Early Removal of the Prophylactic Drain After Distal Gastrectomy : Results of a Randomized Controlled Study.

Background: The optimal timing of the drain removal after gastrectomy has been unclear. The aim of this prospective randomized controlled study was to assess the optimal timing of removal of prophylactic drains after distal gastrectomy (DG) or pylorus-preserving gastrectomy (PPG). Methods: All patients undergoing DG or PPG for gastric cancer were eligible for this study. The exclusion criteria were combined organ resection, the use of postoperative anticoagulant therapy, intraoperative injury of other organs and anastomotic problems. Just after the operation, the eligible patients were randomly assigned to either the early removal group (n=50), where the drain was removed in the morning of the postoperative day (POD) 1, or the control group (n=50), where the drain was removed on POD 3 or later. We compared the surgical outcomes between the groups. Results: The rate of overall postoperative complications was 18% in the early removal group and 18% in the control group, with no significant difference between the groups. The severity of complications was also similar between the groups. There were no significant differences between the groups with regard to the postoperative recovery, pain or the length of the postoperative hospital stay. Conclusions: The present study demonstrated the safety and feasibility of the early removal of prophylactic drains in selected patients undergoing DG or PPG for gastric cancer

ヒト胃癌患者におけるtripartite motif 32の過剰発現は予後不良に関連する

Tripartite motif protein (TRIM) 32 belongs to the TRIM family, which is composed of RING finger, B-box and coiled-coil domains. TRIM32 has been reported to function as an enzyme 3 ubiquitin ligase and is overexpressed in numerous types of cancer. The present study evaluated the clinical significance of TRIM32 expression levels in gastric cancer. The current study also investigated the TRIM32 expression levels in 142 patients with gastric cancer using immunohistochemistry and examined its clinical importance and potential as a prognostic marker. Furthermore, the function of TRIM32 was examined in vitro. High TRIM32 expression levels were detected in gastric cancer tissues. The postoperative overall and relapse-free survival rates were significantly reduced in patients with tumors with high levels of TRIM32 expression compared with those with tumors expressing low levels of TRIM32. Tumors expressing high levels of TRIM32 were associated with an increased risk of postoperative recurrence, particularly hematogenous recurrence. Multivariate analysis identified TRIM32 status as an independent prognostic factor. Furthermore, TRIM32 gene silencing induced apoptosis and inhibited the proliferation of gastric cancer cells in vitro. Therefore, TRIM32 expression levels may be of potential prognostic value in gastric cancer.博士（医学）・乙第1402号・平成29年6月28日Copyright © Spandidos Publications 2017. All rights reserved.The Spandidos Publications link is available at " http://dx.doi.org/10.3892/ol.2017.5806

Lack of association between the CARD10 rs6000782 polymorphism and type 1 autoimmune hepatitis in a Japanese population

Background: Previous genome-wide association studies have evaluated the impact of common genetic variants and identified several non-HLA risk loci associated with autoimmune liver diseases. More recent genome-wide association studies and replication analyses reported an association between variants of the CARD10 polymorphism rs6000782 and risk of type 1 autoimmune hepatitis (AIH). In this case-control study, we genotyped 326 Japanese AIH patients and 214 control subjects. Results: Genomic DNA from 540 individuals of Japanese origin, including 326 patients with type-1 AIH and 214 healthy controls, was analyzed for two single nucleotide polymorphisms (SNPs) in the CARD10 gene. We selected CARD10 rs6000782 SNPs and genotyped these using PCR-RFLP method and direct sequencing. The Chi square test revealed that the rs6000782 variant alle (c) was not associated with the susceptibility for AIH in a Japanese population [p = 0.376, odds ratio (OR) 1.271, 95 % confidence interval (CI) 0.747-2.161] in an allele model. Our data also showed that CARD10 rs6000782 variants were not associated with AIH or with the clinical parameters of AIH. Conclusions: In this study we examined an association between rs6000782 SNPs in the CARD10 gene and type-1 AIH. Results showed no significant association of rs62000782 with type-1 AIH in a Japanese population. This study demonstrated no association between CARD10 rs6000782 variants and AIH in a Japanese population

食道扁平上皮癌における予後因子および腫瘍進展メカニズムとCullin4A高発現との関連性について

Background: Cullin4A (CUL4A), which is a component of E3 ubiquitin ligase, is implicated in many cellular events. Although the altered expression of CUL4A has been reported in several human cancers, the role of CUL4A in esophageal cancer remains unknown. Methods: We investigated the CUL4A expression in primary esophageal squamous cell carcinoma (ESCC) tissue specimens from 120 patients by immunohistochemistry and explored its clinical relevance and prognostic value. Furthermore, the effect of the expression of CUL4A on cancer cell proliferation was analyzed in vitro using an siRNA silencing technique. Results: The higher expression of CUL4A was significantly associated with a deeper depth of tumor invasion (P < 0.001) and the presence of venous invasion (P = 0.014). The disease-specific survival (DSS) rate in patients with tumors that showed high CUL4A expression levels was significantly lower than that in patients whose tumors showed low CUL4A expression levels (P = 0.001). Importantly, the CUL4A status was identified as an independent prognostic factor for DSS (P = 0.045). Our results suggested that the CUL4A expression has significant prognostic value in ESCC. Furthermore, CUL4A gene silencing significantly inhibited the proliferation of ESCC cells in vitro. In addition, the knockdown of the CUL4A expression induced G1 phase arrest and increased the p21 and p27 protein levels. Conclusions: CUL4A might play an important role in regulating the proliferation of ESCC cells and promoting the development of postoperative recurrence.博士（医学）・乙第1449号・令和2年3月16日© Japan Society of Clinical Oncology 2019This is a post-peer-review, pre-copyedit version of an article published in International journal of clinical oncology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s10147-019-01547-2

