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Background Methotrexate (MTX) is a frequently used drug in the treatment of rheumatoid arthritis (RA), but occurrences of lymphoproliferative disorders (LPD) have been reported in patients undergoing an MTX regimen. Almost half of the patients with methotrexate-associated lymphoproliferative disorders (MTX-LPD) have extranodal lesions; moreover, although extremely rare, digestive tract perforations resulting from the extranodal lesions of MTX-LPD have also been reported. Case presentation We describe the case of an 81-year-old woman with RA who had been prescribed MTX at 6 mg per week for the past 11 years. She was admitted to our hospital with occasional abdominal pain and was first diagnosed with enteritis. Her abdominal pain did not improve, and a computed tomography scan showed abdominal effusion and free air in the abdominal cavity. She was diagnosed with a digestive tract perforation and underwent emergency surgery. The perforation site was identified in the jejunum, and she underwent small intestinal resection around the perforated region. The pathological findings showed an ulcer in the jejunum and infiltration of large atypical lymphocytes around the perforated region. An immunohistochemical examination revealed the expression of a cluster of differentiation 20 and latent membrane protein 1. Considering the patient’s history of RA treated with MTX, she was diagnosed as having Epstein–Barr virus (EBV)-related MTX-LPD with a histological diagnosis of EBVMCU. MTX was discontinued after the surgery, and her soluble interleukin-2 receptor (sIL-2R) levels had returned to normal 1 year later. She has had a good course for the 2 years since surgery and remains asymptomatic with no recurrence of MTX-LPD, as confirmed by the sIL-2R levels. Conclusion We experienced a rare case of the jejunum perforation induced by MTX-LPD. Since only a few cases have been reported of a patient with small intestinal perforation induced by MTX-LPD, further research is necessary to evaluate the clinicopathological features of MTX-LPD. The patient had disease remission after surgery and by discontinuing MTX treatment; our case did not require chemotherapy. EBV-positive patients, especially those with a pathological presentation of EBVMCU, could have a higher likelihood of remission, which could have been a factor in the present case.

BackgroundGallbladder neuroendocrine neoplasm is a rare disease that is divided into neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). Clear cell NETs of the gallbladder are extremely rare. We report the case of a patient with polypoid clear cell NET G1 of the gallbladder who underwent laparoscopic cholecystectomy.Case presentationA 10-mm pedunculated polyp in the gallbladder neck was detected on a follow-up abdominal ultrasound in a 60-year-old man with chronic hepatitis and hepatitis B without medication. Six months later, an abdominal ultrasound revealed that the tumor had enlarged to 12 mm in size. He was asymptomatic and had no abnormalities in other laboratory examinations, including the tumor markers, carcinoembryonic antigen and CA19-9. Abdominal ultrasound showed a 12-mm polyp in the neck of the gallbladder with perfusion and focal thickening of the gallbladder wall. A gallbladder stone was also seen in the fundus. An enhanced computed tomography scan and magnetic resonance imaging revealed a polypoid lesion and gallbladder stone located at the neck of the gallbladder and the fundus, respectively. Malignancy could not be excluded, and hence, a laparoscopic cholecystectomy was performed. Pathologically, a pedunculated polyp (14 × 11 × 15 mm) was observed in the neck of the gallbladder, and the polypoid lesion comprised nests or trabecular growths of clear NET cells in the lamina propria (ENETS: T1N0M0; AJCC: T1aN0M0). Immunohistochemical staining with synaptophysin, chromogranin A, and CD56 was confined to the tumor. The pathological diagnosis was clear cell NET G1 of the gallbladder. Although clear cell NET is often described as a distinct manifestation of von Hippel-Lindau disease (VHL), the patient had no past medical or family history of VHL. Until his one-and-a-half-year follow-up, the patient was doing well and without any signs of recurrence.ConclusionWe report an extremely rare case of gallbladder clear cell NET G1. When NET G1 is incidentally identified in a gallbladder surgical specimen, clinical information and pathological findings should be considered as references.

