Isolated IgG4-related cholecystitis with localized gallbladder wall thickening mimicking gallbladder cancer: a case report and literature review.

BACKGROUND: IgG4-related cholecystitis, which is a manifestation of IgG4-related disease in the gallbladder, is associated with autoimmune pancreatitis or IgG4-related sclerosing cholangitis in most cases; isolated gallbladder lesions without systemic manifestations are very rare. Gallbladder wall thickening is often diffuse, but sometimes localized, in which case, differentiation from gallbladder cancer becomes difficult. The characteristic features of IgG4-related cholecystitis on imaging that would enable differentiation from gallbladder cancer remain poorly described. CASE PRESENTATION: We present a rare case of isolated IgG4-related cholecystitis with localized gallbladder wall thickening that was clinically difficult to distinguish from malignancy before resection. An 82-year-old man was referred to our hospital because of gallbladder wall thickening on abdominal ultrasonography without any symptoms. Dynamic computed tomography of the abdomen showed localized wall thickening from the body to the fundus of the gallbladder that was enhanced from an early stage with a prolonged contrast effect. There were no other findings, such as pancreatic enlargement and bile duct dilatation. Magnetic resonance cholangiopancreatography revealed neither dilatation nor stenosis of the bile duct and pancreatic duct. Endoscopic ultrasonography (EUS) showed a smooth layered thickening of the gallbladder wall with a maximum thickness of 6 mm and a well-preserved outermost hyperechoic layer in the same area. Laparoscopic cholecystectomy was performed because malignancy could not be completely ruled out. Pathological examination of a resected specimen revealed IgG4-positive plasma cell infiltration, fibrosis, and phlebitis. Although the serum IgG4 level measured after resection was normal, the condition was ultimately diagnosed as probable IgG4-related cholecystitis according to the 2020 revised comprehensive diagnostic criteria for IgG4-related disease. The EUS images reflected the pathological findings, in which lymphocytic infiltration was distributed in a laminar fashion in the gallbladder wall. CONCLUSIONS: Although rare, isolated IgG4-related cholecystitis with localized wall thickening mimicking gallbladder cancer remains a clinical problem. A smooth laminar thickening of the gallbladder wall on EUS imaging could be one of the most informative characteristics for differentiating IgG4-related cholecystitis from gallbladder cancer.

A prospective feasibility study of one-year administration of adjuvant S-1 therapy for resected biliary tract cancer in a multi-institutional trial (Tokyo Study Group for Biliary Cancer: TOSBIC01).

BACKGROUND: Although surgery is the definitive curative treatment for biliary tract cancer (BTC), outcomes after surgery alone have not been satisfactory. Adjuvant therapy with S-1 may improve survival in patients with BTC. This study examined the safety and efficacy of 1 year adjuvant S-1 therapy for BTC in a multi-institutional trial. METHODS: The inclusion criteria were as follows: histologically proven BTC, Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, R0 or R1 surgery performed, cancer classified as Stage IB to III. Within 10 weeks post-surgery, a 42-day cycle of treatment with S-1 (80 mg/m2/day orally twice daily on days 1-28 of each cycle) was initiated and continued up to 1 year post surgery. The primary endpoint was adjuvant therapy completion rate. The secondary endpoints were toxicities, disease-free survival (DFS), and overall survival (OS). RESULTS: Forty-six patients met the inclusion criteria of whom 19 had extrahepatic cholangiocarcinoma, 10 had gallbladder carcinoma, 9 had ampullary carcinoma, and 8 had intrahepatic cholangiocarcinoma. Overall, 25 patients completed adjuvant chemotherapy, with a 54.3% completion rate while the completion rate without recurrence during the 1 year administration was 62.5%. Seven patients (15%) experienced adverse events (grade 3/4). The median number of courses administered was 7.5. Thirteen patients needed dose reduction or temporary therapy withdrawal. OS and DFS rates at 1/2 years were 91.2/80.0% and 84.3/77.2%, respectively. Among patients who were administered more than 3 courses of S-1, only one patient discontinued because of adverse events. CONCLUSIONS: One-year administration of adjuvant S-1 therapy for resected BTC was feasible and may be a promising treatment for those with resected BTC. Now, a randomized trial to determine the optimal duration of S-1 is ongoing. TRIAL REGISTRATION: UMIN-CTR, UMIN000009029. Registered 5 October 2012-Retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009347.

