[A case of biliary panperitonitis due to intrahepatic bile duct rupture with intrahepatic bile duct tumor].

An 87-year-old man visited his previous doctor because of jaundice, abdominal pain, and disturbance of consciousness. He was diagnosed with cholangitis and panperitonitis and was referred to our hospital. Emergency laparotomy revealed biliary peritonitis. However, the bile leak point was unclear. Two days after surgery, endoscopic retrograde cholangiopancreatography was performed and revealed hilar bile duct stenosis, slight dilation of the intrahepatic bile duct, and bile leakage from the peripheral left intrahepatic bile duct to the abdominal free space. Endoscopic nasobiliary drainage was performed, and bile leakage decreased. He was discharged from our hospital with improvement from jaundice and peritonitis. Intrahepatic bile duct rupture with neoplastic obstruction of the bile duct is extremely rare. To date, only two cases of intrahepatic bile duct rupture with intrahepatic cholangiocarcinoma have been published.

Impact of S-1 adjuvant chemotherapy longer than 6 months on survival in patients with resected pancreatic cancer: a nationwide survey by the Japan Pancreas Society based on real-world data.

BACKGROUND: Based on the Japan Adjuvant Study Group of Pancreatic Cancer 01 study, the standard duration of adjuvant chemotherapy with S-1 (an oral 5-fluorouracil prodrug consisting of tegafur, gimeracil, and oteracil) in patients with resected pancreatic ductal adenocarcinoma (PDAC) was considered to be 6 months, but the impact of increasing its duration on postoperative survival was unknown. Here, the authors investigated this question by reviewing real-world data from a large cohort of patients with PDAC. METHODS: In total, 3949 patients who underwent surgery for PDAC during the study period followed by S-1 adjuvant chemotherapy in board-certified institutions were included. Based on the duration of S-1 chemotherapy, two subgroups were defined: a standard-duration group that included patients who were treated for 180 ± 30 days and a longer duration group that included patients who received treatment for >210 days. RESULTS: The median duration of S-1 chemotherapy was 167 days, with a mean ± standard deviation of 200 ± 193 days. After excluding patients who had a recurrence within 210 days after the initiation of adjuvant chemotherapy, postoperative recurrence-free survival (RFS) and overall survival (OS) in the standard-duration group (n = 1473) and the longer duration group (n = 975) were compared. RFS and OS did not differ significantly between the standard-duration and longer duration groups (5-year RFS: 37.8% vs. 36.2% respectively; p = .6186; 5-year OS: 52.8% vs. 53.4%, respectively; p = .5850). The insignificant difference was verified by multivariate analysis and propensity-score matching analysis. CONCLUSIONS: The current findings suggest that extending S-1 adjuvant chemotherapy beyond 6 months has no significant additional effect on survival in patients with PDAC. This could be useful in determining whether to extend S-1 chemotherapy in patients who have completed the standard 6-month treatment.

Optimal Treatment for Octogenarians With Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma: A Multicenter Retrospective Study.

OBJECTIVES: The objective of this study was to clarify the role of pancreatectomy for patients with resectable and borderline resectable pancreatic ductal adenocarcinoma aged 80 years or older using a nationwide audit by the Japan Pancreas Society. METHODS: Data were collected from 39 institutions from 2007 to 2014. The primary endpoint was overall survival, and secondary endpoints were surgical outcomes and predictive factors for prognosis. RESULTS: Data were obtained from 556 octogenarians who underwent pancreatectomy (n = 369, 66%), chemo(radio)therapy (n = 99, 18%), and palliative therapy (n = 88, 16%). Median survival times were 20.6, 18.6, and 8.8 months in each group, respectively. Even after propensity score matching, median survival time in the surgery group (22.8 months) was significantly higher than that in the chemotherapy group (18.5 months; hazard ratio, 0.64 [95% confidence interval, 0.44-0.93]; P = 0.020). Significant independent prognostic factors were body mass index, lymph node metastasis, and tumor diameter in the surgery group, and serum albumin level, American Society of Anesthesiologists classification, body mass index, modified Glasgow prognostic score, second-line chemotherapy, and tumor diameter in the chemotherapy group. CONCLUSIONS: Octogenarians with resectable/borderline resectable pancreatic ductal adenocarcinoma can be recommended for pancreatectomy according to mental and physical fitness for surgical procedures.

Prognostic importance of peritoneal washing cytology in patients with otherwise resectable pancreatic ductal adenocarcinoma who underwent pancreatectomy: A nationwide, cancer registry-based study from the Japan Pancreas Society.

