Kotaro Maeda

Elevated steroid sulfatase expression in breast cancers

In situ estrogen synthesis makes an important contribution to the high estrogen concentration found in breast cancer tissues. Steroid sulfatase which hydrolyzes several sulfated steroids such as estrone sulfate, dehydroepiandrosterone sulfate, and cholesterol sulfate may be involved. In the present study, we therefore, assessed steroid sulfatase mRNA levels in breast malignancies and background tissues from 38 patients by reverse transcription and polymerase chain reaction. The levels in breast cancer tissues were significantly increased at 1458.4+/-2119.7 attomoles/mg RNA (mean +/- SD) as compared with 535.6+/-663.4 attomoles/mg RNA for non-malignant tissues (P<0.001). Thus, increased steroid sulfatase expression may be partly responsible for local overproduction of estrogen and provide a growth advantage for tumor cells.

Effects of a Diverting Stoma on Symptomatic Anastomotic Leakage after Low Anterior Resection for Rectal Cancer: A Propensity Score Matching Analysis of 1,014 Consecutive Patients

BACKGROUND Routine creation of a diverting stoma (DS) in every patient who undergoes low anterior resection (LAR) remains controversial. We aimed to investigate the effect of DS on symptomatic anastomotic leakage (AL) after LAR. STUDY DESIGN Patients with rectal cancer within 10 cm from the anal verge were eligible for this prospective, multicenter, cohort study (UMIN-CTR, number 000004017). Propensity score matching (PSM) was used to compare groups of patients with and without DS. RESULTS One thousand fourteen consecutive patients were registered, of whom 936 patients who underwent LAR were analyzed. Before PSM, the overall rate of symptomatic AL was 13.2% (52 of 394) in patients with DS vs. 12.7% (69 of 542) in cases without DS (p = 0.84). Symptomatic AL requiring re-laparotomy occurred in 4.7% (44 of 936) of all patients, occurring in 1.0% (4 of 394) of patients with DS vs. 7.4% (40 of 542) of patients without DS (p < 0.001). After PSM, the 2 groups were nearly balanced, and the incidence rates of symptomatic AL in patients with and without DS were 10.9% and 15.8% (p = 0.26). The incidences of AL requiring re-laparotomy in patients with and without DS were 0.6% and 9.1% (p < 0.001). Multivariate analysis identified male sex (p < 0.001; odds ratio [OR] 3.2; 95% confidence interval [CI] 1.8 to 5.7) and tumor size (p < 0.001; OR 1.2; 95% CI 1.1 to 1.4) as independent risk factors of symptomatic AL. CONCLUSIONS Diverting stoma did not have a significant relationship with symptomatic AL before and after PSM. However, DS does seem to mitigate the consequences of leakage, reducing the need for urgent abdominal reoperation.

Does repeated surgery improve the prognosis of colorectal liver metastases

Hepatic resection for colorectal metastases was performed for 188 patients. Overall survival rates after the first hepatectomy are 41.4% and 32.7% for 5 and 10 years, respectively. The survival rate of 116 cases with unilobar hepatic metastases (H1) is significantly higher than those of 48 cases with two to four bilobar metastases (H2) and 24 cases with more than four (H3), respectively. However, the differences between the survival rates from H1 with multiple metastases, H2, and H3 are not significant, even though the H3 group has no 10-year survivors. The 5-year survival rates after the second hepatectomy (30 patients) and the resection of the lung (26 patients) are 30.3% and 35.2%, respectively, in this series. In those patients, the 5-year survival rates from the first metastasectomy are 43.4% and 50.3%, respectively. There are 14 5-year survivors with multiple metastases and 8 of those patients underwent multiple surgeries. There are 13 patients with three or more repeat resections of the liver and/or lung. The 5-year survival rates of the patients from the first and third metastasectomy are 53.9% and 22.5%, respectively. Repeat operations for the liver and the lung contribute to the improving prognosis.

A new antimesenteric functional end-to-end handsewn anastomosis: surgical prevention of anastomotic recurrence in Crohn's disease.

