Cystic lymphangioma of the pancreas with spontaneous rupture: report of a case.

Lymphangioma is a benign and congenital malformation of the lymphatic system. Most lymphangiomas are preferentially located in the head and neck region. The abdominal organs are uncommon sites of origin. Several cases of lymphangioma in abdominal organs were reported, however, the pancreas is one of the rarest origins. Generally, intra-abdominal lymphangioma is asymptomatic and found incidentally, but in some cases, the patient complains of abdominal distension or a palpable mass. We describe the case of a 38-year-old male who presented with sudden-onset upper abdominal pain. Rupture of a cystic tumor of the pancreatic head was suspected, based on the findings of computed tomography, magnetic resonance imaging and endoscopic ultrasonography. Subtotal stomach-preserving pancreaticoduodenectomy was undertaken. The tumor, which was 4 × 4.5 × 8 cm in size, was pathologically diagnosed as a cystic lymphangioma. In conclusion, pancreatic lymphangioma is mostly asymptomatic, a ruptured case causing 'acute abdomen' has never been reported. Since lymphangioma is benign, it could be observed with accurate diagnosis. The surgical indication would be limited to cases of symptomatic lymphangiomas.

[A case with local recurrence of rectal cancer that responded to S-1 and PSK with long-term complete response].

The patient was a 65-year-old male, who underwent low anterior resection for rectal cancer. The pathological diagnosis showed mucinous adenocarcinoma, pSS, and pN0. He complained of diarrhea and melena 4 months after the surgery. Abdominal computed tomography and colonofiberscopy showed a local recurrence of rectal cancer. Because the tumor was diagnosed as unresectable, combined chemotherapy of S-1 (100 mg/day, per os, 4 weeks of treatment and 2 weeks of rest) and PSK (3 g/day, per os, the same schedule as S-1) was started. After the 2 courses of chemotherapy, computed tomography and colonofiberscopy showed a complete disappearance of the tumor. The chemotherapy was continued until the 9th course and then stopped. Five years and 4 months since the induction of a complete response, the patient is still alive without disease recurrence. Combined chemotherapy of S-1 and PSK may be one of useful choices for recurrent colorectal cancer.

[A case of multiple metachronous metastases of colon cancer to the small intestine preoperatively diagnosed by double balloon enteroscopy and radically resected].

The patient was a 75-year-old woman who had undergone resection of a transverse colon cancer two years before. She had anemia and intestinal obstruction, and a diagnosis of multiple metastases to the small intestine was made by double balloon enteroscopy. Eleven metastatic foci were resected by partial resection of the jejunum and ileum. Adjuvant FOLFOX chemotherapy was given, achieving a 26-month disease-free survival. The double balloon enteroscopy was useful in the definitive diagnosis of this case, and aggressive resection with adjuvant chemotherapy contributed to the good outcome.

Laparoscopic cholecystectomy and common bile duct exploration for cholecystocholedocholithiasis with a left-sided gallbladder: report of a case.

A 75-year old woman was admitted to our hospital with right upper quadrant pain, vomiting, and jaundice. Laboratory findings showed elevated total bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase, and C-reactive protein levels. Abdominal ultrasonography (US) and drip infusion cholangiographic computed tomography (DIC-CT) showed not only cholecystocholedocholithiasis, but a gallbladder located left of the round ligament and close to the lateral segments of the liver. We performed laparoscopic cholecystectomy (LC) with choledocholithotomy for suspected cholecystocholedocholithiasis with a left-sided gallbladder. Routine ports were inserted in the American configuration for LC. The gallbladder was normogradely separated from the gallbladder fossa, and the fundus of the gallbladder was lifted ventrally and toward to the patient's right shoulder. These procedures provided the usual view for laparoscopic choledochotomy. The patient recovered uneventfully and was discharged on postoperative day 10. To our knowledge, this is the first report of laparoscopic common bile exploration in a patient with a left-sided gallbladder.

Institutional indications for islet transplantation after total pancreatectomy.

