Is the ISGPS definition of pancreatic fistula applicable after gastrectomy?

BACKGROUND: Pancreatic fistula is one of the most common and potentially fatal surgical complications after radical gastrectomy. The purpose of this study was to assess the validity of extrapolating the definition of pancreatic fistula by the International Study Group on Pancreatic Surgery to include situations surrounding gastric cancer surgery. METHODS: The clinicopathological data of 443 patients who underwent elective gastrectomy with suprapancreatic lymph node dissection (D1+, D2, or D2+ dissection) without pancreatic resection were reviewed. The relationship between postoperative pancreas-related complications (PPRC) and laboratory data, including drain fluid amylase levels on postoperative day 1 (dAmy1) and day 3 (dAmy3), were investigated. RESULTS: Twenty-four patients (5.4%) developed PPRC of ≥ grade II according to Clavien-Dindo classification. Among them, 15 patients had dAmy3 levels ≥ 375 IU/L, while all 24 patients had dAmy1 levels ≥ 375 IU/L. None of the patients with dAmy1 levels < 375 IU/L developed PPRC. The area under the curve of dAmy1 and dAmy3, calculated by drawing receiver operating characteristic curves, were 0.896 and 0.791, respectively. Univariate and multivariate analyses demonstrated that both dAmy1 and dAmy3 were significant predictors of PPRC; however, dAmy1 (p < 0.001) was more strongly correlated with PPRC than dAmy3 (p = 0.049). CONCLUSIONS: DAmy1 is more sensitive than dAmy3 as an indicator of pancreatic fistula after gastric cancer surgery.

The Amount and Concentration of Drain Amylase Together Predict Postoperative Pancreatic Fistula after Gastric Cancer Surgery More Accurately than the Concentration Alone.

INTRODUCTION: The drain amylase concentration (dAmy-C) is a useful marker for predicting pancreatic fistula after gastric cancer surgery. However, dAmy-C might be reduced in cases of high drainage volume. Therefore, we hypothesized that we could accurately assess the amount of amylase leaked from the pancreas by multiplying dAmy-C by the daily drainage volume. In this study, we investigated the clinical utility of the amount of drain amylase (A-dAmy: concentration × volume) for predicting pancreatic fistula. We investigated the clinical utility of the combination of dAmy-C and A-dAmy for predicting pancreatic fistula. METHODS: We investigated patients who underwent gastrectomy for gastric cancer at Yodogawa Christian Hospital between 2012 and 2020. The optimal cutoff levels of dAmy-C and A-dAmy on postoperative day 1 for predicting Clavien-Dindo (CD) grade II or higher pancreatic fistula was calculated using receiver operating characteristic (ROC) curves. We calculate the positive predictive value and negative predictive value for predicting pancreatic fistula using these cutoff levels. RESULTS: A total of 448 patients were eligible for analysis. Twenty-two patients experienced CD grade II or higher pancreatic fistula. ROC curves identified 1,615 IU/L as the optimal cutoff level of dAmy-C, predicting pancreatic fistula. When the simple cutoff level of dAmy-C was 1,600 IU/L, the positive predictive value for was 22.8%, and the negative predictive value was 99.7%. ROC curves identified 177.52 IU as the optimal cutoff level of A-dAmy predicting pancreatic fistula. When the simple cutoff level of A-dAmy was 177 IU, the positive predictive value was 21.2%, and the negative predictive value was 99.7%. Using these two cutoff levels together, the positive predictive value was 34.4%, and the negative predictive value was 99.7%. CONCLUSION: A-dAmy could predict and exclude pancreatic fistula after gastrectomy as with dAmy-C. The combination of dAmy-C and A-dAmy predict pancreatic fistula more accurately than dAmy-C alone.

Influence of the Retrocolic Versus Antecolic Route for Alimentary Tract Reconstruction on Delayed Gastric Emptying After Pancreatoduodenectomy: A Multicenter, Noninferiority Randomized Controlled Trial.

