Phase II study of S-1-based sequential combination chemotherapy including oxaliplatin plus bevacizumab and irinotecan with or without cetuximab for metastatic colorectal cancer: the SOBIC trial.

BACKGROUND: Fluorouracil and leucovorin combined with oxaliplatin or irinotecan plus bevacizumab (Bmab) or cetuximab (Cmab) are now widely accepted treatment options as first-line or second-line chemotherapy for metastatic colorectal cancer (mCRC). Sequential chemotherapy with oral 5-FU backbone for mCRC without using central venous ports is beneficial for both patients and physicians. We designed the SOBIC trial to validate the effectiveness of the first- and second-line oral combination chemotherapy for mCRC. PATIENTS AND METHODS: From May 2010 through March 2013, 52 patients were enrolled from 47 institutions in the Hyogo Colorectal Cancer Surgery Group. First-line chemotherapy was S-1 + oxaliplatin (SOX) plus Bmab, and second-line chemotherapy after first-line failure was irinotecan + S-1 (IRIS) + Cmab, IRIS + Bmab, or IRIS based on the KRAS status. RESULTS: The 50 finally included patients received first-line chemotherapy. Second-line therapy was administered to 20 patients (40%): 12 patients received IRIS + Cmab and 8 patients received IRIS + Bmab. The median follow-up period was 48.6 months (range 35-67 months). The median second progression-free survival was 24.2 months (95% confidence interval [CI] 17.7-35.2). The response rate after first- and second-line chemotherapy was 46.7% and 15%, respectively. The median overall survival was 35.2 months (95% CI: 27.8 to not reached). The main grade 3-4 adverse events were sensory neuropathy (18%) and fatigue (10%). There were no treatment-related deaths. CONCLUSION: Sequential S-1-based combination regimens including oxaliplatin, irinotecan, Bmab, and Cmab were beneficial for patients with mCRC.

A Case of Primary Colonic Signet Ring Cell Carcinoma in a Young Man which Preoperatively Mimicked Phlebosclerotic Colitis.

A 35-year-old man was referred to our hospital for chronic abdominal pain and diarrhea. Computed tomography showed wall thickening, poor contrast enhancement and calcification of the ascending colon, which were consistent with phlebosclerotic colitis. Malignant character was not detected from a biopsy specimen. Operatively, we observed a scirrhous mass of the ascending colon invading surrounding tissue, which was diagnosed as signet ring cell carcinoma based on analysis of an intraoperative frozen section. Right hemicolectomy with regional lymph node dissection was performed. This case was extremely similar to phlebosclerotic colitis in clinical findings; surgical resection was required for correct diagnosis.

Does laparoscopic adhesiolysis decrease the risk of recurrent symptoms in small bowel obstruction? A propensity score-matched analysis.

BACKGROUND: The outcomes of laparoscopic adhesiolysis for small bowel obstruction have generally been satisfactory over the short term. However, the long-term outcomes, including recurrence of symptoms and management of recurrence, remain controversial. This study compares the long-term outcomes of a series of laparoscopic and open surgery procedures for the treatment of small bowel obstruction. METHODS: Patients who underwent adhesiolysis for small bowel obstruction at our institution between 2008 and 2015 were retrospectively reviewed. In total, 156 patients were enrolled, 78 with laparoscopic and 78 with open surgery. Propensity score matching was used to minimize the bias in patient selection. Long-term outcomes included incidence of recurrent symptoms and reoperation. In addition to the comparison of outcomes, risk factor assessment for recurrent symptoms and analysis of detailed information in patients with reoperation were performed. Statistical methods included χ 2 test, Mann-Whitney U test, Cox proportional hazards model, and Kaplan-Meier plots with log-rank comparison. RESULTS: Laparoscopy was performed in a younger population with milder bowel dilation and less complicated etiologies. These factors were used to construct the propensity score model, which yielded a matched cohort of 52 legs in each group. Laparoscopy achieved good short-term outcomes including early recovery of gastrointestinal function, reduced incidence of complications, and shorter hospital stay. For long-term outcomes, while the overall recurrence rate did not differ between the groups (11.5 vs 7.7%), the incidence of reoperation for recurrence was significantly higher in the laparoscopically treated group (7.7 vs 0%, p = .017). The Cox proportional hazards model showed that multiple prior surgeries (≥3 times) were a risk factor for overall recurrence (hazard ratio 7.39, p = .041). CONCLUSION: Laparoscopic adhesiolysis did not decrease the incidence of recurrent symptoms; rather, it was related to higher incidence of recurrent small bowel obstruction requiring surgical treatment.

Outcomes of laparoscopic management of acute small bowel obstruction: a 7-year experience of 110 consecutive cases with various etiologies.

