaging modalities such as CT configurations (narrow main pancreatic duct\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e, thick pancreatic parenchyma\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e, pancreatic border\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e, CT attenuation value\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e), MRI findings\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e, and pancreatic ultrasound elastography\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e et al. Even though these predictors might be clinically useful, most of these factors are strongly associated with the soft parenchymal condition, which cause a technical difficulty of anastomosis. Therefore, whether these risk factors are reproducible or not is also depending on the type of pancreato-enteral anastomosis and maturity of those procedures. On the other hands, the data obtained from \u003csup\u003e13\u003c/sup\u003eC trioctanoin breath test is more objective and quantitative, and especially in patients with Aa\u0026thinsp;\u0026gt;\u0026thinsp;38.0 %dose/h, the PF incidence is extremely high regardless of parenchymal condition. Previous article mentioned the recovery of the \u003csup\u003e13\u003c/sup\u003eC-labeled trioctanoin absorption after PD positively associated with output of pancreatic enzymes such as lipase, amylase, and chymotrypsin \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Thus, we speculated the active production of pancreatic juice might be one of the major causes of PF after PD, and considered that outcome of the present study represented this aspect. In fact, our speculation is supported by the result showing that postoperative maximum drain amylase level (U/L) is significantly higher in patients with Aa\u0026thinsp;\u0026gt;\u0026thinsp;38.0% dose/h than that in those with Aa\u0026thinsp;\u0026lt;\u0026thinsp;38.0 (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAccording to the previous reports regarding the association between PF and results of pancreatic exocrine function test, several reports revealing that higher preoperative level of FE-1 was positively associated with the developments of postoperative PF\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. However, there has been no study revealing the association between the result of \u003csup\u003e13\u003c/sup\u003eC-labeled trioctanoin and occurrence of PF. Therefore, to the best of our knowledge, Aa\u0026thinsp;\u0026gt;\u0026thinsp;38.0% dose/h is considered to be first physiological quantitative predictor of PF.\u003c/p\u003e \u003cp\u003eClinical application of this study is challenging, because prevention of PF is quite difficult even if risky patients were identified preoperatively. the administration of octreotide or somatostatin analogs is well-accepted pharmacological treatment with PF targeting the secretion of pancreatic juice\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e. The effect of somatostatin analogs is to reduce the volume of fistula output, thereby potentially alleviating the PF \u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e. Octreotide also has been considered to reduce the volume and potency of both pancreatic exocrine secretions and hormone production \u003csup\u003e\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e. Since our study demonstrate that the favorable preoperative exocrine function, which in turn high output of pancreatic juice, is regarded as the risk factor of PF, administration of these drugs might become a key treatment of PF in these risky patients. However, prospective or randomized control study should be needed to show this hypothesis.\u003c/p\u003e \u003cp\u003eThe present research has several limitations. The first is that this study included only small number of patients. The second limitation is that the present analysis was a retrospective analysis, and we could not identify the precise mechanism how favorable pancreatic exocrine function cause the PF postoperatively. Therefore, the study is regarded as only an exploratory research. Nonetheless, our study could draw significant attention to the association between PF and preoperative pancreatic exocrine function. In conclusion, favorable pancreatic exocrine function evaluated by \u003csup\u003e13\u003c/sup\u003eC trioctanoin breath test preoperatively, is a feasible and objective predictor of PF after PD, paying attention to the development of PF in such high-risk patients.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003epancreatic fistula (PF), pancreaticoduodenectomy (PD), pancreatic ductal adenocarcinoma (PDAC), fecal elastase-1testing (FE-1), the inferior pancreaticoduodenal artery (IPDA), postoperative day (POD), Receiver operating characteristic (ROC), Area under the curve (AUC)\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets analyzed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHK analyzed and drafted the manuscript. UA and AH participated data collection and assisted with data interpretation. MI, NK, SA, MS, DK, C, KK, TK, TO, HY, TH, DT, UK, HN TU, and AH reviewed and revised the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective study was approved by the ethics committee of Fujita Health University School of Medicine (HM17165). \u0026nbsp;and was conducted in accordance with the principles of the Declaration of Helsinki. Informed consent was obtained from all patients before treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the data generated or analyzed during this study are included within the article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was obtained for this study\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKimura W, Miyata H, Gotoh M, et al. A pancreaticoduodenectomy risk model derived from 8575 cases from a national single-race population (Japanese) using a web-based data entry system: the 30-day and in-hospital mortality rates for pancreaticoduodenectomy. \u003cem\u003eAnnals of surgery\u003c/em\u003e. 2014;259(4):773\u0026ndash;780.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChipaila J, Kato H, Iizawa Y, et al. 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Oct 2008;12(10):1691-7; discussion 1697-8. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s11605-008-0636-2\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiang T-B, Bai X-L, Zheng S-S. Pancreatic fistula after pancreaticoduodenectomy: diagnosed according to International Study Group Pancreatic Fistula (ISGPF) definition. \u003cem\u003ePancreatology\u003c/em\u003e. 2007;7(4):325\u0026ndash;331.