Practice patterns and complications of hysterectomy for invasive cervical cancer after the Laparoscopic Approach to Cervical Cancer trial.

BACKGROUND: After the publication of the Laparoscopic Approach to Cervical Cancer trial, the standard surgical approach for early-stage cervical cancer is open radical hysterectomy. Only limited data were available regarding whether the change to open abdominal hysterectomy observed after the Laparoscopic Approach to Cervical Cancer trial led to an increase in postoperative complication rates as a consequence of the decrease in the use of the minimally invasive approach. OBJECTIVE: This study aimed to analyze whether there was a correlation between the publication of the Laparoscopic Approach to Cervical Cancer trial and an increase in the 30-day complications associated with surgical treatment of invasive cervical cancer. STUDY DESIGN: Data from the American College of Surgeons National Surgical Quality Improvement Program were used to compare the results in the pre-Laparoscopic Approach to Cervical Cancer period (January 2016 to December 2017) vs the results in the post-Laparoscopic Approach to Cervical Cancer period (January 2019 to December 2020). The rates of each surgical approach (open abdominal or minimally invasive) hysterectomy for invasive cervical cancer during the 2 periods were assessed. Subsequently, 30-day major complication, minor complication, unplanned hospital readmission, and intra- or postoperative transfusion rates before and after the publication of the Laparoscopic Approach to Cervical Cancer trial were compared. RESULTS: Overall, 3024 patients undergoing either open abdominal hysterectomy or minimally invasive hysterectomy for invasive cervical cancer were included in the study. Of the patients, 1515 (50.1%) were treated in the pre-Laparoscopic Approach to Cervical Cancer period, and 1509 (49.9%) were treated in the post-Laparoscopic Approach to Cervical Cancer period. The rate of minimally invasive approaches decreased significantly from 75.6% (1145/1515) in the pre-Laparoscopic Approach to Cervical Cancer period to 41.1% (620/1509) in the post-Laparoscopic Approach to Cervical Cancer period, whereas the rate of open abdominal approach increased from 24.4% (370/1515) in the pre-Laparoscopic Approach to Cervical Cancer period to 58.9% (889/1509) in the post-Laparoscopic Approach to Cervical Cancer period (P<.001). The overall 30-day major complications remained stable between the pre-Laparoscopic Approach to Cervical Cancer period (85/1515 [5.6%]) and the post-Laparoscopic Approach to Cervical Cancer period (74/1509 [4.9%]) (adjusted odds ratio, 0.85; 95% confidence interval, 0.61-1.17). The overall 30-day minor complications were similar in the pre-Laparoscopic Approach to Cervical Cancer period (103/1515 [6.8%]) vs the post-Laparoscopic Approach to Cervical Cancer period (120/1509 [8.0%]) (adjusted odds ratio, 1.17; 95% confidence interval, 0.89-1.55). The unplanned hospital readmission rate remained stable during the pre-Laparoscopic Approach to Cervical Cancer period (7.9% per 30 person-days) and during the post-Laparoscopic Approach to Cervical Cancer period (6.3% per 30 person-days) (adjusted hazard ratio, 0.78; 95% confidence interval, 0.58-1.04)]. The intra- and postoperative transfusion rates increased significantly from 3.8% (58/1515) in the pre-Laparoscopic Approach to Cervical Cancer period to 6.7% (101/1509) in the post-Laparoscopic Approach to Cervical Cancer period (adjusted odds ratio, 1.79; 95% confidence interval, 1.27-2.53). CONCLUSION: This study observed a significant shift in the surgical approach for invasive cervical cancer after the publication of the Laparoscopic Approach to Cervical Cancer trial, with a reduction in the minimally invasive abdominal approach and an increase in the open abdominal approach. The change in surgical approach was not associated with an increase in the rate of 30-day major or minor complications and unplanned hospital readmission, although it was associated with an increase in the transfusion rate.

Impact of morcellation on survival outcomes of patients with unexpected uterine leiomyosarcoma: a systematic review and meta-analysis.

