[A case of gastric follicular lymphoma resected and diagnosed with laparoscopy and endoscopy cooperative surgery].

A woman in her 70s was diagnosed with a protruding mucosa-associated lymphoid tissue (MALT) lymphoma during a secondary health examination. After eradication of Helicobacter pylori, a biopsy revealed gastric follicular lymphoma (FL) and the lesion was still protruding one year later. 18F-fluorodeoxyglucose positron emission tomography showed focal nodular hypermetabolic activity, suggesting that FL may have transformed into a diffuse large B-cell lymphoma. Upper gastrointestinal endoscopy, colonoscopy, and capsule endoscopy showed no other lesions in the gastrointestinal tract, and bone marrow biopsy showed no permeation into the marrow. Therefore, this lesion, which appeared as a submucosal tumor, was limited to the stomach. Laparoscopy and endoscopy cooperative surgery was performed, because it allows for correct pathological diagnosis while removing only a minimal portion of the stomach wall. Histological findings showed follicular structures consisting of abnormal lymphoid cells. Immunohistochemical analysis revealed that neoplastic cells were positive for CD20, CD79a, Bcl-2, CD10, and c-MYC, but negative for CD3, CD5, and cyclin D1. Finally, we diagnosed this lesion as a primary gastric FL.

Increase in CD14+HLA-DR -/low myeloid-derived suppressor cells in hepatocellular carcinoma patients and its impact on prognosis.

Myeloid-derived suppressor cells (MDSCs) are known as key immune regulators in various human malignancies, and it is reported that CD14(+)HLA-DR(-/low) MDSCs are increased in hepatocellular carcinoma (HCC) patients. However, the host factors that regulate the frequency and the effect on the prognosis of HCC patients are still unclear. We investigated these issues and clarified the relationships between a feature of MDSCs and host factors in HCC patients. We examined the frequency of MDSCs in 123 HCC patients, 30 chronic liver disease patients without HCC, and 13 healthy controls by flow cytometric analysis. The relationships between the clinical features and the frequency of MDSCs were analyzed. In 33 patients who received curative radiofrequency ablation (RFA) therapy, we examined the impact of MDSCs on HCC recurrence. The frequency of MDSCs in HCC patients was significantly increased. It was correlated with tumor progression, but not with the degree of liver fibrosis and inflammation. In terms of serum cytokines, the concentrations of IL-10, IL-13, and vascular endothelial growth factor were significantly correlated with the frequency of MDSCs. In HCC patients who received curative RFA therapy, the frequency of MDSCs after treatment showed various changes and was inversely correlated with recurrence-free survival time. The frequency of MDSCs is correlated with tumor progression, and this frequency after RFA is inversely correlated with the prognosis of HCC patients. Patients with a high frequency of MDSCs after RFA should be closely followed and the inhibition of MDSCs may improve the prognosis of patients.

Prognostic impact of clinical outcome after endoscopic gastroduodenal stent placement for malignant gastric outlet obstruction: a multicenter retrospective cohort study using a time-dependent analysis.

