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.

Evidence-based wound classification for vulvar surgery: Implications for risk adjustment.

OBJECTIVES: The correct wound classification for vulvar procedures (VP) is ambiguous according to current definitions, and infection rates are poorly described. We aimed to analyze rates of surgical site infection (SSI) in women who underwent VP to correctly categorize wound classification. METHODS: Patients who underwent VP for dysplasia or carcinoma were collected from the National Surgical Quality Improvement Program database (NSQIP). SSI rates of vulvar cases were compared to patients who underwent abdominal hysterectomy via laparotomy, stratified by the National Academy of Sciences wound classification. Descriptive analyses and trend tests of categorical variables were performed. RESULTS: Between 2008 and 2016, 2116 and 31,506 patients underwent a VP or TAH, respectively. Among VP, 1345 (63.6%), 364 (17.2%), and 407 (19.2%) women underwent simple vulvectomy, radical vulvectomy, or radical vulvectomy with lymphadenectomy, respectively. The overall rate of SSI for VP was higher than that observed for TAH (5.6% vs. 3.8%; p < 0.0001). While patients undergoing TAH displayed a corresponding increase in the rate of SSI with wound type (type I: 3.4%; type II: 3.8%, type III: 6.8%; type IV 10.6%; p < 0.001), no such correlation was observed for simple VP (type I: 3.3%, type II: 3.0%; type III: 3.2%; type IV: 0%; p = 0.40). On the other hand, a non-significant correlation was observed for radical VP (type I: 4.0%, type II: 10.1%; type III: 14.3%; type IV: 20.0%; p = 0.08). The overall rate of SSI in patients undergoing any radical VP was similar to patients undergoing hysterectomy with a type IV wound (10.1% vs 10.6%, p = 0.87). CONCLUSION: Patients undergoing VP are at high risk of infection. Simple vulvectomy should be classified as a type II and radical vulvectomy as a type III wound. These recommendations are important for proper risk adjustment.

Prediction of short-term surgical complications in women undergoing pelvic exenteration for gynecological malignancies.

OBJECTIVE: Pelvic exenteration (PE) is an extensive surgery associated with high rates of postoperative morbidity and mortality. The absence of well-defined preoperative selection criteria to identify patients eligible for PE prompted the assessment of pre-operative predictors of 30-day major surgical complications. METHODS: Demographics and surgical characteristics of patients undergoing PE for gynecologic cancer in a single institution between 01/2004-12/2016 were reviewed. Postoperative complications within 30 days following surgery were graded using the Accordion grading system. Logistic regression was used to analyze potential risk factors for severe postoperative complications. RESULTS: A total of 138 patients were included in the cohort. Forty-five patients underwent total PE, 52 anterior PE, and 41 posterior PE. Among the 137 patients with follow-up, a severe postoperative complication was experienced by 37 patients (27.0%) and 3 patients (2.2%) experienced death within 90 days. The most frequent grade 3 complications were complications of urinary reconstruction (n = 15), wound dehiscence (n = 9), and abdominal abscess requiring intervention with drain or return to the operating room (n = 6). On multivariable analysis, independent predictors of severe postoperative complications were anterior or total PE (adjusted odds ratio (aOR): 11.66, 95% CI 2.56-53.18), pre-operative hemoglobin ≤10 mg/dl (aOR 2.70, 95% CI 1.02-7.14) and presence of 3+ comorbidities (aOR: 2.76, 95% CI 1.07-7.10). CONCLUSIONS: Major complications after exenteration are common. Surgical complexity and patient selection play a considerable role in predicting complications. These data can be used to better risk stratify patients undergoing PE.

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.

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.

Management of endometrial cancer: issues and controversies.

Although endometrial cancer (EC) is the most common gynecologic cancer in developed countries, several aspects of its management are still controversial. In particular, the need to perform lymphadenectomy represents an important matter of discussion. Because of the discordant results in the literature, it is still not possible to draft any definitive conclusions regarding the therapeutic value of lymph node dissection. The present review discusses the role of lymphadenectomy in the setting of EC, risk factors for lymphatic spread, identification of patients at risk for lymph node dissemination, and the current evidence for adjuvant therapies in patients with positive nodes. Reasons for the difficulty in demonstrating any therapeutic value of pelvic and para-aortic lymphadenectomy are also discussed.

Intake of coffee, caffeine and other methylxanthines and risk of Type I vs Type II endometrial cancer.

