Patients triaged to neoadjuvant chemotherapy have higher rates of sarcopenia: An opportunity for prehabilitation.

OBJECTIVE: To compare baseline body composition measures (BCM), including sarcopenia, between patients with advanced epithelial ovarian cancer (EOC) undergoing primary cytoreductive surgery (PCS) versus neoadjuvant chemotherapy/interval cytoreductive surgery (NACT/ICS) and evaluate changes in BCM pre-NACT versus pre-ICS. METHODS: Patients with stage IIIC/IV EOC who underwent PCS or NACT with curative intent between 1/1/2012 and 7/31/2016 were included. Computed tomography scans were evaluated via a semi-automated program to determine BCM. Measures evaluated include skeletal muscle area (SMA), skeletal muscle density (SMD), skeletal muscle index (SMI), and skeletal muscle gauge (SMG). Sarcopenia was defined as SMI <39.0 cm2/m2. RESULTS: The study included 200 PCS patients and 85 NACT/ICS patients, of which 76 had both pre-NACT and pre-ICS scans. NACT patients were significantly more likely to be sarcopenic compared to PCS patients (40.0% vs 27.5%, p = 0.04). Mean SMA (107.3 vs 113.4 cm2, p = 0.004) and mean SMG (1344.6 vs. 1456.9 (cm2 x HU)/m2, p = 0.06) were lower in NACT patients. Among NACT/ICS patients, mean SMI significantly decreased -1.4 cm2/m2 (p = 0.005) at the time of surgery, resulting in a non-statistically significant increase in the percentage of sarcopenic patients from baseline (40.8% vs. 50.0%, p = 0.09). CONCLUSIONS: Sarcopenia is more common in patients with advanced EOC undergoing NACT compared to PCS when using an evidence-based triage system for triage decisions. Body composition changes significantly over the course of NACT. Sarcopenia may be an indicator of debility and another factor for consideration in treatment planning. Further research into body composition's effects on prognosis and altering sarcopenia is necessary.

Vaginal vs. robotic hysterectomy for patients with endometrial cancer: A comparison of outcomes and cost of care.

OBJECTIVE: To compare outcomes and cost for patients with endometrial cancer undergoing vaginal hysterectomy (VH) or robotic hysterectomy (RH), with or without lymphadenectomy (LND). METHODS: Patients undergoing planned VH (and laparoscopic LND) or RH (and robotic LND) between January 2007 and November 2012 were reviewed. Patients with stage IV disease, synchronous cancer, synchronous surgery, or treated with palliative intent were excluded. Patients were objectively triaged to LND per institutional protocol based on frozen section. Outcomes were compared between VH and RH groups matched 1:1 on propensity scores. RESULTS: VH was planned in 153 patients; 60 (39%) had concurrent LND while 93 (61%) were low risk and did not require LND. RH was planned in 398 patients; 225 (56%) required concurrent LND and 173 (44%) did not. Among 50 PS-matched pairs without LND, there was no significant difference in complications, length of stay, readmission, or progression free survival. However, median operative time was 1.3h longer and median 30-day cost $3150 higher for RH compared to VH (both p<0.001). Among patients requiring LND, 42 PS-matched pairs were identified. Median operative time was not different when pelvic and para-aortic LND was performed, and 12min longer in the VH group for pelvic LND alone (p=0.03). Median 30-day cost was $921 higher for RH compared to VH when LND was required (p=0.08). CONCLUSION: Utilization of vaginal hysterectomy for endometrial cancer results in similar surgical and oncologic outcomes and lower costs compared to RH and should be considered for appropriate patients with a low risk of requiring LND.

A prospective algorithm to reduce anastomotic leaks after rectosigmoid resection for gynecologic malignancies.

OBJECTIVE: Determine whether a standardized protocol for temporary bowel diversion after rectosigmoid resection (RSR) for cytoreduction can reduce the rate of anastomotic leak (AL). METHODS: A prospective quality improvement project for patients undergoing RSR during debulking surgery from 07/2013 to 01/2016 was conducted. Patients with any of the following underwent temporary diversion: preoperative albumin ≤3.0g/dL, prior pelvic radiation, RSR plus additional large bowel resection (LBR), anastomosis (AS) ≤6cm from the anal verge, failed leak test or contamination of the pelvis with stool. The AL rate was compared to the historic AL rate from 01/04-06/11. RESULTS: Seventy-seven patients underwent RSR, with 27 (35.1%) receiving diverting stomas vs. 25/309 (8.1%) in the historic cohort. Additional LBR (33.3%) and AS at ≤6cm from anal verge (26.3%) were the most common indications for diversion. No AL was observed among diverted patients. If one AL which occurred following protocol violation (failed leak test but not diverted) is excluded, the theoretical AL rate is 1.3% (1/77) vs. 7.8% (24/309; P=0.039) in the historic cohort. Not excluding this case, the AL rate was 2.6% (2/77) vs. 7.8% (P=0.11). Short-term outcomes following primary surgery were not different between diverted and non-diverted patients. Stoma-related complications were observed in 7/27 (25.9%) patients, primarily related to dehydration. Reversal surgery was successfully performed in 24/75 (88.9%) patients. CONCLUSIONS: Criteria-based temporary bowel diversion for patients undergoing RSR for gynecologic cancer reduced the AL rate. Diversion was associated with acceptable morbidity and high reversal rate.

Patterns of Müllerian Inhibiting Substance Type II and Candidate Type I Receptors in Epithelial Ovarian Cancer.

