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Liver cancer, including hepatocellular carcinoma (HCC), is the fifth most common cause of cancer deaths in Japan. The main treatment options for HCC are surgical resection, liver transplantation, radiofrequency ablation (RFA), transarterial chemoembolization (TACE), and systemic chemotherapy. Here, recent medical treatments for HCC, including surgery, percutaneous ablation, transcatheter arterial chemoembolization/transcatheter arterial embolization, and drug therapy, are reviewed with a focus on Japan.

Background We modified and administered capecitabine + epirubicin + cyclophosphamide combination therapy (CEX) as neoadjuvant chemotherapy (NAC) for HER-2-negative breast cancer and retrospectively analyzed its effectiveness and tolerability at our center. Methods The inclusion criteria were presence of breast cancer negative for HER-2 and positive lymph node metastasis, or negative lymph node metastasis when tumor diameter was 20 mm or greater without distant metastasis. Additional inclusion criteria were a performance status of 0 or 1, an EF >60%, and an age of 75 years or less. Clinical outcomes were evaluated after 4 courses of epirubicin 80 mg/m2, cyclophosphamide 500 mg/m2 (administered every 3 weeks), and capecitabine 1,500 mg/m2 (administered for 2 weeks and withdrawn for 1 week). Results A clinical benefit was noted in all 18 patients who received CEX as neoadjuvant chemotherapy during the period from 2009 through 2013. The clinical response rate was 83.3% (15/18), and the clinical complete response rate was 50%. Aesthetic outcomes of breast-conserving surgery were positive in all patients. Among patients with satisfactory outcomes, 33.3% had a pathologic complete response (triple-negative: 6, luminal: 0) and 68.8% were n0 (triple-negative: 8, luminal: 3). All patients with a pathologic complete response are presently alive, free of recurrence, and currently undergoing follow-up. Adverse events were classified as grade 2 or lower in all patients. Conclusions CEX therapy administered as neoadjuvant chemotherapy could be useful for individualized treatment. In particular, this regimen was effective for triple-negative breast cancer.

Introduction The common metastatic sites of renal cell cancer (RCC) are the lung, bone, liver, brain, adrenal glands, and contralateral kidney. Metastasis to the gallbladder is rare, and cystic duct metastasis from RCC has been reported in only one metachronous case. This is the first report of a case of synchronous cystic duct metastasis from RCC. Case report A 72-year-old woman presenting with hematuria had a history of Cushing disease approximately 10 years previously. Enhanced computed tomography of the abdomen showed a mass measuring 5.8 × 3.0 cm in the left kidney, which was strongly enhanced in the early phase and washed out in the late phase. A mass measuring 2 cm in diameter was seen in the left adrenal gland, and a 1.0-cm mass was noted in the right adrenal gland. Multiple tiny masses were detected in the cystic duct. Left renal cell carcinoma, cystic duct metastasis, and bilateral adrenal gland metastases were diagnosed. Because the metastatic tumor was close to the common bile duct, we performed left nephrectomy, bilateral adrenalectomy, cholecystectomy, resection of the extrahepatic bile duct, and hepaticojejunostomy. Pathological findings showed that the renal tumor was clear cell carcinoma, as were the bilateral adrenal tumors and cystic duct tumor. The patient died 30 months after the operation.

Highlights • A single gallbladder with a double cystic duct is a very rare finding. • MRCP showed strong suspicion of a single gallbladder with a double cystic duct and the definite diagnosis of a double cystic duct was made by ERC. • Laparoscopic cholecystectomy could be successfully performed in combination with intraoperative cholangiography for double cystic duct., Introduction A single gallbladder with a double cystic duct is a very rare finding. In addition, few cases with this rare condition are preoperatively diagnosed. However, the preoperative confirmation or suspicion of this rare condition could facilitate safe laparoscopic cholecystectomy, which is a minimally invasive therapeutic modality for gallbladder disease. We herein present a case of gallstone disease in a patient with a double cystic duct who was preoperatively diagnosed and successfully treated with laparoscopic cholecystectomy. Presentation of case A 57-year-old woman was admitted to our hospital with epigastric pain. Gallstone disease in the gallbladder and common bile duct was diagnosed by ultrasonography and computed tomography. Magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiography (ERC) revealed that the aberrant cystic duct arose from the cystic duct and communicated with the intrahepatic bile duct of the posterior segmental branch. Laparoscopic cholecystectomy was successfully performed in combination with intraoperative cholangiography. Discussion If an anomaly of the biliary duct system is not identified during surgery, it may turn out to be a bile leak. The preoperative diagnosis of a double cystic duct allows laparoscopic cholecystectomy to be performed safely in combination with intraoperative cholangiography. Conclusions A single gallbladder with double cystic duct is a very rare anomaly. However, laparoscopic surgery can be facilitated by the use of preoperative and intraoperative images.