Background: Endoscopic gastroduodenal stent (GDS) placement is widely used as a safe and effective method to rapidly improve gastrointestinal symptoms of malignant gastric outlet obstruction (MGOO). While previous studies reported the utility of chemotherapy after GDS placement for prognosis improvement, they did not fully address the issue of immortal time bias. Objectives: To examine the association between prognosis and clinical course following endoscopic GDS placement, using a time-dependent analysis. Design: Multicenter retrospective cohort study. Methods: This study included 216 MGOO patients who underwent GDS placement between April 2010 and August 2020. Data of patient baseline characteristics, including age, gender, cancer type, performance status (PS), GDS type and length, GDS placement location, gastric outlet obstruction scoring system (GOOSS) score, and history of chemotherapy before GDS were collected. The clinical course following GDS placement was evaluated by GOOSS score, stent dysfunction, cholangitis, and chemotherapy. A Cox proportional hazards model was used to identify prognostic factors after GDS placement. Stent dysfunction, post-stent cholangitis, and post-stent chemotherapy were analyzed as time-dependent covariates. Results: Mean GOOSS scores before and after GDS were 0.7 and 2.4, respectively, with significant improvement after GDS placement (p < 0.001). The median survival time after GDS placement was 79 [95% confidence interval (CI): 68-103] days. In multivariate Cox proportional hazards model with time-dependent covariates, PS 0-1 [hazard ratio (HR): 0.55, 95% CI: 0.40-0.75; p < 0.001], ascites (HR: 1.45, 95% CI: 1.04-2.01; p = 0.028), metastasis (HR: 1.84, 95% CI: 1.31-2.58; p < 0.001), post-stent cholangitis (HR: 2.38, 95% CI: 1.37-4.15; p = 0.002), and post-stent chemotherapy (HR: 0.01, 95% CI: 0.002-0.10; p < 0.001) significantly affected prognosis after GDS placement. Conclusion: Post-stent cholangitis and tolerability to receive chemotherapy after GDS placement influenced prognosis in MGOO patients.

Encephalopathy, disseminated intravascular coagulation, and hemolytic-uremic syndrome after infection with enterohemorrhagic Escherichia coli O111.

An outbreak of enterohemorrhagic Escherichia coli (EHEC) occurred in Toyama and other prefectures in Japan during 2011. Some patients, including adults, showed complications such as encephalopathy, disseminated intravascular coagulation, and hemolytic-uremic syndrome, and the disease course was extremely aggressive. This report describes the clinical features of four patients infected with Escherichia coli (E. coli) O111 who developed very severe to fatal complications. The initial symptoms in all patients included abdominal pain, diarrhea, and bloody stools, and neurological abnormalities started to appear from 1 to 3 days after admission. Vomiting and pyrexia developed in three patients. Leukocyte counts, lactate dehydrogenase (LDH), and fibrin/fibrinogen degradation products were elevated, and thrombocytopenia was evident. Extremely elevated LDH and severe thrombocytopenia were characteristic at the time encephalopathy became apparent. All patients received oral fosfomycin, intravenous antibiotics, and anticoagulant therapy, three received gamma globulin, plasma exchange, and blood transfusion, and two received steroids and dialysis. Three patients required mechanical ventilation, and two adult patients died. E. coli O111 positive for Shiga toxin 2 was detected in stool culture in two patients, and serological tests for E. coli O111 were positive in the other two patients. In conclusion, EHEC O111 can cause severe illness in children and adults, and the prognosis becomes poorer as the severity of complications increases. Close monitoring including platelet counts and LDH are useful. Once these clinical parameters change, intensive treatment should be provided to prevent the development of severe complications.

Impact of diabetes mellitus on prognosis of patients infected with hepatitis C virus.

Diabetes is a risk factor for the progression of liver fibrosis and development of hepatocellular carcinoma in chronic hepatitis C. However, the impact of diabetes on the long-term prognosis and the synergistic interactions of various host factors for diabetes to the progression of liver fibrosis are unknown. In the present study, we examined the host factors associated with the progression of hepatitis C in 68 patients with a posttransfusion hepatitis (PTH) and analyzed the relationships. Multivariate analysis showed that age of PTH, being male, and type 2 diabetes mellitus were risk factors for the progression of liver fibrosis. By the Kaplan-Meier method, the cirrhosis-free survival rates after the onset of PTH were significantly lower in the diabetic group than in the nondiabetic group (P < .01). Diabetes also had a great impact on the long-term prognosis of chronic hepatitis C by reducing the time from PTH to the occurrence of hepatocellular carcinoma (P < .01) and to liver-related death (P < .05). Coexistence of obesity (body mass index > or =25 kg/m(2)) or hypertriglyceridemia (> or =150 mg/dL) with diabetes had a synergistic effect on liver fibrosis progression in patients with chronic hepatitis C. Thus, the treatment of diabetes, obesity, and hypertriglyceridemia may hold the key to improving the prognosis of chronic hepatitis.

