The evaluation of the safety and efficacy of intravenously administered allogeneic multilineage-differentiating stress-enduring cells in a swine hepatectomy model.

INTRODUCTION: Multilineage-differentiating stress-enduring (Muse) cells are non-tumorigenic endogenous pluripotent-like cells residing in the bone marrow that exert a tissue reparative effect by replacing damaged/apoptotic cells through spontaneous differentiation into tissue-constituent cells. Post-hepatectomy liver failure (PHLF) is a potentially fatal complication. The main purpose of this study was to evaluate the safety and efficiency of allogeneic Muse cell administration via the portal vein in a swine model of PHLF. METHODS: Swine Muse cells, collected from swine bone marrow-mesenchymal stem cells (MSCs) as SSEA-3(+) cells, were examined for their characteristics. Then, 1 × 107 allogeneic-Muse cells and allogeneic-MSCs and vehicle were injected via the portal vein in a 70% hepatectomy swine model. RESULTS: Swine Muse cells exhibited characteristics comparable to previously reported human Muse cells. Compared to the MSC and vehicle groups, the Muse group showed specific homing of the administered cells into the liver, resulting in improvements in the control of hyperbilirubinemia (P = 0.04), prothrombin international normalized ratio (P = 0.05), and suppression of focal necrosis (P = 0.04). Integrated Muse cells differentiated spontaneously into hepatocyte marker-positive cells. CONCLUSIONS: Allogeneic Muse cell administration may provide a reparative effect and functional recovery in a 70% hepatectomy swine model and thus may contribute to the treatment of PHLF.

Loss of BAP1 expression is associated with genetic mutation and can predict outcomes in gallbladder cancer.

BACKGROUND: BRCA-1 associated protein (BAP1) is a de-ubiquitinating enzyme that regulates gene expression. Recently, the BAP1 mutation and its involvement in cancer survival have been reported in a range of tumor types, including uveal melanoma, mesothelioma, renal cancers, and biliary tract cancers. However, the frequency of BAP1 mutation and down-regulation varies among tumor types, and little is known about the function of BAP1 silencing in cancer cells. Gallbladder carcinoma (GBC) is a type of biliary tract cancer with a poor prognosis. Few mutational studies have investigated the role of BAP1 in GBC, and no functional study in vitro-, or clinical studies about cancer survival have been done. METHODS: GBC cells were studied by following the small interfering RNA mediated silencing of BAP1 with regard to proliferation, migration, invasion, and drug sensitivity. We carried out genomic, epigenomic and immunohistochemical analyses to detect somatic BAP1 alterations in 47 GBC patients undergoing surgical resection. RESULTS: BAP1 depletion resulted in increased migration and invasion, but not proliferation, and also resulted in decreased sensitivity to bortezomib, a proteasome inhibitor. Suppressed expression of BAP1 occurred in 22 GBC cases (46.8%) and showed a strong trend toward a worse median survival time of 13.3 months (95% CI, 17.6-62.6) (p = 0.0034). Sanger sequencing revealed a loss-of-function mutation of BAP1 in 11 out of these 22 GBC cases (50%) with low BAP1 expression, whereas 2 out of 25 GBC cases (8%) were detected in cases with high BAP1 expression. Partial changes in methylation were observed in 6 out of 47 cases, but methylation did not show a strong relationship to BAP1 expression or to the prognosis. CONCLUSION: Our findings showed that genetic mutations are involved in BAP1 down-regulation, leading to promotion of the invasive character of cancer cells and poor prognosis in GBC.

Animal ethics and welfare education in wet-lab training can foster residents' ethical values toward life.

Live animals are used in surgical skills training in wet lab, which has undeniable effectiveness for the development of future surgeons. However, where such training is provided, animal welfare is a major consideration. Increasingly, institutions that offer wet-lab training are incorporating animal ethics and welfare-related content into their training courses, but the effectiveness of such animal ethics education has yet to be evaluated quantitatively. We investigated whether the animal ethics content of a training course affected trainees by measuring increase in ethical awareness using visual analog scale questionnaires before and after training. Our results demonstrated a significant and positive increase in awareness of animal ethics (significance level of 5%; 0.0380≤P≤0.0016).

[A Case of Curatively Resected Ascending Colon Cancer with Ovarian Metastasis and Peritoneal Dissemination after Chemotherapy].