The prognosis of hepatocellular carcinoma (HCC) is unfavorable following complete tumor resection. The aim of the present study was to identify a molecule able to predict HCC prognosis through comprehensive protein profiling and to elucidate its clinicopathological significance. Comprehensive protein profiling of HCC was performed by liquid chromatography-tandem mass spectrometry. Through the bioinformatic analysis of proteins expressed differentially in HCC and non-HCC tissues, protein disulfide-isomerase A3 (PDIA3) was identified as a candidate for the prediction of prognosis. PDIA3 expression was subsequently examined in 86 cases of HCC by immunostaining and associations between PDIA3 expression levels and clinicopathological characteristics were evaluated. The Ki-67 index and apoptotic cell death of carcinoma cells were examined by immunostaining and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay in 24 cases. The results demonstrated that PDIA3 was expressed in all 86 HCC cases; 56 HCC cases (65%) exhibited high expression of PDIA3 and 30 (35%) exhibited low expression. The disease-free and overall survival times of HCC patients with high PDIA3 expression were significantly shorter than in HCC patients with low expression. Furthermore, increased expression of PDIA3 was associated with an elevated Ki-67 index, indicating increased cancer cell proliferation and a reduction in apoptotic cell death. Taken together, these results suggest that PDIA3 expression is associated with tumor proliferation and decreased apoptosis in HCC, and that increased expression of PDIA3 predicts poor prognosis. PDIA3 may therefore be a key molecule in the development of novel targeting therapies for patients with HCC.

Gallbladder rupture due to blunt abdominal injury is rare. There are few reports of traumatic gallbladder injury, and it is commonly associated with other concomitant visceral injuries. Therefore, it is difficult to diagnose traumatic gallbladder rupture preoperatively when it is caused by blunt abdominal injury. We report a patient who underwent laparoscopic cholecystectomy after an exact preoperative diagnosis of traumatic gallbladder rupture. A 43-year-old man was admitted to our hospital due to blunt abdominal trauma. The day after admission, abdominal pain and ascites increased and a muscular defense sign appeared. Percutaneous drainage of the ascites was performed, and the aspirated fluid was bloody and almost pure bile. He was diagnosed with gallbladder rupture by the cholangiography using the endoscopic retrograde cholangiopancreatography technique. Laparoscopic cholecystectomy was performed safely, and he promptly recovered. If accumulated fluids contain bile, endoscopic cholangiography is useful not only to diagnose gallbladder injury but also to determine the therapeutic strategy.

Previously, a single nucleotide polymorphism (SNP) related to gait type was identified at position 22 999 655 of chromosome 23 in the coding region of DMRT3 (DMRT3:Ser301Ter) by showing that a cytosine (C) to adenine (A) mutation of this SNP induced pace in the Icelandic horse. We investigated the effect of DMRT3:Ser301Ter on the gait of Hokkaido Native Horses, a Japanese native breed, and examined genetic factors other than DMRT3 by exploring genome-wide SNPs related to gait determination. All animals exhibiting pace were AA for DMRT3:Ser301Ter, confirming the association of DMRT3:Ser301Ter with gait determination; however, 14.3% of the animals exhibiting trot also had AA for DMRT3:Ser301Ter, suggesting the presence of another factor(s) cooperatively working with DMRT3:Ser301Ter for gait determination. SNPs on chromosomes 13 and 23 were detected by genome-wide association analysis (false discovery rate

Portal vein thrombosis (PVT) is a rare complication of liver transplantation which can lead to graft failure and patient death. Treatment can be difficult, especially in cases of PVT from the intrahepatic portal vein to the proximal jejunal veins. A 55-year-old woman had undergone living-donor liver transplantation with splenectomy for end-stage liver cirrhosis due to hepatitis C with hepatocellular carcinoma. Ten months after transplantation, massive ascites and slight abdominal pain developed, and computed tomography revealed a PVT between the intrahepatic portal vein and the superior mesenteric vein. Repeated interventional radiology procedures were used in combination with thrombolysis, thrombectomy, and metallic stent replacement to obtain favorable portal flow to the graft. Five years after being treated, the patient is well, with favorable portal flow having been confirmed. In conclusion, repeated and assiduous interventional radiological treatment combined with thrombolytic therapy, thrombectomy, and metallic stent replacement could be important for severe PVT.

