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A 73-year-old man with mixed-type intraductal papillary mucinous neoplasm of the pancreas body was followed up for 14 years. Based on imaging findings, the intraductal papillary mucinous neoplasm of the pancreas met the high-risk stigmata, and new hepatic masses were suspected to be intraductal papillary neoplasms of the bile duct. With a diagnosis of intraductal papillary mucinous neoplasm of the pancreas and intraductal papillary neoplasm of the bile duct, the patient had undergone left lateral hepatectomy and distal pancreatectomy. Based on pathology, the pancreatic specimen was diagnosed as a high-grade intraductal papillary mucinous neoplasm of the pancreas, and the hepatic specimen was diagnosed as an intraductal papillary neoplasm of the bile duct and hepatocellular carcinoma. The intraductal papillary neoplasms of the bile duct and hepatocellular carcinoma were adjacent to each other. Fifteen months after surgery, recurrence in the remnant pancreas was detected. The patient had undergone residual total pancreatectomy, with no recurrence thirty months after the second resection. This case demonstrates that second surgery for metachronous high-risk lesions in the remnant pancreas of patients with intraductal papillary mucinous neoplasm of the pancreas and intraductal papillary neoplasm of the bile duct may also be considered to improve survival., (© 2021. Japanese Society of Gastroenterology.)

The prognosis of Stage IV b pancreatic cancer is extremely poor; the mean survival time is 2-4 months. However, new anticancer agents can improve the outcome of advanced pancreatic cancer. We present the case of a 50-year-old female patient with Stage IV b pancreatic head cancer with invasion to the superior mesenteric vein(SMV)and multiple liver metastases. The patient received S-1 as first-line chemotherapy. Three months later, a further CT scan showed reduction of the pancreatic tumor, disappearance of the liver metastases, and reduction in SMV invasion. Therefore, a subtotal stomach-preserving pancreatoduodenectomy with partial SMV resection was performed. Following surgery, the patient received S-1 chemotherapy again. However, lung metastasis appeared. Despite the initiation of gemcitabine(GEM)treatment, the patient developed metastases in other parts of the lung and the abdominal wall. She died 46 months after surgery, but it is noteworthy that the liver metastases were manageable. The combination of chemotherapy and surgery was effective in prolonging survival in this patient with Stage IV b pancreatic head cancer.

Hemosuccus pancreaticus (HP) is mostly induced by a ruptured pseudoaneurysm or hemorrhage from a pseudocyst in chronic pancreatitis. We herein report a rare case with HP induced by tumor hemorrhage. The present patient is a 71-year-old woman referred to us with a diagnosis of severe progressive anemia. Endoscopy revealed hemorrhage from the papilla of Vater. Computed tomography showed a multilocular cystic tumor in the tail of the pancreas. The patient underwent a distal pancreatectomy. The histopathological diagnosis was carcinoma in mucinous cystadenoma. No cancer infiltration into the pancreatic duct was detected. Pancreatography of the resected specimen demonstrated an overt communication between the main pancreatic duct and the cystic cavity of the tumor, which was not demonstrated preoperatively by endoscopic retrograde pancreatography. Although the cause of HP is mainly acute or chronic pancreatitis, we should bear in mind that a pancreatic tumor may be a possible cause of HP and that, as such, prompt and proper treatment is mandatory.

Twenty-one patients with unresectable locally advanced pancreatic cancer were evaluated in this retrospective analysis. They received extra-beam radiotherapy(50.4-54 Gy/28-30 fractions)with concurrent continuous infusion of 5-FU(250 mg/m(2)day)between December 1999 and April 2007. The radiation field included primary tumor and adjacent lymph nodes. Twenty patients(95%)completed chemoradiotherapy, although one patient quit radiotherapy due to vomiting. No lethal side effects were observed. The response rate was 10%. One of the patients judged to have stable disease underwent resection after maintenance chemotherapy. The median progression free survival and the median overall survival were 6.4 and 12 months, respectively. In eleven patients(52%), the initial sites of disease progression were local or peritoneum without liver metastases, suggesting systemic effects of this treatment. In conclusion, 5-FU based chemoradiotherapyis well tolerated and provides definite benefits against unresectable locally advanced pancreatic cancer.