OBJECTIVE: This study aimed to determine whether retrocolic alimentary tract reconstruction is noninferior to antecolic reconstruction in terms of DGE incidence after pancreatoduodenectomy (PD) and investigated patients' postoperative nutritional status. SUMMARY OF BACKGROUND DATA: The influence of the route of alimentary tract reconstruction on DGE after PD is controversial. METHODS: Patients from 9 participating institutions scheduled for PD were randomly allocated to the retrocolic or antecolic reconstruction groups. The primary outcome was incidence of DGE, defined according to the 2007 version of the International Study Group for Pancreatic Surgery definition. Noninferiority would be indicated if the incidence of DGE in the retrocolic group did not exceed that in the antecolic group by a margin of 10%. Patients' postoperative nutrition data were compared as secondary outcomes. RESULTS: Total, 109 and 103 patients were allocated to the retrocolic and antecolic reconstruction group, respectively (n = 212). Baseline characteristics were similar between both groups. DGE occurred in 17 (15.6%) and 13 (12.6%) patients in the retrocolic and antecolic group, respectively (risk difference; 2.97%, 95% confidence interval; -6.3% to 12.6%, which exceeded the specified margin of 10%). There were no differences in the incidence of other postoperative complications and in the duration of hospitalization. Postoperative nutritional indices were similar between both groups. CONCLUSIONS: This trial could not demonstrate the noninferiority of retrocolic to antecolic alimentary tract reconstruction in terms of DGE incidence. The alimentary tract should not be reconstructed via the retrocolic route after PD, to prevent DGE.

Impact of Albumin-Bilirubin Score on Short- and Long-Term Survival After Living-Donor Liver Transplantation: A Retrospective Study.

BACKGROUND: The albumin-bilirubin (ALBI) grade, stratified from the ALBI score, may have prognostic value in patients with hepatocellular carcinoma. We aim to evaluate the prognostic abilities of the ALBI score/grade among living-donor liver transplantation patients. METHODS: We retrospectively collected data of 81 patients who underwent living-donor liver transplant at Kobe University Hospital between June 2000 and October 2018. The efficacy of the ALBI score/grade as a prognostic factor was assessed and compared with that of the well-established Model for End-Stage Liver Disease (MELD) score. MAIN FINDINGS: Multivariate analysis indicated that recipient age (P = .003), donor age (P = .003), ALBI score ≥ -1.28 (P = .002), and ALBI grade III (P = .004) were independently associated with post-transplant survival. A high MELD score was not associated with post-transplant survival in univariate or multivariate analyses. Although there was no significant difference in the overall survival rate relative to recipient and donor age, ALBI score/grade was significantly associated with the 1- and 5-year survival rates (P = .023, P = .005). ALBI scores specifically detected fatal complications of post-transplant graft dysfunction (P = .031) and infection (P = .020). CONCLUSION: ALBI score/grade predicted patient survival more precisely than the MELD score did, suggesting that it is a more useful prognostic factor compared to the MELD score in living-donor liver transplantation cases.

Effectiveness of omega-3 fatty acid administration on completion rate of adjuvant chemotherapy for biliary tract cancer: study protocol for a single-centre, open-label, single-arm, historically controlled study.

INTRODUCTION: Multimodal treatment prolongs the survival of patients with biliary tract cancer (BTC). However, the chemotherapy choices for this disease are few, and completing each chemotherapy session is important. Adjuvant chemotherapy has been attempted for BTC, but has only had a 75% completion rate. Body weight loss and cholangitis are reasons for the interruption of chemotherapy. Previous reports suggested that nutritional intervention with omega-3 fatty acids maintained body weight and improved the completion rate for chemotherapy. Moreover, omega-3 fatty acids have an anti-inflammatory effect. Therefore, we theorised that omega-3 fatty acids would improve the completion rate of adjuvant chemotherapy in patients with BTC. The aim of this study is thus to evaluate the effectiveness of omega-3 fatty acids for patients planning adjuvant chemotherapy for BTC. METHOD AND ANALYSIS: This study is a single-centre, open-label, single-arm, historically controlled study with a planned enrolment of 55 participants. Protocol treatment consists of four courses of S-1 adjuvant chemotherapy and an oral omega-3 fatty acid pharmaceutic adjuvant (LOTRIGA 2 g (Takeda Pharmaceutical Co.)), which includes 2 g of omega-3 fatty acids from day 1 until day 168 of the treatment period. The primary endpoint is the completion rate of four total courses of S-1. Secondary endpoints are postoperative cholangitis, time to recurrence or distant metastasis, changes in nutritional index, changes in the lymphocyte blast transformation test induced by phytohaemagglutinin, and concanavalin A and diamine oxidase serum activity during adjuvant chemotherapy. All adverse events will be evaluated. ETHICS AND DISSEMINATION: This protocol was approved by the Institutional Review Board of Kobe University Hospital. The findings from this study will be presented at national and international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: UMIN000031247.