BACKGROUND: Coffee and other sources of methylxanthines and risk of Type I vs Type II endometrial cancer (EC) have not been evaluated previously. METHODS: Prospective cohort of 23,356 postmenopausal women with 471 Type I and 71 Type II EC cases. RESULTS: Type I EC was statistically significantly associated with caffeinated (relative risk (RR)=0.65 for 4+ cups per day vs ≤1 cup per month: 95% confidence interval (CI): 0.47-0.89) but not decaffeinated (RR=0.76; 95% CI: 0.50-1.15) coffee intake; there were no associations with tea, cola or chocolate, or for Type II EC. The inverse association with caffeinated coffee intake was specific to women with a body mass index 30+ kg m(-2) (RR=0.56; 95% CI: 0.36-0.89). CONCLUSION: Coffee may protect against Type I EC in obese postmenopausal women.

Risk factors that mitigate the role of paraaortic lymphadenectomy in uterine endometrioid cancer.

OBJECTIVE: Paraaortic lymph node (PA) dissemination in endometrial cancer (EC) is uncommon and a systematic infrarenal PA dissection carries morbidity. Our objective was to identify a subgroup of EC patients who may potentially forego PA lymphadenectomy (LND). METHODS: The study endpoint (PA Metastasis or Recurrence; PAMR) was defined as detection of metastasis to PA nodes (among those with any type of PA LND) or PA recurrence within 2 years (among patients without PA LND or those with negative nodes in the context of an inadequate (<5 nodes) PA LND). Patients with non-endometrioid histology, stage IV disease, synchronous cancers, gross extrauterine or gross adnexal disease, neoadjuvant therapy, or insufficient follow-up were excluded. Multivariable logistic regression analysis identified predictors of PAMR. RESULTS: Of the 946 patients, PAMR was observed in 4% (36/946). Multivariable analysis identified positive pelvic nodes (odds ratio (OR) 24.2; p<0.001), >50% MI (OR 5.3; p<0.001) and lymphovascular space invasion (LVSI) (OR 3.7; p=0.005) as the only three independent predictors of PAMR. When all three factors were absent (77% of study cohort), the predicted probability of PAMR was 0.6%. If intraoperative frozen section is not available on pelvic lymph nodes and LVSI, omitting PA LND in all patients with ≤ 50% MI would affect 84% (792/946) of the total cohort, with a 1.1% risk of PAMR (9/792). CONCLUSION: The majority of patients with endometrioid EC may potentially forgo PA LND with expected reductions in surgical morbidity and cost. This cohort may be identified by a combined absence of: positive pelvic nodes, >50% MI and LVSI.

Risk-scoring system for the individualized prediction of lymphatic dissemination in patients with endometrioid endometrial cancer.

OBJECTIVE: To develop a risk-scoring system (RSS) for the prediction of lymphatic dissemination after hysterectomy in endometrioid endometrial carcinoma (EC). METHODS: Patients who underwent surgery from 1/1/1999-12/31/2008 were evaluated. Patients with non-endometrioid histology, stage IV with macroscopic extrauterine disease, or receiving adjuvant therapy (excluding brachytherapy) without pelvic and/or paraaortic (P/PA) lymphadenectomy (LND) were excluded. Lymph node dissemination was defined as nodal metastasis when P/PA LND was performed or P/PA lymph node recurrence after negative LND or when LND was not performed. Logistic regression analysis was used to identify predictors for lymphatic dissemination and develop a RSS and nomogram. The RSS was assessed for calibration and verified for discrimination. RESULTS: Overall, 883 patients were assessed of which 521 (59.0%) underwent P/PA LND and 57 (10.9%) had positive lymph nodes. Of patients who did not undergo P/PA LND (N=362) or had negative nodes (N=464), 10 (1.2%) patients had P/PA lymph node recurrence. Myometrial invasion, tumor diameter (TD), FIGO grade, cervical stromal invasion and lymphovascular space invasion were significant on univariable analysis. All preceding variables were included in a multivariable logistic model. A parsimonious model and an alternative full model not including TD were considered. The full model with TD (illustrated in nomogram) had the highest predictive ability (concordance index 0.88). CONCLUSION: Our RSS allows accurate quantification of the probability of lymphatic dissemination and can be used as an adjunct to clinical decision-making after hysterectomy in the absence of staging. TD is an important component of the RSS and should be routinely assessed.

Identification and evaluation of a potent novel ATR inhibitor, NU6027, in breast and ovarian cancer cell lines.

