Isolation of mucosa-associated microbiota dysbiosis in the ascending colon in hepatitis C virus post-sustained virologic response cirrhotic patients.

Background: Achieving sustained virologic response (SVR) in patients infected with hepatitis C virus (HCV) reduces all-cause mortality. However, the mechanisms and risk factors for liver fibrosis and portal hypertension post-SVR remain incompletely understood. In the gut-liver axis, mucosa-associated microbiota (MAM) substantially influence immune and metabolic functions, displaying spatial heterogeneity at the anatomical intestinal site. We analyzed MAM composition and function to isolate the locoregional MAM involved in chronic liver disease progression in HCV post-SVR patients. Methods: We collected MAM samples from three intestinal sites (terminal ileum, ascending colon, and sigmoid colon) via brushing during colonoscopy in 23 HCV post-SVR patients and 25 individuals without liver disease (controls). The 16S rRNA of bacterial DNA in specimens collected with a brush and in feces was sequenced. The molecular expression of intestinal tissues and hepatic tissues were evaluated by quantitative real-time PCR. Results: In the post-SVR group, the microbial ß-diversity of MAM, especially in the ascending colon, differed from the control group and was associated with liver fibrosis progression. In PICRUSt analysis, MAM in the ascending colon in the liver cirrhosis (LC) group showed compromised functions associated with the intestinal barrier and bile acid production, and FGF19 expression was markedly decreased in the terminal ileum biopsy tissue in the LC group. At the genus level, six short-chain fatty acid (SCFA)-producing bacterial genera, Blautia, Alistipes, Roseburia, Agathobaculum, Dorea, and Pseudoflavonifractor were reduced in the ascending colon of post-SVR LC patients. Conclusion: In patients of HCV post-SVR, we identified the association between the degree of liver fibrosis and dysbiosis of mucosa-associated SCFA-producing bacterial genera that may be related to intestinal barrier and bile acid production in the ascending colon.

Hepatocellular carcinoma progression promoted by 5-lipoxygenase activity in CD163(+) tumor-associated macrophages.

Arachidonic acid 5-lipoxygenase (5-LOX), an enzyme that synthesizes leukotrienes (LTs), is involved in cancer development including proliferation, invasion, metastasis and drug resistance. However, the functional role of 5-LOX in hepatocellular carcinoma (HCC) remains to be elucidated. In this study, we analyzed the contribution of 5-LOX in HCC progression and investigated the potential of targeted therapy. Analysis of 86 resected HCC specimens and the clinical data of 362 cases of liver cancer from The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset, showed that 5-LOX expression was associated with postoperative survival. The cancer proliferative and stem cell potential were correlated with the levels of 5-LOX in CD163(+) tumor-associated macrophages (TAMs). In an HCC mouse model, CD163(+) TAMs expressed 5-LOX and produced LTB4 and LTC/D/E4; the 5-LOX inhibitor, zileuton, suppressed HCC progression. LTB4 and LTC/D/E4 promoted cancer proliferation and stem cell capacity via phosphorylation of extracellular signal-regulated kinase 1/2 and stem cell-associated genes. Taken together, we identified a novel mechanism of HCC progression in which CD163(+) TAMs express 5-LOX and produce LTB4 and LTC/D/E4, thereby enhancing the proliferative and stem cell potential of HCC cells. Furthermore, inhibition of 5-LOX activity regulates HCC progression, suggesting it has potential as a new therapeutic target.

Histology and cytokine levels in hepatic injury accompanying a case of non-severe COVID-19.

The pathogenesis of liver dysfunction that complicates coronavirus disease 2019 (COVID-19) remains unclear, especially in mild to moderate severity cases. In this case, a novel coronavirus infection was detected by polymerase chain reaction (PCR) in a 76-year-old woman hospitalized after presenting with fever. No other abnormal physical findings were observed, and oxygen administration was not required. Chest computed tomography (CT) showed a ground-glass-like and an infiltrative shadow in the right lung, and moderate COVID-19 was diagnosed. Initially, the fever resolved, and PCR turned negative; however, the fever reappeared on hospitalization day 14, and CT showed pneumonia exacerbation accompanied by new onset of fatty liver. Biochemical testing revealed marked liver dysfunction, accompanied by elevated serum interleukin (IL)-6, IL-10, and tumor necrosis factor-α levels. Physical findings and all laboratory parameters improved after conservative treatment, and she was discharged on day 22. A liver biopsy performed 44 days post-discharge showed T-cell-dominant inflammatory cell infiltration, mainly in the portal region. Some hepatocytes showed fatty degeneration.We report a case of moderate COVID-19 in which histological hepatitis persisted after a substantial period had passed since the initial infection had cleared and associated transaminase elevations had resolved, with a comparison of serum cytokine dynamics.

Cholesterol crystal embolism in multiple organs after transarterial chemoembolization for hepatocellular carcinoma: An autopsy case report.