Efficacy of the bile leak test using contrast-enhanced intraoperative ultrasonic cholangiography in liver resection: a study protocol for a non-randomised, prospective, off-label, single-arm trial.

INTRODUCTION: Bile leak is still a major complication after liver resection to be improved. To intraoperatively detect this adverse complication, leak test is commonly performed after hepatic resection. However, by the conventional leak test, it is often difficult to know whether the test reagent reaches to intrahepatic bile duct near cut surface of liver with adequate volume and pressure to identify the existence of bile leak. Thus, in order to perform leak test more accurately, this study aims to evaluate the efficacy and safety of the leak test using contrast-enhanced intraoperative ultrasonic cholangiography (CE-IOUSC), which was reported by our group as a procedure for detection of bile duct. METHODS AND ANALYSIS: The current study is a non-randomised, prospective, off-label, single-arm clinical trial for patients who undergo liver resection. A total of 100 patients will be enrolled. After completion of liver resection, the leak test is performed with CE-IOUSC using Sonazoid as a contrast agent to visualise dye injection into the intrahepatic bile duct. The primary endpoint is the success of the leak test, defined as clear visualisation of intrahepatic bile duct around cut surface by ultrasonography that indicates enough volume of dye injection. Secondary endpoints are postoperative bile leak and all adverse events related to CE-IOUSC. The findings obtained through this study will establish this procedure to assist surgeons for adequately performing the leak test, precisely detecting intraoperative biliary leak strictly and reducing postoperative bile leak. ETHICS AND DISSEMINATION: The protocol is approved by Institutional Review Boards of Kobe University Hospital (No.290069). Our findings will be widely disseminated through conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: UMIN000031236 and jRCTs051180027.

[Analysis of Hepatectomy for Extreme Elderly Patients with Hepatocellular Carcinoma].

Although the first-line treatment for hepatocellular carcinoma(HCC)is hepatectomy, extreme elderly(80 years or older) patients often tend to have a variety of underlying diseases and decreased cardiopulmonary function, which means that surgery involves a high risk. In this case, we examined the safety and efficacy of hepatectomy performed in an extreme elderly patient with HCC. Of the patients with HCC that underwent initial hepatectomy at Kobe University Hospital(n=348)between 2009 and 2015, 23 patients aged 80 years or older at the time of surgery(Group 1, n=23)and those younger than 80 years at the time(Group 2, n=325)were compared, based on parameters related to safety and prognosis. We did not identify differences between the 2 groups with respect to blood loss and operating time. Intraoperative blood transfusion was more common in Group 1. There was no significant difference between the 2 groups with respect to complications of Grade Ⅲ or higher. The median survival of Group 2 patients following hepatectomy(42 months)was better than that of Group 1 patients(34 months), but there was no significant difference between the 2 groups(p=0.429). Furthermore, when the same parameters were compared after adjusting for and matching propensity scores, there were no significant differences in complications, hospitalization periods, and prognosis between the 2 groups. Through proper assessment of oncologic factors and patient risk factors, hepatectomy can be performed safely and effectively even for extreme elderly patients with HCC. If there is no other disease regulating the prognosis, we can expect to achieve similar prognosis in non-extreme elderly patients. Hence, treatments should not be limited solely based on a patient being extremely elderly; rather, proactive treatments should be considered.

[Analysis of Surgical Resection for Elderly Patients with Biliary Tract Cancer].