BACKGROUND: Recurrence of Crohns disease usually occurs at anastomotic sites. OBJECTIVE: A new anastomosis technique (Kono-S anastomosis) designed to minimize anastomotic restenosis was compared with conventional anastomoses. DESIGN AND SETTINGS: The Kono-S anastomosis technique was first used for Crohns disease in 2003 at the Asahikawa Medical University Hospital. The resection is accomplished by transecting the bowel with a linear cutter so that the mesentery side is located in the center of the stump. Both stumps are sutured to create a supporting column to maintain the diameter and dimension of the anastomosis. Longitudinal enterotomies are made at the antimesenteric sides of the 2 segments of intestine. The side-to-side antimesenteric anastomosis is then performed in transverse fashion. The medical records and follow-up details of all patients undergoing this procedure were reviewed. PATIENTS: From 2003 to 2009, 69 patients with Crohns disease who underwent Kono-S anastomosis (group S) were compared with 73 historical patients with Crohns disease who underwent conventional anastomosis (group C) from 1993 to 2003. MAIN OUTCOME MEASURES: A Kaplan-Meier analysis of the follow-up data on surgical recurrence at the anastomosis was performed. The endoscopic recurrence score at the anastomosis was calculated. RESULTS: The median endoscopic recurrence score in group S was significantly lower than that in group C (2.6 vs 3.4; P = .008). The Kaplan-Meier analysis showed a lesser probability of anastomotic surgical recurrence in the S group at 5 years (0% vs 15%; P = .0013). The absence of postoperative infliximab did not affect the restenosis rate in group S. LIMITATIONS: This study was limited by its historical retrospective nature. CONCLUSION: The Kono-S anastomosis appears to be effective in preventing anastomotic surgical recurrence in Crohns disease.

Significance of steroid sulfatase expression in human breast cancer

The sulfatase pathway has been thought to be a primary means of local production of estrone in human breast cancer tissue. We measured steroid sulfatase (STS) mRNA levels in 97 breast cancers and evaluated its association with disease-free survival. High levels of STS mRNA proved to be a significant predictor of reduced relapse-free survival, both as a continuous variable (log STS mRNA; P=0.028) and as a dichotomous variable with an optimized cutoff point (P=0.002). In multivariate analysis a high level of STS mRNA was an independent factor for predicting relapse-free survival. These results suggest a putative role of STS in breast cancer growth and metastasis, and administration of sulfatase inhibitors to breast cancer patients with high levels of STS mRNA might be an additional treatment option.

Immunohistochemical analysis of organic anion transporter 2 and reduced folate carrier 1 in colorectal cancer: Significance as a predictor of response to oral uracil/ftorafur plus leucovorin chemotherapy

Colorectal cancer is one of the most common malignancies in developed countries and chemotherapy is the standard treatment option for advanced colorectal cancer. Identification of biomarkers for predicting response to uracil/ftorafur plus leucovorin (UFT/LV) chemotherapy is an important issue in colorectal cancer treatment. Organic anion transporter 2 (OAT2) and reduced folate carrier 1 (RFC1) are the major uptake transporters of 5-fluorouracil (5-FU) and LV, respectively. In the present study, the correlation between OAT2 and RFC1 expression and histological response to preoperative UFT-based (UFT or UFT/LV) chemotherapy was investigated. Pre-treatment biopsy specimens obtained from 45 patients were evaluated for OAT2 and RFC1 expression levels by using an immunohistochemical approach. A high expression of OAT2 and RFC1 was significantly correlated with good response to UFT-based chemotherapy (P<0.0001 and P= 0.002, respectively). In multivariate logistic regression analysis, a high OAT2 expression was an independent predictor of good response to UFT-based chemotherapy (P=0.02), unlike RFC1 expression. High expression levels of OAT2 were significantly correlated with a good response in the UFT-treated (P= 0.04) as well as the UFT/LV-treated (P<0.0005) groups; however, RFC1 expression levels were significantly correlated with a good response only in the UFT/LV-treated group (P=0.02). Therefore, immunohistochemical analysis of OAT2 and RFC1 may serve as a useful tool for predicting the efficacy of UFT/LV treatment regimens in colorectal cancer patients.

A single-arm Phase II validation study of preventing oxaliplatin-induced hypersensitivity reactions by dexamethasone: the AVOID trial

Background Patients with colorectal cancer treated with oxaliplatin are at risk of hypersensitivity reactions, with the incidence estimated to be 12%–20%. Coinfusion of dexamethasone and oxaliplatin could potentially reduce the incidence of these reactions, but oxaliplatin is reported to be incompatible with alkaline compounds in solution. However, in a previous retrospective study we found that the pH of a solution of dexamethasone and oxaliplatin was less than 7.4, and that hypersensitivity to oxaliplatin could have been prevented by coinfusion of dexamethasone. We aimed to evaluate the effectiveness of coinfusion of dexamethasone and oxaliplatin to prevent oxaliplatin-induced hypersensitivity reactions. Patients and methods The AVOID trial was a prospective, multicenter, open-label, single-arm Phase II trial conducted from January to September 2013. The study included 73 patients who received capecitabine plus oxaliplatin (XELOX) or XELOX plus bevacizumab therapy for colorectal cancer. In all patients, oxaliplatin was administered in combination with dexamethasone. The primary outcome measure was the presence of hypersensitivity reactions. Results Hypersensitivity reactions occurred in three patients (4.1%); all three experienced a cutaneous reaction (grade 1 erythema). None of the 73 patients developed respiratory symptoms, ocular symptoms, or anaphylaxis. Grade 3 or higher hemotoxicity occurred in 13.7% of the patients and grade 3 or higher nonhematological toxicity occurred in 13.7%. The response rate to treatment was 64.4%. Conclusion The coinfusion of dexamethasone and oxaliplatin effectively reduced oxaliplatin-induced hypersensitivity reactions in patients with colorectal cancer. This approach should be considered for all patients treated with oxaliplatin, allowing treatment to be completed as planned.