BACKGROUND/PURPOSE: This study was designed to establish institutional indications for pancreatic islet transplantation by examining patients with total pancreatectomy as candidates for islet allotransplantation. METHODS: In 12 patients who underwent total pancreatectomy, we compared pre-and postoperative plasma glucose level, body mass index, HbA1c, and daily insulin use; we examined candidacy for islet allotransplantation based on the guidelines of Japan's islet transplantation registry. RESULTS: Eight of the 12 patients with total pancreatectomy were operated for intraductal papillary mucinous neoplasm. At our institution, the 5-year survival of patients with intraductal papillary mucinous neoplasm was far better (76.3%) than that of patients with pancreatic cancer. Postoperatively, plasma glucose level, HbA1c, and daily insulin use were increased in all patients with total pancreatectomy. Of the 12 patients treated with total pancreatectomy, 4 (intraductal papillary mucinous neoplasm, n = 2; islet cell tumor, n = 1; and acute pancreatitis due to arteriovenous malformation, n = 1) showed deteriorated diabetic control and therefore were considered to be candidates for islet allotransplantation according to the guidelines. CONCLUSIONS: Islet allotransplantation could be indicated for patients with favorable postoperative survival who have had a total pancreatectomy for either benign or neoplastic disease.

Synchronous and metachronous extrapancreatic malignant neoplasms in patients with intraductal papillary-mucinous neoplasm of the pancreas.

BACKGROUND/AIMS: Patients with intraductal papillary-mucinous neoplasm (IPMN) of the pancreas are likely to have a better prognosis than those with conventional pancreatic ductal adenocarcinoma. Recently there have been some reports on extrapancreatic malignant neoplasms (EPM) occurring in patients with IPMN. The purpose of this study was to discover the characteristic features of IPMN with EPM compared with IPMN without EPM. METHODS: 61 patients with IPMN who underwent surgery at Tohoku University Hospital between 1988 and 2006 were retrospectively analyzed. RESULTS: The 61 patients with IPMN in this study comprised 25 with intraductal papillary-mucinous adenomas (IPMA) and 36 with intraductal papillary-mucinous carcinomas (IPMC) including 6 with invasive carcinomas. Synchronous and metachronous EPM were observed in 15 out of the 61 patients (24.6%). Three of these patients, including 2 with IPMA and 1 with invasive carcinoma associated with IPMC, died of the EPM. None of the features, including sex, age, smoking, family history, macroscopic types (main duct type or branch duct type), histological types (gastric, intestinal, pancreatobiliary or oncocytic), and aberrant expression of molecules including CDKN2A, TP53, SMAD4 and DUSP6, except for the histological diagnoses were associated with the occurrence of EPM, i.e., the EPM occurred more often in patients with IPMA (10 out of 25) than in those with IPMC (5 out of 36) in our series (p = 0.0199 by the chi(2) test, p = 0.0330 by Fisher's exact probability test, p = 0.0422 by Yates' correction). CONCLUSION: Patients with IPMA were more likely to have EPM than those with IPMC. Patients with IPMA are usually expected to have a fair prognosis but EPM could be fatal in some of them, so it must be noted during follow-up.

Characteristic clinicopathological features of the types of intraductal papillary-mucinous neoplasms of the pancreas.

OBJECTIVES: Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas encompasses a spectrum of neoplasms with both morphological and immunohistochemical variations of mucin glycoproteins. Recently, a consensus nomenclature and criteria were histologically defined for classifying these variants of IPMNs into gastric, intestinal, pancreatobiliary, and oncocytic types. The purpose of this study was to determine associations between the histological types and clinicopathological features in patients with IPMN. METHODS: Sixty-one patients with IPMN operated upon at Tohoku University Hospital between 1988 and 2006 were retrospectively analyzed. RESULTS: Our series included 27 gastric-, 29 intestinal-, 4 pancreatobiliary-, and 1 oncocytic-type IPMNs. Statistically, the types of IPMN were significantly associated with the histological diagnoses, macroscopic types, and survival of the patients. Characteristically, the gastric-type IPMNs were likely to be diagnosed as benign, to be confined to branch ducts, and to have fair prognoses. On the other hand, the intestinal-type IPMNs were likely to be diagnosed as malignant, occupy the main duct, and have poor prognoses. Because of the small number of pancreatobiliary-type IPMNs and only 1 case of oncocytic-type IPMN, we were unable to determine any of their clinicopathological characteristics in our series. CONCLUSIONS: Evaluation of the histological types of IPMN may help to predict the clinical course of patients with IPMN and to design improved clinical management for these patients.

Intraductal papillary-mucinous adenocarcinoma in the remnant pancreas after pancreatoduodenectomy for cancer of Vater's papilla associated with intraductal papillary-mucinous adenoma.

