Impact of operative start time on surgical outcomes in patients undergoing primary cytoreduction for advanced ovarian cancer

Objectives

To evaluate the impact of operative start time (OST) on surgical outcomes in patients with advanced ovarian cancer.

Methods

All stage IIIB-IV serous ovarian cancer patients who underwent primary surgery at our institution from 1/01 to 1/10 were identified. Fourteen factors were evaluated for an association with surgical outcomes including OST and OR tumor index (1 point each for carcinomatosis and/or bulky [≥ 1 cm] upper abdominal disease). Univariate logistic regression considering within-surgeon clustering was performed for cytoreduction to ≤ 1 cm versus > 1 cm residual disease. In patients with ≤ 1 cm residual disease, univariate logistic regression considering within-surgeon clustering was performed for 1-10 mm residual disease versus complete gross resection (CGR, 0 mm residual). A multivariate logistic model was developed based on univariate analysis results in the ≤ 1 cm residual disease cohort.

Results

Of 422 patients, residual disease was: 0 mm, 144 (34.1%); 1-10 mm, 175 (41.5%); > 10 mm, 103 (23.3%). OST was not associated with cytoreduction to ≤ 1 cm residual disease on univariate analysis. In the ≤ 1 cm residual disease cohort, albumin, CA-125, ascites, ASA score, stage, OR tumor index, and OST were associated with CGR on univariate analysis. Earlier OSTs were associated with increased rates of CGR. On multivariate analysis, CA-125 was independently associated with CGR. OST was associated with CGR in patients with an OR tumor index of 2 but not an OR tumor index < 2.

Conclusions

OST was not associated with cytoreduction to ≤ 1 cm residual disease in patients with advanced serous ovarian cancer. In the cohort of patients with ≤ 1 cm residual disease, later OSTs were associated with reduced rates of CGR in patients with greater tumor burden.     

Should stage IIIC ovarian cancer be further stratified by intraperitoneal vs. retroperitoneal only disease?: a Gynecologic Oncology Group study

Objective

To examine whether clinical outcomes varied with intraperitoneal (IP) and/or retroperitoneal (RP) involvement in stage IIIC epithelial ovarian cancer (EOC) patients with microscopic residual disease after cytoreduction.

Methods

Retrospective review was performed for EOC patients enrolled in Gynecologic Oncology Group (GOG)-182 who underwent primary cytoreduction to microscopic residual disease. Patients were divided into 3 groups: stage IIIC by lymphadenopathy with < 2 cm IP spread (RP); > 2 cm IP spread and negative nodes (IP/RP−); and > 2 cm IP dissemination and positive lymphadenopathy (IP/RP+). Product-limit and multivariate proportional hazards modeling were used.

Results

Analyses included 417 stage IIIC women who underwent primary cytoreduction with lymphadenectomy to microscopic residual. There were 203, 123, and 91 in the RP, IP/RP−, and IP/RP+ groups, respectively. IP/RP+ and IP/RP− were associated with worse progression-free survival (PFS) (Hazard Ratio (HR) 1.68, 95% confidence interval (CI) 1.23-2.30; HR 1.38, 95% CI 1.04-1.84) vs. RP only. IP/RP+ was associated with worse overall survival (OS) (HR 1.79, 95% CI 1.24-2.57) while IP/RP− trended towards worse OS (HR 1.21, 95% CI 0.85-1.73) vs. RP only. Median PFS for IP/RP+ and IP/RP− groups was 21 and 29 months, respectively, vs. 48 months in the RP group (p = 0.0007) and median OS of 63 and 79 months vs. “not reached,” respectively (p = 0.0038).

Conclusions

Among EOC patients surgically cytoreduced to microscopic residual disease, those upstaged to IIIC by retroperitoneal involvement demonstrated significant improvement in PFS and OS compared to patients with intraperitoneal tumor, suggesting that these women may represent a unique subset of FIGO stage IIIC patients.     

Clinicopathological prognostic factors and the role of cytoreduction in surgical stage IVb endometrial cancer: A retrospective multi-institutional analysis of 248 patients in Japan

Objective

To evaluate clinicopathological prognostic factors and the impact of cytoreduction in patients with surgical stage IVb endometrial cancer (EMCA).