As a strategy to diagnose early-stage pancreatic ductal adenocarcinoma (PDAC) is urgently needed, we aimed to clarify characteristics of early-stage PDAC.We retrospectively reviewed medical records of 299 consecutive patients who underwent R0 or R1 surgical resection for PDAC between 1994 and 2013 and compared clinical characteristics between patients with early-stage (stages 0-I by Japanese General Rules for Pancreatic Cancer) and advanced-stage (stages II-IV) disease. Diagnostic processes were also analyzed.Twenty-four patients (8%) had early-stage PDAC (stage 0: 11; stage I: 13). Univariate and multivariate analyses showed that presence or history of intraductal papillary mucinous neoplasm (P0.01), history of pancreatitis (P0.01), and presence or history of extrapancreatic malignancies (P = 0.01) independently predicted detection of early-stage PDAC. Cytological examination during endoscopic retrograde pancreatography cytology was ∼65% sensitive in preoperative diagnosis of early-stage PDAC, whereas other imaging modalities were only 29% to 38% sensitive; 9 of 24 early-stage PDACs were diagnosed by endoscopic retrograde pancreatography cytology alone.Endoscopic retrograde pancreatography cytology for patients with intraductal papillary mucinous neoplasm or pancreatitis may help diagnose early-stage PDAC. Surveillance of extrapancreatic malignancies might also provide opportunities to detect early-stage PDAC as a second malignancy.

The aims of this study were to investigate the GNAS mutational status in pancreatic intraductal papillary mucinous neoplasm (IPMN) with and without distinct pancreatic ductal adenocarcinoma (PDAC) and to evaluate the significance of GNAS analysis using duodenal fluid (DF) in patients with IPMN.The clinicopathologic features of 110 patients with IPMN including 16 with distinct PDAC were reviewed. The GNAS status in the IPMN tissue and 23 DF specimens was assessed by sensitive mutation scanning methods.The GNAS mutation rate in IPMN with distinct PDAC was significantly lower than that in IPMN without PDAC (4/16, 25%, vs 61/94, 65%; P = 0.0047). By multivariate analysis, GNAS wild-type and gastric type IPMNs were significantly associated with distinct PDAC. Of 45 GNAS wild-type IPMNs, 10 (43%) of 23 gastric type IPMNs had distinct PDAC, whereas only 2 (9%) of 22 non-gastric type IPMNs had distinct PDAC (P = 0.017). The GNAS status in DF was consistent with that in tissue in 21 (91%) of 23 patients.Distinct PDACs frequently develop in the pancreas with gastric type IPMN without GNAS mutations. Duodenal fluid DNA test would predict the GNAS status of IPMN, whereas the detection of the gastric subtype using noninvasive test remains to be determined.

We herein present a 71-year-old man who underwent pancreatoduodenectomy with the diagnosis of follicular pancreatitis. We could not completely deny malignancy by a preoperative imaging study. Endoscopic ultrasonography-guided fine needle aspiration biopsy demonstrated clusters of benign acinar cells and no proliferation of atypical lymphoid cells or rich plasma cells. Histologically, the prominent lymphoid follicle formation was seen in an ill-defined mass, 15 mm in size, in the pancreatic parenchyma. Duct-centered fibrotic rims were seen in the pancreatic ducts accompanied by mild fibrotic change between the follicles and obliterative phlebitis. No neoplastic epithelial cells were observed in the resected specimen, and infiltrating lymphocytes did not show any morphological atypia and monoclonal proliferation by immunohistochemical staining with B and T cell markers. In addition, we could exclude IgG4-related disease, because plasmacytic cells were rarely positive for IgG4. Although follicular pancreatitis is rare, this mass-forming inflammatory disease (pancreatitis) should be included in the preoperative differential diagnosis of pancreatic cancer.

Background Patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas may have concomitant distinct pancreatic ductal adenocarcinoma (PDAC). We evaluated the safety and usefulness of intraoperative irrigation cytology of the remnant pancreas (IICP) during pancreatectomy to detect remnant distinct PDAC in patients with IPMN. Methods The records of all 48 patients with IPMN who underwent IICP during partial pancreatectomy at our institution from April 2007 to March 2012 were reviewed retrospectively. After division of the pancreas, a 4-French tube was inserted into the main pancreatic duct of the remnant pancreas from the cut edge, and fluid for cytologic examination was obtained by saline irrigation through the tube. If the third IICP was positive, patients underwent additional pancreatic resection. Clinical and pathologic outcomes were evaluated. Results The third IICP was positive in 5 patients. Postoperative pathologic examination showed that these patients all had remnant distinct PDAC in the additionally resected specimen, which was not detectable on preoperative imaging examination or on intraoperative macroscopic examination, ultrasonography, or palpation. This PDAC was stage 0 in 4 patients and stage III in 1 patient. No procedure-related complications were observed. One patient developed peritoneal metastasis after 10 months, 1 developed liver metastasis after 20 months, and 1 developed PDAC in the remnant pancreas after 24 months. Conclusion IICP seems to be a safe and useful method for detection of early stage PDAC concomitant with IPMN that cannot be detected by preoperative imaging or intraoperative examination.

