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Cancer immunotherapy using immune checkpoint inhibitors can cause immune reactions at various sites as a side effect called immune-related adverse events (irAEs). The gastrointestinal tract is susceptible to irAEs, however, the degree and presentation vary considerably from case to case. A 76-year-old woman was diagnosed with anal mucosal melanoma. She underwent radical surgery and received postoperative adjuvant therapy. However, because new metastases were also found in bilateral inguinal lymph nodes, immunotherapy with nivolumab was performed. Approximately 10 months after the initiation of nivolumab administration, she presented with epigastric discomfort and nausea, and her laboratory data showed severe eosinophilia (1938/mm

Secondary amyloidosis is a rare complication of chronic inflammatory diseases, such as collagen diseases, and is often difficult to treat. In addition, the gastrointestinal tract is frequently involved in amyloid deposition that often results in various disorders and symptoms. A 70-year-old woman was admitted to our hospital with refractory diarrhea and hypoalbuminemia. Abdominal computed tomography demonstrated extensive edematous wall thickening of the small intestine and colon. Video capsule endoscopy revealed multiple ulcerations with a white mossy appearance of the ileum. Double-balloon endoscopy showed severe circumferential ulcers in the entire ileum. Histological examination of ileum biopsy samples revealed severe amyloid deposition in the lamina propria and perivascular areas of the submucosa. The patient was diagnosed with gastrointestinal AA amyloidosis. The cause of AA amyloid deposition was presumed to be chronic pyelonephritis due to ureteral stones that had been left untreated for 35 years. After treatment with ureteral drainage and antibiotics, the patient's symptoms and serological abnormalities improved dramatically. Here, we describe a case of severe gastrointestinal AA amyloidosis secondary to chronic pyelonephritis. Clinicians should thoroughly investigate the entire gastrointestinal tract in patients with refractory diarrhea and severe hypoalbuminemia considering the possibility of gastrointestinal amyloidosis.

Postoperative pancreatitis is a relatively rare disease and is poorly recognized. Herein, we present a case of necrotizing pancreatitis that developed immediately after non-abdominal surgery under general anesthesia. In this report, 4 h after thyroidectomy under general anesthesia using propofol, the patient developed upper abdominal pain and was diagnosed with severe acute pancreatitis with extensive pancreatic necrosis. Immediately after the diagnosis, the patient received appropriate treatment, and acute pancreatitis was improved. Subsequently, the patient has the formation of non-infectious giant walled-off necrosis and remained in good condition without additional treatment for 1.5 years after pancreatitis onset. In this case report, our detailed causative search suggested that propofol administration could be the cause of this pancreatitis. Propofol-induced pancreatitis is extremely rare but develops often severely, resulting in fatality. In this case, the patient developed severe acute pancreatitis within a very short time after surgery but was able to survive by immediate intervention of treatment. We suggest that clinicians should consider acute pancreatitis as a life-threatening adverse event under general anesthesia with propofol and perform thorough postoperative management.

Primary adenosquamous carcinoma (ASC) of the liver is a rare subtype of cholangiocarcinoma that comprises both adenocarcinoma and squamous cell carcinoma components. We report a 48-year-old woman with advanced primary ASC and small cell carcinoma of the liver who had extrahepatic metastasis and received multiple chemotherapy regimens. After first presenting with upper abdominal pain, imaging revealed a 10.2 × 9.5 cm mass in the right lobe of the liver with lymph node and lung metastases. A liver tumor biopsy revealed adenocarcinoma and squamous cell carcinoma components, leading to a diagnosis of advanced primary ASC of the liver. The tumor shrank with gemcitabine/cisplatin therapy; however, neuron-specific enolase (NSE) and CYFRA levels were increased and the tumor grew. Next, hepatic arterial infusion chemotherapy using 5-fluorouracil and cisplatin decreased NSE and CYFRA levels and suppressed tumor growth. However, due to tumor growth, she died 14 months post-initial diagnosis. Post-autopsy pathology revealed a mixture of CD56- and synaptophysin-positive small cell carcinoma component in addition to ASC. We report a rare advanced primary ASC with small cell carcinoma of the liver diagnosed at autopsy.