A 72-year-old woman, who had undergone pylorus-preserving pancreatoduodenectomy 3 years before for cancer of Vater's papilla associated with a branch-type intraductal papillary-mucinous adenoma (IPMA), developed dilatation of the main duct and a nodular lesion in the remnant pancreas. Total pancreatectomy was performed, which revealed that the lesion was intraductal papillary-mucinous adenocarcinoma (IPMC) with minimal invasion, suggesting the metachronous multicentric occurrence of this intraductal papillary-mucinous neoplasm (IPMN). Because there were no malignant cells at the pancreaticojejunostomy, and because the histological appearance of the main-duct IPMC was different from that of the IPMA in the primary specimen, the main-duct IPMC was thought to be of different origin from the IPMA. These findings suggest that careful surveillance of the gastrointestinal tract and careful follow up are necessary for IPMN, because an IPMN could be associated with other gastrointestinal tract malignancies.

Histologic studies of the bypassed stomach after Roux-en-Y gastric bypass in a porcine model.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGBP) is highly effective for morbid obesity. However, the long-term effects in the bypassed segments are unknown. The aim of this study is to evaluate gastrin and histologic changes in bypassed segments after LRYGBP. METHODS: 10 50-kg pigs were subjected to LRYGBP. Preoperative weight and serum gastrin were compared with similar measures at 6 months postoperatively, when the pigs were euthanized. At necropsy, full-thickness gastric, duodenal, and jejunal biopsies were performed. Normal biopsies were obtained from a control group of 10 pigs. RESULTS: 1 pig died at 3 months postoperatively because of an intestinal intussusception. In the remaining 9 pigs, weight increased after surgery from 52+/-2.2 kg to 55+/-1.9 kg. Serum gastrin was unchanged after surgery (mean 68.2 vs 68.3 pg/mL at 3 months and 61.7 pg/mL at 6 months). Histology showed no abnormalities from sections in all control pigs, and in 7 of the LRYGBP pigs as well. 1 LRYGBP pig was found to have hyperplastic duodenal glands, jejunal mucosa with mild chronic inflammation, and gastric mucosa with focal erosive gastritis. 1 LRYGBP pig had jejunal sections showing Peyer's patches. CONCLUSION: LRYGBP is not associated with gastrin changes and major histologic changes in the bypassed segments, at 6 months postoperatively in the porcine model.

The cannabinoid 1 receptor antagonist, AM251, prolongs the survival of rats with severe acute pancreatitis.

It has recently been recognized that anandamide (arachidonylethanolamide), which is an endogeneous-cannabinoid (endocannabinoid), mediates septic shock. Cannabinoid means a mind-active material in cannabis (marijuana). Anandamide is mainly produced by macrophages. Cannabinoid 1 (CB1) receptor, which is one of the cannabiniod receptors, is also known to mediate hypotensive shock. The role of endocannabinoids in the progression of acute pancreatitis is unclear. The aims of this study are to clarify their relationship and to find a new therapeutic strategy by regulating the endocannabinoid signaling in acute pancreatitis. Male Wistar rats were injected with caerulein intravenously to induce mild edematous pancreatitis or injected with 5% sodium taurocholate to the bilio-pancreatic duct to induce severe necrotizing pancreatitis. The animals in the latter group were also injected with a CB1 receptor antagonist, AM251, or vehicle solution to see if the inhibition of endocannabinoids improves their survival. Plasma anandamide level was measured by the liquid chromatography/tandem mass spectrometry method. In both models of acute pancreatitis, the plasma anandamide levels were increased, and the levels were significantly higher in rats with severe necrotizing pancreatitis than those in rats with mild edematous pancreatitis. The mean arterial pressure and survival rate were significantly improved by the treatment with AM251, despite that the local inflammatory changes in the pancreas and various parameters (white blood cells, hematocrit, serum amylase, and serum interleukin-6) were similar. This is the first report to show that endocannabinoids are involved in the deterioration of acute pancreatitis and that the down-regulation of endocannabinoid signaling may be a new therapeutic strategy for severe acute pancreatitis.

[Clinicopathological aspects of pancreatic cancer].

Using the nationwide database of the Japan Pancreas Society (JPS), the clinicopathological features of 23,284 cases (1981-2000) and 2,298 cases (2001-2002) with pancreatic neoplasms were compared. Intraductal papillary mucinous neoplasms and mucinous cystic neoplasms were increased in the registry. More detailed histological repertoires of endocrine tumors, intraductal tubular tumors and solid-pseudopapillary tumors were registered in the last two years. The numbers of serous cystadenocarcinomas and carcinomas in situ were decreased. The proportion of less differentiated adenocarcinoma was increased in the more advanced stages of the disease. In Stage IVa, the survival of the patients with papillary adenocarcinoma was not statistically different from that of patients with well or moderate tubular adenocarcinoma, though the difference was significant in earlier stages. The survival of the patients with poorly differentiated adenocarcinoma, adenosquamous carcinoma and undifferentiated carcinoma was miserable. Histological confirmation is critically important to prospect the outcome and to determine the treatment modality. Integration of the nationwide registry and pathological information will give new insights for the treatment of pancreatic cancer.