Background: Bile acid has an important role in protecting immune systems related to gut-associated lymphoid tissue. This study was designed to evaluate the effects of internal biliary drainage after a pancreaticoduodenectomy (PD) on postoperative nutrition and complications in a randomized study., Methods: The authors compared the morbidity, mortality, and postoperative nutritional status of 46 patients who had a hepaticojejunostomy (HJ) with a stented external biliary drainage (group E) or with a non-stented internal biliary drainage (group I) after a PD., Results: Systemic infection was recognized in four patients in group E, while no patients in group I. Transthyretin at postoperative 28 days in group I was 15.6 +/- 6.2, higher than that in group E. Retinol-binding protein at postoperative 28 days in group I was 2.6 +/- 1.0 and also higher than that in group E., Conclusion: HJ with no-stented internal biliary drainage was not associated with systemic infections and mortality, but showed the possibility of improving nutritional status.

Background: The prognosis of patients with advanced pancreatic cancer remains very poor. This study was designed to evaluate palliative pancreatic resection with postoperative gemcitabine chemotherapy., Methods: A total of 127 patients underwent palliative pancreatectomy or palliative nonresectable treatment with gemcitabine at Kobe University Hospital and were analyzed., Results: The median survival of patients receiving palliative pancreatectomy with gemcitabine was 15 months, and the 1- and 3-year survival rates were 60% and 13%, respectively, while that of patients receiving gemcitabine alone was only 8 months, and their 1- and 3-year survival rates were 26% and 0%. Multivariate analysis showed that gemcitabine was the strongest factor in survival, and no distant metastasis and pancreatectomy were also significant factors. In addition, the median survival of patients undergoing microscopically incomplete resection with gemcitabine was 22 months, and the 1- and 3-year survival rates were 60% and 40%. Pancreatectomy with gemcitabine improved the performance status 3 months after surgery, with longer survival compared with the gemcitabine alone group., Conclusions: Microscopically incomplete pancreatectomy with postoperative gemcitabine chemotherapy has a possible role in advanced pancreatic cancer.

Background: Our objective was to predict malignancy for intraductal papillary mucinous neoplasms of the pancreas (IPMN) before operation., Methods: Sixty-four resected patients with IPMN were examined and 17 parameters were investigated for their relation to malignancy by univariate and multivariate analysis., Results: Multivariate logistic regression analysis showed that IPMN type, the size of main pancreatic duct, and serum carbohydrate antigen 19-9 were significant for malignancy. Size of the main pancreatic duct > or = 6.5 mm and serum carbohydrate antigen 19-9 > or = 35 U/mL scored 3 points, main duct type scored 2 points, and patulous papilla, jaundice, diabetes mellitus, and tumor size > or = 42 mm scored 1 point. When IPMNs with 3 and more than 3 points using the new score were diagnosed as malignant, accuracy was 90.6%., Conclusion: This scoring system for IPMN is feasible to detect malignancy and useful for selecting an appropriate treatment.

We report herein two patients with acquired fatty replacement of the distal pancreas, who underwent pancreaticoduodenectomy (PD) without reconstruction of remnant pancreas. Slow-growing tumors resulted in obstructive pancreatitis of the distal pancreas and insufficient focal blood flow, resulting in marked atrophy of the pancreas and fatty replacement. Suspected disappearance and fatty replacement of the body and tail of the pancreas were noted. In this situation, the PD procedure can be achieved without the reconstruction of remnant pancreas. Interestingly, the patients did not require insulin support postoperatively.

Objectives: The prognosis of patients with advanced pancreatic cancer remains very poor. This study was designed to elucidate the prognostic factors of patients with pancreatic cancer to evaluate appropriate treatment with gemcitabine., Methods: Ninety-nine consecutive patients with stage IV pancreatic cancer were treated in the gemcitabine era at the Kobe University Hospital. Prognostic variables for survival were analyzed (sex, age, performance status, main site of the tumor, tumor size, major vessel invasion, distal metastasis, resection, gemcitabine, radiation, and pathological factors). The Cox proportional hazards model was used to determine the factors influencing the survival of patients with stage IV pancreatic cancer., Results: Multivariate analysis revealed that pancreatic resection, gemcitabine, and distant metastasis significantly influenced the survival of all patients with stage IV pancreatic cancer. Pancreatic resection and gemcitabine were significant factors influencing the survival of patients with stage IVa pancreatic cancer, whereas gemcitabine was the strongest factor influencing stage IVb pancreatic cancer., Conclusions: Gemcitabine has a possible role for stage IV pancreatic cancer.