Although surgical resection is the first-line treatment for biliary tract cancer(BTC), elderly patients often have underlying diseases and decreased cardiopulmonary function that place them at a high risk of undergoing surgery. We examined the safety and efficacy of surgical resection in elderly BTC patients. Among the BTC cases that underwent surgical resection at Kobe University Hospital from 2009 to 2015, the safety and prognosis ofthose aged 75 years or older(Group 1)were compared to those younger than 75 years(Group 2)at the time ofsurgery. Fifty-two patients with perihilar cholangiocarcinoma( Bp), 29 patients with intrahepatic cholangiocarcinoma(ICC), and 40 patients with ampulla ofVater cancer(AV) were included. There was no significant difference between the 2 groups with respect to complications of Grade Ⅲor above, while surgery-related death was more common in Bp and ICC ofGroup 1. The median survival ofGroup 1 following hepatectomy for Bp and ICC(22 months)was significantly shorter than that of Group 2(40 months)(p=0.023). There was no significant difference in overall survival of Group 1 and Group 2 patients with AV(p=0.094). Surgical resection for BP and ICC for elderly patients has a higher risk of hepatectomy; therefore, precise assessment of oncologic and patient risk factors should be performed. As we can expect to achieve similar prognoses between non-elderly and elderly patients with AV, aggressive treatments should be considered for elderly patients with AV.

Pathological and Radiological Splenic Vein Involvement are Predictors of Poor Prognosis and Early Liver Metastasis After Surgery in Patients with Pancreatic Adenocarcinoma of the Body and Tail.

BACKGROUND: The prognostic impact of pancreatic ductal adenocarcinoma (PDAC) invasion to the splenic vessel is controversial. OBJECTIVE: The aim of this study was to assess the clinical value of pathological and radiological splenic vessel invasion in PDACs of the body and tail. METHODS: Medical records of patients with resectable PDAC of the body and tail who underwent distal pancreatectomy between 2003 and 2016 at the Kobe University Hospital were retrospectively analyzed. RESULTS: Overall, 68 patients (29 female and 39 male patients) were enrolled. Pathologically determined splenic vein invasion (p-SV) and splenic artery invasion (p-SA) were identified in 21 (30.9%) and 5 (7.4%) patients, respectively. The p-SV (but not p-SA) was an independent prognostic factor in multivariate analysis (p = 0.009). On analysis of recurrence patterns, patients with PDAC positive for p-SV were at a higher risk for liver metastasis (p = 0.022); however, the associations were not significant for other recurrence patterns. Liver metastasis occurred earlier in patients who were positive for p-SV (p = 0.015). Preoperative computed tomography effectively diagnosed pathological vessel invasion (SV: sensitivity, 95.2%, specificity, 72.3%; SA: sensitivity, 100%, specificity, 84.1%). Radiological SV invasion remained significant in multivariate analysis regarding postoperative survival (p = 0.007), and was also associated with early liver metastases (p = 0.008). CONCLUSIONS: Pathological/radiological SV invasion were independent adverse prognostic factors associated with early liver metastasis in patients with PDAC of the body/tail. Assessment of these findings may be useful in determining optimal therapeutic options in these patients.

[A case of recurrent sigmoid colon cancer with multiple peritoneal and liver metastases controlled effectively by resection].

A 71 year -old man underwent sigmoid colectomy for sigmoid colon cancer. A solitary liver metastasis found on examination 8 months after the initial surgery was resected. One year after the second surgery, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) revealed multiple peritoneal and liver metastases, and laparotomy was performed. All metastatic lesions were resectable or controllable. Eight peritoneal and 3 hepatic lesions were removed surgically and 1 hepatic lesion was treated with radiofrequency ablation. Eight months after the third surgery FDGPET and CT examination again revealed recurrence of liver and peritoneal metastases. Chemotherapy was ineffective and metastases progressed and resulted in death 26 months after the third surgery (39 months after the initial recurrence). We suggest that aggressive resection for multiple peritoneal and liver metastases can be an effective therapy for selected patients with recurrent colon cancer.

[A case in which chemotherapy-resistant sigmoid colon cancer was controlled effectively by radiotherapy and resection].

A 53-year-old woman underwent sigmoid colectomy for sigmoid colon cancer with peritoneal metastasis. Liver and intrapelvic metastases were found upon examination 6 months after surgery during adjuvant chemotherapy with XELOX plus bevacizumab. After hepatic subsegmentectomy, the patient received S-1 treatment in combination with radiotherapy for the intrapelvic metastasis. One year after the second surgery, abdominoperineal rectal resection was performed as the intrapelvic tumor had increased in size. At 16 months after the third surgery, computed tomography( CT) revealed a small lung nodule that gradually increased in size. The patient underwent partial lung resection. The nodule was a recurrence of the sigmoid colon cancer. During this period, the patient was treated again with S-1 combined with radiotherapy because 2 intrapelvic metastases had been identified. At present, these metastases have been well controlled for 3 years after the initial recurrence. Thus, it is suggested that aggressive radiotherapy and resection are effective therapies for recurrence of chemotherapy-resistant colon cancer.