Rat experimental model of continuous regional arterial infusion of protease inhibitor and its effects on severe acute pancreatitis.

OBJECTIVES: The rat experimental model of continuous regional arterial infusion of protease inhibitor (CRAI) on acute pancreatitis has yet to be established. Therefore, the aims of this study were (1) to establish the rat experimental model of CRAI and (2) to evaluate the effects of nafamostat on rat severe acute pancreatitis via different routes of administration. METHODS: The rat internal jugular vein or the celiac artery was infused with nafamostat, and the concentration of nafamostat in the lung and pancreas was measured. After the induction of severe acute pancreatitis, rats received intravenous or regional intraarterial infusion of nafamostat and then concentrations of trypsinogen activated peptide (TAP) and serum interleukin (IL-6), and histologic sections of the pancreas were examined and the 96-hour survival rate was evaluated. RESULTS: CRAI rats had higher concentrations of nafamostat in the pancreas than those infused intravenously. However, CRAI rats had lower concentrations of nafamostat in the lung that those infused intravenously. CRAI significantly reduced the levels of TAP and pancreatic necrosis. Moreover, the levels of serum IL-6 and the mortality rate were significantly reduced after CRAI compared with the intravenous infusion of nafamostat. CONCLUSION: The effectiveness of the rat experimental model of CRAI on acute pancreatitis was clearly demonstrated. The concentration of nafamostat in the lung and pancreas and the effects of nafamostat differ according to the route of administration.

Pancreatic ischemia associated with vasospasm in the early phase of human acute necrotizing pancreatitis.

OBJECTIVES: The angiographic appearance of acute necrotizing pancreatitis (ANP) demonstrates ischemic change with vasospasm in and around the pancreas. We investigated the role of vasospasm in pancreatic ischemia and necrosis in the early phase of human ANP. METHODS: The relationship between the angiographic abnormalities and the perfusion status of the pancreas documented by contrast-enhanced computed tomography (CE-CT) was examined in 102 patients with ANP who were admitted during the early phase of the disease. RESULTS: Ischemic change with vasospasm on angiography of the intrapancreatic and extrapancreatic arteries was observed and corresponded with the poorly perfused area of the pancreas detected by CE-CT done at admission. Resultant pancreatic necrosis was confirmed on follow-up CE-CT examination consistent with the location where angiography demonstrated ischemic change with vasospasm. Severe ischemic change on angiography was primarily observed in patients in whom more than 50% of the pancreas was poorly perfused. The extent of the ischemic change was correlated with the extent of the poorly perfused area of the pancreas and the mortality rate. CONCLUSION: These results suggest that vasospasm is involved in the development of pancreatic ischemia and necrosis in the early phase of ANP.

[Clinical classification and pathological physiology of acute pancreatitis].

Acute pancreatitis is a protean disease capable of wide clinical variation, ranging from mild discomfort to severe organ failure. Moreover, the inflammatory process may remain localized in the pancreas, spread to regional tissues, or even involve remote organ systems. This variability in presentation and clinical course has plagued the study and management of acute pancreatitis since its original clinical description. However, precise comprehension about the pathological physiology is required for better treatment. We described about the clinical classification and pathological physiology in the general in this

The early effect of the Roux-en-Y gastric bypass on hormones involved in body weight regulation and glucose metabolism.

OBJECTIVE: To evaluate the early effect of Roux-en-Y (RYGB) gastric bypass on hormones involved in body weight regulation and glucose metabolism. SIGNIFICANT BACKGROUND DATA: The RYGB is an effective bariatric procedure for which the mechanism of action has not been elucidated yet. Reports of hormonal changes after RYGB suggest a possible endocrine effect of the operation; however, it is unknown whether these changes are the cause or rather the effect of surgically induced weight loss. We speculated that if the mechanism of action of the RYGB involves an endocrine effect, then hormonal changes should occur early after surgery, prior to substantial body weight changes. METHODS: Ten patients with a mean preoperative body mass index (BMI) of 46.2 kg/m (40-53 kg/m) underwent laparoscopic RYGB. Six patients had type 2 diabetes treated by oral hypoglycemic agents. Preoperatively and 3 weeks following surgery, all patients were tested for fasting glucose, insulin, glucagon, insulin-like growth factor 1 (IGF-1), leptin, gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), adrenocorticotropic hormone (ACTH), corticosterone, and neuropeptide Y (NPY). RESULTS: Changes in mean BMI were rather minimal (43.2 kg/m; P = not significant), but there was a significant decrease in blood glucose (P = 0.005), insulin (P = 0.02), IGF-1 (P < 0.05), leptin (P = 0.001), and an increase in ACTH levels (P = 0.01). The other hormones were not significantly changed by surgery. All the 6 diabetic patients had normal glucose and insulin levels and did not require medications after surgery. The RYGB reduced GIP levels in diabetic patients (P < 0.01), whereas no changes in GIP levels were found in nondiabetics. CONCLUSIONS: Roux-en-Y gastric bypass determines considerable hormonal changes before significant BMI changes take place. These results support the hypothesis of an endocrine effect as the possible mechanism of action of RYGB.