We investigate how large a primary deficit-to-GDP ratio Japan’s government can sustain. For this investigation, we construct an overlapping generations model in which multi-generational households live and the government maintains a constant ratio of the primary deficit to GDP. We numerically show that the primary deficit cannot be sustained unless the rate of economic growth is unrealistically high, which is more than five percent according to our settings. Our result implies that Japan’s government needs to achieve a positive primary balance in the long run in order to avoid the divergence of the public debt-to-GDP ratio.

Bleeding from gastric varices (GVs) is generally considered more severe than that from esophageal varices (EVs) but occurs less frequently. We review the risk factors for bleeding EVs and GVs. GVs were divided into 2 groups: cardiac varices (CVs, Lg-c) and fundal varices (FVs), i.e., varices involving the fundus alone (Lg-f) or varices involving both the cardia and fundus (Lg-cf). Elevated pressure in the portal vein is a risk factor for bleeding EVs. The portal pressure in patients with GVs and a gastrorenal shunt is lower than that in patients with EVs. The large size of varices is a risk factor for bleeding EVs. Red color signs are elevated red areas that are important for predicting the risk of variceal bleeding, and red wale markings, dilated venules oriented longitudinally on the mucosal surface, have been considered to be the sign with the highest risk. Red color signs are rare in FVs, possibly because of the pronounced thickness of the mucosal layer. Bleeding EVs are not associated with use of antiulcer drugs or nonsteroidal anti-inflammatory drugs (NSAIDs). Although, in patients with bleeding GVs, "occasional" use of an oral NSAID is an important step leading to variceal hemorrhage, especially from FVs, even if the mucosa is protected by antiulcer drugs. Constipation, vomiting, severe coughing, and excessive consumption of alcohol may precipitate rupture of EVs.

A liver tumor metastatic from a sigmoid colon carcinoma was diagnosed in a 70-year-old man. Because hepatectomy was not indicated, the patient was treated with a combination of oxaliplatin, levofolinate, and fluorouracil (5-FU) (modified FOLFOX 6 regimen). After 15 cycles of chemotherapy, this regimen was considered to have been ineffective; therefore, treatment was started with the topoisomerase inhibitor irinotecan and an intravenous infusion of 5-FU and levofolinate (FOLFIRI). After receiving irinotecan and levofolinate, the patient had chills, a severe cough, and dyspnea. We diagnosed pulmonary edema as a side effect due to oxaliplatin, and the chemotherapeutic regimen was changed from FOLFIRI to FOLFOX plus bevacizumab. After the third cycle of oxaliplatin and levofolinate, pulmonary edema recurred, and a preshock state developed again. We suspected that either oxaliplatin or irinotecan had caused the pulmonary edema and, therefore, administered levofolinate, 200 mg/m(2); 5-FU, 400 mg/m(2); and bevacizumab, 330 mg/m(2); intravenously on day 1, followed by 5-FU, 2,400 mg/m(2), as a continuous intravenous infusion at 46 hours without either of oxaliplatin, levofolanate, and bevacizumab. After being treated with levofolinate again, the patient suddenly complained of severe dyspnea; this symptom confirmed that levofolinate had caused the pulmonary edema. To our knowledge, severe pulmonary edema caused by levofolinate has not been reported previously. This adverse effect was clinically significant because it led to the patient's death.

We describe a cystic intraductal papillary neoplasm of bile duct (IPNB) of adenocarcinoma treated with surgical resection. An 82-year-old man was admitted to our hospital because of distension of the right upper quadrant of the abdomen. On admission, a huge nontender mass was palpated in the right upper abdomen. Initial laboratory tests revealed the following serum values: aspartate aminotransferase, 123 IU/L; alanine aminotransferase, 113 IU/L; alkaline phosphatase, 376 IU/L; bilirubin, 1.6 mg/dL; alpha-fetoprotein, 7.4 ng/mL; CA19-9, 39.8 U/mL; carcinoembryonic antigen, 4.1 ng/mL; and Duke pancreatic monoclonal antigen type 2, 200 U/mL. Abdominal ultrasonography revealed an anechoic mass with an elevated papillary lesion in the right paramedian section. Computed tomography showed a low-density hepatic lesion, measuring 12 × 10 cm, with thick, irregular walls. A T2-weighted magnetic resonance scan showed mural nodules with signal intensity higher than that of the liver. The cystic lesion was suspected to be a cystic IPNB, but we could not determine whether it was a carcinoma. We performed extensive right paramedian sectionectomy and cholecystectomy. The resected multilocular tumor was filled with a yellow fluid, and the cut surface showed multiple, yellowish papillary nodules lining the cystic wall. On histologic examination, the neoplastic biliary epithelium showed papillary growth in the dilated lumen. Papillary and micropapillary lesions exhibited cellular atypia: nuclear enlargement and hyperchromasia, mutilayering, and mitosis. Ovarian-like stroma was not detected. The tumor was diagnosed as an IPNB (carcinoma in situ lesion). These lesions had expanded into several intrabiliary ducts. No recurrence has been detected 2 year after operation.