OBJECTIVE: To review the current evidence on the effects of intra-abdominal morcellation on survival outcomes of patients affected by unexpected uterine leiomyosarcoma (ULMS) and to estimate the risk of recurrence in those patients. METHODS: PubMed (MEDLINE), Scopus, Embase, Web of Science databases as well as ClinicalTrials.gov, were searched for data evaluating the effects of intra-abdominal morcellation on survival outcomes of patients with undiagnosed ULMS. Studies were evaluated per the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) and the American College of Obstetricians and Gynecologists (ACOG) guidelines. RESULTS: Sixty manuscripts were screened, 11 (18%) were selected and four (7%) were included. Overall, 202 patients were included: 75 (37%) patients had morcellation of ULMS, while 127 (63%) patients had not. A meta-analysis of these studies showed that morcellation increased the overall (62% vs. 39%; OR: 3.16 (95% CI: 1.38, 7.26)) and intra-abdominal (39% vs. 9%; OR: 4.11 (95% CI: 1.92, 8.81)) recurrence rates as well as death rate (48% vs. 29%; OR: 2.42 (95% CI: 1.19, 4.92)). No between-group difference in cumulative extra-abdominal recurrence (OR: 0.34 (95% CI: 0.07, 1.59)) rate was observed. CONCLUSIONS: Our data support a significant correlation between uterine morcellation and an increased risk of intra-abdominal recurrence in patients affected by unexpected ULMS. However, the limited data on this issue and the absence of high level of evidence suggest the need of further studies designed to estimate the risk to benefit ratio of morcellation in patients with uterine fibroids and undiagnosed ULMS.

Evaluation of perioperative management of advanced ovarian (tubal/peritoneal) cancer patients: a survey from MITO-MaNGO Groups.

OBJECTIVE: The European Society of Gynaecological Oncology (ESGO)-quality indicators (QIs) for advanced ovarian cancer (AOC) have been assessed only by few Italian centers, and data are not available on the proportion of centers reaching the score considered for a satisfactory surgical management. There is great consensus that the Enhanced Recovery After Surgery (ERAS) approach is beneficial, but there is paucity of data concerning its application in AOC. This survey was aimed at gathering detailed information on perioperative management of AOC patients within MITO-MaNGO Groups. METHODS: A 66-item questionnaire, covering ESGO-QIs for AOC and ERAS items, was sent to MITO/MaNGO centers reporting to operate >20 AOC/year. RESULTS: Thirty/34 questionnaires were analyzed. The median ESGO-QIs score was 31.5, with 50% of centers resulting with a score ≥32 which provides satisfactory surgical management. The rates of concordance with ERAS guidelines were 46.6%, 74.1%, and 60.7%, respectively, for pre-operative, intra-operative, and post-operative items. The proportion of overall agreement was 61.3%, and with strong recommendations was 63.1%. Pre-operative diet, fasting/bowel preparation, correction of anaemia, post-operative feeding and early mobilization were the most controversial. A significant positive correlation was found between ESGO-QIs score and adherence to ERAS recommendations. CONCLUSION: This survey reveals a satisfactory surgical management in only half of the centers, and an at least sufficient adherence to ERAS recommendations. Higher the ESGO-QIs score stronger the adherence to ERAS recommendations, underlining the correlations between case volume, appropriate peri-operative management and quality of surgery. The present study is a first step to build a structured platform for harmonization within MITO-MaNGO networks.

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<0.001), positive cytologic washings vs. negative (22.4% vs. 9.1%, p=0.012), ascites vs. no ascites (28.2% vs. 9.3%, p=0.002), serous vs. other histology (28% vs. 9%, p=0.001), grade 1 vs. grade 2 vs. grade 3 disease (2.7% vs. 1.9% vs. 23.2%, p<0.001), and preoperative CA 125 levels of >35 vs. ≤ 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.

Identification of patient groups at highest risk from traditional approach to ovarian cancer treatment.