Efficacy and safety of preoperative 5-fluorouracil, cisplatin, and mitomycin C in combination with radiotherapy in patients with resectable and borderline resectable pancreatic cancer: a long-term follow-up study.

BACKGROUND: We aimed to evaluate the efficacy and safety of 5-fluorouracil-based neoadjuvant chemoradiotherapy (NACRT) in patients with resectable/borderline resectable pancreatic ductal adenocarcinoma (PDAC). METHODS: This retrospective study investigated the clinicopathological features and > 5-year survival of patients with T3/T4 PDAC who underwent NACRT at our institute between 2003 and 2012. RESULTS: Seventeen resectable and eight borderline resectable patients were included. The protocol treatment completion and resection rates were 92.0% and 68.0%, respectively. Two patients failed to complete chemotherapy owing to cholangitis or anorexia. Common grade 3 toxicities included anorexia (12%), neutropenia (4%), thrombocytopenia (4%), anemia (4%), and leukopenia (12%). Pathologically negative margins were achieved in 94.1% of patients who underwent pancreatectomy. Pathological response according to Evans' classification was grade IIA in 10 patients (58.8%), IIB in 5 patients (29.4%), and IV in 2 patients (11.8%). Postoperative pancreatic fistulas were observed in four patients (23.5%), delayed gastric emptying in one patient (5.9%), and other operative morbidities in four patients (23.5%). The 1-, 2-, 5-, and 10-year overall survival rates were 73.9%, 60.9%, 60.9%, and 39.1%, respectively (median follow-up period, 80.3 months). CONCLUSIONS: NACRT is tolerable and beneficial for resectable/borderline resectable PDAC, even in the long-term.

Development of a novel mouse model of hepatocellular carcinoma with nonalcoholic steatohepatitis using a high-fat, choline-deficient diet and intraperitoneal injection of diethylnitrosamine.

BACKGROUND: The incidence of hepatocellular carcinoma with nonalcoholic steatohepatitis is increasing, and its clinicopathological features are well established. Several animal models of nonalcoholic steatohepatitis have been developed to facilitate its study; however, few fully recapitulate all its clinical features, which include insulin resistance, inflammation, fibrosis, and carcinogenesis. Moreover, these models require a relatively long time to produce hepatocellular carcinoma reliably. The aim of this study was to develop a mouse model of hepatocellular carcinoma with nonalcoholic steatohepatitis that develops quickly and reflects all clinically relevant features. METHODS: Three-week-old C57BL/6J male mice were fed either a standard diet (MF) or a choline-deficient, high-fat diet (HFCD). The mice in the MF + diethylnitrosamine (DEN) and HFCD + DEN groups received a one-time intraperitoneal injection of DEN at the start of the respective feeding protocols. RESULTS: The mice in the HFCD and HFCD + DEN groups developed obesity early in the experiment and insulin resistance after 12 weeks. Triglyceride levels peaked at 8 weeks for all four groups and decreased thereafter. Alanine aminotransferase levels increased every 4 weeks, with the HFCD and HFCD + DEN groups showing remarkably high levels; the HFCD + DEN group presented the highest incidence of nonalcoholic steatohepatitis. The levels of fibrosis and steatosis varied, but they tended to increase every 4 weeks in the HFCD and HFCD + DEN groups. Computed tomography scans indicated that all the HFCD + DEN mice developed hepatic tumors from 20 weeks, some of which were glutamine synthetase-positive. CONCLUSIONS: The nonalcoholic steatohepatitis-hepatocellular carcinoma model we describe here is simple to establish, results in rapid tumor formation, and recapitulates most of the key features of nonalcoholic steatohepatitis. It could therefore facilitate further studies of the development, oncogenic potential, diagnosis, and treatment of this condition.

