Multiple large bowel resections: Potential risk factor for anastomotic leak

Objectives Identify risk factors of anastomotic leak (AL) after large bowel resection (LBR) for ovarian cancer (OC) and compare outcomes between AL and no AL. Methods All cases of AL after LBR for OC between 01/01/1994 and 05/20/2011 were identified and matched 1:2 with controls for age (\ub1 5 years), sub-stage (IIIA/IIIB; IIIC; IV), and date of surgery (\ub1 4 years). Patient-specific and intraoperative risk factors, use of protective stomas, and outcomes were abstracted. A stratified conditional logistic regression model was fit to determine the association between each factor and AL. Results 42 AL cases were evaluable and matched with 84 controls. Two-thirds of the AL had stage IIIC disease and > 90% of both cases and controls were cytoreduced to < 1 cm residual disease. No patient-specific risk factors were associated with AL (pre-operative albumin was not available for most patients). Rectosigmoid resection coupled with additional LBR was associated with AL (OR = 2.73, 95% CI 1.13-6.59, P = 0.025), and protective stomas were associated with decreased risk of AL (0% vs. 10.7%, P = 0.024). AL patients had longer length of stay (P < 0.001), were less likely to start chemotherapy (P = 0.020), and had longer time to chemotherapy (P = 0.007). Cases tended to have higher 90-day mortality (P = 0.061) and were more likely to have poorer overall survival (HR = 2.05, 95% CI 1.18-3.57, P = 0.011). Conclusions Multiple LBRs appear to be associated with increased risk of AL and protective stomas with decreased risk. Since AL after OC cytoreduction significantly delays chemotherapy and negatively impacts survival, surgeons should strongly consider temporary diversion in selected patients (poor nutritional status, multiple LBRs, previous pelvic radiation, very low anterior resection, steroid use)

Influence of intraoperative capsule rupture on outcomes in stage i epithelial ovarian cancer

Objective: To evaluate the effect of tumor capsule rupture on disease prognosis in stage I epithelial ovarian cancer. Methods: All patients with International Federation of Gynecology and Obstetrics stage I epithelial ovarian cancer operated on at the Mayo Clinic and The Ohio State University between January 1991 and December 2007 were identified. Relevant tumor characteristics, procedures performed, adjuvant therapies, and follow-up were recorded and analyzed. Inclusion criteria included comprehensive staging. Cox proportional hazards, Kaplan-Meier estimation, log rank test, and \u3c7 test were used for statistical analyses. Results: There were 161 cases that met inclusion criteria. Seventy-four (46%) patients had intact capsules without positive cytology or surface involvement; 61 (38%) had capsule rupture; 33 (20%) had positive cytology; and 22 (14%) had surface involvement. Overall, 22 of 161 (14%) patients recurred and 12 of 161 (7%) patients died of their disease. In univariable analysis, both intraoperative capsule rupture and positive cytologic washings portended worse disease-free survival (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.5-8.9; P=.004 and HR 5.2, 95% CI 2.1-12.3; P<.001, respectively) and disease-specific survival (HR 4.1, 95% CI 1.3-15.4; P=.018 and HR 5.9, 95% CI 1.8-19.3; P=.005, respectively). In multivariable analysis, capsule rupture (HR 4.2, 95% CI 1.8-10.9; P=.001) and positive cytologic washings (HR 6.4, 95% CI 2.5-16.0; P<.001) remained independent predictors of worse disease-free survival. Disease-free survival and disease-specific survival were shortest for stage IC cases with positive cytology, surface involvement, or both, that also had intraoperative rupture. Conclusion: In stage I epithelial ovarian cancer, intraoperative capsule rupture portends a higher risk of disease recurrence and death from disease. Careful intraoperative removal of ovarian masses is important, and recognizing the higher-risk nature of such cases is imperative

Risk factors for lymph node metastasis in apparent early-stage epithelial ovarian cancer : implications for surgical staging