A man in his 70s received anticancer chemotherapy with the anti-programmed cell death protein–ligand 1 antibody atezolizumab for non-small cell lung cancer. Ten days later, he developed diarrhea and skin rash, which were suspected to be due to immune-related adverse events, and was treated with prednisolone for 2 weeks. Five weeks after atezolizumab administration, he was admitted to our hospital for Common Terminology Criteria for Adverse Events Grade 3 diarrhea and hematochezia. Sigmoidoscopy revealed a dark red color in the mucosa of the transverse colon and multiple whitish mucosal plaques extending from the transverse colon to the rectum. Biopsy specimens revealed empty vacuoles in the lamina propria with infiltration of numerous inflammatory cells, including CD8+ T cells. Based on the findings of sigmoidoscopy and histology, the diagnosis was immune checkpoint inhibitor-related colitis with colonic pseudolipomatosis. The endoscopic findings and symptoms were markedly improved by prednisolone administration. We herein report the first case of immune checkpoint inhibitor-related colitis with characteristic endoscopic findings of colonic pseudolipomatosis. It is important to perform endoscopy and histological evaluation to determine the differential diagnosis and treatment strategy for patients treated with immune checkpoint inhibitors.

Idiopathic portal hypertension (IPH) is one of the background diseases causing nodular regenerative hyperplasia (NRH). Furthermore, IPH patients accompanied with autoimmune diseases, such as systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), are more likely to form NRH in the liver. A 76-year-old woman had been aware of the Raynaud's phenomenon and scleroderma for the past 30 years. In this case, she presented with abdominal fullness, and her imaging analysis revealed ascites and multiple liver nodules. On Gd-EOB-DTPA enhanced magnetic resonance imaging (EOB-MRI), donut-like uptake was observed in the nodules in the hepatobiliary phase. Liver biopsy of a nodule demonstrated that it was composed of hyperplastic hepatocytes without fibrous septa, and dilated sinusoids were observed beside the nodule. Conversely, background liver showed that peripheral portal veins appeared stenotic with dense fibrosis in the portal area. The final diagnosis was that multiple NRH of the liver developed in SSc patient accompanying IPH. This case suggests that NRH may be unexpectedly diagnosed in patients with autoimmune diseases accompanying IPH.

Endoscopic submucosal dissection (ESD) is a technically difficult and time-consuming procedure for the treatment of large colorectal tumors. In Japan, the ball-tip bipolar-current needle-knife (BB-knife) has been used in ESD as a safe device that minimizes the damage to deeper tissues of colorectal neoplasms. In May 2012, a BB-knife combined with a water jet function (Jet B-knife) was newly developed. This retrospective study was aimed at examining the effectiveness and safety of the Jet B-knife. The BB-knife was used in 276 lesions (BB-knife group), while the Jet B-knife was used in 245 lesions (Jet B-knife group). We evaluated tumor characteristics and the results of the ESD procedures, including the size of the resected tumor, histological diagnosis, time required for resection, frequency of using other electrical devices, en bloc resection rate, and incidence rate of associated complications. Then, the data obtained were compared between the two groups. The histological evaluation of the resected tumors revealed that the incidence of cancer was not significantly different between the two groups. The median time required for resection was 103 min (45–255) in the BB-knife group and 51 min (28–210) in the Jet B-knife group. The difference was statistically significant (p

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), formerly known as enteropathy-associated T-cell lymphoma (EATL) type II, is a rare disease with a poor prognosis that is often diagnosed when patients present with intestinal perforation or obstruction. Our patient, a man in his 60 s, had a 5-month history of persistent watery diarrhea. Upper and lower gastrointestinal endoscopy, abdominal computed tomography (CT), and stool culture results were unremarkable. He was admitted to our hospital 8 months later with a weight loss of 20 kg, general fatigue, and hypokalemia. Contrast-enhanced CT of the abdomen revealed mild thickening and contrast enhancement of the small intestinal wall. Video capsule endoscopy and double-balloon enteroscopy were performed to reveal a broad ulcer in the jejunum and multiple erosions throughout the small intestine. Examination of the biopsy specimens showed infiltration of atypical lymphocytes with pale cytoplasm in the glandular epithelium. The atypical lymphocytes were positive for CD3, CD8, CD56, granzyme B, and T-cell intracellular antigen-1 by immunostaining. Early diagnosis of MEITL was made, and the patient survived for 21 months with continuous chemotherapy. Aggressive examination of the small intestine is effective for the early diagnosis of serious diseases, such as MEITL, in patients with chronic diarrhea of unknown origin.