Adenovirus-mediated p14ARF gene transfer cooperates with Ad5CMV-p53 to induce apoptosis in human cancer cells.

p14(ARF), a product of the INK4A/ARF locus, induces p53 upregulation by neutralizing the effects of MDM2, a transcriptional target of p53 that antagonizes its function. Here we report that adenovirus-mediated p14(ARF) gene transfer leads to the accumulation of ectopically transduced p53 and to apoptosis in human cancer cells. We constructed an adenoviral vector expressing p14(ARF) (Ad-ARF) and examined its synergistic effect with p53-expressing adenovirus (Ad5CMV-p53 or Ad-p53) in human lung and esophageal cancer cells. Simultaneous Ad-ARF and Ad-p53 infection increased p53 protein levels not only in a wild-type p53-expressing cell line, but also in cell lines with deleted p53. This resulted in a significant in vitro cytotoxicity compared with Ad-p53 infection alone. Coinfection of Ad-ARF and Ad-p53 also resulted in an increase in expression of p53-inducible genes, including p21(WAF-1/Cip1), p53R2, and Noxa. In addition, the growth of human lung cancer tumors subcutaneously implanted into nu/nu mice was inhibited significantly by intratumoral injection with Ad-ARF and Ad-p53. Our data demonstrate that overexpression of ectopic p14(ARF) may render cells more sensitive to p53-mediated apoptosis, an outcome that has important implications for the treatment of human cancers.

Frequency of CD45RO+ subset in CD4+CD25(high) regulatory T cells associated with progression of hepatocellular carcinoma.

The purpose of this study was to assess the properties of CD4+CD25(high/low/negative) T cell subsets and analyze their relation with dendritic cells (DCs) in patients with hepatocellular carcinoma (HCC). In HCC patients, the prevalence of CD45RO+ cells in CD4+CD25(high) T cells was increased and associated with higher frequencies of plasmacytoid DCs. Larger proportions of this T cell subset were detected in the patients with larger tumor burdens. These results suggest that increased frequencies of the CD45RO+ subset in CD4+CD25(high) Tregs in HCC patients may establish the immunosuppressive environment cooperatively with tolerogenic plasmacytoid DCs to promote disease progression of liver cancer.

Impact of diabetes on recurrence of hepatocellular carcinoma after surgical treatment in patients with viral hepatitis.

OBJECTIVES: Consensus has been reached that diabetes is a risk factor for development of HCC, but the impact on postoperative recurrence is still controversial. To clarify this point, we analyzed the relationship of postoperative recurrence rate of HCC and coexistence of diabetes in the patients with viral hepatitis. METHODS: A total of 90 patients who had undergone curative resection for HCC were analyzed. They were divided into two groups with and without diabetes, and the recurrence-free survival rates after surgical treatment and the factors contributing to recurrence were examined. RESULTS: Kaplan-Meier survival analysis showed the recurrence-free survival rates in the diabetic group were significantly lower than those in the nondiabetic group (P= 0.005) and overall survival rates in the diabetic group were significantly lower than those in the nondiabetic group (P= 0.005). These results were emphasized in the analysis of patients infected with hepatitis C virus. Univariate and multivariate analyses showed diabetes was a significant factor contributing to HCC recurrence after treatment. Furthermore, multivariate analysis in HCC patients with diabetes showed Child-Pugh classification B (P= 0.001) and insulin therapy (P= 0.049) were significant factors contributing to HCC recurrence after treatment. CONCLUSIONS: The results of the present study suggest that diabetes is a risk factor for the recurrence of HCV-related HCC and decreases the overall survival rates after surgical treatment. HCV-related HCC patients with diabetes should be closely followed for postoperative recurrence.