Successful resolution of a hemorrhagic pancreatic pseudocyst ruptured into the stomach complicating obstructive pancreatitis due to pancreatic cancer: a case report.

BACKGROUND: Hematemesis is uncommon as an initial presenting symptom in pancreatic cancer. We present herein a case of a pseudoaneurysm that ruptured and fistulized into the stomach. The pseudoaneurysm was secondary to a pancreatic pseudocyst complicating obstructive pancreatitis due to pancreatic cancer. The patient was successfully treated using trans-arterial embolization followed by curative surgery. CASE PRESENTATION: A 61-year-old man presented to the emergency room with hematemesis. Laboratory examinations revealed a low level of hemoglobin (5.0 g/dl). The patient had presented to another hospital due to hematemesis 1 month before presenting to our hospital. A low-density mass in the pancreatic body with dilatation of the distal main pancreatic duct and a pseudocyst in the pancreatic tail had been observed by radiology at the previous hospital. Further investigation had been planned. Abdominal computed tomography on admission to our hospital demonstrated a pseudoaneurysm in close contact with the wall of the pseudocyst of the pancreatic tail, compressing the stomach. The pseudoaneurysm had not been detected by abdominal computed tomography at the previous hospital. Emergency selective angiography revealed that the pseudoaneurysm arose from the left gastroepiploic artery branching from the splenic artery. Trans-arterial embolization of the left gastroepiploic artery through the splenic artery was successfully performed. Elective distal pancreatectomy and splenectomy with regional lymph node dissection combined with partial resection of the stomach was performed 3 weeks after coil embolization. Pathological examination revealed a moderately differentiated tubular adenocarcinoma in the pancreatic body with regional lymph node metastasis and revealed the pseudoaneurysm rupturing into the pancreatic pseudocyst. The patient has experienced no tumor recurrence or metastasis during 1 year of follow-up. CONCLUSIONS: Spontaneous rupture of a pseudoaneurysm is a rare and potentially lethal complication of a pancreatic pseudocyst. Most affected patients have a history of alcoholism and suffer from acute or chronic pancreatitis. To our knowledge, this is the first reported case of a hemorrhagic pancreatic pseudocyst complicating obstructive pancreatitis due to pancreatic cancer.

Phase I pilot study of Wilms tumor gene 1 peptide-pulsed dendritic cell vaccination combined with gemcitabine in pancreatic cancer.

This study aimed to evaluate the feasibility of and immune response to Wilms tumor gene 1 (WT1) peptide-pulsed dendritic cell vaccination combined with gemcitabine (DCGEM) as a first-line therapy among patients with advanced pancreatic cancer. Ten HLA-A*2402 patients were treated with WT1 peptide-pulsed DC vaccination (1 × 10(7) cells) on days 8 and 22 and gemcitabine (1000 mg/m(2) ) on days 1, 8 and 15. Induction of a WT1-specific immune response was evaluated using the delayed-type hypersensitivity (DTH) skin test, interferon-γ enzyme-linked immunospot and HLA tetramer assays, along with assays for various immunological factors. DCGEM was well-tolerated, and the relative dose intensity of gemcitabine was 87%. Disease control associated with a low neutrophil/lymphocyte ratio was observed in all three patients with DTH positivity; it was also correlated with a low percentage of granulocytic myeloid derived suppressor cells in the pretreatment peripheral blood (P = 0.017). Patients with liver metastases and high levels of inflammatory markers such as C-reactive protein and interleukin-8 (IL-8) showed poor survival even though a WT1-specific immune response was induced in them. WT1 peptide-pulsed DCGEM is feasible and effective for inducing anti-tumor T-cell responses. Our results support future investigations for pancreatic cancer patients with non-liver metastases and favorable immunological conditions. This trial was registered with the University hospital Medical Information Network (UMIN) Clinical Trials Registry (http://www.umin.ac.jp/ctr/ number: UMIN-000004855).