Methods

The records of 248 patients with stage IVb EMCA who underwent primary surgery including hysterectomy at multiple institutions from 1996 to 2005 were retrospectively analyzed. Data regarding disease distribution, surgical procedures, adjuvant therapy, and survival times were collected. Univariate and multivariate analyses were performed to identify factors associated with overall survival (OS).

Results

The median OS was 24 months. The most common histological types were endometrioid (grade 1: 15%, grade 2: 20%, grade 3: 24%) and serous (17%). The most common sites of intra-abdominal metastases were pelvis (65%), ovaries (58%), omentum (58%), retroperitoneal lymph nodes (52%), and upper abdominal peritoneum (44%). In 93 patients with extra-abdominal metastases, the most common site was the lung (n = 49). Complete resection of extra-abdominal metastases was achieved in only 13 patients. Complete resection of intra-abdominal metastases was achieved in 101 patients, 52 had ≤ 1 cm residual disease, and 95 had > 1 cm residual disease; the median OS times in these groups were 48, 23, and 14 months, respectively (p < 0.0001). Multivariate analysis showed that performance status, histology/grade, adjuvant treatment, and intra-abdominal residual disease were independent prognostic factors. Intra-abdominal residual disease was an independent prognostic factor in patients with and without extra-abdominal metastases.

Conclusions

Cytoreductive surgery and adjuvant therapy may improve survival in stage IVb EMCA, particularly in patients with favorable prognostic factors, even in the presence of extra-abdominal metastases.     

Outcomes of primary surgical cytoreduction in patients with BRCA-associated high-grade serous ovarian carcinoma

Objective

BRCA-associated and sporadic ovarian cancers have different pathologic and clinical features. Our goal was to determine if BRCA mutation status is an independent predictor of residual tumor volume following primary surgical cytoreduction.

Methods

We conducted a retrospective analysis of patients with FIGO stage IIIC-IV high-grade serous ovarian cancer classified for the presence or absence of germline BRCA mutations. The primary outcome was tumor-debulking status categorized as complete gross resection (0 mm), optimal but visible disease (1-10 mm), or suboptimal debulking (> 10 mm) following primary surgical cytoreduction. Overall survival by residual tumor size and BRCA status was also assessed as a secondary endpoint.

Results

Data from 367 patients (69 BRCA mutated, 298 BRCA wild-type) were analyzed. Rate of optimal tumor debulking (0-10 mm) in BRCA wild-type and BRCA-mutated patients were 70.1% and 84.1%, respectively (P = 0.02). On univariate analysis, increasing age (10-year OR, 1.33; 95% CI, 1.07-1.65; P = 0.01) and wild-type BRCA status (OR, 0.47; 95% CI, 0.23-0.94, P = 0.03) were both significantly associated with suboptimal surgical outcome. On multivariate analysis, BRCA mutation status was no longer associated with residual tumor volume (OR, 0.63; 95% CI, 0.31-1.29; P = 0.21) while age remained a borderline significant predictor (10-year OR, 1.25; 95% CI, 1.01-1.56; P = 0.05). Both smaller residual tumor volume and mutant BRCA status were significantly associated with improved overall survival.

Conclusion

BRCA mutation status is not associated with the rate of optimal tumor debulking at primary surgery after accounting for differences in patient age. Improved survival of BRCA carriers is unlikely the result of better surgical outcomes but instead intrinsic tumor biology.     

Surgical cytoreduction in stage IV endometrioid endometrial carcinoma

Objective

To evaluate the role of surgical cytoreduction and the amount of residual disease in patients with newly diagnosed stage IV endometrioid endometrial carcinoma (EC).

Methods

Patients with stage IV EC of endometrioid histology who underwent surgery at our institution from 1977 to 2003 were identified. Patients with microscopic stage IV disease were excluded. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan Meier method and compared with log-rank test.

