Published papers

© 2018 Japan Gastroenterological Endoscopy Society. All Rights Reserved. Background and Aim: Autoimmune bullous disease (ABD) is induced by autoantibodies against cell adhesion molecules, and blistering may occur on the mucous membranes of the eyes, nose, mouth, oral cavity, laryngopharynx, and esophagus. Endoscopic prevalence and features of ABD-associated esophageal lesions are not well known. We conducted the present study to assess the endoscopic prevalence of ABD-associated mucosal lesions. Methods: Endoscopic prevalence of mucosal lesions, particularly laryngopharyngeal and esophageal lesions, was used as the primary endpoint to assess the significance of upper gastrointestinal endoscopy, and clinical and endoscopic features were secondary endpoints. Results: Of 123 ABD patients, 50.4％ had apparent oral or laryngopharyngeal lesions and 30.8％had laryngopharyngeal lesions. Esophageal lesions were detected through normal observation in 16.8％ of affected patients, whereas 40.6％ exhibited epidermolysis or blood blisters by mechanical inducement, regardless of esophageal mucosal lesion detection by normal observation. Additionally, 56.0％ exhibited the Nikolsky sign with mechanical inducement. Of the 123 patients, 29.2％ did not have exposed skin lesions. Of these patients, 77.7％ had oral cavity or laryngopharyngeal lesions, 36.1％ had esophageal lesions, and 58.3％ exhibited the Nikolsky sign on esophageal mucosa. Conclusion: It is important to determine the endoscopic characteristics and findings of ABD. ABD can be suspected from endoscopic findings.

Heat shock protein 27 (Hsp27) is a chaperone protein of low molecular weight that is produced in response to various stresses and has a cytoprotective function. In the present study we found that there is a strong correlation between sensitivity to 5-fiuorouracil (5-FU) and the expression of Hsp27 in colorectal cancer. Apatorsen is an antisense oligonucleotide that targets Hsp27 and has various antitumor effects in some types of cancer, such as bladder and prostate. Although several clinical studies are currently studying apatorsen in many malignancies, to date no promising results have been reported for colorectal cancer. In the present study, we examined the impact of Hsp27 downregulation (via apatorsen) on 5-FU sensitivity in colon cancer both in vitro and in vivo. In vitro, apatorsen significantly decreased the levels of Hsp27 in a dose-dependent manner in human colon cancer SW480 cells. A cell proliferation assay revealed that although apatorsen did not inhibit tumor growth, it resulted in greater 5-FU sensitivity in comparison with treatment with OGX-411 (control). In vivo, intraperitoneal injection of apatorsen decreased the levels of Hsp27 in subcutaneous tumors in a xenograft mouse model using SW480 cells and enhanced 5-FU sensitivity, compared to controls. Although further research is warranted, the present study confirmed that concurrent treatment with Hsp27 knockdown using apatorsen and 5-FU could be a promising therapy for colon cancer.

© 2017 The Japan Society of Hepatology Growing evidence suggests a relationship between antibody-mediated rejection (AMR) and early graft failure due to a previously unknown etiology in liver transplantation (LTx). We herein report a 3-year-old boy who developed rapid graft failure due to de novo donor-specific antibody (DSA)-driven AMR a week after living donor LTx, requiring a second transplant on the 10th day after the first LTx. The pathology of the first graft showed massive necrosis in zone 3 along with positive C4d and inflammatory cell infiltrates in portal areas. The mean fluorescence intensity against human leukocyte antigen (HLA)-DR15, which was possessed by both the first and the second donor, peaked at 12 945 on the day before the second LTx. Antithymocyte globulin, plasma exchange along with i.v. immunoglobulin, rituximab, and the local infusion of prostaglandin E1, steroids, and Mesilate gabexate through a portal catheter were provided to save the second graft. To our knowledge, this is the first report to show a clear association between de novo DSA and acute AMR within 7 days of a LTx. Furthermore, we successfully rescued the recipient with a second graft despite possessing the same targeted HLA. The rapid decision to carry out retransplantation and specific strategies overcoming AMR were crucial to achieving success in this case of immunologically high-risk LTx.