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKang JH, Park JS, Yu JS, et al. Prediction of pancreatic fistula after pancreatoduodenectomy by preoperative dynamic CT and fecal elastase-1 levels. \u003cem\u003ePLoS One\u003c/em\u003e. 2017;12(5):e0177052. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1371/journal.pone.0177052\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShi Y, Liu Y, Gao F, et al. 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Somatostatin analogues and the risk of post-operative pancreatic fistulas after pancreatic resection - A systematic review \u0026amp; meta-analysis. \u003cem\u003ePancreatology\u003c/em\u003e. Mar 2020;20(2):158\u0026ndash;168. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.pan.2019.12.015\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchorn S, Vogel T, Demir IE, et al. Do somatostatin-analogues have the same impact on postoperative morbidity and pancreatic fistula in patients after pancreaticoduodenectomy and distal pancreatectomy? - A systematic review with meta-analysis of randomized-controlled trials. \u003cem\u003ePancreatology\u003c/em\u003e. Oct 2020;doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.pan.2020.10.043\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan Buren G, Vollmer CM. The Landmark Series: Mitigation of the Postoperative Pancreatic Fistula. \u003cem\u003eAnn Surg Oncol\u003c/em\u003e. Oct 2020;doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1245/s10434-020-09251-6\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWilliams ST, Woltering EA, O'Dorisio TM, Fletcher WS. Effect of octreotide acetate on pancreatic exocrine function. \u003cem\u003eAm J Surg\u003c/em\u003e. May 1989;157(5):459\u0026ndash;62. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/0002-9610(89)90634-x\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Background of 80 patients who underwentpancreaticoduodenectomy\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.943502824858754%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"45.056497175141246%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePD (n=80)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.943502824858754%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Pre-operative variables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"45.056497175141246%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.943502824858754%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Age (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"45.056497175141246%\"\u003e\n \u003cp\u003e69.5 (26-88)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.943502824858754%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Gender \u0026nbsp;(male / female)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"45.056497175141246%\"\u003e\n \u003cp\u003e46/34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.943502824858754%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Body weight (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"45.056497175141246%\"\u003e\n \u003cp\u003e51.5 (33.0-96.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.943502824858754%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Diagnosis \u0026nbsp;PDAC/ non PDAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"45.056497175141246%\"\u003e\n \u003cp\u003e30/50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.943502824858754%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Hemoglobin (g/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"45.056497175141246%\"\u003e\n \u003cp\u003e12.7 (8.7-15.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.943502824858754%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;White blood cell counts (/mm2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"45.056497175141246%\"\u003e\n \u003cp\u003e5200 (620-11300)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.943502824858754%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Neutrophil (/mm2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"45.056497175141246%\"\u003e\n \u003cp\u003e3200 (1365-8512)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.943502824858754%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Lymphocyte (/mm2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"45.056497175141246%\"\u003e\n \u003cp\u003e1470 (400-2940)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.943502824858754%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Total protein (mg/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"45.056497175141246%\"\u003e\n \u003cp\u003e6.9 (5.7-8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.943502824858754%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Albumin (mg/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"45.056497175141246%\"\u003e\n \u003cp\u003e4.0 (2.5-5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.943502824858754%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Serum amylase (U/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"45.056497175141246%\"\u003e\n \u003cp\u003e90 (12-604)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.943502824858754%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Total cholesterol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"45.056497175141246%\"\u003e\n \u003cp\u003e182 (120-282)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.943502824858754%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Breath test (%dose/h)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"45.056497175141246%\"\u003e\n \u003cp\u003e34.4 (16.4-69.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.943502824858754%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Intra-operative variables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"45.056497175141246%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.943502824858754%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Operation time (min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"45.056497175141246%\"\u003e\n \u003cp\u003e469.0 (296-842)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.943502824858754%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Blood loss (g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"45.056497175141246%\"\u003e\n \u003cp\u003e325 (23-4900)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.943502824858754%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Post-operative variables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"45.056497175141246%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.943502824858754%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Pancreatic fistula (yes/no)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"45.056497175141246%\"\u003e\n \u003cp\u003e10/70\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable. 