Results

A total of 58 patients were identified, of which 9 (15.5%) had no gross residual (NGR) after surgery, 11 (19.0%) had residual disease ≤ 1 cm, 32 (55.1%) had residual disease > 1 cm, and 6 (10.3%) had no cytoreduction attempted. The median PFS was 11.1 months (95% CI, 9.8-12.3) and the median OS was 19.2 months (95% CI, 8.5-29.9) for the cohort. The median PFS was 40.3 months (95% CI, 0-93.9) for patients with NGR disease, 11 months (95% CI, 9.9-12.1) for patients with any residual disease, and 2.2 months (95% CI, 0.1-4.2) for patients who did not have attempted cytoreduction (P < 0.001). The median OS was 42.2 months (95% CI, not estimable) for patients with NGR disease, 19 months (95% CI, 13.9-24.1) for patients with any residual disease, and 2.2 months (95% CI, 0.1-4.2) for patients that did not have attempted cytoreduction (P < 0.001).

Conclusion

Though stage IV endometrioid EC has a poor prognosis, surgical cytoreduction to no gross residual disease in a highly select group of patients is associated with improved survival.     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as upfront therapy for advanced epithelial ovarian cancer: multi-institutional phase-II trial

Objective.

The primary end-point of this multi-institutional phase-II trial was to assess results in terms of overall survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in treatment-naive epithelial ovarian cancer (EOC) with advanced peritoneal involvement. Secondary end-points were treatment morbi-mortality and outcome effects of time to subsequent adjuvant systemic chemotherapy (TTC).

Methods.

Twenty-six women with stage III-IV EOC were prospectively enrolled in 4 Italian centers to undergo CRS and closed-abdomen HIPEC with cisplatin and doxorubicin. Then they received systemic chemotherapy with carboplatin (AUC 6) and paclitaxel (175 mg/m²) for 6 cycles.

Results.

Macroscopically complete cytoreduction was achieved in 15 patients; only minimal residual disease (≤ 2.5 mm) remained in 11. Major complications occurred in four patients and postoperative death in one. After a median follow-up of 25 months, 5-year overall survival was 60.7% and 5-year progression-free survival 15.2% (median 30 months). Excluding operative death, all the patients underwent systemic chemotherapy at a median of 46 days from combined treatment (range: 29-75). The median number of cycles per patient was 6 (range: 1-8). The time to chemotherapy did not affect the OS or PFS.

Conclusions.

In selected patients with advanced stage EOC, upfront CRS and HIPEC provided promising results in terms of outcome. Morbidity was comparable to aggressive cytoreduction without HIPEC. Postoperative recovery delayed the initiation of adjuvant systemic chemotherapy but not sufficiently to impact negatively on survival. These data warrant further evaluation in a randomized clinical trial.     

Micropapillary pattern in serous borderline ovarian tumors: does it matter?

Objective

To evaluate the clinical and prognostic impact of micropapillary pattern in patients with serous borderline ovarian tumors (SBOT).

Methods

We retrospectively assessed 130 consecutive patients with typical (n = 97, 74.6%) or micropapillary (n = 33, 25.4%) SBOT. Clinicopathologic factors and outcomes were compared between these two groups.

Results

There were no significant between-group differences in age, menopausal status, parity, body mass index, cancer antigen 125 concentration, tumor size, tumor rupture, positive cytology, ovarian surface involvement, retrieved lymph nodes, use of laparoscopy, fertility-sparing and ovary-sparing procedures, complete staging and restaging, and adjuvant chemotherapy. However, the incidences of advanced stage (II-III) tumors (10.3% vs 36.4%, P = 0.001), microinvasion (2.1% vs 15.2%, P = 0.012), peritoneal implants (8.3% vs 33.4%, P < 0.001), and lymph node involvement (0% vs 21.2%, P < 0.001) were significantly higher in patients with micropapillary than with typical SBOT. Five patients with typical (5.2%) and three with micropapillary (9.1%) SBOT had recurrent disease (P = 0.418), and one patient (3%) in micropapillary SBOT group died due to the disease (P = 0.254). The 5-year disease-free survival (DFS) rates for patients with typical and micropapillary SBOT were 96% and 86%, respectively (P = 0.148). All three patients with micropapillary SBOT who had recurrence had peritoneal implants (one noninvasive and two invasive). Multivariate analysis showed that peritoneal implant was the only significant factor related to DFS (P = 0.002).

Conclusions

Because micropapillary SBOT was significantly associated with peritoneal implants, especially invasive implants, and lymph node involvement, complete staging procedures, including lymph node dissection, are recommended. However, micropapillary SBOT itself was not significantly associated with DFS. Peritoneal implant was the only factor independently associated with tumor recurrence.     