© 2018, Springer Nature Singapore Pte Ltd. Purpose: We aimed to clarify the impact of the apparent diffusion coefficient (ADC) value of the mesorectum from preoperative magnetic resonance imaging (MRI) on surgical difficulty in laparoscopic anterior resection (Lap-AR) for rectal cancer. Methods: In total, 67 patients who had undergone curative Lap-AR for rectal cancer in our hospital from January 2008 to March 2015 and had preoperative MRI findings available were included. We randomly calculated the average ADC in three regions of the mesorectum at the level of the upper edge of the superior border of the femur. Univariate and multivariate analyses were performed to evaluate the correlation between the patients’ clinicopathological characteristics, including the ADC value and short-term surgical outcomes. Results: The univariate analysis revealed that a lower ADC value was associated with a significantly increased operative blood loss (p = 0.008) and prolonged operative time (p < 0.001). The multivariate analysis adjusted for the body mass index, anal verge, tumor location, covering stoma, clinical T factor and conversion revealed that the ADC value was an independent risk factor for a prolonged operative time (R 2 = 0.6003, p < 0.001). Furthermore, the multivariate analysis adjusted for the body mass index, anal verge, covering stoma, clinical T factor and conversion revealed that the ADC value was an independent risk factor for an increased blood loss (R 2 = 0.4345, p = 0.008). Conclusion: A lower ADC value of the mesorectum might be a predictor of surgical difficulty in Lap-AR for rectal cancer.

© 2018 Elsevier Inc. Perigraft seroma (PGS) is a relatively rare complication of aortoiliac reconstructive surgery. We, herein, describe a case of a large PGS that was managed by using a hybrid technique of relining the original graft with simultaneous open drainage. An 86-year-old man with a 17.3-cm diameter PGS after prosthetic bifurcated graft replacement for abdominal aortic aneurysm was admitted to our hospital. He presented with abdominal distension and discomfort and had difficulty in taking food. The entire relining of the original covered stent graft with GORE ® EXCLUDER ® using aortic extension cuff and iliac extenders and simultaneous open evacuation of PGS were successfully performed. The symptoms of the patient totally improved, and no recurrence was detected at 2 years after the operation. This technique would be a feasible treatment option for this rare complication.

© 2018, Société Internationale de Chirurgie. Background: Although esophagectomy is the only curative option for esophageal cancer, the associated invasiveness is high. Nasogastric (NG) tube use may prevent complications; however, its utility remains unclear, and the decompression period depends on the doctor. This study aimed to reveal the effect of conventional versus early NG tube removal on postoperative complications after esophagectomy. Methods: This single-center prospective randomized controlled clinical trial enrolled patients aged 20–80 years with histologically proven primary esophageal squamous cell carcinoma. Eighty patients admitted for transthoracic first-stage esophagectomy reconstructed with gastric conduit were randomly assigned (1:1) to the conventional and early NG tube removal groups. In the conventional NG tube removal group, the tube was removed on postoperative day (POD) 7; in the other, it was removed on POD 1. The occurrence rate of major complications, length of postoperative hospital stay, and NG tube reinsertion rate were compared between the groups. Results: The incidence of postoperative major complications such as pneumonia, anastomotic leakage, recurrent nerve palsy and gastrointestinal bleeding, and the NG tube reinsertion rate was not different between the groups. However, recurrent nerve palsy was more commonly observed in the conventional removal group; this difference was not significant. In terms of postoperative pneumonia, tumor location and field of lymph node dissection were significant risk factors. Conclusion: Although early NG tube removal did not reduce the rate of postoperative pneumonia, it could be performed safely. Hence, the NG tube can be removed earlier than conventional methods.

Copyright © Spandidos Publications 2017. All rights reserved. The human epidermal growth factor receptor 2 (HER2)-targeting agent, lapatinib, combined with oral fluoropyrimidine capecitabine, has been previously demonstrated to be an effective treatment option for patients with trastuzumab-resistant HER2-positive metastatic breast cancer. To investigate the molecular mechanisms associated with the interactions between lapatinib and capecitabine, the effect of treatment with lapatinib and phosphatidylinositol-4,5-bispho-sphate 3-kinase (PI3K) inhibitors on the expression of E2F transcription factor 1 (E2F1) and thymidylate synthase (TS), which is associated with an increased response to 5-fluorouracil (5-FU)-based chemotherapy, was determined in HER2-positive breast cancer cells. The results of reverse transcription-quantitative polymerase chain reaction demonstrated that administration of lapatinib and PI3K inhibitors decreased the mRNA expression of TS and E2F1, a transcription factor that promotes TS gene expression, in SKBR3 and T47D cell lines. Furthermore, treatment with lapatinib and PI3K inhibitors also suppressed the mRNA expression of ribonucleotide reductase M1 subunit (RRM1), an important determinant of gemcitabine resistance, and DNA topoisomerase II-? (TOP2A), a molecular target of anthracyclines, in SKBR3 and T47D cell lines. Western blot analysis further demonstrated that the phosphorylation of Akt was inhibited by lapatinib, and the results of the MTT assay revealed that the combination of lapatinib with either 5-FU or gemcitabine demonstrated synergistic antitumor effects, whereas a combinatory treatment of lapatinib with epirubicin, a typical anthracycline drug, exhibited antagonistic antitumor effects in HER2-positive breast cancer cells. These results indicate that the synergistic antitumor effects exhibited by combinatory treatment of lapatinib with capecitabine may be induced via the suppression of E2F1-mediated TS expression.