A52 -year-old woman was diagnosed with ascending colon cancer with ovarian metastasis and peritoneal dissemination. Since the patient did not have symptoms with intestinal obstruction, mFOLFOX6 plus bevacizumab(Bmab)was performed for 12 cycles. After chemotherapy, the tumors of ascending colon and ovary were significantly shrunken and novel distant metastasis was not observed by CT scans. Therefore, the tumors were considered to be resectable and curative resection was performed. In the surgical findings, the peritoneal disseminations were localized, and right colectomy, bilateral oophorectomy and extirpation of the peritoneal disseminations were performed. R0 resection was pathologically achieved and adjuvant chemotherapy with UFT/UZEL was administrated for 6 months. The patient is alive without recurrence for 1 year. Since right sided colon cancer is less likely to have obstruction, upfront chemotherapy can be a strategy for locally advanced right sided colon cancer with distant metastasis.

[A case report of complete pathological response of a locally advanced rectal cancer after long term chemotherapy].

A-39-year-old man presented to a nearby clinic owing to long-term diarrhea and painful defecation. He was diagnosed with a well-differentiated tubular adenocarcinoma of the rectosigmoid and underwent a laparotomy at another hospital. At surgery, the tumor was seen to deeply invade into the urinary bladder with the presence of intra-abdominal abscess. Loop sigmoid colostomy was performed due to possible invasion into the pelvic wall and peritoneal dissemination. The patient was referred to the our hospital for systemic chemotherapy. After 32 courses of FOLFIRI, 10 courses of CapeOX + Bmab, and 34 courses of LV5FU2 + Bmab, radiographic examination revealed complete response (CR) of the rectal tumor, and low anterior resection of the rectum was carried out. Since pathological examination showed no viable cancer cells in any specimen, the patient was considered to have achieved a CR from a pathological standpoint.

[Carcinoma arising from ileorectal fistula in a patient with Crohn's disease].

A 72-year-old man was given a diagnosis of Crohn's disease in 1976 at age 44, and partial resection of is ileum was performed. In November 1982, barium enema examination revealed on ileorectal fistula. As he had no complaint, conservative therapy was chosen. In August 2003, he had high fever and CT scan revealed presacral abscess. Ileocecal resection, partial resection of is small intestine and loop sigmoid colostomy were performed. In December 2004, the serum level of CEA was gradually elevated and he complained of anal mucus discharge. Endoscopic examination showed a fistula orifice in the rectum and biopsy of the fistula revealed mucinous adenocarcinoma. We performed abdominoperineal resection of the rectum with partial resection of the sacrum. We thought that careful observation helped the detection of such a rare case of carcinoma arising from a fistula tract.

Assessment of the Japanese Inflammatory Bowel Disease Questionnaire in patients after ileal pouch anal anastomosis for ulcerative colitis.

BACKGROUND: The Inflammatory Bowel Disease Questionnaire (IBDQ) is the most widely used disease-specific health-related quality of life questionnaire for patients with inflammatory bowel disease. However, little has been reported about the validation of IBDQ for patients with ulcerative colitis after surgery. The aim of this study was to assess the validity and reliability of the Japanese version of IBDQ in patients with ulcerative colitis after total proctocolectomy and ileal pouch anal anastomosis (IPAA). METHODS: The validity and reliability of the Japanese IBDQ were assessed in patients with ulcerative colitis who had received IPAA in our hospital. We mailed them the Japanese IBDQ and a supplemental questionnaire on bowel function, which was developed at our institution. Internal consistency, discriminative validity, and factor validity were assessed. RESULTS: Of the 121 patients to whom we sent the questionnaires, 64 patients (53%) participated in this study. The Japanese IBDQ scores correlated well with Cronbach's alpha value (0.800 to 0.923) and daily life satisfaction score (Pearson's r, 0.492 to 0.700). The total IBDQ score and two subscale scores of the IBDQ, "bowel symptoms" and "systemic symptoms," correlated well with daily bowel-movement frequency (Pearson's r, -0.256 to -0.329). Factor analysis revealed a four-factor structure, and all correlations among factors were moderately positive (0.337 to 0.465). Although the factor distribution was not clearly divided into the four IBDQ subscales, these four factors showed a marked tendency to represent the IBDQ subscales independently. CONCLUSIONS: The Japanese IBDQ is a valid and reliable instrument for the assessment of Japanese patients with ulcerative colitis after IPAA.