Surgical staging and adjuvant chemotherapy in the management of patients with adult granulosa cell tumors of the ovary

Objective

To analyze the role of surgical staging and adjuvant chemotherapy in patients with adult type granulosa cell tumor (GCT) of the ovary.

Methods

Patients were divided into those with early-stage (stages I-II, n = 93) and advanced-stage (stages III-IV, n = 13) GCT and analyzed separately in this retrospective study.

Results

Of the 93 patients with early-stage GCT, 30 were completely staged and 25 underwent lymph node dissection. After surgery, 17 patients received adjuvant chemotherapy with bleomycin/etoposide/cisplatin (BEP). None had lymph node metastasis. Completely staged patients had no recurrence or deaths. However, recurrences were observed in 9 of 63 patients (14.3%) who did not undergo complete staging, with four (6.3%) dying due to disease. The 5-year disease-free survival (DFS) rates of groups with and without complete staging were 100% and 84%, respectively (P = 0.037). Adjuvant chemotherapy was not significantly associated with DFS (P = 0.193). All patients with advanced-stage GCT underwent optimal cytoreduction and received adjuvant chemotherapy with BEP. None of the 6 patients who completed 6 cycles of BEP had recurrence, whereas 5 of the 7 patients (71.4%) who received fewer than 6 cycles of BEP had recurrences and 3 (42.9%) died due to disease. The 5-year DFS rates of these two groups were 100% and 50%, respectively (P = 0.022), with cycles of chemotherapy being the only significant factor for DFS in patients with advanced-stage GCT.

Conclusions

Complete surgical staging is recommended, but lymph node removal is not recommended for early-stage GCT. Optimal debulking followed by six cycles of BEP chemotherapy is recommended for advanced-stage GCT.     

Synchronous early-stage endometrial and ovarian cancer

Objective

To explore the clinicopathologic findings and oncological outcome of early-stage synchronous endometrial and ovarian malignancies.

Methods

A retrospective study of 93 women with synchronous stage I ovarian and stage I-II endometrial cancer treated between December 1981 and August 2005 in the gynecologic oncology department of San Gerardo Hospital, Italy.

Results

Fifty-one percent of the ovarian tumors were stage Ia and 71% of the endometrial cancers had minimal myometrial invasion. Endometrioid histology and grade 2 disease were prevalent in both sites. Hyperplasia and endometriosis coexisted in 71% and 22% of endometrial and ovarian cancers, respectively. The actuarial 5-year disease-free and overall survival rates were 83% and 96%, respectively.

Conclusion

The incidence of synchronous endometrial and ovarian cancer is not negligible, especially among young women. Synchronous cancers show very favorable pathologic features and have an excellent oncologic outcome. Adjuvant therapy should be tailored according to surgical staging and histology.     

HIPEC in recurrent ovarian cancer patients: morbidity-related treatment and long-term analysis of clinical outcome

Objective

To evaluate morbidity and mortality rates associated with the use of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) after optimal cytoreduction (CRS) in a large single-institutional series of platinum-sensitive recurrent ovarian cancer patients. Moreover, disease free (DFS) and overall survival (OS) of previously studied patients have been assessed after a longer follow-up period.

Method

From May 2005 to October 2010, recurrent ovarian cancer patients with a platinum-free interval of at least 6 months have been prospectively enrolled in a protocol of CRS plus HIPEC with oxaplatinum (460 mg/m²) heated to 41.5 °C for 30 min, followed by 6 cycles of systemic chemotherapy with taxotere 75 mg/m² and oxaliplatin 100 mg/m².

Results

Forty-one patients experienced 43 procedures (CRS + HIPEC). An optimal cytoreduction was achieved in all cases (CC-0 95.3%; CC-1 4.7%). A complication rate of 34.8% was registered, with no case of intraoperative death or within 30 days after surgery. Survival curves have been calculated in a group of 25 patients with a minimum follow-up of 18 months, obtaining a median DFS and OS of 24 (range 6-60) and 38 months (range 18-60), respectively.

Conclusion

In recurrent platinum-sensitive ovarian cancer patients, the use of CRS plus HIPEC represents a safe treatment, able to significantly influence the survival rates compared to chemotherapy alone or surgery plus standard chemotherapy.     