Clinicopathological Factors Associated with Recurrence and Prognosis after R0 Resection for Stage IV Colorectal Cancer with Peritoneal Metastasis.

Background/Aims: Peritoneal metastasis (PM) is a well-known predictor of poor prognosis. This study aims at identifying factors affecting recurrence and prognosis after R0 resection for colorectal cancer (CRC) with synchronous PM. Methods: A multi-institutional, retrospective analysis of 172 patients with R0 surgery for CRC with PM was conducted. Clinicopathological variables were analyzed for their significance in contributing toward recurrence and prognosis. Results: Lymph node (LN) metastasis was an independent factor affecting recurrence as indicated by logistic regression analyses. The following factors were independent predictors of poor prognostic using the Cox proportional hazard model: LN metastasis, no postoperative adjuvant chemotherapy, five or fewer dissected LNs, and preoperative high serum carbohydrate antigen 19-9 levels. Of the patients undergoing postoperative adjuvant chemotherapy, no significant differences were observed in recurrence rate and disease-free interval between those with intensive adjuvant chemotherapy and those with non-intensive chemotherapy. After R0 surgery for PM, 90 patients (76.3%) experienced recurrence by 18 months, and hematogenous recurrence occurred significantly more often than peritoneal recurrence. Conclusion: Harvesting of more than 5 LNs and administration of postoperative adjuvant chemotherapy after R0 surgery are recommended for prognosis improvement. Intensive follow-up should be performed within 18 months after R0 surgery for CRC with synchronous PM.

Surgical management of colorectal cancer for the aging population—A survey by the Japanese Society for Cancer of Colon and Rectum

OBJECTIVE The treatment policy of colorectal cancer in elderly patients is controversial due to a lack of specific guidelines. To clarify the present management of colorectal cancer for aged patients, a questionnaire survey was conducted by the Japanese Society for Cancer of the Colon and Rectum. METHODS Questionnaire forms were sent to the 430 member institutions of the Japanese Society for Cancer of the Colon and Rectum. RESULTS The response rate of the surgical department to the questionnaire was 39%. Performance status was used for preoperative assessments, and electrocardiogram and ultrasonic cardiograms were conducted for cardiovascular evaluations in many institutions. The same extent of surgical procedures was often adopted for elderly and younger patients, and the frequency of a laparoscopic procedure was the same regardless of a patients age. A simultaneous hepatectomy for hepatic metastasis was considered in one-third of institutions. In many institutions, intersphincteric resection for patients with possible sphincter-saving surgery was not considered for elderly patients with low rectal cancer. CONCLUSION Japanese Society for Cancer of the Colon and Rectum member institutions often used the same surgical treatment strategies for both elderly and younger patients with the exception of performing intersphincteric resection.

Successful repair of a rectovaginal fistula caused by a tension-free vaginal mesh (TVM): a case report

Rectovaginal fistula caused by a tension-free vaginal mesh (TVM) is a rare condition. Moreover, a rectovaginal fistula is a challenging issue to address for surgeons regardless of causes. Due to a low rate of occurrence, treatment modality for a rectovaginal fistula caused by a TVM has previously received little attention. A successful surgery using several key techniques to address a rectovaginal fistula caused by a TVM is herein reported. A 78-year-old woman who underwent a TVM for a rectocele three months ago was referred to our hospital with a two-month history of anal bleeding. Mesh protruding into both the vagina and the rectum was confirmed. The patient was operated on under diagnosis of a rectovaginal fistula caused by TVM. TVM was removed by transvaginal dissection of the rectovaginal septum with division of both anterior and posterior arms of the TVM. Layer-to-layer sutures of rectal and vaginal walls were crossly performed with a drain placed in the rectovaginal septum after saline irrigation followed by a covering sigmoid colostomy. The wound healed without infection after surgery, and a water-soluble contrast enema demonstrated the healing of the rectovaginal fistula two months after surgery. No recurrent fistula was confirmed 15 months after stoma closure.