Congenital hepatic fibrosis is a rare autosomal recessive disorder caused by ductal plate malformation that can manifest as hepatic fibrosis alone or as a component in various fibropolycystic diseases including renal involvement. It is often diagnosed early in life, presenting with ascites and esophageal variceal bleeding due to non-cirrhotic portal hypertension. Here, we report a rare case of congenital hepatic fibrosis with portal hypertension diagnosed at an advanced age. A 78-year-old woman with a 6 history of recurrent cholangitis experienced abdominal distension. Imaging revealed ascites and esophageal varices. Histopathologic analysis of the liver revealed the fibrous expansion of portal tracts accompanying increased bile ducts with irregular contours in the portal area. These characteristic findings are consistent with the diagnosis of congenital hepatic fibrosis. The present case showed an extremely unique clinical course, because she did not develop any associated renal abnormalities or any disease-related symptoms until old age. Because of the variability of this disease, the slowly progressive type may be difficult to diagnose and cause non-cirrhotic portal hypertension even in the elderly. Although an unusual clinical course may suggest the presence of the disease, timely histologic assessment is crucial for the definitive diagnosis of congenital hepatic fibrosis.

AIM Curing hepatitis B virus (HBV) infection requires elimination of covalently closed circular DNA (cccDNA). Interferon (IFN)-γ has noncytolytic antiviral potential; however, elimination of cccDNA could not be achieved. To enhance the regulatory effect, we comprehensively analyzed the host factors associated with cccDNA amplification and IFN-γ and IFN-α effects using an in vitro HBV infection system showing various transcription levels. METHODS Primary human hepatocytes were infected with HBV using genomic plasmids carrying the basic core promoter mutation A1762T/G1764A and/or the precore mutation G1896A and treated with IFN-γ and IFN-α. Comprehensive and functional studies involving microarray and small interfering RNA analysis revealed the host factors related to cccDNA regulation. RESULTS The HBV infection system reproduced the HBV life cycle and showed various propagation levels. Microarray analysis revealed 53 genes correlated with the cccDNA levels. Of the 53 genes, expression of IFN-induced protein 44-like (IFI44L) was significantly upregulated by IFN-γ and IFN-α. The anti-HBV effect of IFI44L is exerted regardless of IFN-γ or IFN-α by inhibiting the activation of nuclear factor-κB and signal transducer and activator of transcription 1 pathways. CONCLUSIONS Using the in vitro HBV infection system, an IFN-inducible molecule, IFI44L, associated with cccDNA amplification, was identified. These results suggest an innovative molecular strategy for the regulation of HBV cccDNA by controlling a novel host factor, IFI44L.

We investigated the [18F]-fluoro-2-deoxy-d-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) findings of pancreatic and extrapancreatic lesions in patients with autoimmune pancreatitis (AIP) and pancreatic cancer (PC) and evaluated the usefulness of 18F-FDG-PET/CT for differentiating between AIP and PC.Eighty-five patients, 19 with AIP and 66 with PC, who underwent 18F-FDG-PET/CT were studied retrospectively. We evaluated the maximum standardized uptake value (SUVmax), patterns and distributions of FDG activity in pancreatic lesions, as well as FDG uptake in extrapancreatic lesions.The levels of SUVmax of pancreatic lesions in PC patients were significantly higher than those in AIP patients (P0.05). Focal/segmental distribution of FDG activity was found in 61.1% of the AIP patients and 98.4% of the PC patients. Heterogeneous FDG activity patterns were found in 61.1% of the AIP patients and 18.7% of the PC patients. Activities of FDG in pancreatic lesions were significantly different between AIP and PC. Extrapancreatic activities of salivary glands, extraperitoneal lymph nodes, prostate, retroperitoneum, and kidneys in the AIP patients were significantly higher than those in the PC patients (P0.05). Multivariate analysis revealed that SUVmax (7.08) and focal/segmental FDG distribution were independent predictors of PC (P0.05).The 18F-FDG-PET/CT findings are useful for differentiating between AIP and PC.