OBJECTIVE: Define subgroups of patients at highest risk for major morbidity and mortality after a traditional approach of maximal surgical efforts followed by chemotherapy for advanced ovarian cancer (AOC). METHODS: Preoperative health, intra-operative findings and outcomes were assessed in consecutive patients with primary AOC from 4 centers. Initial tumor dissemination was stratified into 3 groups based on volume of disease. Surgery was categorized using a previously described surgical complexity score (SCS). Statistical analysis was directed toward validating a multivariable risk-adjusted model. RESULTS: 576 patients with stage IIIC (N=447, 77.6%) or IV AOC (N=129, 22.4%) were analyzed. Age (HR (per year): 1.02; 95%CI: 1.01-1.03), high tumor dissemination (HTD) (HR: 1.73; 95%CI: 1.19-2.56), residual disease (RD) >1 cm (HR: 2.46; 95%CI: 1.74-3.53), and stage IV (HR: 1.93; 95% CI: 1.51-2.45), independently correlated with OS. We identified a small subgroup of patients who comprised a high-risk group (N=38, 6.6%) characterized by all of the following characteristics: high initial tumor dissemination (HTD) or stage IV plus poor performance or nutritional status plus age ≥ 75. In this group, high SCS to achieve low RD was associated with morbidity of 63.6% and limited survival benefit. CONCLUSIONS: Optimal management of AOC requires accurate, risk-adjusted predictors of outcomes allowing a tailored approach starting with primary therapy. Complex surgical procedures to render low RD improve survival, and in the majority of cases, the benefits of such surgery appear to outweigh the morbidity. However careful analysis identifies a subgroup of patients in whom an alternative approach may be the better strategy.

Management of ovarian cancer: guidelines of the Italian Medical Oncology Association (AIOM).

INTRODUCTION: Ovarian cancer is the most lethal gynecologic malignancy. Over 5200 new cases of this tumor are diagnosed yearly in Italy, resulting in more than 3600 deaths. In terms of molecular biology, five different ovarian cancer subtypes should be distinguished. METHOD: This article summarizes the evidence-based guidelines that the Italian Medical Oncology Association (AIOM) has developed with a multidisciplinary panel of experts, including pathologists, gynecologic oncologists, medical oncologists, and radiotherapists, with the support of methodologists, to help clinicians involved in the management of patients with ovarian cancer in their daily clinical practice. RESULTS: The most relevant randomized clinical trials regarding surgery, chemotherapy, and molecularly targeted agents (bevacizumab and PARP inhibitors) in early, advanced, and recurrent disease have been critically analyzed. The levels of evidence and strength of recommendation have been reported for any issue. CONCLUSION: Women with a clinical suspicion of ovarian cancer should be centralized in referral centers. The BRCA test should be requested for all women with nonmucinous and nonborderline tumors, regardless of age and family history. BRCA testing could be preferentially performed on neoplastic tissue. In the presence of a positive tumor test, a genetic test should always be performed on a blood sample to differentiate between germline mutations, which require counseling and genetic testing of family members, and somatic mutations.

Role of maximal primary cytoreductive surgery in patients with advanced epithelial ovarian and tubal cancer: Surgical and oncological outcomes. Single institution experience.

OBJECTIVE: To determinate the impact of maximal cytoreductive surgery on progression free survival (PFS), overall survival (OS) rates and morbidity, in patients with advanced epithelial ovarian or fallopian tube cancer. METHODS: We reviewed all medical records of patients with stages IIIC-IV epithelial ovarian and fallopian tube cancer that were managed at our institution between January 2001 and December 2008. The following information was collected: demographics, tumor characteristics, operative information, surgical outcomes and peri-operative complication. RESULTS: A total of 288 patients with advanced epithelial ovarian and fallopian tube cancer were referred to our institution between January 2001 and December 2008, 259 consecutive patients were enrolled in the study. After a median follow-up of 29.8 months, the PFS and OS were 19.9 and 57.6 months, respectively. At univariate analysis, factors significantly associated with decreased PFS included: age greater than median (>60 years), stage IV, presence of ascites >1000 cc, presence of diffuse peritoneal carcinomatosis and diameter of residual disease. This was confirmed also at multivariate analysis with age greater than 60 years (P=0.025), stage IV vs IIIC (P=0.037) and any residual disease (P=0.032) having an independent association with worse PFS. CONCLUSIONS: Our study seems to demonstrate that a more extensive surgical approach is associated with prolonged disease-free interval and improved survival in patients with stages IIIC-IV epithelial ovarian and fallopian tube cancer. Moreover all patients with no residual tumor seem to have the best prognosis and in view of these results we believe that the goal of primary surgery should be considered as leaving no macroscopic disease.