Objectives: The extent of lymphadenectomy to be performed in apparent early-stage epithelial ovarian cancer (EOC) is not well defined. We evaluated the patterns of lymphatic spread in apparent early-stage EOC and risk factors for lymph node metastasis, as these have potential implications for clinical decision making. Methods: All cases of apparent early-stage EOC diagnosed at our institution between January 1994 and December 2003 were retrospectively identified. Apparent early-stage EOC was defined as gross disease that appeared confined to the pelvis without abdominal spread at the time of initial exploration. Demographics, pathologic findings, staging procedures performed, and clinical impression at surgery were analyzed. Patterns of lymph node positivity and risk factors associated with upstaging were assessed. Results: One hundred and ninety patients with apparent early-stage EOC undergoing primary surgical staging met criteria for inclusion. All patients had at least some pathologic assessment of lymph nodes, with 115 having both bilateral pelvic and paraaortic lymphadenectomy performed. After review of pathology and operative reports, the final FIGO staging within the cohort was 54 IA (28.4%), 10 IB (5.3%), 51 IC (26.8%), 1 IIA (0.5%), 4 IIB (2.1%), 37 IIC (19.5%), 8 IIIA (4.2%), 25 IIIC (13.2%). Overall 25/190 (13%) had lymph nodes metastasis as follows: 8 (32%) had positive pelvic nodes, 12 (48%) had positive paraaortic nodes, and 5 (20%) had both positive pelvic and paraaortic lymph nodes. Significant risk factors for lymph node metastasis included bilateral vs. unilateral primary lesion (26.8% vs. 7.5%, p 35 vs. 64 35 U/ml (22.4% vs.0% p = 0.006). No patients with mucinous cancers (n = 29) had lymph node metastases. Patterns of LN metastases were largely independent of laterality of primary lesions: among those with unilateral lesions and positive nodes (n = 10), 5 (50%) had ipsilateral lymph node involvement, 4 (40%) had bilateral involvement, and 1 (10%) had isolated contralateral lymph nodes positive. Conclusions: Complete surgical staging in EOC patients with gross disease confined to the ovaries and pelvis should include bilateral pelvic and paraaortic lymphadenectomy. Even in patients with unilateral lesions, lymph node metastases are commonly bilateral. Bilateral ovarian lesions, positive cytology, presence of ascites, high grade histology, and serous histology are risk factors for lymph node involvement. This information may be helpful in counseling patients presenting for consideration of re-staging after unexpected findings of malignancy

Random peritoneal biopsies have limited value in staging of apparent early stage epithelial ovarian cancer after thorough exploration

Objective: The relative value of abdominal exploration, lymphadenectomy, omentectomy and random peritoneal biopsies in the staging of apparent early stage epithelial ovarian cancer (EOC) has not been rigorously evaluated. We sought to define the clinical significance of random peritoneal biopsies of otherwise benign appearing tissues in staging of grossly early EOC. Methods: All patients with apparent early stage EOC undergoing staging from 1/1994 to 12/2003 were evaluated to identify surgical-pathologic findings responsible for upstaging at time of exploratory surgery. Demographics, surgical findings and operative outcomes were abstracted. Results: A total of 211 patients with apparent early EOC were included. Only 9 patients were upstaged based on pathology indicating a high negative predictive value of thorough exploration and lymphadenectomy. One patient (1/118; 0.8%) was upstaged from stage I disease to stage II disease based on random biopsy of pelvic peritoneum: all other stage II patients had visible disease. No patients were upstaged from stage I disease to stage III disease due to random biopsies or microscopic omental disease. Eight patients (3.8%) were upstaged from stage II to stage III disease based on random biopsies of upper abdominal peritoneum or the omentum. Conclusions: In our study of apparent early stage EOC, random peritoneal biopsies and omentectomy added little diagnostic value beyond careful inspection of all peritoneal surfaces when EOC is grossly limited to the ovaries. Within our study, less than 4% of patients with pelvic metastasis were upstaged due to these particular staging procedures. No patients in our cohort had a change in treatment recommendations based on these biopsies

Utility of closed suction pelvic drains at time of large bowel resection for ovarian cancer

Objective: To test the hypothesis that the use of closed suction pelvic drains placed at time of large bowel resection (LBR) for ovarian cancer (OC) decreases morbidity following anastomotic leak (AL). Methods: Consecutive cases of LBR for OC between 01/01/1994 and 06/20/2011 were retrospectively identified. Drains were routinely used until bowel movement. AL was defined as: 1) feculent fluid from drains/wound/vagina, 2) radiographic evidence of AL, or 3) AL found at reoperation. Descriptive statistics, Wilcoxon rank-sum, Pearson's chi-square and Fisher's exact test were used. Results: 43 cases met inclusion criteria. AL was characterized by method of diagnosis as follows: change in drain output only (DO, n = 8); change in drain output associated with ambiguous clinical signs/symptoms (D-SSX, n = 11); or clinical signs/symptoms only (SSX, n = 24). The sensitivity of drains in diagnosing AL was 50%. Time to diagnosis was earlier in DO/D-SSX (median 7 vs. 11 days, P = 0.003), however, no significant differences were observed in rates of reoperation, length of stay, time to chemotherapy (TTC), and 30- and 90-day mortality between DO/D-SSX and SSX. Comparing cases where no drains were placed (n = 5) vs. those with drain (n = 38), we observed no differences in outcomes. TTC though statistically significant (47 vs. 59 days, P = 0.023) was not clinically significant. Conclusions: Though a change in drain output correlated with earlier diagnosis, this did not appear to impact overall outcomes. We did not find strong evidence supporting routine prolonged drainage after LBR for OC. Additionally, absence of change in drain output does not rule out presence of AL