Ring box protein-1 は食道癌の予後不良因子であり、腫瘍の進行と関連している

Ring box protein-1 (RBX1) is an essential component of the S-phase kinase-associated protein, Cullin and F-box containing ubiquitin ligases. Overexpression of RBX1 has been reported in several cancer types; however, little is known regarding the prognostic value and role of RBX1 in esophageal cancer. The present study examined 120 patients with esophageal cancer (EC) who underwent curative esophagectomy and 61 patients with EC who underwent neoadjuvant combination chemotherapy with docetaxel, cisplatin and 5-fluorouracil (5-FU; DCF) using immunohistochemistry. All specimens were classified into two groups according to the percentage of RBX1-positive tumor cells. In addition, the impact of RBX1 expression on cancer cell proliferation was analyzed in vitro using a small interfering RNA silencing technique. RBX1 expression levels showed significant differences according to tumor size (P<0.001), tumor depth (P=0.002), lymph node metastasis (P=0.004), pathological stage (P=0.001), lymphatic invasion (P=0.001) and venous invasion (P=0.001). The overall survival (OS) rate in the RBX1 high expression group was significantly lower compared with that in the low group (P=0.004). Multivariate analysis demonstrated that RBX1 status was an independent prognostic factor. RBX1 gene silencing inhibited the proliferation of human EC cells and enhanced the antitumor effect of 5-FU. Among patients who underwent neoadjuvant DCF therapy, the RBX1 high expression group had a significantly lower OS rate compared with that of the RBX1-low group (P<0.001). In conclusion, RBX1 has notable prognostic value, and RBX1 may serve an important function in the tumor progression of EC.博士（医学）・乙第1480号・令和2年12月24日Copyright: © Kunishigeet al. This is an open access article distributed under theterms of CreativeCommons Attribution License(https://creativecommons.org/licenses/by-nc-nd/4.0/)

Familial Mediterranean Fever with Onset at 66 Years of Age

The patient was a 68-year-old woman who had experienced recurrent febrile episodes since 66 years of age. Despite various examinations and treatments, the etiology remained unclear. Further examinations following another referral failed to uncover the cause. Therefore, despite her age, it was presumed that she had familial Mediterranean fever. An analysis of the familial Mediterranean fever (MEFV) gene detected heterozygous L110P, E148Q, and R202Q mutations. No further febrile episodes occurred after colchicine treatment was initiated. Familial Mediterranean fever presenting in patients in their sixties is extremely rare

A neuroendocrine carcinoma with a well-differentiated adenocarcinoma component arising in Barrett’s esophagus: a case report and literature review

Abstract Background An esophageal neuroendocrine carcinoma arising in Barrett’s esophagus is extremely rare. Here, we report a case of an esophageal neuroendocrine carcinoma with a well-differentiated adenocarcinoma component arising in Barrett’s esophagus and review the literature. Case presentation A 71-year-old man with no symptoms was admitted to our hospital because of the detection of an esophagogastric junction tumor on regular upper endoscopy screening. Endoscopy revealed a sliding hiatal hernia and an approximately 10 mm elevated mass at the esophagogastric junction. Biopsy showed a moderately differentiated tubular adenocarcinoma. Computed tomography did not indicate lymph node metastasis or distant metastasis. Proximal gastrectomy with D1 lymph node dissection was performed along with jejunal interposition. On immunohistochemical staining, the tumor was positive for chromogranin A and synaptophysin. Ki-67 was positive in 40% of the tumor cells. The histological diagnosis was a neuroendocrine carcinoma with a well-differentiated adenocarcinoma component arising in Barrett’s esophagus. The postoperative course was good, and the patient was discharged on the twentieth postoperative day. He has remained free of the disease at 36 months postoperatively. Conclusions Barrett’s esophagus may be related to the development of a neuroendocrine carcinoma

Successful Treatment with Intravenous Cyclophosphamide for Refractory Adult-Onset Still’s Disease

We report a 64-year-old female case of intractable adult-onset Still’s disease (AOSD). Initial high-dose steroid therapy combined with cyclosporin A was ineffective against macrophage-activation syndrome (MAS), which was accompanied by the systemic type of AOSD. Treatment for MAS with intravenous cyclophosphamide resulted in remission of AOSD and a reduction in the high doses of steroids. Efficacy of biologics against MAS in AOSD is unclear. Cyclophosphamide, a conventional cytotoxic agent, should be considered as one of the therapeutic options for refractory types of AOSD with MAS

A Case of Relapsing Polychondritis Initiating with Unexplained Fever

Relapsing polychondritis (RP) is a rare autoimmune disease affecting the multiple organ system. Here, we describe a case of RP initially presenting with high fever. The patient was referred to our hospital for further examination of fever of unknown origin (FUO). On admission, the patient reported dry cough in addition to fever. On physical examination, her red, swollen ears were noted, attributed on histology to inflammation with auricular perichondritis. She was diagnosed with RP and treated with oral prednisone (50 mg/day); her fever and auricular inflammation resolved. The patient no longer reported cough and body temperature returned to normal and the elevated levels of C-reactive protein (CRP) were normalized. In this case, identification of the origin of fever was a challenge because of unspecific symptoms; however, awareness of the systemic manifestations of RP may lead to the prompt diagnosis and therapeutic intervention