Adenosquamous carcinoma of the ampulla of Vater: a case report and literature review.

BACKGROUND: Adenosquamous carcinoma of the ampulla of Vater is extremely rare, and its clinicopathological features are limited and described in few previous case reports. Here, we report curative resection of adenosquamous carcinoma of the ampulla of Vater at an early stage. CASE PRESENTATION: An 81-year-old woman was referred to our hospital for investigation of the frequent elevation of hepatic and biliary enzymes and dilatation of the intrahepatic bile ducts. Preoperative examinations revealed an exposed reddish tumor in the ampulla of Vater, which was diagnosed on biopsy to be adenocarcinoma with squamous cell carcinoma component. Pylorus-preserving pancreaticoduodenectomy with regional lymph node dissection was performed. Pathological examinations revealed the presence of two malignant components in the lesion, including poorly differentiated tubular adenocarcinoma and squamous cell carcinoma, without invasion beyond the sphincter of Oddi or into the duodenal submucosa. These squamous cell carcinoma and adenocarcinoma components in the tumor comprised approximately 30 and 70% of the lesion, respectively. No metastasis into regional lymph nodes was observed, and the patient experienced no tumor recurrence or metastasis until 20 months after surgery. CONCLUSION: We identified only six reported cases of adenosquamous carcinoma of the ampulla of Vater in the English literature, and all of these patients died of recurrence within 14 months after surgery. To the best of our knowledge, this is the first report of adenosquamous carcinoma of the ampulla of Vater that was curatively resected at an early stage. Although more number of studies on clinicopathological findings are required to determine the appropriate surgical indication, we suggest that surgery remains the mainstay therapy for adenosquamous carcinoma of the ampulla of Vater detected at an early stage.

Long-term complete response of advanced hepatocellular carcinoma treated with multidisciplinary therapy including reduced dose of sorafenib: case report and review of the literature.

An 83-year-old man underwent computed tomography during a routine check-up due to a history of surgical treatment for pancreatic cancer. Two tumors were detected in the anterior segment of the liver. A needle biopsy of the larger tumor was performed, and pathological examination showed that the tumor was a poorly differentiated hepatocellular carcinoma. Resection was not performed considering the patient's poor physical condition. Thus, transcatheter arterial chemoembolization and radiofrequency ablation of the tumors were performed. Three months later, residual tumor of the larger lesion and multiple pulmonary metastases were detected. This time, continuous hepatic arterial infusion chemotherapy was performed. Although the pulmonary metastases markedly reduced, tumor thrombi appeared in the right portal vein on computed tomography. Finally, sorafenib was administered, which led to disappearance of the tumor thrombi and no other signs of recurrence 8 months after initiation of sorafenib on computed tomography. Although sorafenib administration has continued at reduced doses of 200 mg per day or less due to hypertension, complete response has persisted for the past 34 months. It is noteworthy that sorafenib has been given at reduced doses, but a long-term complete response is maintained in a patient who had portal tumor thrombi and distant metastasis. Herein, we present this rare case of advanced hepatocellular carcinoma controlled with reduced doses of sorafenib following multidisciplinary therapy, describe our single center experience with sorafenib use in patients with hepatocellular carcinoma, and review previous reports that focused on dose reduction of sorafenib.

Adjuvant 5-fluorouracil and portal vein infusion chemotherapy followed by gemcitabine for pancreatic cancer.