[A case of advanced gastric cancer responding to combined systemic and intraperitoneal chemotherapy with docetaxel, cisplatin, and S-1].

The patient was a 50-year-old man diagnosed as having a large type 3 advanced gastric cancer with para-aortic lymph node metastasis and with positive peritoneal cytology. We administered a combined systemic and intraperitoneal chemotherapy involving docetaxel, cisplatin, and S-1 (DCS). After 2 courses of treatment, the primary tumor and lymph nodes were significantly reduced in size, suggesting that this therapy induced a partial response (PR). No cancer cells were observed in the peritoneal cytology, and therefore, we performed curative total gastrectomy with para-aortic lymph node dissection. Histological findings revealed that there were no cancer cells in either the primary tumor or the lymph nodes, and pathological grading indicated that the resected lesions were grade 3. Adjuvant chemotherapy with S-1 was administered after surgery. At 18 months after surgery, the patient is still alive and free of disease.

[A case of recurrent duodenal carcinoma successfully controlled with FOLFOX treatment].

A 60-year-old woman was diagnosed as having duodenal cancer by upper gastrointestinal endoscopy and biopsy. Pylorus-preserving pancreatoduodenectomy was performed. Pathological findings suggested T4(CBD)N1M0 primary duodenal carcinoma. Adjuvant chemotherapy with S-1(80 mg/m² of S-1 administered for 2 weeks followed by a 1-week drug-free period)was administered after surgery. One year after the surgery, computed tomography(CT)scans showed swelling of the paraaortic lymph nodes. Recurrence of the duodenal carcinoma was diagnosed, and gemcitabine chemotherapy was initiated. Eight months later, CT scans revealed lung metastasis. The patient was then treated with oxaliplatin in combination with infusional 5-fluorouracil/Leucovorin(FOLFOX regimen). After completing 6 courses of the chemotherapy regimen, CT scans showed a partial response(PR). Currently, at 1 year, PR has been maintained. Therefore, we suggest that the FOLFOX regimen can be highly effective for the treatment of patients with duodenal carcinoma.

[A case involving long-term survival following bile duct cancer with para-aortic lymph node metastasis that was treated by multidisciplinary therapy].

Complete resection of advanced bile duct cancer is difficult due to the anatomical location of the tumor and invasion into other organs. Even if a complete resection is achieved, the survival rates of patients with bile duct cancer after surgery are lower as compared to those associated with other gastrointestinal tumors. Certain cases with para-aortic lymph node metastasis have a poor prognosis. In the present report, we describe a case involving long-term survival following bile duct cancer that was treated by multidisciplinary therapy (particle radiotherapy, surgical resection, chemotherapy). In the present case, we detected lymph node (LN) metastasis only in LN#16, but not in LN#13 or LN#17. We believe that particle radiotherapy, consisting of proton and carbon-ion, can be used to control the lymphatic metastasis around the pancreas head and hepatoduodenal ligament. Our findings suggest that particle radiotherapy can be a standard neoadjuvant therapy for bile duct cancer.

[Mucinous cystic neoplasm of the pancreas associated with pregnancy: report of two cases].

Pancreatic neoplasms during pregnancy are rare. We describe two cases of mucinous cystic neoplasm (MCN) associated with pregnancy. A 34-year-old woman in the 26th week of pregnancy was given a diagnosis of MCN measuring 19 cm in diameter. We decided to resect it post partum in consideration of the risk of abortion. She had a healthy infant in the 40th week of pregnancy and three months later, distal pancreatectomy was performed. Pathological analysis revealed a mucinous cystadenoma of the pancreas. The second case was a 36-year-old woman. She was given a diagnosis of MCN, measuring 16 cm in diameter, post partum and distal pancreatectomy was performed. Pathologically, the tumor was an invasive mucinous cystadenocarcinoma of the pancreas. In this report, we did an extensive literature review and discussed the management of MCN during pregnancy with special reference to the timing of the operation and the relationship between tumor growth and sex hormones.