BACKGROUND: The importance of peritoneal washing cytology status both as a sign of irresectability and as a prognostic factor for pancreatic ductal adenocarcinoma remains controversial. The purpose of this nationwide, cancer registry-based study was to clarify the clinical implications of operative resection in patients who had positive cytology status. METHODS: Clinical data from 1,970 patients who underwent tumor resection were collected from the Pancreatic Cancer Registry in Japan. Clinicopathologic factors and overall survival curves were analyzed, and multivariate Cox proportional hazard models were evaluated. RESULTS: Among the 1,970 patients analyzed, positive cytology status was found in 106 patients and negative cytology status was found in 1,864 patients. The positive cytology status group had a greater frequency of pancreatic body and tail cancer and greater preoperative serum carbohydrate antigen 19-9 levels than the negative cytology status group (P < .001 each). The ratio of peritoneal recurrence tended to be greater in the positive cytology status group (14% vs 43%; P < .001). Overall median survival times were less in the positive cytology status group (17.5 months vs 29.4 months; P < .001). The 5-year survival rates were 13.7% and 31.1% in the positive cytology status and negative cytology status groups, respectively. Multivariate analysis of positive cytology status patients revealed that adjuvant chemotherapy was an independent prognostic factor. CONCLUSION: Positive cytology status was an adverse prognostic factor in patients who underwent resection for pancreatic ductal adenocarcinoma but did not preclude attempted curative resection. Curative resection followed by adjuvant chemotherapy may contribute to long-term prognosis in patients with positive cytology status.

Clinicopathological Characteristics of Young Patients With Pancreatic Cancer: An Analysis of Data From Pancreatic Cancer Registry of Japan Pancreas Society.

OBJECTIVES: The aim of this study was to determine the characteristics of patients with pancreatic ductal adenocarcinoma younger than 40 years. METHODS: Data from the Japan Pancreas Society's nationwide Pancreatic Cancer Registry were analyzed retrospectively. Clinicopathological characteristics were compared in patients who were grouped according to age, namely, younger than 40 years versus 40 years and older. RESULTS: Of the 36 145 patients in the database, the younger group included 526 (1.5%) patients. A family history of pancreatic cancer was not more frequent in the younger group. The frequency of Union Internationale Contre le Cancer T4 and M1 were both significantly higher in younger patients, resulting in a higher percentage of patients with Union Internationale Contre le Cancer stage IV. Pancreatectomy was performed less frequently in the younger group, and R0 resection was also less frequent. The overall survival rate was significantly better in the older group, whereas in surgically resected patients, the overall survival and recurrence-free survival rates were not different between the 2 groups. CONCLUSIONS: Younger patients with pancreatic adenocarcinoma were more often diagnosed at advanced stages, and the overall survival rate was worse than that in older patients. Family genetic background and the prognoses of patients who underwent surgery were similar between the 2 groups.

Natural history of branch duct intraductal papillary mucinous neoplasm with mural nodules: a Japan Pancreas Society multicenter study.

OBJECTIVE: This study aimed to elucidate the natural history of intraductal papillary mucinous neoplasm (IPMN) of the pancreas with mural nodules (MNs) in branch duct IPMN (BD-IPMN). METHODS: Among the 402 registered patients with BD-IPMN on long-term follow-up at 10 institutions in Japan, 53 patients with MNs of less than 10 mm in height detected by endosonography were included in this study. The morphological changes of the BD-IPMN in these patients and histologic findings of the resected specimen were investigated. RESULTS: The median height of the MNs at the initial diagnosis was 3 mm (range, 1-8 mm), and 12 (23%) of the 53 patients showed an increase in the height of the MNs during follow-up (mean duration, 42 months). Six patients underwent surgery because of an increase in the height of MNs, yielding high-grade dysplasia in 1 patient and low-grade dysplasia in 5 patients. No patients developed invasive carcinoma derived from IPMN, and distinct pancreatic ductal adenocarcinoma developed in 1 (2%) patient. The incidence of the development of malignancy in BD-IPMNs, including distinct pancreatic ductal adenocarcinoma, was similar to that of those without MNs. CONCLUSIONS: In patients who have BD-IPMN with MNs of less than 10 mm in height, observation instead of immediate resection is considered to be possible.

Multicenter study of serous cystic neoplasm of the Japan pancreas society.