BACKGROUND: Although adjuvant gemcitabine (GEM) monotherapy improves the overall survival (OS) of patients with resected pancreatic cancer, its efficacy requires further improvement. This multicenter, phase II study investigated the efficacy of adjuvant portal vein infusion (PVI) chemotherapy followed by GEM therapy in patients with resected pancreatic cancer. METHODS: 5-fluorouracil (250 mg/day) and heparin (2000 IU/day) PVI chemotherapy were combined with systemic administration of mitomycin C (4 mg; days 6, 13, 20, and 27) and cisplatin (10 mg; days 7, 14, 21, and 28) for 4 weeks (PI4W), followed by GEM (1000 mg/m2; days 1, 8, and 15 every 4 weeks for 6 months). The primary endpoint was relapse-free survival (RFS) and the secondary endpoints were OS and treatment completion. RESULTS: Between November 2010 and August 2013, 53 patients who underwent complete resection were enrolled, including 30, 20, and 3 patients who underwent pancreaticoduodenectomies and distal and total pancreatectomies, respectively. In total, 51 (96.2%) patients underwent R0 resection, of whom 3, 2, 12, 35, 0, and 1 had stages IA, IB, IIA, IIB, III, and IV cancer, respectively, and 47 (88.7%) patients completed PI4W. The median RFS was 22.0 months (1-, 3-, 5, and 10 years RFS: 64.9%, 38.1%, 38.1%, and 38.1%, respectively), whereas the median OS was 32.0 months (1-, 3-, 5, and 10 years OS:86.6%, 47.2%, 44.4%, and 44.4%, respectively). CONCLUSION: Treatment with PI4W followed by GEM for 6 months after surgery may be beneficial in patients undergoing curative resection of pancreatic cancer.

Mesenchymal stem cells regulate epithelial-mesenchymal transition and tumor progression of pancreatic cancer cells.

Cancer-associated fibroblasts contribute to cancer progression that is caused by epithelial-mesenchymal transition (EMT). Recently, mesenchymal stem cells (MSCs) were found to be the major candidate involved in the development of tumor-promoting cancer stroma. Here we report that α-smooth muscle actin-positive myofibroblast-like cells originating from MSCs contribute to inducing EMT in side population cells of pancreatic cancer. More importantly, MSC-derived myofibroblasts function to maintain tumor-initiating stem cell-like characteristics, including augmenting expression levels of various stemness-associated genes, enhancing sphere- forming activity, promoting tumor formation in a mouse xenograft model, and showing resistance to anticancer drugs. Furthermore, both γ-secretase inhibitor and siRNA directed against Jagged-1 attenuated MSC-associated E-cadherin suppression and sphere formation in pancreatic cancer side population cells. Thus, our results suggest that MSC-derived myofibroblasts play important roles in regulating EMT and tumor-initiating stem cell-like properties of pancreatic cancer cells through an intermediating Notch signal.

Concomitant pancreatic endocrine neoplasm and intraductal papillary mucinous neoplasm: a case report and literature review.

We report a case of concomitant pancreatic endocrine neoplasm (PEN) and intraductal papillary mucinous neoplasm (IPMN). A 74-year-old man had been followed-up for mixed-type IPMN for 10 years. Recent magnetic resonance images revealed an increase in size of the branch duct IPMN in the pancreas head, while the dilation of the main pancreatic duct showed minimal change. Although contrast-enhanced computed tomography and magnetic resonance imaging did not reveal any nodules in the branch duct IPMN, endoscopic ultrasound indicated a suspected nodule in the IPMN. A malignancy in the branch duct IPMN was suspected and we performed pylorus-preserving pancreatoduodenectomy with lymphadenectomy. The resected specimen contained a cystic lesion, 10 x 10 mm in diameter, in the head of the pancreas. Histological examination revealed that the dilated main pancreatic duct and the branch ducts were composed of intraductal papillary mucinous adenoma with mild atypia. No evidence of carcinoma was detected in the specimen. Incidentally, a 3-mm nodule consisting of small neuroendocrine cells was found in the main pancreatic duct. The cells demonstrated positive staining for chromogranin A, synaptophysin, and glucagon but negative staining for insulin and somatostatin. Therefore, the 3-mm nodule was diagnosed as a PEN. Since the mitotic count per 10 high-power fields was less than 2 and the Ki-67 index was less than 2%, the PEN was pathologically classified as low-grade (G1) according to the 2010 World Health Organization (WHO) criteria. Herein, we review the case and relevant studies in the literature and discuss issues related to the synchronous occurrence of the relatively rare tumors, PEN and IPMN.

