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.

Molecular signature of hepatitis B virus regulation by interferon-γ in primary human hepatocytes.

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.

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.

Long-term prognosis after biliary stenting for common bile duct stones in high-risk elderly patients.

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.

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 .

Genetic polymorphism and decreased expression of HLA class II DP genes are associated with HBV reactivation in patients treated with immunomodulatory agents.

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/ß-actin vs 371.4 ± 407.5/ß-actin [P < 0.05]). These results suggest the involvement of HLA class II molecules in HBV reactivation after treatment with immunomodulatory agents.

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.

Tubulointerstitial Nephritis with IgM-Positive Plasma Cells.

Infiltration by IgG-positive plasma cells is a common finding in tubulointerstitial nephritis. Indeed, it has been thought that CD138-positive mature plasma cells secrete mainly IgG, and the occurrence of tubulointerstitial nephritis with CD138-positive plasma cells secreting IgM has rarely been reported. Routine immunofluorescence of fresh frozen sections is considered the gold standard for detection of immune deposits. However, the immunoenzyme method with formalin-fixed, paraffin-embedded sections is superior for detecting IgM- or IgG-positive cells within the renal interstitium, thus histologic variants may often go undetected. We recently discovered a case of tubulointerstitial nephritis showing IgM-positive plasma cell accumulation within the interstitium. To further explore the morphologic and clinical features of such cases, we performed a nationwide search for patients with biopsy-proven tubulointerstitial nephritis and high serum IgM levels. We identified 13 patients with tubulointerstitial nephritis and IgM-positive plasma cell infiltration confirmed with the immunoenzyme method. The clinical findings for these patients included a high prevalence of distal renal tubular acidosis (100%), Fanconi syndrome (92%), and anti-mitochondrial antibodies (82%). The pathologic findings were interstitial nephritis with diffusely distributed CD3-positive T lymphocytes and colocalized IgM-positive plasma cells, as well as tubulitis with CD3-positive T lymphocytes in the proximal tubules and collecting ducts. Additionally, levels of H+-ATPase, H+, K+-ATPase, and the HCO3--Cl- anion exchanger were markedly decreased in the collecting ducts. We propose to designate this group of cases, which have a common histologic and clinical form, as IgM-positive plasma cell-tubulointerstitial nephritis.

A case of protein-losing enteropathy caused by sclerosing mesenteritis diagnosed with capsule endoscopy and double-balloon endoscopy.

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.

Identification of novel variants in HLA class II region related to HLA DPB1 expression and disease progression in patients with chronic hepatitis C.

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 < 0.01). Of 24 SNPs, allele frequencies were statistically different in two SNPs (rs2071025 and rs3116996) between PNALT groups and ALD group (P < 0.01). In rs2071025, TT genotype was frequently detected in ALD group and expression level was significantly higher than the other genotypes (449.2 vs 312.9, P < 0.01). In rs3116996, TA or TT (non AA) genotype was frequently detected in ALD group and expression level was significantly higher than genotype AA (457.1 vs 220.9, P < 0.01). Genotyping and expression analysis in HLA class II gene revealed that two SNPs of HLA-DPB1 (rs2071025 and rs3116996) were significantly correlated to RNA expression and progression of HCV-related liver diseases.

[Recurrent multiple lung lesions synchronizing with the disease activity of multiple myeloma].

A 68-year-old male patient, who was diagnosed with MGUS (IgG-λ) 11 years ago, was referred to our hospital because of a progressing pancytopenia. He was diagnosed with multiple myeloma (MM) and was hospitalized because of fever and pneumonia. Although empiric antibiotic and antifungal therapies were promptly initiated, his pneumonia worsened. Chest CT images revealed diffuse interstitial pneumonia. Although bortezomib/dexamethasone therapy was initiated as a treatment for MM and pneumonia, he showed little response. His pneumonia worsened and progressed to acute respiratory distress syndrome. Using mPSL (500 mg/day), sivelestat, and MM treatment switching to lenalidomide/dexamethasone (Rd), his respiratory status and CT findings rapidly improved. He received Rd therapy as an outpatient; however, after the completion of six cycles of therapy, his MM progressed, with a recurrence of pneumonia and high fever again. The onset of pneumonia was closely associated with MM progression. His pneumonia improved by treatment with mPSL half-pulse and MM treatment switching to carfilzomib/Rd. In the present study, we report the case of a patient with myeloma, who presented with multiple interstitial pneumonia, resulting in respiratory failure twice in concordance with myeloma progression.