The effect of cetuximab plus mFOLFOX on downsizing of the tumors for curative resection has yet to be assessed for patients with advanced colorectal liver metastases (CRLMs). This study aimed to assess the oncologic benefit of cetuximab plus mFOLFOX for wild-type KRAS patients with advanced CRLMs. In this multicenter phase 2 trial, patients with technically unresectable tumor and/or five or more CRLMs harboring wild-type KRAS were treated with mFOLFOX plus cetuximab. The patients were assessed for resectability after 4 treatments, and then every 2 months up to 12 treatments. Patients with resectable disease were offered surgery after a waiting period of 1 month. The primary end point of the study was the R0 resection rate. The secondary end points were safety, progression-free survival (PFS), and overall survival (OS). The study is registered with the University Hospital Medical Information Network-Clinical Trials Registry Clinical Trials Registry (no. C000007923). Between 2012 and 2015, 50 patients from 13 centers were enrolled in this trial. Two patients were excluded because they had not received induction therapy. The 48 patients had a complete response rate of 0% and a partial response rate of 64.6%. For 26 R0 resections (54.2%) and 5 R1 resections (10.4%), no mortality occurred. During a median follow-up period of 31 months, the median OS for all the patients was calculated to be 41 months (95% confidence interval, 28–not reached). The 3-year OS rate was 59%. For patients with advanced CRLMs harboring wild-type KRAS, cetuximab administered in combination with mFOLFOX yields high response rates, leading to significantly high R0 resection rates and favorable prognoses.

The psychiatric population has been reported to be accompanied with a higher morbidity and mortality in several situations. However, little is known about the effect of co-morbid psychiatric disorders on surgical risk during major digestive surgery for malignancies. Our purpose in the present study, therefore, was to evaluate the impact of co-morbid psychiatric disorders on the outcome of surgery for digestive malignancies. We retrospectively reviewed medical records of 568 consecutive patients who underwent hepatectomies, gastrectomies, or colorectal resections between June 1998 and May 2006. Of these, 86 patients had psychiatric disorders (disorder group: DG) and the remaining 482 patients did not (non-disorder group: NG). Postoperative parameters including morbidity, mortality, length of postoperative hospital stay in the surgical ward, and the incidence of psychiatric disorder-associated problems were assessed. Overall, there was 1 patient who died within 30 days in hospital in the DG and 2 patient deaths in the NG. Thirty complications developed in 24 patients of the DG, whereas 138 complications developed in 129 patients of the NG. There was no significant difference in the morbidity or mortality rate between the two groups. The length of the postoperative hospital stay was also similar between the two groups, and the incidence of psychiatric disorder-associated postoperative problems was about ten times higher in the DG than in the NG. Patients with psychiatric disorders are not accompanied with excess surgical risk during major surgery for digestive malignancies as compared to patients without psychiatric disorders.

経過観察中に増大傾向を呈し, 胆嚢摘出により除去しえた胆嚢嚢胞の1例を報告する. 症例は80歳の男性で, 胃癌術後の経過観察中に胆嚢底部に径8mmの嚢胞性小隆起性病変を指摘された. この嚢胞性病変は1年の経過観察にて径13mmと増大した. 診断的治療として胆嚢摘出術が施行された. 標本では胆嚢底部に径13mmの単房性嚢胞を認め, 内腔は黄白色の粘液で満たされていた. 組織学的には嚢胞内面は1層の円柱～立方上皮でおおわれており, 外面の胆嚢粘膜は軽度の炎症所見のみで, 異型性を認めなかった. 周囲にRokitansky-Aschoff sinus(以下, RASと略記)の散在を認め, RASの閉塞による貯留嚢胞と考えられた. 胆嚢嚢胞はまれな疾患であるが, 超音波機器の性能が向上した近年では報告例も増えつつあり, 胆嚢の小隆起性病変の鑑別診断として念頭におく必要があると考えられた.