RATIONALE: Transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) rarely causes cholesterol crystal embolism (CCE). In our case, the histological findings suggested that the onset of CCE occurred at different time points in different organs. PATIENT CONCERNS: A 72-year-old Japanese woman with HCC underwent TACE. After TACE, serum creatinine level and eosinophil count gradually increased. Three months later, she was admitted to our department with a fever and back pain. DIAGNOSIS: Laboratory examinations showed sepsis with disseminated intravascular coagulation. She was treated with antimicrobial agents and anticoagulants, but died of multiple organ failure. INTERVENTIONS: An autopsy was performed to examine the cause of multiple organ failure after 3 months of TACE. OUTCOMES: A mixture of both chronic phase emboli with intimal thickening and fibrosis and acute phase emboli with inflammatory cell infiltration were observed in the small intestine. Moreover, multiple intravascular cholesterol fissures were observed in the kidney, stomach, duodenum, colon, pancreas, and spleen, which were the vascular dominant organs of the celiac artery and superior mesenteric artery. These histological findings suggested that cholesterol crystals were continuously disseminated after TACE. LESSONS: TACE for HCC may cause progressive CCE and damage in multiple organs. When progressive renal dysfunction, eosinophilia, or multiple organ dysfunction is observed after TACE, the CCE should be suspected.

A rare case of eosinophilic gastritis induced by nivolumab therapy for metastatic melanoma.

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/mm3). Computed tomography demonstrated a diffuse thickening of the gastric wall. Esophagogastroduodenoscopy and endoscopic ultrasonography showed mucosal thickening due to edema, and histologic examination revealed severe invasion of eosinophils in the lamina propria. Subsequently, she was diagnosed with eosinophilic gastritis due to irAEs induced by nivolumab. Oral administration of prednisolone rapidly normalized her endoscopic and histologic findings, dramatically reducing her symptoms. This is a very rare and important case report of nivolumab-induced severe eosinophilic gastritis. Although gastric lesions as IrAEs is rare, it is necessary to differentiate eosinophilic gastritis if unexplained nausea occurred during the administration of immune checkpoint inhibitors.

Successful early diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma manifesting as chronic diarrhea and hypokalemia using video capsule endoscopy and double-balloon enteroscopy.

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.

Clinical Usefulness of [18F]-Fluoro-2-Deoxy-d-Glucose-Positron Emission Tomography/Computed Tomography for Distinguishing Between Autoimmune Pancreatitis and Pancreatic Cancer.

OBJECTIVES: 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. METHODS: 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. RESULTS: The levels of SUVmax of pancreatic lesions in PC patients were significantly higher than those in AIP patients (P < 0.05). 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 (P < 0.05). Multivariate analysis revealed that SUVmax (>7.08) and focal/segmental FDG distribution were independent predictors of PC (P < 0.05). CONCLUSIONS: The 18F-FDG-PET/CT findings are useful for differentiating between AIP and PC.

Gastrointestinal AA amyloidosis secondary to chronic pyelonephritis presenting with refractory diarrhea and severe hypoalbuminemia.

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.

Severe necrotizing pancreatitis immediately after non-abdominal surgery under general anesthesia with propofol.

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.

Pembrolizumab-induced autoimmune side effects of colon and pancreas in a patient with lung cancer.

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.

Advanced primary adenosquamous carcinoma of the liver with a small cell carcinoma component: an autopsy case report.

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 case of immune checkpoint inhibitor-related colitis with a distinctive endoscopic finding of colonic pseudolipomatosis.

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.

A case of idiopathic portal hypertension accompanying multiple hepatic nodular regenerative hyperplasia in a patient with systemic sclerosis.

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.

Circulating tumor cells detected with a microcavity array predict clinical outcome in hepatocellular carcinoma.

The present study aimed to establish a novel isolation strategy for circulating tumor cells (CTCs) using a microcavity array (MCA) system and to evaluate the clinical significance of CTCs in hepatocellular carcinoma (HCC). We examined recovery rates of HCC cell lines spiked into whole blood in MCA assay. Circulating tumor cells were isolated from peripheral blood samples (3 mL) of 7 healthy donors (HD), 14 patients with liver cirrhosis (LC), and 31 patients with HCC using the MCA system. Additionally, we investigated the mRNA expression of liver-specific genes in isolated CTCs using qPCR. The recovery rates were 65.1% (HepG2), 76.7% (HuH7), and 99.0% (PLC/PRF/5). In HD and patients with LC and HCC, the CTC positivity rate (CTCs ≥10) and average CTC number were as follows: HD 0% and 0.1, LC 14.3% and 5.3, HCC 54.8% and 47.6, respectively. The CTC positivity rate in HCC was significantly higher than that in LC (p < 0.05). The number of CTCs was significantly higher in metastatic HCC (102.2 ± 160.6) than in localized HCC (8.2 ± 7.7) (p < 0.05). The expression of AFP, glypican-3, EpCAM, and albumin (ALB) genes was detected in isolated CTCs. The positive CTCs (CTCs ≥10) significantly reduced the cumulative survival in patients with HCC (p = 0.025), especially in localized patients with HCC (p = 0.046). The newly developed MCA system has the potential to isolate CTCs from HCC with high sensitivity, and mRNA expression could be measured from CTCs. Identification of positive CTCs can help predict clinical outcome of patients with HCC. Thus, analysis of CTCs in patients with HCC may provide important information as a novel biomarker in disease progression.