PURPOSE: Laparoscopic surgery is emerging as an alternative to open surgery for treating acute small bowel obstruction (SBO). While postoperative adhesion is the most frequent etiology, the optimum treatment for all types of SBO needs to be evaluated. METHODS: A retrospective review was performed of 110 consecutive patients who underwent laparoscopic surgery at our institution between 2009 and 2015. The short-term outcomes included perioperative factors, while the long-term outcome included the recurrence rate. RESULTS: Of the 110 patients, 55 were female. The median age at surgery was 69.5 years. Laparoscopic surgery was completed in 91.8 %. The median operative time was 82 min, median amount of bleeding was 0 ml, and median postoperative hospital stay was 8 days. Intraoperative major organ injury was seen in 2.7 %. The complication rate (Clavien-Dindo ≥ class II) was 8.2 %, and the mortality rate was 3.6 %. The recurrence rate was 8.2 %. Only dense and matted adhesion was a predictive factor for conversion (OR 30.244). CONCLUSION: Good short-term outcomes and feasible long-term outcomes were achieved with a laparoscopic approach to treating acute SBO. It was a safe and effective method, especially in patients with isolated bands, simple enteral angulation, and foreign body or tumor, while dense and matted adhesions were still challenging.

Presensitization accelerates chronic allograft rejection in a heterotopic rat tracheal allograft model with immunosuppression.

BACKGROUND: In the field of organ transplantation, the effect of pretransplant humoral allosensitization on the organ transplant outcome has been highlighted. To clarify the correlation of presensitization with chronic rejection that can lead to a poor prognosis in transplant recipients, we examined humoral alloreactivity and allograft rejection in sensitized recipients by using a rat heterotopic tracheal transplant model. METHODS: An MHC fully incompatible combination strain was used in this study. Lewis (LEW) rats sensitized by transplantation with Brown Norway (BN) skin grafts received tracheal segments from BN rats in the dorsal subcutaneous pouch. Four allogenic groups (n=5) were investigated. Group 1, non-sensitized recipients without cyclosporine A (CsA) administration; group 2, non-sensitized recipients with CsA administration; group 3, sensitized recipients without CsA administration; and group 4, sensitized recipients with CsA administration. In the immunosuppressant groups (groups 2 and 4), the recipients were administered a subcutaneous injection of CsA (25 mg x kg(-1) x day(-1)) for 3 days from the day of operation. All recipients were sacrificed 21 days after transplantation. Tracheal segments were extracted from the recipients and histologically evaluated with regard to the following parameters: (1) airway lining epithelial loss, (2) lymphocyte/plasma cell infiltration, and (3) luminal obliteration due to granulation tissue formation and/or fibrosis. In order to analyze alloantibody (allo-Ab) responses, sera samples were tested by the flow cytometric cross-match (FCXM) technique. RESULTS: Histological findings revealed that the chronic rejection score in sensitized recipients treated with CsA was significantly higher than that in non-sensitized recipients treated with CsA (9.0+/-1.2 vs. 3.0+/-0.54, p<0.05). In other words, CsA therapy reduced the rejection score in non-sensitized recipients, but not in sensitized recipients. No significant differences were observed in the level of IgM Abs among the groups. However, donor-specific IgG Abs were induced after presensitization by donor skin grafting prior to tracheal transplantation. Heterotopic tracheal implantation also induced IgG Ab production. This elevation in the Ab levels was inhibited by CsA treatment in non-sensitized recipients. Conversely, the Ab levels were significantly higher in sensitized recipients than in non-sensitized recipients, regardless of CsA administration. CONCLUSIONS: Our data showed that presensitization accelerates chronic allograft rejection with a marked elevation in the level of donor specific IgG Abs. These results suggest that presensitization will be a significant risk factor for the lung transplant recipient, furthermore, the effect of immunosuppression might be insufficient in sensitized recipients.

[A case of malignant lymphoma of the stomach in which preoperative chemotherapy provided a complete response].

We have encountered a case of malignant lymphoma of the stomach in which a complete remission was confirmed in a resected specimen after chemotherapy. A 75-year-old woman complained of vomiting blood. A biopsy from gastric endoscopy indicated malignant lymphoma of diffuse large B-cell type. The patient was assumed to be inoperable due to enlargement of the tumor and lymph node metastasis, and THP-COP chemotherapy was carried out. After four courses of the THP-COP regimen, endoscopic examination revealed a significant tumor reduction. Total gastrectomy and splenectomy with lymph node dissection (D2) were performed after chemotherapy. No tumor cells were detected in any sections of the specimen or regional lymph nodes.