Improving quality of care: development of a risk-adjusted perioperative morbidity model for vaginal hysterectomy.

OBJECTIVE: We sought to develop and evaluate a risk-adjusted perioperative morbidity model for vaginal hysterectomy. STUDY DESIGN: Medical records of women who underwent vaginal hysterectomy during 2004 and 2005 were retrospectively reviewed. Morbidity included hospital readmission, reoperation, and unplanned medical intervention or intensive care unit admission; urinary tract infections were excluded. Multivariate logistic regression identified factors associated with perioperative morbidity (adjusted for urinary tract infection). The resulting model was validated using a random 2006 sample. RESULTS: Of 712 patients, 139 (19.5%) had morbidity associated with congestive heart failure or prior myocardial infarction, perioperative hemoglobin decrease >3.1 g/dL, preoperative hemoglobin <12.0 g/dL, and prior thrombosis (c-index = 0.68). Predicted morbidity was similar to observed rates in the validation sample. CONCLUSION: History of congestive heart failure or myocardial infarction, prior thrombosis, perioperative hemoglobin decrease >3.1 g/dL, or preoperative hemoglobin <12.0 g/dL were associated with increased perioperative complications. Quality improvement efforts should modify these variables to optimize outcomes.

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.

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 chi 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. LEVEL OF EVIDENCE: III.

Stage IV ovarian cancer: disease site-specific rationale for postoperative treatment.

OBJECTIVES: We aimed to define the site-specific patterns of treatment failure in stage IV ovarian cancer. METHODS: Data from all consecutive Mayo Clinic patients with stage IV epithelial ovarian cancer, from 1994 through 2003, were collected and analyzed. Statistical analyses included the chi(2) test and Kaplan-Meier curves with log-rank tests. RESULTS: Review of our patient database identified 109 patients with stage IV ovarian cancer: mean age, 62 years (range, 36-83 years); 5-year overall survival, 15%. Most patients (74%) had intraperitoneal disease at the time of relapse, 36% had pleural effusion, and 49% had extraperitoneal metastases. At the time of death 75% had intraperitoneal localizations, 51% had pleural effusion, and 46% had extraperitoneal metastases. Patients with pleural effusion were more likely to have pleural disease at relapse and at last follow-up. Extrapleural disease at the time of diagnosis predicted extrapleural disease at relapse and at last follow-up. Most patients classified as having stage IV disease by pleural cytology only, as opposed to all other patients, had intraperitoneal disease at relapse (88% vs 58.7%, P=.001) and last follow-up (88.5% vs 59.6%, P=.001). Patients having stage IV disease by pleural cytology only had survival benefit when disease was optimally debulked in the abdomen and pelvis (median survival, 3.1 years vs 1.3 years; P=.001). Patients with multiple unresectable liver metastases had poor prognosis (median survival, 1.2 years) owing to progression of liver disease. CONCLUSIONS: Clinical trials for stage IV ovarian cancer should reflect the site-specific risks for recurrence according to disease location at diagnosis.

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.

Aggressive and complex surgery for advanced ovarian cancer: an economic analysis.