BACKGROUND: The ataxia telangiectasia mutated and Rad3-related kinase (ATR) has a key role in the signalling of stalled replication forks and DNA damage to cell cycle checkpoints and DNA repair. It has long been recognised as an important target for cancer therapy but inhibitors have proved elusive. As NU6027, originally developed as a CDK2 inhibitor, potentiated cisplatin in a CDK2-independent manner we postulated that it may inhibit ATR. METHODS: Cellular ATR kinase activity was determined by CHK1 phosphorylation in human fibroblasts with inducible dominant-negative ATR-kinase dead expression and human breast cancer MCF7 cells. Cell cycle effects and chemo- and radiopotentiation by NU6027 were determined in MCF7 cells and the role of mismatch repair and p53 was determined in isogenically matched ovarian cancer A2780 cells. RESULTS: NU6027 is a potent inhibitor of cellular ATR activity (IC(50)=6.7 µM) and enhanced hydroxyurea and cisplatin cytotoxicity in an ATR-dependent manner. NU6027 attenuated G2/M arrest following DNA damage, inhibited RAD51 focus formation and increased the cytotoxicity of the major classes of DNA-damaging anticancer cytotoxic therapy but not the antimitotic, paclitaxel. In A2780 cells sensitisation to cisplatin was greatest in cells with functional p53 and mismatch repair (MMR) and sensitisation to temozolomide was greatest in p53 mutant cells with functional MMR. Importantly, NU6027 was synthetically lethal when DNA single-strand break repair is impaired either through poly(ADP-ribose) polymerase (PARP) inhibition or defects in XRCC1. CONCLUSION: NU6027 inhibits ATR, impairing G2/M arrest and homologous recombination thus increasing sensitivity to DNA-damaging agents and PARP inhibitors. It provides proof of concept data for clinical development of ATR inhibitors.

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.

From randomized trial to practice: single institution experience using the GOG 172 i.p. chemotherapy regimen for ovarian cancer.

BACKGROUND: The objective of the study was to evaluate completion rates and toxic effects of an i.p. chemotherapy regimen in a cross-section of nonselected patients with ovarian cancer (OC). PATIENTS AND METHODS: All patients with stage IIIC OC consecutively operated at our institution from January 2006 to December 2007 were prospectively collected and analyzed. RESULTS: Eighty-nine patients with stage IIIC OC optimally debulked were evaluated for this study. An i.p. port was primarily placed in 53 of 89 (60%), and i.p. chemotherapy was recommended in 55 patients. Reasons for not recommending i.p. chemotherapy in patients optimally debulked included postoperative complications (n = 7: 8%), poor nutritional/functional status (n = 5: 6%), and extensive surgery including bowel resection (n = 9: 10%). Thirty-three patients (33/55: 60%) recommended to receive i.p. chemotherapy-initiated i.p. treatment. Fifty-two percent of those beginning i.p. therapy (17/33) received three or more cycles with 36% (12/33) successfully completing six cycles. Reasons for discontinuation included grade 3-4 nephrotoxicity in 3 of 21 (14%), febrile neutropenia/sepsis in 3 of 21 (14%), port infection or malfunction in 8 of 21 (38%). CONCLUSIONS: The i.p. chemotherapy regimen used in a consecutive cohort of patients carries could be completed in only a small percentage of patients. Less toxic regimens with higher acceptability should be considered.

Comparison of loss of heterozygosity patterns in invasive low-grade and high-grade epithelial ovarian carcinomas.

Loss of heterozygosity (LOH) studies were performed to investigate the genetic differences which separate low-grade (LG), high-grade (HG), and borderline epithelial ovarian carcinomas. Fresh tumor samples and blood were obtained from 58 patients (20 LG, 34 HG, and 4 borderline tumor specimens) undergoing surgery for ovarian carcinoma at Mayo Clinic. Tumors were graded using a modified Broder's classification with invasive grades 1 and 2 considered LG, invasive grades 3 and 4 considered HG, and tumors with no evidence of stromal invasion classified as borderline. Polymorphism analysis was performed using 76 restriction fragment length polymorphisms and variable number of tandem repeats and 59 microsatellite markers representing all chromosome arms. Chromosome arms 6p, 17p, 17q, and 22q were found to be frequently lost in LG as well as HG tumors. Chromosome arms 13q and 15q were lost to a significantly greater extent in HG tumors compared to LG neoplasms (P = 0.003 and P = 0.08, respectively). Conversely, 3p loss was seen more frequently with LG tumors (P = 0.02). The majority of LG tumors (65%) did not show frequent LOH in the allelotype analysis. In fact, a subset of 7 (7 of 20) LG tumors accounted for 76% of the total allelic loss in the LG category. These tumors showed LOH almost identical to that of the HG neoplasms. Borderline tumors showed a low rate of allelic loss. There were no common events found between borderline and invasive tumors. Our data suggest that most HG tumors and a subset of LG tumors share genetic alterations at putative tumor suppressor genes detected by LOH studies. Chromosome 6 and 17 losses appear to be early events while 13q and 15q losses appear to be critical late events. However, a majority of LG tumors appear to develop as a consequence of an alternative mechanism(s) which is not detected by LOH studies. Possibilities include: (a) inactivation of tumor suppressor genes without LOH; (b) dominant negative gene(s) in which only one allele requires mutation; and (c) changes in dominant acting oncogenes. This unidentified phenomenon may be operative in borderline tumors as well.