Aim A complete cure for chronic hepatitis B virus (HBV) infection requires elimination of covalently closed circular DNA; however, this remains to be clinically achieved. Interferon (IFN)-γ, a type II IFN, is produced by intrahepatic cytotoxic T lymphocytes and has non-cytolytic antiviral potential. However, the mechanism by which IFN-γ regulates HBV infection has not been fully elucidated. Thus, we developed an in vitro HBV infection assay system and analyzed the molecular signature of HBV regulation by IFN-γ. Methods The in vitro HBV infection assay system was established in primary human hepatocytes infected with HBV derived from the plasmid containing 1.3-mer HBV genome, and treated with IFN-γ. The antiviral effects and signaling pathways of IFN-γ were examined using microarray, and assessed by siRNA knockdown experiments of the related genes. Results IFN-γ treatment suppressed both HBV propagation and transcription as efficiently as IFN-α. Microarray analysis showed that IFN-γ stimulation induced the activation of both IFN-γ and IFN-α signaling, regulating HBV covalently closed circular DNA. HBV production was decreased by IFN-γ through Janus kinase/signal transducer and activator of transcription signaling and interferon-stimulated genes, such as 2'-5'-oligoadenylate synthase 2 and apolipoprotein B mRNA editing enzyme catalytic subunit 3G. Conclusions IFN-γ can suppress HBV propagation and transcription in hepatocytes by activating specific intracellular signaling pathways in hepatocytes, and suggests the future application of these particular signaling pathways or genes for the complete elimination of HBV.

Objective Immunoglobulin (Ig) A vasculitis (IgAV) is a systemic vasculitis characterized by purpura and gastrointestinal involvement showing abdominal pain that usually occurs after the emergence of purpura. Criteria for evaluating gastrointestinal manifestations of IgAV are unavailable at present, so we conducted a study to investigate the usefulness of video capsule endoscopy (VCE) for detecting gastrointestinal manifestations of IgAV. Methods The clinical data of 10 patients who underwent VCE for IgAV at our hospital from 2012 to 2017 were collected. Nine patients underwent esophagogastroduodenoscopy, and five underwent colonoscopy. We compared the endoscopic severity determined by VCE to the findings of esophagogastroduodenoscopy and colonoscopy. Results The rates of positive findings of esophagogastroduodenoscopy, VCE, and colonoscopy were 56%, 100%, and 80%, respectively. In 70% of cases, the most severe gastrointestinal findings were detected by VCE. VCE was performed on average 16.8 days after the emergence of purpura, and in 8 of 10 patients, its result triggered the initiation of steroid therapy or the control of the steroid dose. Conclusion VCE is very useful for confirming gastrointestinal involvement in IgAV and may be used to determine the timing of steroid therapy initiation. We recommend performing VCE when IgAV is suspected in patients with gastrointestinal symptoms.

Immune checkpoint inhibitors have been shown to be effective for treating many carcinomas. However, the activated immune response may lead to the development of multiple immune-related adverse events, including rare immune-mediated inflammation due to autoimmune mechanisms. An 82-year-old man was diagnosed with large cell lung cancer (T1aN3M1 stage IVB) and was treated with inhibitors of the programmed cell death receptor-1, pembrolizumab. Diarrhea and melena occurred after six doses of pembrolizumab, and colonoscopy revealed mucosal inflammation of the rectum and sigmoid colon in a continuous manner, resembling the typical endoscopic findings of ulcerative colitis. Subsequently, fever and hyperamylasemia appeared, and the patient was diagnosed with pancreatitis resembling type 2 autoimmune pancreatitis on imaging tests and cytological examination, which showed infiltration of inflammatory cells, mainly neutrophils. Steroid therapy was administered and both, colitis and pancreatitis markedly improved. Here, we present a patient who developed colitis and pancreatitis after ICI treatment for advanced lung cancer. Both are thought to be due to autoimmune side effects of pembrolizumab. Although pancreatitis is a rare irAE, clinicians should be aware of the development of pancreatitis, especially in the case of irAE colitis resembling ulcerative colitis.