2\u003c/strong\u003e Univariate analysis for identifying risk factor of PF\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.83050847457627%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.785310734463277%\"\u003e\n \u003cp\u003e\u003cstrong\u003enon-PF (n=70)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.327683615819208%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePF (n=10)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.056497175141242%\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.83050847457627%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Pre-operative variables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.785310734463277%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"21.327683615819208%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.056497175141242%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.83050847457627%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Age (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.785310734463277%\"\u003e\n \u003cp\u003e69.0 (43-88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.327683615819208%\"\u003e\n \u003cp\u003e71.0 (26-79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.056497175141242%\"\u003e\n \u003cp\u003e0.961\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.83050847457627%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Gender \u0026nbsp;(male / female)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.785310734463277%\"\u003e\n \u003cp\u003e38/32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.327683615819208%\"\u003e\n \u003cp\u003e8/2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.056497175141242%\"\u003e\n \u003cp\u003e0.114\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.83050847457627%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Body weight (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.785310734463277%\"\u003e\n \u003cp\u003e50.6 (33.0-83.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.327683615819208%\"\u003e\n \u003cp\u003e63.9 (44.3-96.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.056497175141242%\"\u003e\n \u003cp\u003e0.075\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.83050847457627%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Diagnosis\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; PDAC/ non PDAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.785310734463277%\"\u003e\n \u003cp\u003e30/40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.327683615819208%\"\u003e\n \u003cp\u003e0/10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.056497175141242%\"\u003e\n \u003cp\u003e*0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.83050847457627%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Hemoglobin (g/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.785310734463277%\"\u003e\n \u003cp\u003e12.8 (8.9-15.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.327683615819208%\"\u003e\n \u003cp\u003e12.1 (9.1-15.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.056497175141242%\"\u003e\n \u003cp\u003e0.708\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.83050847457627%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;White blood cell counts (/mm2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.785310734463277%\"\u003e\n \u003cp\u003e5100 (3300-11300)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.327683615819208%\"\u003e\n \u003cp\u003e4950 (2100-8000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.056497175141242%\"\u003e\n \u003cp\u003e0.782\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.83050847457627%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Neutrophil (/mm2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.785310734463277%\"\u003e\n \u003cp\u003e3245 (2046-8512)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.327683615819208%\"\u003e\n \u003cp\u003e2718 (1365-4880)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.056497175141242%\"\u003e\n \u003cp\u003e0.106\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.83050847457627%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Lymphocyte (/mm2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.785310734463277%\"\u003e\n \u003cp\u003e1428 (630-2438)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.327683615819208%\"\u003e\n \u003cp\u003e1760 (400-2940)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.056497175141242%\"\u003e\n \u003cp\u003e0.135\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.83050847457627%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Total protein (mg/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.785310734463277%\"\u003e\n \u003cp\u003e6.9 (4.7-8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.327683615819208%\"\u003e\n \u003cp\u003e6.6 (6.7-7.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.056497175141242%\"\u003e\n \u003cp\u003e0.923\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.83050847457627%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Albumin (mg/dl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.785310734463277%\"\u003e\n \u003cp\u003e4.0 (2.5-4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.327683615819208%\"\u003e\n \u003cp\u003e4.0 (2.7-5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.056497175141242%\"\u003e\n \u003cp\u003e0.857\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.83050847457627%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Serum amylase (U/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.785310734463277%\"\u003e\n \u003cp\u003e90 (12-604)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.327683615819208%\"\u003e\n \u003cp\u003e94.5 (45-218)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.056497175141242%\"\u003e\n \u003cp\u003e0.903\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.83050847457627%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Total cholesterol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.785310734463277%\"\u003e\n \u003cp\u003e179 (120 -282)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.327683615819208%\"\u003e\n \u003cp\u003e195 (120-282)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.056497175141242%\"\u003e\n \u003cp\u003e0.295\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.83050847457627%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Breath test (%dose/h)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.785310734463277%\"\u003e\n \u003cp\u003e33.4 (16.3-69.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.327683615819208%\"\u003e\n \u003cp\u003e40.2 (29.1-51.