Bipolar-current needle-knife with a water jet function (Jet B-knife) shortens the procedure time of endoscopic submucosal dissection for colorectal tumors.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 < 0.05). Furthermore, the median tumor diameters were 23.1 mm (18-50) and 26.2 mm (20-60) in the BB-knife and Jet B-knife groups, respectively, demonstrating a statistically significant difference (p < 0.05). Multivariate logistic regression analysis revealed that short resection time (p < 0.001) and reduced use of hemostatic devices (p < 0.01) were independent favorable features of Jet B-knife. The en bloc resection rate and the perforation rate were not statistically significant between the two groups. CONCLUSIONS: Use of the Jet B-knife may contribute to the development of a time-saving, cost-effective, and safe procedure for ESD of colorectal tumors.

The Usefulness of Video Capsule Endoscopy in Evaluating Gastrointestinal Manifestations of Immunoglobulin A Vasculitis.

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.

Reactivation of intraabdominal tuberculous lymphadenopathy after drug-eluting beads transcatheter arterial chemoembolization in a patient with hepatocellular carcinoma.

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.

Duplication cyst of the ileum presenting with severe anemia detected by double-balloon endoscopy.

Background and study aims Duplication cysts of the ileum are rare and present with non-specific clinical manifestations such as abdominal pain, vomiting, melena, and intussusception. Therefore, preoperative diagnosis is difficult. Here, we report a case of duplication cyst of the small intestine that was diagnosed preoperatively using double-balloon enteroscopy. A 19-year-old man presented with severe iron deficiency anemia, abdominal pain, and exertional dyspnea. Gastroscopy and colonoscopy revealed no remarkable findings. Abdominal computed tomography revealed a cystic structure in the ileum. Therefore, we performed double-balloon enteroscopy via the anal route. The intestinal tract was bifurcated, with one segment ending in a blind sac containing normal villi and an ulceration. Tc-99 m pertechnetate scintigraphy showed no accumulation in the lesion. Accordingly, we diagnosed a duplication cyst and suspected that this was the cause of severe anemia. Following small bowel resection with cyst excision and anastomosis, the anemia and presenting symptoms resolved. This report highlights the usefulness of double-balloon enteroscopy of the small intestine for preoperative diagnosis of the obscure gastrointestinal bleeding, including duplication cysts .

Gene expression profiling of hepatocarcinogenesis in a mouse model of chronic hepatitis B.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common complication of chronic viral hepatitis. In support of this notion, we have reported that hepatitis B surface antigen (HBsAg)-specific CD8+ T lymphocytes critically contribute to inducing chronic liver cell injury that exerts high carcinogenic potential in a hepatitis B virus (HBV) transgenic mouse model. The dynamics of the molecular signatures responsible for hepatocellular carcinogenesis are not fully understood. The current study was designed to determine the serial changes in gene expression profiles in a model of chronic immune-mediated hepatitis. METHODS: Three-month-old HBV transgenic mice were immunologically reconstituted with bone marrow cells and splenocytes from syngeneic nontransgenic donors. Liver tissues were obtained every three months until 18 months at which time all mice developed multiple liver tumors. Nitrative DNA lesions and hepatocyte turnover were assessed immunohistochemically. Gene expression profiles were generated by extracting total RNA from the tissues and analyzing by microarray. RESULTS: The nitrative DNA lesions and the regenerative proliferation of hepatocytes were increased during the progression of chronic liver disease. In a gene expression profile analysis of liver samples, the chemokine- and T cell receptor (TCR)-mediated pathways were enhanced during chronic hepatitis, and the EGF- and VEGF-mediated pathways were induced in HCC. Among these molecules, the protein levels of STAT3 were greatly enhanced in all hepatocyte nuclei and further elevated in the cytoplasm in HCC tissue samples at 18 months, and the levels of phosphorylated TP53 (p-p53-Ser 6 and -Ser 15) were increased in liver tissues. CONCLUSIONS: HBV-specific immune responses caused unique molecular signatures in the liver tissues of chronic hepatitis and triggered subsequent carcinogenic gene expression profiles in a mouse model. The results suggest a plausible molecular basis responsible for HBV-induced immune pathogenesis of HCC.