S状結腸憩室の遊離穿孔に対し縫合閉鎖にて1期的に治療しえた2例を経験した.症例1は66歳,男性.朝排便後に急な腹痛にて発症.腹部所見は下腹部正中を中心とした腹膜炎で,発症後7時間で開腹. S状結腸に1cm程の憩室が多発しており,そのうちの一つが5mm大に穿孔していた.穿孔部が小さく炎症所見が軽いため単純縫合閉鎖し,洗浄,誘導とした.第47病日退院した.症例2は79歳,男性.午後2時に急な腹痛にて発症.腹部所見は汎発性腹膜炎で,発症後5時間で開腹. S状結腸に3mm大の憩室穿孔を認めた.穿孔部が小さく炎症所見が軽いため同様に単純縫合閉鎖し,洗浄,誘導とした.第49病日退院した.左側結腸憩室の遊離穿孔は一般に重篤な糞便性腹膜炎を伴い2期的術式を採用されることが多い.だが最近では2期的術式と1期的術式に合併症,死亡率において差はないとする報告もあり,症例の的確な選択により1期的縫合閉鎖も可能と思われる.

Surgical treatment of 45 patients presenting with extremely thick and contracted gallbladder of less than 5 cm in length has been reviewed. They corresponded to 4.8% of 938 patients with benign biliary diseases operated on during the last 12 years in our hospital. Though 44 patients had stones in the biliary trees, coexistence of background lesions was noted, that is, internal biliary fistula in 15, confluence stones in 5, and endoscopic papillotomy in 10 cases. Preoperative detection of contracted gallbladder was capable in 86% by computerized tomography, while it was not easy to visualize by ultrasound, and 61% of the cases were therefore estimated as such by acoustic shadow and/or strong echo.Surgical treatment principally consisted of cholecystectomy with or without T tube drainage. Standard cholecystectomy with serosal dissection, however, was possible in only 5 cases. Partial resection of the gallbladder with remnant mucosal destruction was the choice of operation in 10 difficult cases. Bile duct injury as the main complication in the operation was repaired by hepaticojejunostomy in one case. Association of cancer of the gallbladder was noted in 2 cases (4.4%).We conclude from this study that operation of contracted gallbladder should intend as much mucosal removal as possible within the limits of safety. Since preoperative evaluation for coexistence of cancer is almost impossible, intraoperative pathological diagnosis of the specimen is indispensable.

Relatively rare hernias include obturator hernia in aged patients. We experienced 3 cases of obturator hernia presenting with complicated manifestations. Case 1 presented with an intermuscular abscess in the left thigh. The abscess was drainaged, and the herniation was cured thereafter. Case 2 showed recurrent ipsilateral obturator hernia ten years after former herniation was cured operatively. Case 3 presented with panperitonitis due to perforation of iluem, and emergent operation saved the patient. All 3 cases had peculiar manifestations and we had difficulties in the preoperative diagnosis and treatment. The key points for diagnosing obturator hernia are: 1) to doubt of its existence; and 2) to relay on CT among imaging methods. While it is emphasized for treatment that the hilus should be reinforced by covering not only with peritoneum but also with ovary and its ligament. A review of more than 200 cases of obturator hernia reported in Japan since 1926 is also described.

Interleukin-3 (IL-3), a multilineage colony stimulating factor, has been shown to augment alloreactive bone marrow-derived suppressor cell activity in vivo and in vitro. The present study examined the effect of IL-3 on autoimmune-mediated diabetes in NOD mice. Administration of IL-3 twice weekly starting at 2-4 weeks of age delayed the onset and reduced the overall incidence of diabetes. Bone marrow cells obtained from IL-3-treated NOD mice protected NOD mice from cyclophosphamide-induced diabetes but failed to prevent adoptively transferred diabetes. In vitro culture of bone marrow cells in medium containing IL-3 produced a Thy-1+CD3epsilonloCD4-CD8-CD25- immature T cell clone which prevented cyclophosphamide-induced diabetes. The cloned cells also effectively delayed the development of diabetes induced by transfer of T cells in adult thymectomized, irradiated, bone marrow-reconstituted NOD mice. These results suggest that IL-3 is capable of regulating extrathymic T cell development from the bone marrow and that these cells mediate strong immunoregulatory function.