Introduction. We retrospectively examined the relationship between daily proton pump inhibitor (PPI) use and severity of upper gastrointestinal bleeding (UGIB), mainly in the elderly. Methods. We included 97 patients with nonvariceal UGIB diagnosed at our hospital from January 2012 to October 2017. Bleeding severity was assessed using the shock index (SI) and estimated bleeding volume; 49 patients met the criterion for the mild group and 48 for the moderate/severe group. The effect of PPI use on bleeding severity was compared between the groups. The relationships of PPI use and dose with the clinical symptoms of UGIB were also analyzed. Results. Among the 97 patients, 17 (17.5%) habitually used PPIs. The rate of habitual PPI use was significantly higher in the mild group, indicating as an independent factor contributing to a reduction in the severity of UGIB in a multiple logistic regression analysis (30.6% vs. 4.2%; OR 10.147; 95% CI 2.174–47.358, P<0.01). When analyzing data for a subgroup of patients older than 75 years, we found the protective PPI effect to be even higher in the mild UGIB group than in the moderate/severe group (37.0% vs. 5.6%; OR 10.000; 95% CI 1.150–86.951, P<0.05). Conversely, we found no association between PPI prescription and UGIB symptoms in patients younger than 75 years. The mean estimated bleeding volume and SI in the 17 habitual PPI users were both significantly less than those among the 80 nonhabitual users, respectively (P<0.05). The proportion of patients with mild UGIB was similar between the low- and high-dose PPI users. Conclusions. Particularly in elderly patients with nonvariceal UGIB, habitual PPI use can alleviate the clinical symptoms of UGIB by suppressing the volume of bleeding, regardless of the adapted dose of PPIs.

OBJECTIVE To evaluate the long-term outcomes of complete common bile duct (CBD) stone removal and biliary stenting in elderly patients (≥85 years) with CBD stones. METHODS We retrospectively examined 65 patients who underwent complete CBD stone removal (the duct clearance group) and 40 patients who underwent biliary stenting (the biliary stenting group) between July 2006 and March 2016. To reduce selection bias, we also conducted a propensity score matching analysis and generated 30 pairs of patients. Cholangitis recurrence-free survival and overall survival were compared between the two groups and independent prognostic factors of survival were identified by univariate and multivariate analyses. RESULTS Cholangitis recurrence-free survival was significantly better in the duct clearance group than in the biliary stenting group (P < 0.001). Their overall survival did not significantly differ after propensity score matching (P = 0.388). In all cohorts, univariate analysis demonstrated that poor performance status and biliary stenting were factors of poor prognosis, and in multivariate analysis only performance status remained associated with poor prognosis for survival. Similarly, in the propensity score-matched cohort, only performance status independently predicted poorer survival (hazard ratio [HR] 2.726, 95% confidence interval [CI] 1.105-6.675, P = 0.029). The choice of endoscopic treatment was not a significant factor associated with prognosis (HR 1.354, 95% CI 0.678-2.701, P = 0.391). CONCLUSIONS Biliary stenting was similar to complete stone removal in terms of prognosis for long-term survival. Biliary stenting for CBD stones could be an effective therapeutic tool in high-risk elderly patients.

Owing to effective treatments and sanitary improvements, the incidence of latent tuberculosis infection (LTBI) has decreased. However, approximately one-quarter of the world's population is thought to have LTBI, and the reactivation of tuberculosis (TB) sometimes occurs in immunocompromised hosts. A 54-year-old man presented with a fever. The patient had past histories of alcoholic and hepatitis C virus-related cirrhosis and hepatocellular carcinoma (HCC). He was treated with drug-eluting beads transarterial chemoembolization (DEB-TACE) for HCC three times, beginning 10 months before his current visit. A computed tomography scan showed enlarged intraabdominal lymph nodes with calcification, and the interferon-gamma release assay for TB infection was positive. The patient was diagnosed with tuberculous reactivation. Anti-TB therapy was administered to the patient, after which we restarted TACE and the TB infection remains controlled. In this case, we presumed that DEB-TACE is associated with the reactivation of TB infection and that anthracycline increases the risk of reactivating TB infection. In summary, we experienced a case of TB reactivation during the clinical course of a patient with HCC who was treated with DEB-TACE. When patients with HCC are treated with TACE, their symptoms, laboratory data, and imaging results should be monitored when latent TB infections are suspected.