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.056497175141242%\"\u003e\n \u003cp\u003e*0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.83050847457627%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Intra-operative variables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.785310734463277%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"21.327683615819208%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.056497175141242%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.83050847457627%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Operation time (min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.785310734463277%\"\u003e\n \u003cp\u003e466.5 (296-842)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.327683615819208%\"\u003e\n \u003cp\u003e489.0 (338-607)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.056497175141242%\"\u003e\n \u003cp\u003e0.813\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"39.83050847457627%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Blood loss (g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.785310734463277%\"\u003e\n \u003cp\u003e325.5 (23-4900)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.327683615819208%\"\u003e\n \u003cp\u003e321.0 (205-1545)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.056497175141242%\"\u003e\n \u003cp\u003e0.745\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable. 3\u0026nbsp;\u003c/strong\u003eResults of multivariate analysis for identifying risk factor of PF There is no patients with PF in PDAC group PDAC:pancreatic ductal adenocarcinoma\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.94915254237288%\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.45762711864407%\"\u003e\n \u003cp\u003e\u003cstrong\u003eOdd\u0026rsquo;s ratio\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.06779661016949%\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.52542372881356%\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.94915254237288%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePDAC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.45762711864407%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNot applicant*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.06779661016949%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.00-0.00\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.52542372881356%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.998\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"41.94915254237288%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePreoperative breath test (\u0026gt;38)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.45762711864407%\"\u003e\n \u003cp\u003e\u003cstrong\u003e16.7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.06779661016949%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.007-0.522\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.52542372881356%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsur","sideBox":"Learn more about [BMC Surgery](http://bmcsurg.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bsur/default.aspx","title":"BMC Surgery","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"13C trioctanoin breath test, pancreatic fistula, postoperative fat absorption","lastPublishedDoi":"10.21203/rs.3.rs-668860/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-668860/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eAim\u003c/h2\u003e \u003cp\u003eThe association between the pancreatic fistula (PF) after pancreaticoduodenectomy (PD) and preoperative exocrine function has yet to be elucidated. The aim of this study is to evaluate the association between the preoperative results of \u003csup\u003e13\u003c/sup\u003eC-trioctanoin breath test and occurrence of PF, showing the clinical relevancy of the breath test to predict the PF.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e \u003cp\u003eIn the present study, the subject were 80 patients who underwent \u003csup\u003e13\u003c/sup\u003eC trioctanoin breath test prior to PD from 2006 to 2018. We conducted the uni- and multivariate analyses to reveal the preoperative predictor of PF, showing the association of the \u003csup\u003e13\u003c/sup\u003eC trioctanoin absorption and incidence of PF.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eAmong 80 patients (Age:68.0+/-11.9, male/female:46/34, pancreatic ductal adenocarcinoma: PDAC/non-PDAC: 30/50), the incidence of PF is 12.5% (10/80). When we compared the levels of \u003csup\u003e13\u003c/sup\u003eC trioctanoin absorption between PF and non-PF group, preoperative fat absorption level is significantly higher than in the PF group than in the non-PF group (41.2+/-5.9 vs. 33.9+/-8.1, p\u0026thinsp;=\u0026thinsp;0.019). Moreover, optimal cut-off value of the preoperative fat absorption level to predict PF was 38.0 (sensitivity:90%, specificity:74%, AUC:0.78, p\u0026thinsp;=\u0026thinsp;0.005). Indeed, the incidence of PF was extremely higher in the patients whose value of breath test was greater than 38.0 (33%, 9/27) compared to the patients with those less than 38.0 (1.8%, 1/53).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eFavorable preoperative fat absorption evaluated by \u003csup\u003e13\u003c/sup\u003eC trioctanoin breath test is a feasible and objective predictor of PF after PD.\u003c/p\u003e","manuscriptTitle":"Favorable Preoperative Exocrine Function Evaluated by 13C Trioctanoin Breath Test is a Significant Physiological Predictor of Pancreatic Fistula After Pancreaticoduodenectomy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-08-09 17:51:23","doi":"10.21203/rs.3.rs-668860/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2021-09-03T06:28:49+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2021-08-09T13:21:27+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2021-08-07T08:23:19+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2021-08-07T08:18:08+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Surgery","date":"2021-06-29T14:25:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsur","sideBox":"Learn more about [BMC Surgery](http://bmcsurg.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bsur/default.aspx","title":"BMC Surgery","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2d6697b3-74a5-4372-9d17-dacec0464ec5","owner":[],"postedDate":"August 9th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":6303253,"name":"Surgery"},{"id":6303254,"name":"General Surgery"}],"tags":[],"updatedAt":"2022-01-27T06:14:12+00:00","versionOfRecord":[],"versionCreatedAt":"2021-08-09 17:51:23","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-668860","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-668860","identity":"rs-668860","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}