Bleeding from esophageal varices (EVs) or gastric varices (GVs) is a catastrophic complication of chronic liver disease. In this paper, we review the management of bleeding EVs and GVs. DIAGNOSIS OF EVS AND GVS: The grading system for esophagogastric varices proposed by the Japan Society for Portal Hypertension classifies GVs into those involving the cardia (Lg-c), the fundus (Lg-f), and both the cardia and the fundus (Lg-cf). In this review, we divide GVs into 2 categories: Lg-c (cardiac varices: CVs) and Lg-cf or Lg-f (fundal varices: FVs). TREATMENT MODALITIES FOR EVS AND GVS: Treatment modalities for EVs and GVs include placement of a Sengstaken-Blakemore tube, pharmacologic therapy, surgery, interventional radiology, and endoscopic treatment. MANAGEMENT OF BLEEDING EVS AND GVS: In Japan, endoscopic treatment has recently become the therapy of choice for bleeding EVs or GVs. In other countries, especially the United States, vasoactive drugs and endoscopic treatment are routinely used to manage variceal hemorrhage. BLEEDING EVS: Endoscopic variceal ligation is useful for controlling bleeding from EVs. However, confirmation of ligation precisely at the site of bleeding is usually difficult in patients with massive variceal bleeding. The site of acute bleeding can generally be identified by means of water instillation and suction. Ligation is then performed at the bleeding point. If endoscopic hemostasis is unsuccessful, a Sengstaken-Blakemore tube is used as a temporary bridge to other treatments. Transportal obliteration is useful for blocking variceal blood flow. BLEEDING GVS: Endoscopic injection sclerotherapy with a tissue adhesive, such as N-butyl-cyanoacrylate or isobutyl-2-cyanoacrylate, is effective for acute bleeding from GVs. However, bleeding from the GV injection site and rebleeding from the rupture point have been reported in patients receiving endoscopic injection sclerotherapy. If endoscopic hemostasis is unsuccessful, a Sengstaken-Blakemore tube is used as a temporary bridge to other treatments. Balloon-occluded retrograde transvenous obliteration and transportal obliteration are useful for the treatment of uncontrolled bleeding from GVs. PREVENTION OF RECURRENT VARICEAL HEMORRHAGE: Given the high recurrence rate, survivors of an acute variceal hemorrhage should receive treatment to prevent recurrence. Complete eradication of EVs or GVs and maintenance of low portal venous pressure are essential for preventing recurrence of variceal hemorrhage.

A hypoxic microenvironment is a characteristic feature of pancreatic cancer, and induces the expressions of various genes involved in malignant behaviors. Insulin-induced gene 2 (Insig2) has recently been shown to be correlated with cellular invasion in colon cancer. However, there have been no reports regarding its expression in pancreatic cancer. In this study, we evaluated Insig2 mRNA expression and the biological function of Insig2 in pancreatic cancer. We measured Insig2 mRNA expression in cultured pancreatic cancer cell lines and invasive ductal carcinoma (IDC) cells, normal pancreatic epithelial cells, and pancreatic intraepithelial neoplasia cells obtained by laser-capture microdissection. We also investigated the effects of Insig2-targeting siRNAs on the cell proliferation and cell invasion of pancreatic cancer cell lines. All pancreatic cancer cell lines expressed Insig2 mRNA. The PANC-1 and MIA PaCa-2 pancreatic cancer cell lines showed >2-fold higher Insig2 mRNA expression levels under hypoxic conditions (1% O2) than under normoxic conditions (21% O2). Cell proliferation was significantly decreased in SUIT-2 cells and cell invasion was significantly decreased in SUIT-2, Capan-2, and CFPAC-1 cells after transfection of the Insig2-targeting siRNAs. In analyses of microdissected cells, cells from IDC tissues expressed significantly higher levels of Insig2 mRNA than normal pancreatic cells (P