Hepatitis B virus (HBV) reactivation can be triggered by immunosuppressive chemotherapy. HLA class II molecules may play a role in HBV reactivation. Genetic polymorphism and mRNA expression of HLA class II were examined in patients with latent HBV infection treated with immunosuppressive therapies. Subjects with resolved HBV infection who had undergone treatment with immunosuppressive chemotherapies were retrospectively enrolled (n = 42) and divided into reactivated (n = 9) and non-reactivated groups (n = 33). Patients were genotyped for 17 single nucleotide polymorphisms (SNPs) within HLA class II DPA1, and DPB1, and mRNA expression levels of HLA class II genes were assessed. The frequency of the AA genotype of rs872956, a SNP in HLA-DPB1, was significantly higher in the reactivated group than in the non-reactivated group (55.6% vs 12.1%, P < 0.05). The frequencies of the T allele and non-AA genotypes (AT/TT) of rs3116996 (located in DPB1) were significantly higher in the reactivated group (T allele frequency: 16.7% vs 0.0% [P < 0.01], non-AA genotype frequency: 22.2% vs 0.0% [P < 0.05]). Multivariate logistic regression identified the AA genotype of rs872956 as an independent protective factor against HBV reactivation (odds ratio [OR] = 18.1, 95% confidence interval [CI] = 2.6-126.7, P < 0.01). mRNA expression of HLA-DPB1 was lower in the HBV reactivated group than in the non-reactivated group (median 276.1 ± 165.6/β-actin vs 371.4 ± 407.5/β-actin [P < 0.05]). These results suggest the involvement of HLA class II molecules in HBV reactivation after treatment with immunomodulatory agents.

A 75-year-old man presented with abdominal distension, hypoproteinemia, ascites and a 35-mm mass in the small bowel mesentery. Laparotomy was performed, and he was diagnosed with sclerosing mesenteritis. His clinical condition improved, with computed tomography (CT) showing tumor shrinkage and decreasing ascites after administration of prednisolone; however, on drug withdrawal, abdominal fullness recurred and CT revealed an enlarging tumor and increasing ascites. Capsule endoscopy (CE) and double-balloon enteroscopy (DBE) were performed to further investigate hypoalbuminemia, which revealed white villi, white nodules, white debris, and mucosal edema in the jejunum. Biopsies from the jejunal mucosa demonstrated infiltration by chronic inflammatory cells consisting mostly of lymphocytes and plasma cells, with marked lymphangiectasia of the lamina propria and submucosa. A fecal alpha-1-antitrypsin clearance test revealed abnormal leakage from the gastrointestinal tract, confirming that hypoalbuminemia was secondary to protein-losing enteropathy (PLE). The incidence of sclerosing mesenteritis accompanied by PLE is very rare. Only six cases have been reported so far. CE and DBE were helpful for diagnosing this condition, and should be performed in patients in whom the cause of hypoalbuminemia is unknown, and in those with PLE.