Prognostic determinants in patients with uterine and ovarian clear carcinoma

Objective

The purpose of this study is to analyze and compare the demographics, treatment, recurrence, and survival rates in patients with uterine clear cell carcinoma (UCCC) and ovarian clear cell carcinoma (OCCC).

Methods

A retrospective review of the Cancer Registry database was performed. All patients with UCCC and OCCC who underwent surgical staging at the two participating institutions, between January, 1995 and December, 2007, were identified. Categorical variables were evaluated by Chi square test. Survival estimates were plotted utilizing the Kaplan-Meier method.

Results

Analysis of 41 women with UCCC and 121 with OCCC was performed. In patients with OCCC, 48.4% had localized disease, 18.9% had regional spread, 31.1% had distant metastasis, and in 1.6% spread is unknown; compared to UCCC, 41.5% had localized disease, 12.2% regional spread, and 46.3% distant metastasis (p = 0.2). The median progression free survival was 31.4 months in women with UCCC, compared to 145 months in patients with OCCC (p = 0.04). UCCC women had a median overall survival of 39.5 months, compared to 155.8 months in patients with OCCC (p = 0.002). In the multivariate Cox regression model, age > 55 years old, tumor extension, optimal cytoreduction, and platinum-based chemotherapy were identified as independent predictors of overall survival. UCCC vs. OCCC was not associated with decreased overall survival in multivariate analysis.

Conclusion

OCCC and UCCC have the same rate of localized disease, regional spread and distant metastasis. After controlling for age, tumor extension, optimal cytoreduction, and platinum based chemotherapy, UCCC was not associated with decreased overall survival compared to OCCC.     

Video-assisted thoracic surgery (VATS) evaluation of intrathoracic disease in patients with FIGO III and IV stage ovarian cancer

Objectives

The aim of this study was to assess the influence of video-assisted thoracic surgery (VATS) on our treatment decisions in FIGO III and IV ovarian cancer patients.

Methods

Patients with ovarian cancer and suspected supra-diaphragmatic involvement (pleural effusions, pleural carcinomatosis, lung metastasis, or enlarged supra-diaphragmatic lymph nodes) at chest computer tomography (CT) scan underwent VATS with or without laparoscopy (LSC) to decide for primary cytoreduction or neoadjuvant chemotherapy. Operation time, VATS complications (intrapleural hematoma, secondary hemorrhage with intervention, pneumonia and empyema) and shift in the therapeutic strategy due to VATS were evaluated.

Results

17 patients were included into this study (1 patient with FIGO stage IIIb, 1 with IIIc and 15 with stage IV). The median operation time for VATS only was 46.5 min (range: 20-50 min, n = 3). Perioperatively, no complications occurred. After surgical staging, the tumor was confined to the abdomen in four patients in whom primary cytoreduction was attempted. All other 13 patients underwent neoadjuvant chemotherapy. VATS altered the therapeutic management in 6/17 ovarian cancer patients (3 times upstaging, 3 times downstaging). Negative predictive values (NPV) for local and diffuse pleural carcinomatosis ranged between 0.5 and 0.71.

Conclusion

In this case series, VATS in addition to LSC showed negligible morbidity related to surgery and a short operation time. We were able to improve the accuracy of the FIGO staging and assessed operability more reliably in these patients than through imaging techniques alone.     

Neoadjuvant chemotherapy in the Medicare cohort with advanced ovarian cancer

Objective

The value of neoadjuvant chemotherapy (NAC) for the treatment of advanced ovarian cancer has yet to be determined. While NAC may facilitate and simplify complete cytoreduction and reduce the risk of surgery, the delay of surgery related to NAC needs to be balanced against any potential benefit.

Methods

Surveillance, Epidemiology and End-Results (SEER) data linked to Medicare claims were used to identify 6844 women with treated stage III/IV epithelial ovarian cancer (1995-2005). Patients were classified by primary treatment (surgery (PDS) or chemotherapy), and the primary chemotherapy group was characterized as having NAC or palliative chemotherapy (PC) based on whether there was documentation that surgery was recommended. We compared surgical complications and survival between the groups.