Background To improve the prognosis of patients after resection of pancreatic cancer, the most appropriate and efficient treatment should be provided to specific subsets of patients. Our aim was to identify promising microRNAs as markers to predict responses to gemcitabine in patients with resected pancreatic cancer. Methods Two gemcitabine-resistant pancreatic cancer cell lines were established, and global microRNA expression analyses was performed by quantitative reverse transcription–polymerase chain reaction (qRT-PCR). Eleven miRNAs were selected as putative predictive markers and analyzed by means of macrodissected formalin-fixed, paraffin-embedded samples obtained from 90 patients with or without gemcitabine treatment after resection of pancreatic cancer. Results We identified 24 microRNAs whose expression was altered in gemcitabine-resistant cells. qRT-PCR analyses showed that patients with high miR-142-5p and miR-204 expression had significantly longer survival times than those with low miR-142-5p (P = 0.0077) and miR-204 (P = 0.0054) expression in the gemcitabine-treated group. This was not seen in the nontreated group. Multivariate analyses showed that miR-142-5p expression was an independent prognostic marker only in patients treated with gemcitabine (P = 0.034). Conclusions miR-142-5p is a promising predictive marker for gemcitabine response in patients with resected pancreatic cancer.

We report a case of xanthogranulomatous cholecystitis (XGC) that was diagnosed preoperatively by means of ultrasonography (US) with the contrast-enhancement agent Sonazoid after a false-positive result had been obtained with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET). A 69-year-old woman was admitted because of right upper quadrant pain. Blood tests revealed a serum CA19-9 level of 749.8 IU/L. Computed tomography (CT), US, and magnetic resonance imaging of the abdomen showed abnormal thickening of the gallbladder wall but no stones. The border between the gallbladder and the liver was unclear. FDG-PET revealed a lesion with increased uptake of tracer in the gallbladder wall. The thickness of the lesion was similar to that on CT. We suspected gallbladder carcinoma with hepatic invasion. To confirm the tentative diagnosis, we performed US with the contrast-enhancement agent Sonazoid. The gallbladder wall was homogeneously enhanced in the early vascular phase and remained enhanced for 90 seconds. Enhancement of the gallbladder wall was smooth and regular. The border between the gallbladder and liver was clear and smooth. On the basis of these examinations, we diagnosed chronic cholecystitis (XGC suspected), not gallbladder carcinoma. At surgery, the gallbladder wall was observed to be extremely thick because of severe inflammation, and cholecystectomy was performed. XGC was diagnosed on intraoperative pathological examination. Histopathological examination showed XGC, severe proliferative fibrosis with formation of multiple yellow-brown intramural nodules, and foamy histiocytes without malignant cells. In conclusion, the present case of XGC was diagnosed preoperatively with contrast-enhanced US after a false-positive result had been obtained with FDG-PET. Contrast-enhanced US can thus play important roles in diagnosing gallbladder disease and selecting treatment.

Hepatic angiomyolipoma is a rare hepatic mesenchymal tumor. We report a case of hepatic angiomyolipoma that was successfully resected along with a giant hemangioma. A 53-year-old Japanese woman was admitted to our hospital for further evaluation of a liver tumor in segment 4. The tumor was detected on positron emission tomography during a health check-up. Abdominal ultrasonography revealed a well-defined mass of mixed echogenicity, 1.5 cm in diameter, in segment 4, and a giant hemangioma of mixed echogenicity, 7 cm in diameter, in segment 7. On enhanced computed tomography, the tumor in segment 4 showed hyperattenuation in the early phase and hypoattenuation in the delayed phase. On magnetic resonance imaging, the tumor in segment 4 showed hypointensity on T1-weighted images, hyperintensity on T2-weighted images, and hyperintensity on diffusion-weighted images. On angiography, the tumor in segment 4 appeared as a circumscribed hypervascular mass in the early phase and a slightly hypovascular mass in the delayed phase. The imaging findings suggested a primary hepatocellular carcinoma. The patient consented to resection of the tumor in segment 4 along with the giant hemangioma in segment 7. These tumors were resected with tumor-free surgical margins by partial resection of segments 4 and 7 of the liver. The cut surface of the resected specimen of segment 4 showed a yellowish tumor consisting of mature adipose tissue. The histopathological diagnoses of the resected specimens were angiomyolipoma in segment 4 and cavernous hemangioma in segment 7. The tumor in segment 4 consisted of mature lipocytes with angiomatous and small lymphocytic components, but no mitotic figures. The tumor showed immunoreactivity to smooth muscle antigen and homatropine methylbromide 45 and no immunoreactivity to AE/E3. The postoperative course was uneventful, and the patient remains well 1 year after the operation.