Recent genome-wide studies have demonstrated that HLA class II gene may play an important role in viral hepatitis. We studied genetic polymorphism and RNA expression of HLA class II genes in HCV-related liver diseases. The study was performed in groups consisting of 24 patients with HCV-related liver disease (12 of persistent normal ALT: PNALT group and 12 of advanced liver disease: ALD group) and 26 patients without HCV infection (control group). In PBMC samples, RNA expression of HLA class II genes (HLA-DPA1, DPB1, DQA1, DQB1, and DRB1) was analyzed by real-time RT-PCR. Furthermore, 22 single nucleotide polymorphisms (SNPs) in HLA class II gene and two SNPs in IL28B gene were genotyped by genetic analyzer (GENECUBE®). In expression analysis, only DPB1 level was significantly different. Mean expression level of DPB1gene in control group was 160.0, PNALT group 233.8, and ALD group 465.0 (P

Accurate determination of the stage of liver fibrosis is an essential component in choice of treatment and assessment of cancer risk in patients with chronic viral hepatitis. The aim of this study was to evaluate the usefulness of strain elastography based on tissue Doppler imaging for liver fibrosis in chronic viral hepatitis.A total of 37 patients with chronic viral hepatitis and 8 healthy volunteers were enrolled. Strain value was measured by using a conventional ultrasound machine that included strain imaging technolo- gy. Strain elastography was performed at the right subcostal area with manual compression. Liver fibrosis stages were assessed by using liver biopsy and compared with strain values. Diagnostic performance of the strain value for fibrosis stage 4, cirrhosis, was determined by performing a receiver-operating characteristics (ROC) curve analysis.Twenty-seven patients were positive for HCV RNA, 9 were positive for HBs antigen, and 1 was positive for both (Fibrosis stage F1, n=11; F2, n=7; F3, n=15; F4, n=4). The strain value of F3 and F4 was 0.066±0.02 and 0.042±0.011, respectively. These strain Values were significantly lower compared to those of healthy volunteers (0.112 ±0.018) (P0.05). Using a cutoff value of 0.042, the area under ROC curve was 0.88 for the diagnosis of F4. The sensitivity, specificity, positive predictive value, and negative predictive value were 75%, 92%, 50%, and 94%, respectively.Strain elastography based on tissue Doppler imaging with manual compression appears to be a useful tool to diagnose cirrhosis in patients with chronic viral hepatitis. [Original].

To evaluate the long-term outcomes of complete common bile duct (CBD) stone removal and biliary stenting in elderly patients (≥85 years) with CBD stones.We retrospectively examined 65 patients who underwent complete CBD stone removal (the duct clearance group) and 40 patients who underwent biliary stenting (the biliary stenting group) between July 2006 and March 2016. To reduce selection bias, we also conducted a propensity score matching analysis and generated 30 pairs of patients. Cholangitis recurrence-free survival and overall survival were compared between the two groups and independent prognostic factors of survival were identified by univariate and multivariate analyses.Cholangitis recurrence-free survival was significantly better in the duct clearance group than in the biliary stenting group (P0.001). Their overall survival did not significantly differ after propensity score matching (P = 0.388). In all cohorts, univariate analysis demonstrated that poor performance status and biliary stenting were factors of poor prognosis, and in multivariate analysis only performance status remained associated with poor prognosis for survival. Similarly, in the propensity score-matched cohort, only performance status independently predicted poorer survival (hazard ratio [HR] 2.726, 95% confidence interval [CI] 1.105-6.675, P = 0.029). The choice of endoscopic treatment was not a significant factor associated with prognosis (HR 1.354, 95% CI 0.678-2.701, P = 0.391).Biliary stenting was similar to complete stone removal in terms of prognosis for long-term survival. Biliary stenting for CBD stones could be an effective therapeutic tool in high-risk elderly patients.

A woman in her 30s visited our hospital with stool abnormality. Esophagogastroduodenoscopy revealed a depressed lesion on the greater curvature of the gastric antrum. The tumor was diagnosed as a well-differentiated tubular adenocarcinoma based on the analysis of the biopsy specimen. The rapid urease test, histological examination, and serum anti-Helicobacter pylori antibody indicated that the patient was Helicobacter pylori negative. Gastric mucosal atrophy was not evident on esophagogastroduodenoscopy. Complete cure en bloc resection was successfully performed. The tumor was confined to the mucosa (pT1a-M). Immunohistochemistry showed positive CD10, MUC2, and CDX2 expression and negative MUC5AC and MUC6 expression. Thus, the phenotype was diagnosed as the intestinal phenotype. Helicobacter pylori-negative, well-differentiated early gastric cancer with intestinal phenotype has not been previously reported. Here, we report a rare and valuable case of Helicobacter pylori-negative early gastric cancer with intestinal phenotype treated by endoscopic submucosal dissection.