Results

4827 (71%) of women were treated with PDS, 958 received NAC (14%) and 1059 (15%) had PC. Only 577 (60%) of women with NAC underwent surgery and they had fewer ostomies (8.5% vs. 19.2%, p < 0.001) and fewer infections, gastrointestinal and pulmonary complications than PDS (all p < 0.01). Comparing NAC to PDS there was a 16% increase in the risk of death at 2 years (RR 1.16, 95%CI 1.01-1.34) for women with stage III disease and a 15% reduction in the risk for women with stage IV disease (RR 0.85, 95%CI 0.73-0.99).

Conclusions

NAC followed by surgery was associated with fewer surgical complications than PDS. The direction and magnitude of the difference in survival between women receiving NAC and those receiving PDS differed according to the stage of disease and follow up time.     

Surgical staging of early stage epithelial ovarian cancer: results from the CDC-NPCR ovarian patterns of care study

Objectives

The objectives of this study were to determine the adequacy of surgical staging performed on surgically treated epithelial ovarian cancer (EOC) patients with apparent early stage disease and to determine if receipt of surgical staging had an influence on survival.

Methods

Detailed surgical staging information was collected from medical records for 721 patients diagnosed between 1998 and 2000 with EOC. Patients resided in California or New York and were identified through population-based cancer registries.

Results

Nearly 90% of patients had removal of the omentum and evaluation of bowel serosa and mesentery but only 72% had assessment of retroperitoneal lymph nodes and the majority of patients did not receive biopsies of other peritoneal locations. Only lymph node assessment (as well as node assessment combined with washings and omentectomy) had a statistically significant association with improved survival. The 5-year survival for women with node sampling was 84.2% versus 69.6% for those without this surgical procedure, and patients who did not have lymph node assessment had nearly twice the risk of death as those who did. When patients were stratified by receipt of chemotherapy, lack of node sampling had an effect only on patients who also had no chemotherapy (adjusted HR = 2.2, CI = 1.0-4.5).

Conclusions

The results of this population-based study confirm the prognostic importance of surgical staging for women with EOC, and the important role of gynecologic oncologists in treating these patients. Adjuvant chemotherapy does not appear to further improve survival for those women who receive adequate surgical staging.     

Progression-free and overall survival of a modified outpatient regimen of primary intravenous/intraperitoneal paclitaxel and intraperitoneal cisplatin in ovarian, fallopian tube, and primary peritoneal cancer

Objective

GOG study 172 demonstrated improved progression-free (PFS) and overall (OS) survival for patients with stage III optimally debulked ovarian and peritoneal carcinoma treated with IV/IP paclitaxel and IP cisplatin compared to standard IV therapy. The inpatient administration, toxicity profile, and limited completion rate have been blamed for the lack of acceptance and widespread use of this regimen. We sought to evaluate the PFS, OS, toxicity, and completion rate of a modified outpatient IP regimen.

Methods

Using a prospectively maintained database, we evaluated the outcomes of patients who underwent primary optimal cytoreduction for stage III ovarian, tubal, or peritoneal carcinoma followed by IV/IP chemotherapy from 1/05-3/09. Our modified regimen was as follows: IV paclitaxel (135 mg/m²) over 3 h on day 1, IP cisplatin (75 mg/m²) on day 2, and IP paclitaxel (60 mg/m²) on day 8, given every 21 days for 6 cycles.

Results

We identified 102 patients who initiated the modified IV/IP regimen and completed chemotherapy. The median follow-up was 43 months. The median age at diagnosis was 57 years (range, 23-76). Primary disease site was: ovary, 77 (75%); fallopian tube, 13 (13%); peritoneum, 12 (12%). FIGO stage was: IIIA, 8 (8%); IIIB, 4 (4%); IIIC, 90 (88%). Residual disease after cytoreduction was: none, 58 (57%); ≤ 1 cm, 44 (43%). The most frequent grade 3/4 toxicities were: neutropenia, 12 (12%); gastrointestinal, 8 (8%); neurologic, 6 (6%). Eighty-two (80%) of 102 patients completed 4 or more cycles of IV/IP therapy; 56 (55%) completed all 6 cycles. The median PFS and OS were 29 and 67 months, respectively.

Conclusions

By modifying the GOG 172 treatment regimen, convenience, toxicity, and tolerability appear improved, with survival outcomes similar to those of GOG 172. This modified IV/IP regimen warrants further study.     