OBJECTIVES: There have been only a few reports on follow-up results of serous cystic neoplasm (SCN) of the pancreas. The frequency of malignancy and surgical indication of SCN are not determined yet. METHODS: In this multi-institutional study of the Japan Pancreas Society, a total of 172 patients with SCN were enrolled. The mean follow-up period was 4.5 years. Surgical resection was performed in 90 patients, whereas the remaining 82 were simply observed. RESULTS: Of all patients, 20% were symptomatic. The tumor was located in the pancreatic head (39%), body (35%), and tail (22%). The mean diameter of the tumor was 4.1 cm. None of the patients showed distant or lymph node metastasis except for liver metastasis found in 2 patients (1.2%). No patient died during the follow-up. The preoperative diagnosis did not correctly identify SCN in 57 (63%) of 90 resected cases. A honeycomb appearance, which is one of the most characteristic findings of SCN, could be diagnosed better by endoscopic ultrasonography than by other imaging diagnostic modalities. CONCLUSIONS: Surgical resection should be considered only when clear distinction from other surgical diseases is difficult, when symptoms or mass effects are present, and when the tumor size is large.

The rate of polymyalgia rheumatica (PMR) and remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome in a clinic where primary care physicians are working in Japan.

We analyzed the rate of polymyalgia rheumatica (PMR) and remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome, both characterized as seronegative inflammatory arthritis in elderly, in an outpatient unit where primary care physicians are working in Japan to better understand the epidemiological characteristics of the diseases in Japan. Consecutive outpatients who newly visited at Department of General Medicine, Asahikawa Medical University Hospital, Japan, between April 2004 and March 2010 were analyzed. Each parameter such as age, sex, diagnosis, and biochemical examination was investigated. During the 6 years, 10 or 3 patients were diagnosed as PMR or RS3PE syndrome, respectively. The patients with PMR were 7 women and 3 men, and the average age at diagnosis was 69. Out of all patients aged over 50 (n = 3,347), the rate of PMR was 0.22% in men or 0.36% in women, respectively. On the other hand, RS3PE syndrome was diagnosed in 3 men (76, 76, and 81 years old). The rate of patients with RS3PE syndrome was 0.09% among outpatients aged over 50 indicating that the rate of PMR in an outpatient clinic in Japan is not far from previous findings reported from western countries. When compared with PMR, the rate of RS3PE syndrome was approximately one-third, providing for the first time the rate of RS3PE syndrome when compared with PMR. These epidemilogical data might help us pick up the diseases in primary care setting in Japan.

Localization of the most severely dysplastic/invasive lesions and mucin phenotypes in intraductal papillary mucinous neoplasm of the pancreas.

OBJECTIVE: The aim of this study was to define the relevance of mural nodules (MNs) as a "direct" indicator of malignancy of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. METHODS: Thirty-nine surgically resected IPMNs excluding obviously invasive carcinomas were examined. The distribution of the most severely dysplastic lesions was mapped on specimens. Immunohistochemical analysis for MUC1 and MUC2 was performed on sections containing the histologically predominant lesions and the most severely dysplastic areas. RESULTS: The presence of MNs correlated well with the histological grade of IPMN (P < 0.01); however, the most severely dysplastic lesions were associated with a flat/nonelevated area rather than MNs (78.9%). In the MUC1-positive subgroup, minimally invasive carcinoma was colocalized to MNs, whereas most severely dysplastic foci including minimally invasive carcinoma with components of mucinous and tubular adenocarcinoma were observed in the areas apart from MNs in the MUC2-positive and MUC1/2-negative subgroups, respectively. CONCLUSIONS: Although our data support the concept that MNs represent areas of higher-grade dysplasia within IPMN, development of invasive lesions from MNs may be limited to cases that are MUC1-positive. Careful attention should be paid to the emergence of invasive IPMN from flat foci in MUC2-positive and MUC1/2-negative cases.

Natural history of branch duct intraductal papillary mucinous neoplasms of the pancreas: a multicenter study in Japan.

OBJECTIVE: The aim of this study was to evaluate the long-term follow-up results of patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) without mural nodules (MNs) at 10 representative institutions in Japan. METHODS: We analyzed 349 follow-up BD-IPMN patients who had no MNs on endoscopic ultrasonography at initial diagnosis. RESULTS: Observation periods ranged from 1 to 16.3 years (median, 3.7 years). Sixty-two (17.8%) patients exhibited disease progression during follow-up. Twenty-two underwent surgery, leading to a pathological diagnosis of carcinoma in 9 and adenoma in 13. Although the remaining 287 (82.2%) showed no changes, 7 underwent surgery because of symptoms (n = 2), choice (n = 2), or development of pancreatic ductal adenocarcinoma (n = 3); all of them were diagnosed pathologically as adenomas. Of the 29 patients undergoing surgery, all 9 with carcinoma exhibited signs of progression, such as increased main pancreatic duct diameter and/or appearance of MNs. Pancreatic ductal adenocarcinomas and additional BD-IPMNs developed in 7 (2.0%) and 13 (3.7%), respectively. Overall, 320 (91.7%) patients were followed without surgery. CONCLUSIONS: Most BD-IPMN patients who had no MNs on endoscopic ultrasonography could be managed without surgery. However, careful attention should be paid to disease progression and the development of pancreatic ductal adenocarcinomas during follow-up.