Pancreatic Cancer Registry in Japan: 20 years of experience.

The prognosis of pancreatic cancer is defined by the histology and extent of disease. Preoperative histologic diagnosis and diagnostic imaging are fundamentals in managing the disease, but it is not rare to find unexpected peritoneal dissemination or liver metastasis at the time of operation. The overall resectability rate of pancreatic cancer is 40% in Japan. Resecting the portal vein and peripancreatic plexus were performed on 40% of the patients who underwent pancreatectomy for invasive cancer in the head of the pancreas. Long-term survival was only found in patients who underwent pancreatectomy. Radical lymph node dissection, or combined resection of the large vessels, did not seem to improve survival further than the standard resection. Multidisciplinary treatments combined with surgery were performed, and various effects of postoperative chemotherapy after pancreatectomy, intraoperative- and postoperative-radiation therapy, or postoperative chemotherapy for unresectable tumor, were shown. Development of unconventional therapies and refinement of the conventional therapy should be promoted on a randomized prospective trial basis. To promote this effort, which requires the international comparisons and cooperation, JPS developed a computerized JPS registration system downloadable from the JPS website (http://www.kojin.or.jp/suizou/index.html).

Clinicopathological aspects of small pancreatic cancer.

Small pancreatic cancers, intractable diseases, offer the possibility of cure. Can this be true? Through the National Pancreatic Cancer Registry, the Japan Pancreas Society (JPS) has collected 822 cases of invasive cancer with tumors <2 cm in diameter (TS1 pancreatic cancer). Papillary adenocarcinoma and the well-differentiated type of tubular adenocarcinoma are more frequent in TS1 pancreatic cancer than the larger tumors, suggesting that further genetic and phenotypic changes occur during their progression. Patients with TS1 pancreatic cancer presented with abdominal pain, jaundice, and exacerbation of diabetes, while 17.3% of them had no symptoms. Further imaging diagnosis should be employed to detect TS1 pancreatic cancer, but conventional US and ERCP play an important role in the diagnostic process. In this study, of 822 patients with TS1 pancreatic cancer, only 216 patients (26.3%) had T1 tumors because of invasion to adjacent tissue. There were 306 patients (37.2%) with lymph node metastasis, of whom 63 (7.7%) had N3 metastasis that is counted as a distant metastasis. As a result, only 136 patients (16.5%) had stage I disease with a median survival time of 78.2 months and a 5-year survival rate of 58.1%. Small pancreatic cancer does not necessarily mean early pancreatic cancer, and surgery alone is not sufficient to cure this disease.

[Chemotherapy for pancreatic cancer].

Pancreatic cancer has one of the worst prognosis of any malignant disease. The National Registry of Japan Pancreas Society has reported that only 13% of patients achieve 5 years survival after surgical resection. The vast majority of patients present with metastatic or unresectable disease. Gemcitabine (GEM) has replaced 5-fluorouracil (5-FU)-based chemotherapy as the standard of care. GEM first generated improvements in symptom control and survival in advanced disease, spurring further research. For locally advanced disease, most recent studies have incorporated GEM into combined-modality therapy. However, subsequent trials have not demonstrated that combinations of other agents with GEM extend clinical benefits yet. Similarly, in surgically resectable disease, current trials are incorporating GEM into adjuvant therapy. According to several clinical trials it has been demonstrated that improvements in locoregional control and survival may be achieved when chemotherapy using 5-FU is added to radiation for locally advanced pancreatic cancer. The new regimen for locally advanced disease has demonstrated that the better outcome is expected by chemoradiation therapy with 5-FU followed by GEM treatment. Furthermore, one of the patients showed the significant regression of pancreas tumor, resulting in the successful surgical resection. In order to develop chemotherapy for pancreatic cancer, we are analyzing mRNA expression of pancreas cancer cell lines and examined their resistant against to GEM. One of the genes is demonstrated to be a responsible for drug sensitivity by clustering analysis.