INTRODUCTION: In an initial cohort we demonstrated that aggressive surgery correlates with improved survival in patients with advanced ovarian cancer yet the economic implications of maximal surgical efforts are unknown. OBJECTIVE: To evaluate inpatient costs, survival, and cost-effectiveness of alternative primary surgical approaches among advanced ovarian cancer patients. METHODS: All patients with a diagnosis of stage IIIC-IV ovarian cancer between 1994 and 2003 were identified and classified by surgical complexity score (SCS) (1=simple, 2=intermediate, and 3=complex). We used clinical and administrative data to estimate costs associated with inpatient stay, survival, and the 5-year cost-effectiveness of complex vs. simple surgery measured in costs per life-year gained. RESULTS: 486 consecutive patients were identified of whom 28%, 50%, and 22% were classified as SCS 1, 2, and 3, respectively. Kaplan-Meier estimated survival differed by SCS group (p<0.001) with an average survival gain of 1.32 years with complex vs. simple surgery (SCS group 3 vs. 1). Inpatient costs significantly differed between SCS groups (mean costs SCS 1: $21,914; SCS 2: $27,408; SCS 3: $33,678; p<0.001). Analyses suggest incremental cost-effectiveness ratios of $4950 and $8912 per life-year gained, comparing SCS groups 2 vs. 1 and 3 vs. 1 respectively. CONCLUSIONS: Complex surgery for ovarian cancer cytoreduction carries a survival benefit at increased direct medical cost. However, preliminary cost-effectiveness results suggest complex surgery provides good value for money spent. Future research on the cost and quality of life implications of surgical morbidity during follow-up is warranted to formally assess the cost-effectiveness of complex vs. simple surgical procedures.

Pattern of retroperitoneal dissemination of primary peritoneum cancer: basis for rational use of lymphadenectomy.

INTRODUCTION: The rationale for lymphadenectomy in primary peritoneal cancer (PPC) is unclear. We sought to define the pattern of lymphatic metastasis in PPC and propose evidence-based rationale for lymphadenectomy in relevant cases. METHODS: Patients with PPC undergoing primary surgery at Mayo Clinic were identified. Demographics, tumor characteristics, procedures performed and follow up were analyzed. RESULTS: Forty eight patients with PPC were identified; 39 had stage IIIC (81.2%) and 9 (18.8%) had stage IV. Residual disease (RD) after primary surgery was microscopic in 6 cases (12.5%), less than 1 cm in 33 (68.8%), more than 1 cm in 9 patient (18.7%) with median survivals of 5.8, 3.2 and 1.3 years, respectively. Overall, 24 patients had lymphadenectomy performed (pelvic (PND) or paraortic (PAND) or both). Pelvic nodes were involved in 12/23 (52.7%) cases, while para-aortic nodes were involved in 5/21 (23.8%) of cases. The rate of simultaneously positive pelvic and para-aortic nodes was 20% (4/20). Nodal involvement was a poor prognostic factor with 5 year overall survival 63% vs. 25% (p=0.014) in node positive vs. negative cases. Compared to patients with primary ovarian cancer (OC), OC cases had a higher rate of positive para-aortic nodes (57.6%: 77/132; p=0.004). CONCLUSIONS: Retroperitoneal lymph nodes are a common site of metastases in PPC, therefore it is logically consistent to perform PND and PAND if a patient can be cytoreduced to microscopic RD in other sites or remove grossly positive nodes in patients with RD<1 cm.

Current management strategies for ovarian cancer.

Epithelial ovarian cancer originates in the layer of cells that covers the surface of the ovaries. The disease spreads readily throughout the peritoneal cavity and to the lymphatics, often before causing symptoms. Of the cancers unique to women, ovarian cancer has the highest mortality rate. Most women are diagnosed as having advanced stage disease, and efforts to develop new screening approaches for ovarian cancer are a high priority. Optimal treatment of ovarian cancer begins with optimal cytoreductive surgery followed by combination chemotherapy. Ovarian cancer, even in advanced stages, is sensitive to a variety of chemotherapeutics. Although improved chemotherapy has increased 5-year survival rates, overall survival gains have been limited because of our inability to eradicate all disease. Technologic advances that allow us to examine the molecular machinery that drives ovarian cancer cells have helped to identify numerous therapeutic targets within these cells. In this review, we provide an overview of ovarian cancer with particular emphasis on recent advances in operative management and systemic therapies.

How relevant are ACOG and SGO guidelines for referral of adnexal mass?