Background: Our objective was to evaluate outcomes of surgery for intraductal papillary mucinous neoplasms of the pancreas (IPMN) in terms of the clinicopathological features., Methods: Fifty-seven patients with IPMN were examined using clinicopathological analyses to evaluate appropriate surgical treatment, including total pancreatectomy (TP). IPMN was classified into two types: main-duct type (MD, n = 33) and branch-duct type (BD, n = 24)., Results: Ultrasound (US) and computed tomography (CT) examinations easily revealed the main site of the lesions. Intraoperative US was the most useful device for diagnosis of lateral spreading, and accuracy rates were 74% for MD and 96% for BD. TP was performed on 16 patients and was appropriate for removing neoplastic lesions with malignancy or malignant potential in 12. Three patients who underwent partial pancreatectomy with involved cancer died of progressive disease. MD is a strong predictive factor in malignancy and indicative of TP. Concerning long-term outcomes, 5 of 16 patients suffered from severe hypoglycemia, and 2 of 16 died from this condition., Conclusion: Partial resection with cancer clearance was applied for BD-type IPMN. TP should be performed on selected patients with MD-type IPMN.

Mortality rate following pancreaticoduodenectomy has markedly decreased in high-volume centers. We achieved zero mortality among 100 pancreaticoduodenectomies in a middle-volume center. The purpose of this study was to review our experience and analyze factors contributing to the zero mortality. Patient backgrounds, intraoperative variables, postoperative complications, and surgical, radiologic, and other medical interventions for the complications were retrospectively analyzed for 100 consecutive pancreaticoduodenectomies for malignant or benign disease. The mean age of the patients was 63 years. Altogether, 59 patients had preoperative co-morbidity, and 35 had a past history of abdominal surgery. The median operating time and blood loss were 525 minutes and 1215 ml, respectively. Postoperative complications occurred in 42 patients. The most frequent complication was pancreatic stump leak (n = 12), but no life-threatening pancreatic anastomotic leak occurred. This may result from the duct invagination anastomosis applied to 67 pancreases with a small duct. Serious complications were seen in six patients; two patients required surgical intervention, but four were successfully treated with the help of interventional radiologists or internists. Radiologic intervention was applied to 13 patients: drainage of an intraabdominal abscess/collection and vascular intervention. In addition to advances in surgical techniques to reduce local complications, particularly pancreatic anastomotic leak, intimate collaboration with experienced interventional radiologists and internists allows zero mortality even in middle-volume centers.

Simultaneous resection of the colon with pancreaticoduodenectomy (PD) is occasionally inevitable to accomplish curative resection in instances when a periampullary tumor involves the mesentery of the colon. However, there is little information regarding short- and long-term outcomes of this aggressive surgery. Among 95 consecutive patients who underwent PD for periampullary malignant tumors, 12 had simultaneous resection of the right colon (group 1) and 83 underwent PD alone (group 2). Intraoperative variables, postoperative morbidity and mortality, and the length of the hospital stay were comparatively analyzed. Survival was also compared between the groups in a subset of 36 pancreatic adenocarcinoma patients. Group 1 included more patients with pancreatic cancer, and portal vein resection was more frequently performed, which seemed to be associated with a significantly longer operating time (640 vs. 510 minutes) and increased total blood loss (1965 vs. 1220 ml). However, morbidity and mortality rates did not differ between the groups (50,0% and 0%, respectively, in group 1; 44.6% and 1.2%, respectively, in group 2). The median hospital stays were 67 and 48 days in groups 1 and 2, respectively. In a subset of 36 pancreatic adenocarcinoma patients, the median progression-free survivals were 6 months in both groups 1 and 2; the median overall survivals were 14 months in group 1 and 12 months in group 2. There was no statistically significant difference in survival between the groups. Simultaneous right hemicolectomy with curative intent at the time of PD could thus be performed safely and may offer a survival benefit even for individuals who have advanced pancreatic cancers with involvement of the transverse mesocolon.

Background/aims: To achieve complete resection of pancreatic cancer, portal vein resection has been performed with increasing frequency at the time of pancreaticoduodenal resection (pancreaticoduodenectomy or total pancreatectomy). In the meantime, visceral congestion and liver ischemia are of great concern during the procedure. We investigated safety of portal vein resection using a centrifugal pump-assisted bypass between the superior mesenteric vein and the umbilical vein., Methodology: A retrospective comparison was performed in 49 consecutive patients who underwent pancreatoduodenal resection with or without portal vein resection using the bypass for pancreatic cancer. Twenty-two patients underwent portal vein resection using the bypass (group 1). The other 27 patients undergoing pancreatoduodenal resection without portal vein resection comprise the control group (group 2)., Results: Total operative time was 756 +/- 159 min and 526 +/- 109 min (p<0.001) and median blood loss was 2090 mL and 1200 mL in groups 1 and 2, respectively. However, the centrifugal pump-assisted bypass allowed stable bypass flow, and neither intestinal edema nor ischemic change of the liver was observed during portal vein resection and the subsequent reconstruction. Postoperatively, the peak postoperative AST, ALT and total bilirubin levels showed no significant difference and postoperative day of starting a liquid diet was similar between the groups (9.0 +/- 5.4 vs. 9.8 +/- 3.8 days, p=0.48). In addition, the rates of morbidity (55% vs. 48%) including biliary and pancreatic leak as well as mortality (9% vs. 4%) did not significantly differ between the 2 groups., Conclusions: The centrifugal pump-assisted bypass may be useful to prevent hepatic ischemia and visceral congestion during portal vein resection procedures, resulting in similar postoperative outcomes to the control after pancreaticoduodenal resection for pancreatic cancer.