Background and study aims: Primary neoplasms of the small intestine are relatively rare in all age groups, accounting for about 5 % of all gastrointestinal tumors 1 . Cavernous hemangiomas of the small intestine are also rare, can cause gastrointestinal bleeding, and are extremely difficult to diagnose preoperatively 2 . We present a patient who presented with melena and iron deficiency anemia, for whom wireless capsule endoscopy and single-balloon enteroscopy facilitated the diagnosis of cavernous hemangioma.

Green tea catechins (GTCs) have been implicated in various physiological effects, including anti-carcinogenic activities. In the present study, we evaluated the effects of GTCs specifically on the development of gastritis and pre-malignant lesions in insulin-gastrin mice. Nine-week-old male INS-GAS mice (n=38) were supplemented with GTCs for 4 and 28 weeks, and their body weights, serum gastrin levels, histopathology and pro-inflammatory cytokine levels in gastric tissue and mucosal cell proliferation were monitored. Body weights of the GTC-treated mice were significantly lower than those of the untreated controls (P≤0.05). Serum gastrin levels were suppressed at the age of 37-weeks (P≤0.05). The histopathological scores indicated that the extent of dysplasia was significantly diminished (P≤0.05), although GTC supplementation did not affect the inflammation scores. The messenger RNA levels of interferon (IFN)-γ were significantly reduced at the age of 13 weeks (P≤0.05), although the changes did not reach statistical significance at the age of 37 weeks (P=0.056). The labeling index of Ki-67 immunohistochemistry was significantly decreased (P≤0.05). These results demonstrated that GTCs may play a protective role in the development of gastritis and pre-malignant lesions via an IFN-γ, gastrin, and mucosal cell proliferation-dependent mechanism in this rodent model and potentially in humans.

Background The spontaneous rupture of hepatic metastases is rare compared to that of primary hepatic tumors. In addition, vemurafenib, a selective inhibitor of the mutant BRAF protein or gene product, has been reported to be extremely effective in patients with metastatic melanoma who harbor a BRAF V600E mutation. Case presentation A 44-year-old female had previously undergone surgery for resection of a malignant melanoma in the lower right leg. Four years later, hepatic metastases became apparent, and transcatheter arterial embolization (TAE) was performed. Then she underwent treatment with vemurafenib. The size of the hepatic metastases markedly decreased. Two months later, they enlarged rapidly and ruptured, requiring emergency TAE. However, the patient developed hemorrhagic shock and died of renewed intra-abdominal bleeding on the 26th postoperative day. Conclusions This is a rare case of ruptured hepatic metastases of malignant melanoma during treatment with vemurafenib. Postmortem examination and immunohistochemical analysis indicated reactivation of the mitogen-activated protein kinase pathway in the metastatic tumor, suggesting secondary resistance to vemurafenib as the possible underlying mechanism.

Background Metastasis to the pituitary gland is extremely rare and is often detected incidentally by symptoms associated with endocrine dysfunction. Breast and lung cancer are the most common primary metastasizing to pituitary gland. Metastasis from hepatocellular carcinoma to the pituitary gland is extremely rare, with only 10 cases having been previously reported. We present here the first case of pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism diagnosed by magnetic resonance imaging. Case presentation We report the case of an 80-year-old Japanese woman who presented with the sudden onset of hypotension and bradycardia after having previously been diagnosed with hepatocellular carcinoma. Based on low levels of pituitary hormones, she was diagnosed with panhypopituitarism caused by metastasis of the hepatocellular carcinoma to the pituitary gland. Magnetic resonance imaging with arterial spin-labeling was effective in the differential diagnosis of the intrasellar tumor. The patient died despite hormone replacement therapy because of hypovolemic shock. Conclusion Metastasis to the pituitary gland causes various non-specific symptoms, so it is difficult to diagnose. The present case emphasizes the importance of diagnostic imaging in identifying these metastases. Clinicians should consider the possibility of pituitary metastasis in patients with malignant tumors who demonstrate hypopituitarism.