Incidence of and risk factors for postoperative ileus in women undergoing primary staging and debulking for epithelial ovarian carcinoma

Objective

Thorough primary cytoreduction for epithelial ovarian carcinoma (EOC) improves survival. The incidence of postoperative ileus (POI) in these patients may be underreported because of varying POI definitions and the evolving, increasingly complex contemporary surgical approach to EOC. We sought to determine the current incidence of POI and its risk factors in women undergoing debulking and staging for EOC.

Methods

We retrospectively identified the records of women who underwent primary staging and cytoreduction for EOC between 2003 and 2008. POI was defined as a surgeon's diagnosis of POI, return to nothing-by-mouth status, or reinsertion of a nasogastric tube. Perioperative patient characteristics and process-of-care variables were analyzed. Univariate analyses were used to identify POI risk factors; variables with P ≤ .20 were included in multivariate analysis.

Results

Among 587 women identified, the overall incidence of POI was 30.3% (25.9% without bowel resection, 38.5% with bowel resection; P = .002). Preoperative thrombocytosis, involvement of bowel mesentery with carcinoma, and perioperative red blood cell transfusion were independently associated with increased POI. Postoperative ibuprofen use was associated with decreased POI risk. Women with POI had a longer length of stay (median, 11 vs 6 days) and increased time to recovery of the upper (7.5 vs 4 days) and lower (4 vs 3 days) gastrointestinal tract (P < .001 for each).

Conclusions

The rate of POI is substantial among women undergoing staging and cytoreduction for EOC and is associated with increased length of stay. Modifiable risk factors may include transfusion and postoperative ibuprofen use. Alternative interventions to decrease POI are needed.     

Radical surgical cytoreduction in the treatment of ovarian carcinosarcoma

Objective

Carcinosarcomas are rare and aggressive ovarian malignancies. Treatment recommendations, which include surgical cytoreduction followed by platinum based chemotherapy, have been based on small amounts of retrospective data or extrapolated from experience with high-grade epithelial ovarian adenocarcinoma. Our objective was to determine the effects of radical primary cytoreduction on progression-free survival (PFS) and overall survival (OS).

Methods

Following IRB approval, records of women with ovarian carcinosarcomas diagnosed between 2000 and 2012 at our institution were reviewed. Demographics, tumor characteristics, treatments, PFS, and OS were collected. Patients were divided into three groups based on the amount of residual disease: > 1 cm of disease, ≤ 1 cm of disease, or no visible disease. Chi-square and student's t-test were used to compare variables among groups. Kaplan–Meier survival curves were generated and compared with the log-rank test.

Results

51 patients with ovarian carcinosarcoma were identified and all underwent primary cytoreductive surgery. Following surgical cytoreduction, 18 patients (35%) had no visible disease, 20 (39%) had ≤ 1 cm of disease, and 13 (25%) had > 1 cm of residual disease. Median PFS varied significantly among groups: 29 vs. 21 vs. 2 months (p = 0.036) as did median OS: 57 vs. 32 vs. 11 months (p = 0.015). When patients with stage 3 disease were analyzed separately, median OS still varied significantly among groups: 57 versus 31 versus 3 months (p = 0.009).

Conclusion

Degree of surgical cytoreduction appears to correlate with PFS and OS. Radical surgery resulting in no visible disease is recommended for the upfront surgical treatment of ovarian carcinosarcoma.     

An analysis of patients with bulky advanced stage ovarian, tubal, and peritoneal carcinoma treated with primary debulking surgery (PDS) during an identical time period as the randomized EORTC-NCIC trial of PDS vs neoadjuvant chemotherapy (NACT)

Objective

The recent EORTC-NCIC randomized trial comparing primary debulking surgery (PDS) to neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian carcinoma (EOC) reported a median progression-free survival (PFS) of 12 months and overall survival (OS) of 30 months for both arms. Due to the equivalent survival and decreased morbidity with NACT, many now consider it the preferred approach. We analyzed the outcomes of patients treated with PDS at our institution during the same time period in which the EORTC-NCIC trial was conducted, using identical inclusion criteria.

Methods

We identified all patients undergoing primary treatment for advanced EOC at our institution from 9/98-12/06. Study inclusion and exclusion criteria were identical to those of the EORTC-NCIC trial. Standard statistical tests were used.