Human liver-specific nanocarrier in a novel mouse xenograft model bearing noncancerous human liver tissue.

For the targeted delivery of genes and drugs to the human liver, hepatitis B virus (HBV) envelope L particles, which form hollow nanoparticles and display a peptide that is indispensable for liver-specific infection by HBV in humans, should be a useful tool. To test the efficacy of these particles in vivo, in the present study we generated a small animal model harboring a functional human liver tissue xenograft. An anti-asialo GM1 antibody was administered to SCID mice to induce the depletion of natural-killer-cell-dependent immune responsibility and then the mice underwent transplantation of a noncancerous liver tissue originating in humans into the kidney capsule. Interestingly, human liver tissues were engrafted in 58% of the animals at least for 14 days shown by a human hepatocyte-specific antibody. The engineered HBV nanoparticles which contained fluorescent chemicals could selectively bind to the xenograft in these immune-deficient mice when they were administered systemically. These results suggested that the model animal was usable to demonstrate the efficacy of the nanoparticles that could deliver chemicals specific to the normal human liver tissue by systemic administration, which will facilitate the study of human liver cell biology, drug metabolism and infections with hepatotropic viruses.

Intrahepatic cholangiocarcinoma arising 33 years after excision of a choledochal cyst: report of a case.

We report a case of intrahepatic cholangiocarcinoma arising 33 years after excision of a choledochal cyst. A 61-year-old woman was admitted to our hospital complaining of fever. Thirty-three years ago she had undergone extrahepatic choledochal cystectomy and choledochojejunostomy for a choledochal cyst. Computed tomography showed a tumor in the anterior segment of the liver, extending to the posterior and medial segments and the right portal vein. Intrahepatic biliary stones were seen in the bile ducts. We performed extended right lobectomy. Microscopically, the tumor was cholangiocarcinoma. Most of the tumor area was composed of invasive adenocarcinoma but a carcinoma-in-situ component was also observed in some regions including the hilar bile duct, where an intrahepatic biliary stone was seen. This suggests that the cancer development could be related to intrahepatic cholestasis. Patients with choledochal cyst may have to be carefully followed up for more than 30 years even after diversion surgery.

Intraoperative laparoscopic detection of sentinel lymph nodes with indocyanine green and superparamagnetic iron oxide in a swine gallbladder cancer model.

Mapping of sentinel lymph nodes (SLNs) can enable less invasive surgery. However, mapping is challenging for cancers of difficult-to-access visceral organs, such as the gallbladder, because the standard method using radioisotopes (RIs) requires preoperative tracer injection. Indocyanine green (ICG) and superparamagnetic iron oxide (SPIO) have also been used as alternative tracers. In this study, we modified a previously reported magnetic probe for laparoscopic use and evaluated the feasibility of detecting SLNs of the gallbladder using a laparoscopic dual tracer method by injecting ICG and SPIO into five swine and one cancer-bearing swine. The laparoscopic probe identified SPIO nanoparticles in the nodes of 4/5 swine in situ, the magnetic field counts were 2.5-15.9 µT, and fluorescence was detected in SLNs in all five swine. ICG showed a visual lymph flow map, and SPIO more accurately identified each SLN with a measurable magnetic field quite similar to the RI. We then developed an advanced gallbladder cancer model with lymph node metastasis using recombination activating gene 2-knockout swine. We identified an SLN in the laparoscopic investigation, and the magnetic field count was 3.5 µT. The SLN was histologically determined to be one of the two metastatic lymph nodes. In conclusion, detecting the SLNs of gallbladder cancer in situ using a dual tracer laparoscopic technique with ICG and SPIO was feasible in a swine model.