Safety and long-term outcomes of endoscopic papillary balloon dilation in children with bile duct stones.

BACKGROUND: Although experience with diagnostic and therapeutic ERCP in children is growing, little is known about the safety and technical outcomes of endoscopic papillary balloon dilation (EPBD) in pediatric patients with bile duct stones (BDSs). OBJECTIVE: To assess the safety and long-term outcomes of EPBD in pediatric patients with BDSs. DESIGN: Case study. SETTING: Tertiary referral center. PATIENTS AND INTERVENTIONS: This study involved 5 children who had BDSs combined with gallstones who underwent EPBD. MAIN OUTCOME MEASUREMENTS: Successful EPBD, successful stone removal, procedure-related complications, and long-term outcomes. RESULTS: ERCP was successful in all cases, with cannulation and subsequent EPBD. Stone removal was performed in 1 session in all patients. No EPBD-related complications were observed in any patient. After EPBD, 1 patient subsequently underwent laparoscopic cholecystectomy for gallstones. The remaining 4 were followed without surgery. In 2 patients, gallstones were spontaneously passed from the bile duct into the duodenum. During the follow-up period, over a mean of 7.1 years (range 3.7-9.3 years), no recurrence of BDSs was observed in any patient. LIMITATIONS: Small number of patients. CONCLUSIONS: Although BDSs are rare in pediatric patients, EPBD may be a safe and effective technique for the management of such stones in some children.

Clinicopathological features and prognosis of mucinous cystic neoplasm with ovarian-type stroma: a multi-institutional study of the Japan pancreas society.

OBJECTIVE: The aim of this study was to elucidate the clinicopathological features and prognosis of mucinous cystic neoplasms (MCNs). MATERIALS AND METHODS: We performed a multi-institutional, retrospective study on a collected series of patients with MCN pathologically defined by ovarian-type stroma. Clinicopathological features and prognosis were investigated. RESULT: Mucinous cystic neoplasm was confirmed in 156 cases, including 129 adenomas (82.7%) and 21 noninvasive (13.4%) and 6 invasive carcinomas (3.9%). Patients with MCN were exclusively women (98.1%) with the mean age of 48.1 years. All but 1 MCN were in the pancreatic body/tail region with a mean size of 65.3 mm. Communication between the cyst and the pancreatic duct was found in 18.1%. The 3-, 5-, and 10-year survival rates were 97.6%, 96.6%, and 96.6%, respectively. A significant difference in the survival rates was observed between adenomas and carcinomas and between minimally invasive carcinomas and invasive carcinomas. Cyst diameter and presence of mural nodule were predictive of malignant MCN. CONCLUSIONS: Mucinous cystic neoplasm is a rare but distinctive pancreatic cystic neoplasm with a favorable overall prognosis. All MCNs should be resected to prevent malignant changes but can be observed for an appropriate time when the lesion is small without the presence of mural nodules.

Characteristics in patients with headache in an outpatient clinic in Japan.

BACKGROUND: Little is known about the prevalence of primary and secondary headache in clinics in Japan. The aim of this study is to characterize patients with headache in an outpatient unit where primary care physicians are working in Japan. METHODS: Consecutive outpatients who newly visited the Department of General Medicine, Asahikawa Medical College Hospital, Asahikawa, Japan between April 2005 and March 2009 were analyzed. Each parameter such as age, sex or diagnosis was investigated. RESULTS: Out of 4693 patients, 418 patients visited to our department because of headache. Primary headache was found in 167 patients (39.9%). The rate of tension-type headache (TTH) (30.8%) was highest, followed by migraine (9.1%). Approximately 3 times higher rate of migraine was observed in female patients when compared with male patients. In female patients, migraine was observed more frequently in younger patients. On the other hands, TTH was observed in almost all aged patients in males and females, and the rate of TTH peaks between the ages of 40 and 49 years in both sex. The present study also demonstrated that 8.4% of patients who chiefly complained of headache had been diagnosed as depression while 1.7% of remained patients had been diagnosed as depression, indicating 5-times higher rate of depression in patients with headache. CONCLUSION: All these results suggest that primary headache, especially TTH, is highly observed and depression should be considered in patients with headache in an outpatient clinic where primary care physicians are working in Japan.