Evidence of functional RB protein in epithelial ovarian carcinomas despite loss of heterozygosity at the RB locus.

The presence of retinoblastoma (RB) protein was evaluated by immunohistochemical staining and correlated with loss of heterozygosity (LOH) at the RB locus in 52 primary epithelial ovarian carcinomas. Forty-eight tumors were informative at the RB locus by molecular genetic analysis. Twenty-five tumors (52%) showed loss of heterozygosity at the RB locus. RB protein expression was found in 23 of these tumors. The remaining two tumors were negative for RB protein product by immunohistochemical staining. All 23 tumors showing no LOH at the RB locus had a normal RB protein pattern. All but three tumors revealed either no LOH with any marker or, if LOH was found for one chromosome 13 marker, all other informative markers also showed LOH. The three recombinant tumors included two which retained alleles at one or more loci distal and one which retained alleles proximal to the RB locus. LOH at the RB locus was significantly more common in invasive high-grade (grades 3 and 4) tumors as compared to invasive low-grade (grades 1 and 2) tumors (P < 0.001). Our data suggest that while molecular genetic studies reveal frequent LOH at the RB locus, particularly in high-grade tumors, normal RB protein expression is present in the majority (96%) of these tumors. This implies that another, unidentified, gene or genes located on chromosome 13 may be important in the progression of most epithelial ovarian carcinomas. Additionally, it is likely that the specific chromosome 13 alteration(s) associated with sporadic ovarian neoplasms will be extremely difficult to identify using allelic loss and deletion mapping studies.

Overexpression of p34cdc2 protein kinase in epithelial ovarian carcinoma.

OBJECTIVE: To investigate the role of expression of p34cdc2 protein kinase in normal, benign, and malignant ovarian epithelium. MATERIAL AND METHODS: Tissue sections from 24 patients with epithelial ovarian carcinoma (EOC) along with 6 normal ovarian specimens and 12 benign cystadenomas were incubated with mouse IgG monoclonal antibody to human p34cdc2 protein kinase, followed by detection with use of a standard peroxidase-labeled streptavidin-biotin technique. Immunohistochemical staining was graded and compared. Clinical data were also reviewed. RESULTS: Normal surface epithelium and 10 of 12 benign cystadenomas failed to stain for p34cdc2 protein kinase. Of the 24 EOC specimens, however, 19 (79%) stained positively. The staining pattern or intensity was not associated with the histologic grade or surgical stage. CONCLUSION: Expression of p34cdc2 protein kinase is strongly up-regulated in most cases of EOC but not in normal epithelial ovarian tissue or in most cases of benign epithelial tumors evaluated. Therefore, it may be associated with early events in carcinogenesis. Redundant overexpression of cyclin-dependent kinases such as p34cdc2 may contribute to deranged cell cycle progression and proliferation of EOC. Observation of overexpression of p34cdc2 protein kinase in other malignant lesions suggests a common mechanism.

Cervical cancer complicated by pregnancy: episiotomy site recurrences following vaginal delivery.

OBJECTIVE: To determine the optimal diagnostic and therapeutic modalities relevant to episiotomy site recurrence of cervical cancer after vaginal delivery. METHODS: Records from the past 30 years were reviewed to identify patients treated at the Mayo Clinic with episiotomy site recurrence of cervical cancer complicated by pregnancy with vaginal delivery. RESULTS: Four patients with episiotomy site recurrence of squamous cell carcinoma of the cervix were treated primarily at the Mayo Clinic. These cervical cancers were originally diagnosed at delivery or in the immediate postpartum period and were treated by radical hysterectomy. Episiotomy site recurrences were detected less than 12 weeks after surgery in three patients and at 2 years in one patient. Three patients have died of recurrent cancer and one is disease-free at 1 year. CONCLUSIONS: Careful screening and examination of cervical abnormalities during pregnancy is required. The primary cancer was not diagnosed until delivery or postpartum in all patients who developed episiotomy site recurrences. If vaginal delivery is elected in a patient with cervical cancer, perineal inspection becomes critical. Including other cases reported in the literature, six of nine with stage IB disease were diagnosed with episiotomy site recurrence within 12 weeks of primary therapy. Consideration should be given to colposcopy of the episiotomy site or random biopsy in these women preoperatively to rule out occult implantation, and this site warrants careful postoperative surveillance.

