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Background and study aims The safety and efficacy of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in very elderly patients remains unclear. The aim of this study was to evaluate the safety and efficacy of ESD for EGC in patients age 85 years and older. Patients and methods Patients who underwent ESD for EGC between September 2003 and April 2015 were divided into 3 groups: the very elderly (≥ 85 years; 43 patients), the elderly (65 – 84 years; 511 patients), and the non-elderly ( ≤ 64 years; 161 patients). Adverse events (AEs) were used as the primary endpoint to assess the safety of ESD, and the ESD treatment outcomes (i. e., en bloc resection rate, complete en bloc resection rate, and curative resection rate) and the overall survival rate after ESD were the secondary endpoints. These parameters were retrospectively evaluated in the 3 groups. Results There were no significant differences in AEs (non-elderly, elderly, and very elderly: 7.3, 9.5, and 12.5 %, respectively, P = 0.491) or in the en bloc resection and complete en bloc resection rates among the three groups. However, there was a significant difference in the curative resection rates (non-elderly, elderly, and very elderly: 91.5, 84.1, and 77.1 %, respectively, P = 0.014). Regarding overall survival, there was a significant difference among the three groups (1-, 5-, and 10-year overall survival rates: non-elderly: 98.6, 90.2, and 74.7 %; elderly: 97.2, 86.2, and 61.9 %; and very elderly: 92.7, 66.8, and 34.4 %, respectively, P = 0.001). Moreover, the overall survival rate in the very elderly patients with cardiovascular disease was significantly lower than that in the very elderly patients without cardiovascular disease (P < 0.001). Conclusions ESD is an acceptable treatment for EGC in patients 85 years of age or older in terms of safety. However, the overall survival after ESD in the very elderly patients with cardiovascular disease was short.

Our results suggest that IgG4 may participate in the activation of complement in IgG4RD patients with hypocomplementemia.

Abstract.As gemcitabine is a key anti-tumor agent for unresectable pancreatic ductal adenocarcinoma (PDAC), it is important to predict the outcomes of gemcitabine chemotherapy. The present study aimed to confirm whether the derived neutrophil-to-lymphocyte ratio (dNLR) is able to predict chemotherapy outcomes. To elucidate the role of dNLR in patients that underwent chemotherapy, the current study evaluated clinicopathological variables in 31 patients with unresectable PDAC treated with gemcitabine. The correlation between clinicopathological variables, and progression-free survival (PFS) and overall survival (OS) time were investigated. Univariate analysis revealed that there were no significant differences in PFS and OS as a function of age (<65 vs. ≥65 years), gender, tumor location (pancreas head vs. body/tail), tumor diameter (<23 vs. ≥23 mm) or serum carbohydrate antigen 19-9 concentration level (<3,800 vs. ≥3,800 U/ml). However, disease stage (locally advanced vs. metastatic) and the dNLR (<2.5 vs. ≥2.5) significantly affected PFS and OS. Multivariate analysis subsequently revealed that a dNLR of ≥2.5 was an independent prognostic factor for poor PFS (P=0.003) and OS (P=0.026). In conclusion, data from the present study suggests that the pre-treatment dNLR is an independent prognostic factor to predict PFS and OS in patients with unresectable PDAC treated with gemcitabine. This indicates that dNLR has a potential role in stratifying patients that may benefit from gemcitabine therapy.

AIM:To evaluate the efficacy of endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) for grading pancreatic neuroendocrine tumors (PNETs). In the two cases treated with chemotherapy, the effects and prognoses were evaluated. METHODS: RESULTS:The sampling rate for histological diagnosis by EUS-FNA was 100%. No adverse effects were observed. The concordance rate between specimens obtained by EUS-FNA and surgery was 87.5% (7/8). For the two cases treated with chemotherapy, case 1 received somatostatin analog therapy and transcatheter arterial infusion (TAI) targeting multiple liver metastases. Subsequent treatment consisted of everolimus. During chemotherapy, the primary tumor remained unconfirmed, although the multiple liver metastases diminished dramatically. Case 2 was classified as neuroendocrine carcinoma (NEC) according to the Ki-67 index of a specimen obtained by EUS-FNA; therefore, cisplatin and irinotecan therapy was started. However, severe adverse effects, including renal failure and diarrhea, were observed, and the therapy regimen was changed to cisplatin and etoposide. TAI targeting multiple liver metastases was performed. Although the liver metastases diminished, the primary tumor remained unconfirmed. These chemotherapy regimens had immediate effects for both unresectable neuroendocrine tumor (NET) and NEC cases. These two subjects are still alive. Core tip: This is a retrospective study to evaluate the efficacy of endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) for grading pancreatic neuroendocrine tumors (PNETs). The concordance rate for grading between specimens obtained by EUS-FNA and surgery using the World Health Organization 2010 classification (Ki-67 indexing) was 87.5% in eight evaluated patients. In the two unresectable cases, chemotherapy was performed after grading was established based on the analysis of specimens obtained by EUS-FNA. Both treatments were adequately effective. EUS-FNA was useful for diagnosing PNET and enabled informed decisions on appropriate treatment plans by identifying neuroendocrine tumor or neuroendocrine carcinoma. CONCLUSION: EUS-Sugimoto M, Takagi T, Hikichi T, Suzuki R, Watanabe K, Nakamura J, Kikuchi H, Konno N, Waragai Y, Asama H, Takasumi M, Watanabe H, Obara K, Ohira H. Efficacy of endoscopic ultrasonography-guided fine needle aspiration for pancreatic neuroendocrine tumor grading.