Results

Of 316 eligible patients, 285 (90%) underwent PDS and 31 (10%) received NACT due to extra-abdominal disease, medical comorbidities, and/or advanced age (> 85 years). Of the 285 patients who underwent PDS, most had carcinoma of ovarian origin (248, 87%); stage IIIC disease (249, 87%); grade 3 tumors (237, 83%); and serous histology (249, 87%). Optimal cytoreduction (≤ 1 cm residual) was achieved in 203 patients (71%). Postoperative platinum-based chemotherapy was given to 281 of 285 patients (99%). The median PFS and OS were 17 and 50 months, respectively.

Conclusion

PDS should continue to be the preferred initial management for patients with bulky stages IIIC-IV ovarian carcinoma. NACT should be reserved for those who cannot tolerate PDS and/or for whom optimal cytoreduction is not feasible.     

Defining the limits of radical cytoreductive surgery for ovarian cancer

Objective

Despite significant morbidity, surgical cytoreduction is the standard of care for ovarian cancer. We examined the outcomes of cytoreductive surgery to determine if there are groups of patients in which the morbidity is so substantial that alternate treatment strategies are warranted.

Methods

The Nationwide Inpatient Sample was used to identify women who underwent surgery for ovarian cancer from 1998 to 2007. The effect of age, number of radical procedures performed, and clinical characteristics on morbidity and mortality were examined.

Results

A total of 28,651 women were identified. The complication rates increased with age from 17.1% in those < 50 years of age to 29.7% in women age 70-79 and to 31.5% in those ≥ 80 (p < 0.05). The number of extended procedures performed was also a predictor of morbidity; complications increased from 20.4% for women with 0 procedures to 34.0% for 1 and 44.0% for ≥ 2 procedures (p < 0.0001). In multivariable analysis age, comorbidity, and the number of procedures performed were the strongest predictors of outcome. The morbidity associated with additional procedures was greatest in the elderly. Medical complications in women < 50 years of age occurred in 10.2% of those who underwent 0 radical procedures vs. 23.7% in those who underwent 2 or more procedures. For women ≥ 80 years, complications were noted in 18.3% for 0 procedures, and 33.3% for 2 or more procedures.

Conclusion

The morbidity of cytoreduction is greatest in elderly women where the effects of age and the number of radical procedures performed have an additive effect on complication rates.     

Beyond mere obesity: Effect of increasing obesity classifications on hysterectomy outcomes for uterine cancer/hyperplasia

Objective

To assess the impact of obesity severity on hysterectomy outcomes for uterine hyperplasia/cancer.

Methods

The data from women undergoing hysterectomies for endometrial hyperplasia/uterine cancer with a BMI ≥ 30 kg/m² were abstracted from records at the University of Virginia and Duke University following IRB approval. Univariate and multivariate statistical analyses were performed.

Results

Mean age of the 659 patients was 58.1 yrs; mean body mass index (BMI) was 43 kg/m². Women were grouped based on BMI: 39.6% (261) were obese (30-39 kg/m²), 41.7% (275) were morbidly obese (40-49 kg/m²) and 18.7% (123) were super obese (≥ 50 kg/m²). Minimally invasive surgical procedures (MIS) were attempted in 280 patients with a conversion rate of 16.1%; BMI was higher in the converted group (47.3 vs. 40.6 kg/m²; p < 0.001). As obesity group increased, there was a decreased frequency of lymphadenectomy (63.8% vs. 37.1% vs. 20.3%; p < 0.001), increased blood loss (242 vs. 281 vs. 378 mL; p < 0.001) and fewer nodes removed (p < 0.001). On multivariate analysis, type of surgery (open vs. MIS) and obesity classification were independently and significantly associated with wound complications (p < 0.001) and the presence of postoperative complications (p < 0.001, p = 0.003). Surgical staging with lymphadenectomy was significantly associated with obesity (p < 0.001) but not procedure type (p = 0.11). Blood transfusion (p < 0.001), hospital readmission (p = 0.025), and ileus (p < 0.001) were significantly associated with open procedures but not obesity. There were no significant differences in progression-free or disease-specific survival based on obesity group.

Conclusion

Women with BMI's exceeding 40 kg/m² have worse surgical outcomes than their less obese counterparts.