Long-Term Endoscopic Follow-Up of Patients with Chronic Radiation Proctopathy after Brachytherapy for Prostate Cancer.

Background. Chronic radiation proctopathy (CRP) is late toxicity and associated with morbidity. Aim. To investigate the predictors of prognosis in patients with CRP after brachytherapy (BT). Methods. One hundred four patients with prostate cancer were treated with BT or BT followed by external-beam radiotherapy (BT + EBRT). We retrospectively investigated the 5-year incidence of rectal bleeding and endoscopic findings of CRP using the Vienna Rectoscopy Score (VRS). Twenty patients with VRS ≥ 1 were divided into the improved VRS group without treatment, unchanged VRS group, and treated group. The parameters associated with alteration of VRS were analyzed. Results. The incidence of rectal bleeding was 24%. The risk of rectal bleeding was higher in patients treated with BT + EBRT compared to those treated with BT (p < 0.0001). The incidence of superficial microulceration was higher in the improved VRS group than in the unchanged VRS group (p < 0.05). The incidence of multiple confluent telangiectasia or superficial ulcers > 1 cm(2) was higher in the treated group than in both the improved and unchanged VRS groups (p < 0.05). Conclusions. Patients treated with BT + EBRT have a high risk of CRP. Endoscopic findings were useful for prognostic prediction of CRP.

Effect of green tea catechins on gastric mucosal dysplasia in insulin-gastrin mice.

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.

Preoperative diagnosis of cavernous hemangioma presenting with melena using wireless capsule endoscopy of the small intestine.

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.

[The Usefulness of Strain Elastography for Determining Liver Fibrosis Stage in Chronic Viral Hepatitis: An Analysis Using Tissue Doppler Imaging with Manual Compression].

BACKGROUND/AIM: 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. METHODS: 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. RESULTS: 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) (P< 0.05). 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. CONCLUSIONS: 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].

Pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism: a case report.

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.

Ruptured hepatic metastases of cutaneous melanoma during treatment with vemurafenib: an autopsy case report.

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.

A case of Helicobacter pylori-negative intramucosal well-differentiated gastric adenocarcinoma with intestinal phenotype.

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.

Comparison of hepatic arterial infusion chemotherapy and sorafenib in elderly patients with advanced hepatocellular carcinoma: A case series.

Sorafenib and hepatic arterial infusion chemotherapy (HAIC) are both indicated for unresectable hepatocellular carcinoma (HCC). In this study, we compared the efficacy and safety of HAIC to that of sorafenib in elderly patients with HCC. Eligible patients included those aged ≥70 years, with histologically or clinically confirmed advanced HCC. A total of 12 patients received sorafenib (800 mg per day) and 8 patients received HAIC with 5-fluorouracil (300 mg/m2 on days 1-5 and 8-12) with or without cisplatin (20 mg/m2 on days 1 and 8), with interferon-α (3 times per week for 4 weeks). The response rate was significantly higher in patients treated with HAIC (37.5%) compared to that in patients treated with sorafenib (no response). The median overall survival (18.6 and 11.7 months) and progression-free survival (4.0 and 5.0 months) were similar between the sorafenib and HAIC groups, respectively. In the sorafenib group, 58.3% of the patients discontinued treatment compared to none in the HAIC group. The most frequent adverse event leading to discontinuation of sorafenib was anorexia. Similar to sorafenib, HAIC appears to be a feasible treatment and may also have the advantage of an adequate safety profile for elderly patients with advanced HCC. Further study of HAIC in a larger population of elderly patients is required to assess its potential as an alternative to sorafenib for HCC.