Predicting the prognosis of unresectable pancreatic ductal adenocarcinoma (PDAC) is useful in determining the appropriate management strategy. The present study aimed to investigate the association between PDAC prognosis and inflammation-based markers, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, prognostic nutritional index, modified Glasgow prognostic score (mGPS) and controlling nutritional status score. A total of 72 patients with unresectable PDAC who received chemotherapy were included. Inflammation-based markers were measured prior to treatment. The median progression-free survival (PFS) and overall survival (OS) were 117 days (range, 10-781 days) and 244 days (range 43-781 days), respectively. The cut-off value of continuous variables that predicted the median OS (244 days) was calcualted. Univariate analysis of PFS showed that disease stage, first-line chemotherapy regimen, carcinoembryonic antigen (CEA), NLR, platelet-to-lymphocyte ratio (PLR), mGPS and controlling nutritional status (CONUT) scores were associated with PFS. Among them, stage, first-line chemotherapy regimen, CEA, NLR and mGPS were independent prognostic factors for PFS in multivariate analysis. Univariate analysis of OS showed that stage, first-line chemotherapy regimen, CA19-9, NLR, PLR, prognostic nutritional index (PNI), mGPS and CONUT score were associated wtih OS. Among them, first-line chemotherapy and mGPS were independent prognostic factors for OS according to multivariate analysis. Univariate and multivariate analyses revealed that a NLR ≥4.0 and mGPS 2 were independent prognostic factors for PFS. For OS, mGPS 2 was an independent prognostic factor. In conclusion, mGPS was the most useful marker in predicting the prognosis of patients with unresectable PDAC who received chemotherapy.

The efficacy of sedation during endoscopic injection sclerotherapy (EIS) for esophageal varices (EVs) in patients with liver cirrhosis remains unclear. The aim of this study is to compare the efficacy and safety between propofoland midazolambased sedation for EIS. Methods : Twentythree patients with EVs were prospectively and randomly assigned to midazolambased (Midazolam group) or propofolbased (Propofol group) sedation. All patients underwent a number connection test (NCT) to evaluate minimal hepatic encephalopathy (MHE) on the day before and at 2 and 24 hours following EIS. The primary endpoint was exacerbation of MHE after EIS, which was defined as deterioration of the NCT. The secondary endpoints were postoperative awareness, technical success rate, frequency of body movement, patient and operator satisfaction, cardiorespiratory dynamics during EIS, and adverse events. Results : Exacerbations of MHE at 2 hours after EIS compared with those before EIS were not significantly different between the two groups. In both groups, the deterioration of NCT scores before and 2 hours after EIS was observed (Propofol group : 60.0 vs. 70.0 s, P = 0.026 ; Midazolam group : 42.5 vs. 67.0 s, P = 0.002). There were no significant differences in awareness, technical success rate, or patient satisfaction. However, the frequency of body movement in the Propofol group was significantly lower than that in the Midazolam group (1 vs. 4, P = 0.045), and operator satisfaction in the Propofol group was significantly higher than that in the Midazolam group (P = 0.016). No adverse events were observed. Conclusions : Propofolbased sedation exacerbated MHE after EIS similarly to midazolambased sedation in patients with liver cirrhosis. However, propofolbased sedation provided stable sedation with a lower frequency of body movements and high operator satisfaction.

BackgroundAlthough increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear. Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases. This study determined the concentration of N-linked glycans (N-glycan) released from serum IgG4 in IgG4RD patients and compared the difference of glycosylation changes to those in healthy controls. We also compared the concentration of each IgG4 glycoform between patients with and without hypocomplementemia and individual organ involvement (kidney, pancreas, lymph node) in IgG4RD.MethodsWe collected sera from 12 IgG4RD patients and 8 healthy controls. IgG4 was isolated from sera via Melon™ Gel IgG Spin Purification Kit followed by Capture Select IgG4 (Hu) Affinity Matrix. IgG4 N-glycans were analyzed by S-BIO GlycanMap® Xpress methodology.ResultsSignificant increases of IgG4 G0 N-glycan and IgG4 fucosylated N-glycan (F1 N-glycan) concentrations were observed in IgG4RD compared with healthy controls. Although we observed decreased levels of IgG4 F0 glycan in IgG4RD with hypocomplementemia, there were no significant differences in the galactosylation and sialyation of IgG4 N-glycans. Furthermore, there were no significant differences in the glycosylation of IgG4 N-glycans between patients with and without individual organ involvement of IgG4RD.ConclusionsAlthough IgG4 has anti-inflammatory properties, IgG4 G0 and F1 glycans were increased in patients with IgG4RD. Our results suggest that decreased galactosylation of IgG4 is not related to complement activation and the differences of individual organ involvement in IgG4RD. IgG4 fucosylation change may be related to complement activation in IgG4RD. Further investigation is needed to clarify the role of IgG4 in IgG4RD.