We describe a 35-year-old man with hepatocellular carcinoma (HCC) that recurred in the diaphragm after right hepatic lobectomy. The patient had undergone right hepatic lobectomy for HCC with chronic hepatitis B virus infection 1 year previously. On pathological examination, the tumor measured 15 × 14.4 × 11 cm and was moderately well differentiated. The surgical margins were negative. After 1 year, computed tomography of the abdomen revealed a mass extending from the right side of the diaphragm to the retroperitoneal space. The mass was enhanced in the early phase and washed out in the late phase. Extrahepatic recurrence of HCC in the diaphragm was diagnosed. We performed tumor resection with partial resection of the right side of the diaphragm and wedge resection of the right lower lobe of the lung. The diaphragm was reconstructed with a sheet of artificial pericardium. The histopathological diagnosis was recurrence of HCC in the diaphragm with invasion of the right lung. The postoperative course was uneventful, and the patient was discharged on postoperative day 8. He underwent chemotherapy with cisplatin and 5-fluorouracil. After 9 months, the patient died of unresectable recurrence of HCC in the brain. No recurrence was detected in the right subphrenic area.

Laparoscopic distal pancreatectomy (LDP) has been shown to be an effective surgical option for benign lesions in the body and tail of the pancreas. However, its advantages and disadvantages have not been well characterized. In this study, we compared the outcomes of LDP and open pancreatectomy performed in our clinic.Peri- and postoperative outcomes were retrospectively compared between patients with benign pancreatic disorders who underwent open distal pancreatectomy (ODP) (n = 35) and those who underwent LDP (n = 40). The peri- and postoperative factors analyzed included operative time, blood loss, hospital stay, postoperative recovery, biochemical findings, and complications.LDP was associated with significantly less operative blood loss (363 versus 606 mL; P = 0.001) and shorter hospital stay (22 versus 27 day; P = 0.009), but longer operative time (342 versus 250 min; P = 0.000), compared with ODP. There were no significant differences between the two groups in complication rates or postoperative recovery, except for the significantly shorter duration of postoperative pain-killer intake and earlier improvement of the biochemical analysis in LDP than in ODP.LDP appears to be a safe, desirable procedure for the management of benign pancreatic diseases, with outcomes similar to ODP.

Feline chronic progressive polyarthritis is a rare immune-mediated disease that has only previously been reported in male cats. A one-year-old female cat was presented with anorexia, lassitude and lameness. The tarsal, carpal and elbow joints revealed swelling, pain, stiffness, crepitus and regional lymphadenopathy, and fever was present. The cat was clinically diagnosed with chronic progressive polyarthritis based on the fever, swelling of joints, imaging of erosive proliferative periosteal polyarthritis, positivity for antinuclear antibody, synovial fluid analyses and urinalyses. Both feline leukemia virus antigen and feline immunodeficiency virus antibody were positive. Using hair root DNA, polymerase chain reaction amplification targeting the sex-determining region on the Y chromosome gene amplified the fragment of DNA from a normal male cat, but not amplified from a normal female cat or the present cat. Accordingly, the present cat was classified as genetically female. Cyclosporine treatment was started, and the general condition and movement quickly improved and continued for 8 months post-diagnosis. This is the first report of chronic progressive polyarthritis in a female cat.

We describe the spontaneous rupture of a simple hepatic cyst associated with a benign course. A 64-year-old woman was admitted for right upper quadrant pain. The patient denied a history of abdominal trauma. Abdominal computed tomography (CT) showed a huge solitary hepatic cyst (diameter, 10 cm) in the right lobe. Part of the cyst surface was irregular, and the interior was heterogeneous on ultrasonography. Fluid retention was detected under the liver capsule. Spontaneous rupture of a nonparasitic hepatic cyst was suspected. The patient was admitted to our hospital for further evaluation and treatment. Examination of the abdomen revealed right upper quadrant pain but no signs or symptoms of peritonitis. One week after admission, CT revealed that the volume of fluid retained under the liver capsule had decreased. Percutaneous puncture was performed with a needle and an 8-French pigtail catheter under ultrasonographic guidance. Serous, brown fluid was aspirated. After percutaneous aspiration, the patient's symptoms resolved. Minocycline hydrochloride was given daily by intravenous injection for 7 days. The catheter was then removed. There has been no evidence of recurrence after 1 year.

We describe a 43-year-old woman who underwent laparoscopic distal pancreatectomy preserving the spleen and splenic vessels for the treatment of insulinoma in the pancreatic body. The patient experienced cold sweats on fasting, received diagnosis of insulinoma, and was referred to our hospital for laparoscopic surgery. Blood biochemistry studies showed low fasting blood glucose of 42 mg/dL, serial immunoreactive insulin of 15.2 microU/mL, and a Fajans index (immunoreactive insulin/blood glucose) of 0.36 (normal