The MIS pathway is a potential therapeutic target in epithelial ovarian cancer (EOC): signaling requires both type II (T2R) and type I receptors (T1R), and results in growth inhibition. MISR2 is expressed in EOC, but the prevalence and relative contributions of candidate T1R remain unknown. We sought to: a) determine expression of T1R in EOC; b) assess impact of T1R expression with clinical outcomes; c) verify MIS-dependent Smad signaling and growth inhibition in primary EOC cell cultures. Tissue microarrays (TMA) were developed for analysis of T1Rs (ALK2/3/6) and MISR2 expression. Primary cell cultures were initiated from ascites harvested at surgery which were used to characterize response to MIS. TMA's from 311 primary cancers demonstrated the most common receptor combinations were: MISR2+/ALK2+3+6+ (36%); MISR2+/ALK2+3+6- (34%); MISR2-/ALK2+3+6- (18%); and MISR2-/ALK2+3+6+ (6.8%). No differences in overall survival (OS) were noted between combinations. The ALK6 receptor was least often expressed T1R and was associated with lower OS in early stage disease only (p =0.03). Most primary cell cultures expressed MISR2 (14/22 (63.6%)): 95% of these express ALK 2 and ALK3, whereas 54.5% expressed ALK6. MIS-dependent Smad phosphorylation was seen in the majority of cultures (75%). Treatment with MIS led to reduced cell viability at an average of 71% (range: 57-87%) in primary cultures. MIS signaling is dependent upon the presence of both MISR2 and specific T1R. In the majority of EOC, the T1R required for MIS-dependent signaling are present and such cells demonstrate appropriate response to MIS.

Evaluating the prognostic significance of preoperative thrombocytosis in epithelial ovarian cancer.

OBJECTIVE: Preoperative thrombocytosis has been implicated as a negative prognostic marker for epithelial ovarian cancer (EOC). We assessed whether thrombocytosis is an independent risk factor for EOC recurrence and death. METHODS: Perioperative patient characteristics and process-of-care variables (National Surgical Quality Improvement Program (NSQIP)-defined) were retrospectively abstracted from 587 women who underwent EOC staging between 1/2/03-12/29/08. Thrombocytosis was defined as platelet count > 450 × 10(9)/L. Disease-free survival (DFS) and overall survival (OS) were determined using Kaplan-Meier methods. Associations were evaluated with Cox proportional hazards regression and hazard ratios (HR). RESULTS: The incidence of preoperative thrombocytosis was 22.3%. DFS was 70.8% and 36.0% at 1 and 3 years. OS was 83.3% and 54.3% at 1 and 3 years. Ascites, lower hemoglobin, advanced disease, and receipt of perioperative packed red blood cell transfusion were independently associated with thrombocytosis. Older age and the presence of coronary artery disease were associated with lower likelihood of thrombocytosis. Overall, thrombocytosis was an independent predictor of increased risk of recurrence. Among early stage (I/II) cases, there was a 5-fold increase in the risk of death and nearly 8-fold risk of disease recurrence independently associated with thrombocytosis. CONCLUSION: Preoperative thrombocytosis portends worse DFS in EOC. In early stage disease, thrombocytosis is a potent predictor of worse DFS and OS and further assessment of the impact of circulating platelet-derived factors on EOC survival is warranted. Thrombocytosis is also associated with extensive initial disease burden, measurable residual disease, and postoperative sequelae. Preoperative platelet levels may have value in primary cytoreduction counseling.

Morbidity, mortality and overall survival in elderly women undergoing primary surgical debulking for ovarian cancer: a delicate balance requiring individualization.

OBJECTIVE: To assess outcomes and identify underlying predictors of outcomes in a cohort of women over the age of 65 treated for primary ovarian cancer (OC). METHODS: Consecutive patients ≥ 65 with stage IIIC or IV OC treated with primary surgery and adjuvant chemotherapy at Mayo Clinic between January 1, 1994 and December 31, 2004 were retrospectively assessed. We analyzed the impact of perioperative factors (age, albumin, CA125, American Society of Anesthesiologist (ASA) score, amount of ascites, presence of carcinomatosis, creatinine, need for urgent surgery, stage of disease, surgical complexity score and amount of residual disease) on surgical outcomes (morbidity, mortality, overall survival (OS) and ability to receive chemotherapy). RESULTS: Two hundred eighty patients met inclusion criteria. Age was associated with higher ASA score, lower albumin, and higher creatinine; stage, diffuse peritoneal disease, and surgical complexity were not associated with age. Median OS decreased with increasing age and residual disease (RD), and the impact of RD was greater on older patients. All patients benefited similarly when RD=0 [median OS 5.9 years for age 65-69 vs. 5.0 years in those ≥ 80 (p=0.5516)], for RD<1cm, and OS was 3.4 vs. 2.1 years respectively for youngest vs. oldest patients (p=0.068). Perioperative morbidity was observed in 37.5% of patients ≥ 75. Independent predictors of poor perioperative outcome included preoperative albumin ≤ 3g/dL, urgent surgery, age, and stage (p<0.05). Independent predictors of overall survival included creatinine, albumin, surgical complexity score, amount of residual disease, stage and age. CONCLUSION: Age is an independent predictor of OS in OC. A significant number of elderly women are able to undergo a complete cytoreduction and experience OS similar to that of younger patients. However, the benefits to incomplete cytoreduction are less clear in women ≥ 75. These observations highlight the need to use emerging predictors of outcomes in decision making and to focus care in centers able to render patients with no visible residual disease.