M&#252;llerian inhibiting substance type II receptor (MISIIR): A novel, tissue-specific target expressed by gynecologic cancers

Objective.: M\ufcllerian inhibiting substance type II receptor (MISIIR) is expressed by ovarian, breast, and prostate cancers [Masiakos PT, et al. Human ovarian cancer, cell lines, and primary ascites cells express the human Mullerian inhibiting substance (MIS) Type II Receptor, bind, and are responsive to MIS. Clin Cancer Res 1999;5:3488-99; Hoshiya Y, et al. Mullerian inhibiting substance promotes interferon gamma-induced gene expression and apoptosis in breast cancer cells. J Biol Chem 2003;278:51703-12; Hoshiya Y, et al. Mullerian inhibiting substance induces NFkB signaling in breast and prostate cancer cells. Mol. Cell. Endocrinol. 2003;211:43-9. [1-3]]. We investigated the expression patterns of MISIIR in benign and malignant gynecologic tissues and benign non-gynecologic tissues to better assess the relevance of MISIIR as a target for new therapeutic and diagnostic approaches to gynecologic cancers. Secondarily, we examined the impact of MISIIR expression on overall survival (OS) and disease-free survival (DFS) in a cohort of epithelial ovarian cancers (EOC). Methods.: Reverse-transcription polymerase chain reaction (RT-PCR), immunoblotting, and immunohistochemistry (IHC) were used to determine MISIIR expression. EOC cell lines (10), primary EOCs (12), and tissue microarrays (TMAs) containing benign gynecologic (179) and non-gynecologic tissues (25), EOC (182), endometrial carcinomas (109), uterine sarcomas (98), and ovarian dysgerminomas (22) were examined for MISIIR expression. Clinical data were collected for a cohort of 182 EOCs. Results.: Ninety-two percent of primary EOCs and 44% of EOC cell lines expressed MISIIR mRNA. We observed moderate or strong MISIIR expression via IHC in the majority of gynecologic cancers: EOC 69% (125/182), ovarian dysgerminomas 77% (17/22), endometrial cancers 75% (82/109), uterine malignant mixed M\ufcllerian tumors (MMMT) 59% (30/51), uterine leiomyosarcomas (LMS) 52% (15/29), and endometrial stromal sarcomas (ESS) 22% (4/18). Over 74% of normal non-gynecologic tissues did not express MISIIR. There was a significant correlation between MISIIR expression and improved OS (p = 0.025, Chi square). Conclusions.: In the largest study to date, we report that MISIIR is highly expressed by a wide variety of gynecologic cancers, including cancers currently without effective systemic therapies. Low levels of expression in select non-gynecologic tissues coupled with high expression in gynecologic malignancies make MISIIR an attractive target for novel therapeutics and tumor-directed imaging in the management of gynecologic cancers. Further investigation into the impact of MISIIR expression and OS is also warranted

Is there a high-risk subgroup of stage i epithelial ovarian cancer that is most likely to benefit from 6 versus 3 cycles of adjuvant chemotherapy?

Objective: Despite results from Gynecologic Oncology Group (GOG) 157 showing no statistically significant survival differences in patients treated with 3 versus 6 cycles of carboplatin and paclitaxel, further analysis of GOG 157 data suggested that certain early-stage epithelial ovarian cancers (EOCs) might benefit from extended chemotherapy. We sought to determine those stage I EOC cases at highest risk of failing 3 cycles of therapy. Methods: All patients with surgical International Federation of Gynecology and Obstetrics stage I EOC operated on at the Mayo Clinic and The Ohio State University between January 1991 and December 2007 were identified through retrospective chart review. A cohort of patients who received 6 cycles of adjuvant carboplatin and paclitaxel chemotherapy was compared with a cohort of patients who received 3 cycles. Disease-free survival and disease-specific survival were primary outcomes analyzed. Results: There were 107 patients who received either 3 or 6 cycles of adjuvant carboplatin and paclitaxel. Among all stage I EOCs, the number of cycles did not influence disease-free survival or disease-specific survival. The highest recurrence rate (7 [46.7%] of 15 cases) was among stage IC cases with fixed tumors and positive cytology and/or surface involvement. Among this cohort, 6 (66.7%) of the 9 patients who received 3 cycles recurred, whereas only 1 (16.7%) of the 6 patients who received 6 cycles recurred (hazard ratio, 5.97; 95% confidence interval [CI], 0.98-114.46; P = 0.05, Cox proportional hazards regression model) for an odds ratio of 3.94. The absolute risk reduction for 6 cycles in this highest risk cohort was 50%. Conclusions: Patients with stage IC cancer and with fixed tumors and positive cytology and/or tumor surface involvement appear to have a higher risk of recurrence after 3 cycles (compared with 6) of platinum-based chemotherapy. The clinical behavior of this highest risk cohort implies a more aggressive tumor biology, and further understanding of such stage I EOCs is warranted