Laparoscopy-assisted distal gastrectomy (LADG) has been widely accepted for the treatment for early gastric cancer. Obesity is a rapidly growing epidemic, and the number of obese patients with gastric cancer is increasing, but the impact of visceral fat (VF) accumulation on laparoscopic gastric surgery remains unknown. The aim of the present study was to determine the impact of VF accumulation on LADG.The medical charts of 30 patients who underwent LADG for early gastric cancer in our hospital between November 2000 and November 2006 were analyzed retrospectively. The patients were divided into two groups on the basis of VF accumulation measured on cross-sectional computed tomography at the level of the umbilicus. Twelve patients had high VF accumulation (or =100 cm2) and 18 had low VF accumulation (100 cm2).Although subcutaneous fat accumulation was not correlated with operation time or operative blood loss, VF accumulation was strongly, and significantly, correlated with both operation time and operative blood loss. The high-VF-accumulation group had a significantly longer operation time and significantly more operative blood loss than the low-VF-accumulation group. There was no significant difference in the rate of postoperative complications or conversion to open laparotomy between the two groups. There were no operative deaths or requirements for blood transfusion in either group.VF accumulation was significantly correlated with operative difficulties during LADG. Although LADG was as safe for patients with high VF accumulation as for patients with low VF accumulation, a longer operative time and more operative blood loss were observed in patients with high VF accumulation. VF accumulation appears to be a possible risk factor in LADG and should be considered when making a decision about treating early gastric cancer with LADG.

We have previously demonstrated that the phosphatidylinositol-3 kinase (PI3K)/Akt signaling is essential for pancreatic regeneration after partial pancreatectomy in mice. In the present study, we examined a role of PI3K/Akt signaling for pancreatic duct cell differentiation into insulin-producing cells. Epithelial-like cells were isolated from mouse pancreas and confirmed to be positive for a duct cell marker cytokeratin-20 (CK-20) but negative for insulin. Incubation of these cells with epidermal growth factor, exhibited a gradual increase in Akt phosphorylation and expression of pancreatic duodenal homeobox-1 (PDX-1), a regulator of beta-cell differentiation. Three weeks later, these CK-20-positive cells were noted to express insulin as determined by immunofluorescent double-staining. Akt phosphorylation, PDX-1 expression, and insulin production were effectively reduced by blocking the PI3K/Akt pathway using siRNA to the p85alpha regulatory subunit of PI3K. Our results demonstrate that PI3K/Akt activation has a critical role for pancreatic duct cell differentiation into insulin-producing cells.

The purpose of our study was to determine whether the phosphatidylinositol 3-kinase (PI3K)/Akt pathway contributes to expression of pancreatic duodenal homeobox-1 (PDX-1) in duct cells and the cell differentiation during pancreatic regeneration.The role of PI3K in PDX-1 expression and duct cell differentiation with pancreatic regeneration in mice after partial pancreatectomy (Px) was examined using either wortmannin, a pharmacological PI3K inhibitor, or small-interfering RNA directed to the p85alpha regulatory subunit of PI3K. Akt phosphorylation, a marker of PI3K activation, and PDX-1 expression were assessed by Western blot analysis and immunohistochemistry.Both PDX-1 levels and Akt phosphorylation were concomitantly increased in pancreatic ducts after partial Px and, conversely, blocked by treatment with wortmannin or p85alpha small-interfering RNA. Pancreatic duct cell differentiation, as assessed by appearance of insulin-positive cells 3 days after partial Px, was effectively reduced by wortmannin.The PI3K/Akt activation plays a critical role for both PDX-1 expression and pancreatic duct cell differentiation into insulin-producing cells during pancreatic regeneration.

Summary The porcine MX1 and MX2 promoters were characterized in this study. Sequencing of the 332-bp MX1 promoter region identified 15 substitutions and insertions at three positions in 21 pigs from 15 breeds, in which nine genotypes were classified. Among the nine genotypes, no statistically significant differences in the promoter activities were observed after interferon (IFN-α 2b) treatment of transiently transfected cells containing constructs with luciferase reporter plasmids. The 341-bp MX2 promoter region contained regulatory sequences for ISRE, GC box, Sp1 and AP-1, as well as a TATA box. Nucleotide sequences of the MX2 promoter region revealed four substitutions and one deletion, in which six genotypes were classified. Among the six genotypes, a statistically significant difference (P

A single amino acid substitution between Asn and Ser at position 631 in the chicken Mx protein has been reported to determine resistant and sensitive antiviral activity. In this study, we investigate whether various kinds of chicken breeds and jungle fowls carry the resistant or sensitive Mx allelic gene by using the mismatched PCR-restriction fragment length polymorphism (RFLP) technique. In total, 271 samples from 36 strains of 17 chicken breeds and from 3 kinds of jungle fowls were examined. The rates of the resistant Mx gene and sensitive gene were 59.2% and 40.8%, respectively. Only a Red jungle fowl captured in Laos carried the resistant Mx gene, and the other three Red jungle fowls from Indonesia and Gray and Green jungle fowls all had the sensitive Mx gene. These results were confirmed by the determination of amino acid sequences in the GTPase effector domain of jungle fowls.