Beneficial effects of 5-Fluorouracil and heparin-based portal infusion chemotherapy combined with mitomycin C and cisplatin after curative resection of pancreatic cancer.

AIMS: We retrospectively assessed the benefits of 5-fluorouracil (5-FU)- and heparin-based portal infusion chemotherapy combined with systemic administration of mitomycin C (MMC) and cisplatin (CDDP) for 4 weeks following surgery (PI4W). The goal was to determine if this treatment prevented liver metastasis and improved survival for patients with potentially curative resection of pancreatic cancer. METHODS: 68 patients who underwent pancreatectomy from January 1995 to August 2007 were treated. Of these cases, 22 patients received portal infusion with 5-FU (250 mg/day) for 2 weeks (PI2W) following surgery, while 25 patients received PI4W therapy (250 mg/day of 5-FU with 2,000 IU/day of heparin everyday for 4 weeks, 4 mg MMC on days 6, 13, 20, 27, and 10 mg CDDP on days 7, 14, 21, 28). The remaining 21 patients were treated without adjuvant therapy during the perioperative period. RESULTS: All patients except one completed the portal infusion chemotherapy without toxicity. The cumulative liver metastasis-free survival rate in the PI4W group was significantly higher than those in the other two groups. Furthermore, in the PI4W group, 3-year survival was 82.9% and 5-year survival was 63.8%, rates which were significantly better than those observed in the other two groups. CONCLUSION: PI4W therapy after surgery is feasible and could become a promising adjuvant therapy in patients with potentially curative resection of pancreatic cancer. and IAP.

Synuclein-gamma is closely involved in perineural invasion and distant metastasis in mouse models and is a novel prognostic factor in pancreatic cancer.

PURPOSE: Perineural invasion is associated with the high incidence of local recurrence and a dismal prognosis in pancreatic cancer. We previously reported a novel perineural invasion model and distinguished high- and low-perineural invasion groups in pancreatic cancer cell lines. This study aimed to elucidate the molecular mechanism of perineural invasion. EXPERIMENTAL DESIGN: To identify key biological markers involved in perineural invasion, differentially expressed molecules were investigated by proteomics and transcriptomics. Synuclein-gamma emerged as the only up-regulated molecule in high-perineural invasion group by both analyses. The clinical significance and the biological property of synuclein-gamma were examined in 62 resected cases of pancreatic cancer and mouse models. RESULTS: Synuclein-gamma overexpression was observed in 38 (61%) cases and correlated with major invasive parameters, including perineural invasion and lymph node metastasis (P < 0.05). Multivariate analyses revealed synuclein-gamma overexpression as the only independent predictor of diminished overall survival [hazard ratio, 3.4 (95% confidence interval, 1.51-7.51)] and the strongest negative indicator of disease-free survival [2.8 (1.26-6.02)]. In mouse perineural invasion and orthotopic transplantation models, stable synuclein-gamma suppression by short hairpin RNA significantly reduced the incidence of perineural invasion (P = 0.009) and liver/lymph node metastasis (P = 0.019 and P = 0.020, respectively) compared with the control. CONCLUSIONS: This is the first study to provide in vivo evidence that synuclein-gamma is closely involved in perineural invasion/distant metastasis and is a significant prognostic factor in pancreatic cancer. Synuclein-gamma may serve as a promising molecular target of early diagnosis and anticancer therapy.

Autofluorescence videoendoscopy system using the SAFE-3000 for assessing superficial gastric neoplasia.