Total abdominal hysterectomy.

Total abdominal hysterectomy will be performed on one of every three women in the USA. While few changes have occurred in modern times, operative laparoscopy is being used for hysterectomy, though its true role remains unclear. This chapter reviews the indications, preparation and common complications related to total abdominal hysterectomy. A detailed description of abdominal hysterectomy as it is performed at the Mayo Clinic is presented. Key features are pointed out, and the need for proper surgical technique is stressed; specifically, the proper dissection of ureter, bladder and rectum are reviewed and emphasis placed on the need for every pelvic surgeon to possess the skills required for performing these.

Second-look surgery in the management of epithelial ovarian carcinoma.

The constructs for incorporating second-look surgery (SLL) in the treatment schema for ovarian epithelial carcinoma are being challenged. Although second-look surgery remains the hallmark for assessing disease status at the completion of adjuvant chemotherapy, its continued utility must demonstrate potential benefits in both the presence and absence of disease. While critics cite as unacceptable the recurrence rates (20-50%) after negative SLL, the patients so identified have demonstrated chemosensitivity and harbor optimal tumor volumes if present and possibly more biologically favorable tumors. These very characteristics should render negative SLL patients ideal candidates for consolidation therapy. Furthermore, age, histologic grade, and residual volume stratifies patients into high- and low-risk categories for recurrence after negative second look and should further facilitate consolidation therapy selection. Similarly, longevity, following positive SLL is correlated adversely to advancing age and the histologic grade and the residuum of the tumor identified at reexploration. Recognizing that age and grade are predetermined factors, aggressive secondary cytoreduction has the potential of extending longevity. The latter is supported by mathematical tumor kinetic models and several focused, large, single-institution retrospective analyses. Therefore, the value of SLL is apparent but the criteria for its continued utilization in advanced ovarian cancer should include its performance by appropriately trained surgeons and the availability of (and preferably prospective trials for) both consolidation and salvage therapy to which all patients would optimally be afforded access.

Uterine prolapse complicated by endometrial cancer.

OBJECTIVE: An infrequent clinical dilemma arises when a patient with uterine prolapse that is best treated vaginally is discovered to have coexisting endometrial cancer. Often the underlying cancer is only discovered intraoperatively or postoperatively. We have reviewed our experience in this situation in an effort to evaluate efficacy of treatment, strategies to avoid late postoperative discovery of cancer, and general guidelines for optimal treatment. STUDY DESIGN: At the Mayo Clinic from 1950 to 1993, 54 patients with coexisting endometrial carcinoma underwent vaginal hysterectomy with repairs for uterine prolapse. RESULTS: We have retrospectively reviewed these cases for relevant data and survival analysis. Complete follow-up is available for 53 patients, and there were four recurrences. In 19 patients bilateral oophorectomy was not performed for multiple reasons, and one of these patients had a recurrence. Twenty-five percent of all patients had disease confined to the endometrium, and 80% overall had low-grade lesions with superficial or no myometrial invasion. Of the four recurrences, three would have been considered low risk of extrauterine spread, and it is doubtful that an abdominal approach would have yielded additional useful information. No patient required reoperation for recurrent pelvic relaxation. CONCLUSION: We believe that for certain selected patients vaginal surgery for uterine prolapse is adequate treatment in the presence of endometrial cancer. We discuss the selection strategies, exclusion criteria, and general guidelines to optimize care for these challenging patients.

Stage III papillary serous cystadenocarcinoma of the ovary in a 15-year-old female.

Epithelial ovarian cancer is the most common cause of death due to gynecologic malignancies in adults, but is rare in children and adolescents. The majority of ovarian cancers in children and adolescents are stage I at diagnosis and conservative management with preservation of fertility is often possible. Twenty-nine serous epithelial cancers have been reported in females under age 20, only two of which are known to be advanced stage (both stage III). We present a case of advanced stage papillary serous cystadenocarcinoma in a 15-year-old female treated with bilateral salpingo-oophorectomy and debulking surgery followed by combination chemotherapy.