Background The pathogenesis and clinicopathologic characteristics of Epstein-Barr virus (EBV)-negative lymphoepithelioma-like gastric carcinoma (LELC) are still unclear. In addition, it remains controversial whether EBV infection itself affects the prognosis of LELC. Methods Between 1995 and 2011, 145 LELC patients (124 patients with EBV infection and 21 patients without EBV infection) underwent radical gastrectomy with D2 lymph node dissection. The clinicopathologic features and prognosis of EBV-negative LELC cases were compared with those of EBV-positive LELC cases. The median duration of follow-up after surgery was 55 months. Microsatellite instability (MSI) analysis was performed on 20 EBV-negative LELC cases. Results EBV-negative LELC accounted for 14.5 % of the total LELC cases. EBV-negative LELC was significantly associated with older age, female sex, advanced T stage, and advanced American Joint Committee on Cancer (AJCC) tumor stage compared with EBV-positive LELC. In univariate analysis, patients with EBV-negative LELC had significantly shorter overall, disease-specific, and recurrencefree survival than those with EBV-positive LELC. The 5-year overall survival rates were 81.0 % for patients with EBVnegative LELC and 96.2 % for patients with EBV-positive LELC. In a Cox proportional hazards model, EBV infection, age, and AJCC tumor stage were identified as independent predictors of overall survival. MSI-high, MSI-low, and microsatellite-stable tumors accounted for 25, 10, and 65 % of EBV-negative LELC cases, respectively. MSI status did not affect the prognosis of EBV-negative LELC cases. Conclusions EBV infection serves as an independent predictor of survival in patients with LELC. EBV-negative LELC exhibited clinicopathologic features and prognosis distinct from those of EBV-positive LELC.

Higher disease activity in SLE and initial severe neurologic deficits might be associated with the poor outcome of ATM. Corticosteroid slowly tapering-off therapy might be helpful in preventing the recurrence of ATM.

The prognostic effects of tumor infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs) and myeloid derived suppressing cells (MDSCs) are inconclusive in gastric cancers. We investigated the frequencies of TILs including CD8+ T cells, CD45+CD4+CD25± FOXP3+ Tregs, CD45+CD11b+ CD14+ HLA−DR− MDSCs in 28 gastric cancer tissues by using multicolor flow cytometry. In gastric cancer tissue, the percentage of Tregs among the CD4+ T cell subset was substantially increased compared to that of Tregs among peripheral blood CD4+ T cells from the controls. High frequency of CD8+ T cells among CD3+ T cells correlated with increased overall survival (OS) (p = 0.005). High frequency of Tregs among CD4+ T cells correlated with increased OS (p < 0.001), and disease-free survival (DFS) (p = 0.039) and was an independent prognostic factor in OS (Hazard ratio: 0.047; 95% confidence interval, 0.006-0.372; p = 0.004). High frequency of MDSCs among total examined cells correlated with decreased OS (p = 0.027) and was an independent prognostic factor in OS (Hazard ratio 8.601; 95% confidence interval, 1.240-59.678; p = 0.029). We have demonstrated that high levels of Tregs among tumor-infiltrating CD4+ T cells were favorable, but an increased proportion of MDSCs was an adverse independent prognostic factor in gastric cancer. Our results may provide important insights for future immunotherapy in gastric cancer.

BackgroundWe have investigated the incidence of NTRK1 rearrangements in metastatic gastrointestinal cancer patients and demonstrated the potential for clinical response of these patients to targeted therapy.MethodsWe prospectively collected tumor tissue specimens for one year and simultaneously generated patient-derived tumor cells (PDCs). Specimens were initially screened for TrkA protein expression using TrkA immunohistochemistry (IHC). In the case of TrkA IHC positive results, samples were further examined by fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) to confirm the presence of NTRK1 rearrangements.ResultsFrom January 2014 to December 2014, a total of 74 metastatic colorectal cancer (CRC) patients and 66 gastric cancer (GC) patients were initially screened by TrkA IHC. Two of the 74 CRC patients (2.7%) and one of the 66 GC patients (1.5%) were positive for TrkA expression by IHC. All three IHC positive cases had evidence of NTRK1 rearrangements by FISH. NGS was performed on the 3 IHC positive cases and confirmed TPM3-NTRK1 rearrangements in the two CRC cases. One GC patient with TrkA expression by IHC did not harbor an NTRK1 rearrangement. PDCs established from the NTRK1 positive CRC patients were positive for the NTRK1 rearrangement. Entrectinib, a pan-TRK inhibitor, profoundly inhibited cell proliferation of NTRK1-rearranged PDCs with such inhibition associated with inactivation of TrkA, and down-regulation of downstream signaling pathways.ConclusionTrkA IHC is an effective, initial screening method for NTRK1 rearrangement detection in the clinic. Inhibition of the TrkA kinase is a promising targeted therapy for cancer patients whose tumors harbor a NTRK1 rearrangement.

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Objective. Autoimmune hepatitis (AIH) is a chronic progressive liver disease characterized by circulating autoantibodies and hyperglobulinemia. This study was conducted to identify the features of AIH accompanied by systemic lupus erythematosus (SLE-AIH) that differ from those of primary AIH (P-AIH), and to evaluate factors that affect the outcome for SLE-AIH patients. Methods. From May 1995 to April 2014, clinical data (including liver pathology) from 164 patients with P-AIH and 23 patients with SLE-AIH were collected from an electronic database at a tertiary referral center. AIH was diagnosed according to the diagnostic scoring system for AIH (revised in 1999). SLE patients fulfilled at least 4 of the 1997 revised American College of Rheumatology criteria. Progression was defined as occurrence of cirrhosis, hepatocellular carcinoma, liver transplantation, or death from hepatic failure. Results. The age at the time of AIH diagnosis was lower and initial levels of serum IgG were higher in SLE-AIH than in P-AIH patients. Progression was more common in P-AIH, and hepatocellular carcinoma, liver transplantation, or death occurred only in P-AIH patients. Among 23 patients with SLE-AIH, 8 with cirrhosis had higher levels of serum IgG than 15 patients without cirrhosis (mean 6 SD 4,077.4 6 1,641.0 mg/dl and 2,560.7 6 932.2 mg/dl, respectively; P 5 0.017). Moreover, a serum IgG level more than 2-fold the upper normal limit was associated with a high risk of cirrhosis in SLE-AIH (odds ratio 11.00 [95% confidence interval 1.420-85.201]; P 5 0.026). Conclusion. Initially high levels of serum IgG are a poor prognostic factor for SLE-AIH. Additionally, the long-term outcome for SLE-AIH might be better than for P-AIH.

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