Transplanting normal vascular proangiogenic cells to tumor-bearing mice triggers vascular remodeling and reduces hypoxia in tumors.

Blood vessels deliver oxygen and nutrients to tissues, and vascular networks are spatially organized to meet the metabolic needs for maintaining homeostasis. In contrast, the vasculature of tumors is immature and leaky, resulting in insufficient delivery of nutrients and oxygen. Vasculogenic processes occur normally in adult tissues to repair "injured" blood vessels, leading us to hypothesize that bone marrow mononuclear cells (BMMNC) may be able to restore appropriate vessel function in the tumor vasculature. Culturing BMMNCs in endothelial growth medium resulted in the early outgrowth of spindle-shaped attached cells expressing CD11b/Flt1/Tie2/c-Kit/CXCR4 with proangiogenic activity. Intravenous administration of these cultured vascular proangiogenic cells (VPC) into nude mice bearing pancreatic cancer xenografts and Pdx1-Cre;LSL-Kras(G12D);p53(lox/+) genetically engineered mice that develop pancreatic ductal adenocarcinoma significantly reduced areas of hypoxia without enhancing tumor growth. The resulting vasculature structurally mimicked normal vessels with intensive pericyte coverage. Increases in vascularized areas within VPC-injected xenografts were visualized with an ultrasound diagnostic system during injection of a microbubble-based contrast agent (Sonazoid), indicating a functional "normalization" of the tumor vasculature. In addition, gene expression profiles in the VPC-transplanted xenografts revealed a marked reduction in major factors involved in drug resistance and "stemness" of cancer cells. Together, our findings identify a novel alternate approach to regulate abnormal tumor vessels, offering the potential to improve the delivery and efficacy of anticancer drugs to hypoxic tumors.

Incidence of synchronous and metachronous pancreatic carcinoma in 168 patients with branch duct intraductal papillary mucinous neoplasm.

BACKGROUND/AIMS: Although branch duct intraductal papillary mucinous neoplasms of the pancreas (BD-IPMN) are being diagnosed with increasing frequency, the incidence of concomitant pancreatic carcinoma (PC) is not well known. We investigated the incidence and clinical features of synchronous and metachronous PC in patients with BD-IPMN. METHODS: We studied 168 BD-IPMN patients diagnosed by various imaging modalities, including endoscopic retrograde pancreatography, between 1990 and 2008. We reviewed the medical records and clinical features in both patients developing and not developing PC. The diagnosis of PC was histologically verified in all patients. RESULTS: PC was observed in 9 (5.4%) of 168 patients. Five were synchronously detected at the time of BD-IPMN diagnosis, whereas four were metachronously identified during the follow-up period. All PCs occurred in regions separate from the BD-IPMN lesion. All PCs represented histologically invasive ductal adenocarcinomas, whereas the BD-IPMN lesion was diagnosed as adenoma. Patients developing PC were significantly older than patients not developing PC (p = 0.017). The diameters of the BD-IPMN lesions and main pancreatic ducts were significantly smaller in patients developing PC than patients not developing PC (p = 0.013 and p < 0.001, respectively). CONCLUSIONS: It was not infrequent for PC to occur in the pancreas with BD-IPMN. Particular attention should therefore be paid to the development of PC, even in low-risk BD-IPMN, as well as to changes in BD-IPMN.

[A case of pancreatic carcinoma presenting as pancreaticopleural fistula with pancreatic pleural effusion].

A 63-year-old man was admitted with left pleural effusion, and an amylase level of 30994IU/l. A diagnosis of pancreaticopleural fistula was made, based on the findings of magnetic resonance cholangiopancreatography and endoscopic retrograde pancreatography (ERP). After the placement of an endoscopic naso-pancreatic drainage tube, the pleural effusion markedly reduced. When ERP was performed for internal drainage, the main pancreatic duct and stricture were biopsied and showed pancreatic ductal adenocarcinoma histologically. CT revealed a mass in the head of the pancreas. He underwent pylorus-preserving pancreaticoduodenectomy. To the best of our knowledge this is the first case of pancreatic carcinoma presenting as pancreaticopleural fistula with pancreatic pleural effusion. Clinicians should pay attention to the possible presence of cancer and pancreaticopleural fistula in patients with pancreatic pleural effusion.