OBJECTIVE: To evaluate referral guidelines published by American College of Obstetricians and Gynecologists (ACOG) and Society of Gynecologic Oncologists (SGO), which provide guidance about when to refer a patient with a pelvic mass to a gynecologic oncologist. METHODS: Data from consecutive patients evaluated for pelvic mass were collected prospectively over a 5-year period. The performance characteristics of the ACOG/SGO referral guidelines for detection of primary and metastatic ovarian cancer were calculated by using menopausal status, CA 125 level, imaging results, physical findings, and family history. RESULTS: Eight hundred thirty-seven patients met inclusion criteria. Forty-four percent (263/597) of postmenopausal women were diagnosed with ovarian cancer, whereas 20% (48/240) of premenopausal women had ovarian cancer. Seventy-four percent of primary cancers were stage III or IV. The referral guidelines were 79.2% sensitive and 69.8% specific for premenopausal women, with a positive predictive value of 39.6%. For postmenopausal women, the guidelines were 93.2% sensitive and 59.9% specific, and positive predictive value was 64.6%. The referral guidelines performed better for late-stage than early-stage cancers in both sensitivity and positive predictive value, especially in postmenopausal women. Although only 28 patients would not have been referred by the guidelines, the majority of these had early stage (I or II) disease. Lowering the CA 125 cutoff level required for referral of premenopausal patients increased the sensitivity of the guidelines in this group. CONCLUSION: The ACOG/SGO guidelines perform well in predicting advanced-stage ovarian cancer, probably owing to the nature of advanced-stage disease. The guidelines perform poorly in identifying early-stage disease, especially in premenopausal women, primarily due to lack of early markers and signs of ovarian cancer.

Relationship among surgical complexity, short-term morbidity, and overall survival in primary surgery for advanced ovarian cancer.

BACKGROUND: Advanced ovarian cancer (OC) is associated with impaired performance status and comorbidities for many patients. These factors have an impact on the decision to perform extended surgical cytoreduction. However, the trade-off between short-term morbidity and overall survival is complex, and few data are available analyzing the combined effects of these variables. PURPOSE: The purpose of the study was to evaluate the impact of patients' age and American Society of Anesthesiologists (ASA) and surgical complexity score (SCS) on short-term morbidity and overall survival. STUDY DESIGN: Presurgical patient characteristics, surgical procedures performed, and outcomes were assessed in a cohort of consecutive primary OC patients. An SCS from 1 to 3 was developed to adjust for the extent of surgery (simple to complex, respectively). Primary outcomes were 30 day major morbidity (sepsis, thromboembolic, cardiac, or reoperation), 3 month mortality, and overall survival (OS). RESULTS: Two hundred nineteen consecutive patients with stage IIIC-IV OC were included. We observed a correlation between ASA and both short-term morbidity (P = .006) and 3 month mortality (P = .006). Age was independently associated with both short-term morbidity (P = .010) and 3 month mortality (P = .005). SCS correlated directly with morbidity (P < .001) but was not correlated with mortality (P = .266). The independent predictors of morbidity (ASA, age, and SCS) were used to develop risk prediction categories: risk of expected complications ranged from 2.5% to 67.6%, depending on category. Despite the increased risk of complications, however, more complex surgery carried a survival benefit in all the risk groups, owing to the observation that residual disease (RD) and SCS held a prognostic significance independent of age and ASA (P < .001 and P = .001, respectively). CONCLUSION: Because of the survival benefit from lower RD, a less aggressive surgical effort results in poorer OS. However, the risk of complications are substantial for complex surgeries in the highest-risk patients: risk stratification should be used to help plan perioperative care and consider optimal treatment planning.

Quality control in ovarian cancer surgery.

The optimal surgical management of patients with ovarian cancer includes a thorough staging with peritoneal and retroperitoneal assessment for early disease stages and a complete debulking with the removal of all macroscopic tumor for advanced disease stages. Disparities across different institutions in terms of optimal surgical management have been described. Surgical quality control programs constitute a real possibility to ensure and improve the quality of the surgery performed. Guidelines for surgery in early and advanced disease stages have been recently reviewed by the National Comprehensive Cancer Network (NCCN), and several quality indicators (QIs) have been proposed. These QIs can be used as a powerful tool to monitor, compare, and improve the quality of surgery across different centers and institutions. Furthermore, a transparent report of surgical outcomes through the creation of National and International Networks, adherence to the NCCN guidelines, and the establishment of quality control programs with a strong training and education component are key factors in enhancing the quality of surgery for patients with ovarian cancer.