Background: Recently a few centers reported promising results of regional intra-arterial chemotherapy for pancreatic cancer. However, the detailed pharmacokinetics and the side effects of anticancer agents remain unclear., Methods: Catheters were introduced into the gastroduodenal artery and the splenic artery of dogs. In group I, arterial infusion of 5-fluorouracil (5-FU) was performed over 10 minutes. In group II, 5-FU was infused systemically. In group III, an intra-arterial infusion was repeated weekly three times. Blood samples and liver and pancreas tissue samples were obtained to determine 5-FU levels. In a subset of each group, the pancreas, duodenum, and liver were excised for histological analyses., Results: Immediately after the infusion of 5-FU, the portal level in group I was higher than that in group II. However, the mean systemic level in group I was lower than in group II. The mean tissue concentration in the pancreas in group I was significantly higher than that of group II. Histological examination revealed no microscopic alterations after treatment in all groups, including group III., Conclusions: This fundamental study suggested that intra-arterial chemotherapy of 5-FU for pancreatic cancer allows higher regional drug delivery without adverse effects on normal regions of the pancreas, the duodenum, and the liver.

Background/aims: When pancreatic cancer cannot be resected, palliative procedures including gastroenteric bypass and biliary bypass may be selected. However, since predicting survival is difficult, indication of these procedures remains unclear. This study was designed to elucidate the prognostic factors of patients with unresectable pancreatic cancer in order to improve their quality of life., Methodology: We treated 187 consecutive patients with unresectable pancreatic cancer at the Kobe University Hospital. Fifteen prognostic variables for survival were analyzed (sex, age, the degree of pain, diet, presence of jaundice, main site of the tumor, tumor size, major vessel invasion, liver metastasis, peritoneal dissemination, distal metastasis and operative procedures) in surgically treated patients (n = 125). All patients were followed until death. Cox's proportional hazard model and logistic regression models were used to determine the factors influencing the survival of patients with unresectable pancreatic cancer., Results: Cox's proportional hazard model revealed that duodenal invasion (p = 0.001) and liver metastasis (p < 0.0001) significantly influenced the survival of the patients with unresectable pancreatic cancer. In multivariate logistic regression analysis, liver metastasis (p = 0.009) and peritoneal dissemination (p = 0.004) were significant factors on the six-month survival after palliative operation., Conclusions: Liver metastasis and peritoneal dissemination were negative predictive factors for the six-month survival of patients with unresectable pancreatic cancer. Palliative bypass surgery is recommended for patients expected to survive long-term (more than six-months).

Background/aims: This study was designed to evaluate risk factors influencing pancreatic leakage and pancreatic leakage-related mortality in a medium-volume hospital., Methodology: We retrospectively reviewed the clinical records of 107 patients who underwent pancreaticoduodenectomy at the Kobe University Hospital. Fourteen predictive factors for pancreatic leakage and the pancreatic leakage-related mortality were evaluated using univariate and multivariate logistic regression models., Results: In univariate analysis, the degree of pancreatic fibrosis, type of resection (PD/PPPD), anastomosis techniques (invagination or duct-to-mucosa anastomosis), anastomosis sites (jejunum/stomach), and the presence of congestion in anastomosis sites significantly influenced pancreatic leakage, and the degree of pancreatic fibrosis influenced pancreatic leakage-related mortality. Multivariate logistic regression analysis revealed that congestion in anastomosis sites was the strongest parameter for pancreatic leakage. Univariate analysis of the patients with normal/mild fibrosing pancreas revealed that pancreatic leakage was influenced by type of resection, anastomosis techniques, anastomosis sites, congestion in anastomosis sites and the management of pancreas parenchyma., Conclusions: In a medium-volume hospital, reconstruction after pancreaticoduodenectomy should be performed with careful attention to pancreas and anastomosis sites. In the patients with normal/mild fibrosing pancreas, duct-to-mucosa anastomosis without suturing the pancreas parenchyma may be a useful technique for reconstruction.