BACKGROUND: Autofluorescence (AF) videoendoscopy has an advantage over ordinary videoendoscopy in the diagnosis of gastric neoplasias, and the aim of the present study was to evaluate the effectiveness of using the SAFE-3000 videoendoscopy system to diagnose superficial gastric neoplasias. METHODS: Ordinary videoendoscopy, AF videoendoscopy, and chromoendoscopy (CE) were used to diagnose the tumor existence and extent in 14 patients with gastric adenoma, 40 patients with intestinal-type early gastric cancer (EGC) (10 protruded, and 30 depressed), and nine patients with diffuse-type EGC. The diagnostic accuracies of the three kinds of images were evaluated by comparison with the results of histopathological assessment of resected specimens. RESULTS: For gastric adenomas the diagnostic accuracy between the AF images and white light (WL) images did not differ significantly, and for protruded intestinal-type EGCs and diffuse-type EGCs the diagnostic accuracy did not differ significantly between any of the types of images. For depressed intestinal-type EGCs, the diagnostic accuracy of AF images tended to be higher than that of the WL images (P < 0.05) and it was not significantly different from that of the CE images. The detection rate of pink or orange color in AF images was significantly higher for protruded intestinal-type EGCs than gastric adenomas (P = 0.005), depressed intestinal-type EGCs (P < 0.001), and diffuse-type EGCs (P = 0.027). CONCLUSIONS: Autofluorescence videoendoscopy using the SAFE-3000 system for gastric neoplasias might be useful for diagnosing depressed intestinal-type early gastric cancers. The detection of orange or pink color in AF images may be efficacious in discriminating protruded intestinal-type early gastric cancers from gastric adenomas.

Successful outcomes after laparoscopic spleen-preserving pancreatic resection for a desmoid tumor: A case report.

INTRODUCTION: Desmoid tumors are slowly growing neoplasms that arise from fibroblasts. These tumors are locally aggressive and have a high rate of recurrence after surgery. Pancreatic desmoid tumors are extremely rare. The indications and outcomes of laparoscopic surgery for pancreatic desmoid tumors have not been fully elucidated. This report therefore aimed to describe a rare case of a pancreatic desmoid tumor in a patient who was successfully treated with laparoscopic spleen-preserving pancreatic resection. PRESENTATION OF CASE: We report a case of a 60-year-old man who presented with back pain. Contrast-enhanced computed tomography scan revealed a circumscribed tumor in the pancreatic tail measuring 3 cm. The patient underwent laparoscopic spleen-preserving distal pancreatectomy. Pathological analysis revealed a desmoid tumor infiltrating the pancreatic parenchyma. There was no evidence of recurrence at 36 months of follow-up. DISCUSSION AND CONCLUSION: Isolated sporadic pancreatic desmoid tumors are extremely rare. Laparoscopic radical resection could be a safe and effective treatment for this benign but locally aggressive tumor. To the best of our knowledge, this is the first study to report a patient with a pancreatic desmoid tumor who was successfully treated with laparoscopic surgery.

Clinical results of endoscopic hemostasis using a short transparent hood and short hemoclips for non-variceal upper gastrointestinal bleeding.

AIM: Endoscopic hemostasis using hemoclips is useful, but there are technical difficulties because the angle of the approach is tangential. A transparent hood facilitates the observation and treatment of these lesions, and a shorter hood provides a wider visible field. Endoscopic hemoclipping of hard lesions with hemoclips of the conventional size does not reliably result in sustained hemostasis because the clips slip. Short clips, however, can be easily clamped on protruded visible vessels without slip. The aim of the present study was to evaluate the efficacy of endoscopic hemostasis with a short transparent hood and short clips. METHODS: Subjects were 198 patients with 214 lesions of non-variceal upper gastrointestinal bleeding at Keio University Hospital. We used a video endoscope with a short transparent hood attached to its distal tip and carried out hemostasis using short hemoclips. RESULTS: The short transparent hood provided a good visual field. If the lesions were in the tangential, the short hood made it possible to observe them in the frontal view and made clip hemostasis much easier. The short clip could be securely clamped against protruded visible vessels. Of 214 lesion, 211 (98.6%) had temporal hemostasis. Rebleeding occurred in 13 of 211 lesions (6.2%), and 205 of 214 lesions (95.8%) had permanent hemostasis. Nine cases were endoscopically difficult. CONCLUSION: Endoscopic hemostasis with a short transparent hood and short clips is useful for non-variceal upper gastrointestinal bleeding.