Endometrial cancer: a review and current management strategies: part I.

Endometrial carcinoma is the most common gynecologic malignancy. A thorough understanding of the epidemiology, pathophysiology, and management strategies for this cancer allows the obstetrician-gynecologist to identify women at increased risk, contribute toward risk reduction, and facilitate early diagnosis. The Society of Gynecologic Oncology's Clinical Practice Committee has reviewed the literature and created evidence-based practice recommendations for diagnosis and treatment. This article examines: • Risk factors, including genetic predisposition • Diagnostic and metastatic evaluation • Surgical management of early and advanced cancer, including lymphadenectomy in early cancer.

Endometrial cancer: a review and current management strategies: part II.

Endometrial carcinoma is the most common gynecologic malignancy. A thorough understanding of the epidemiology, pathophysiology, and management strategies for this cancer allows the obstetrician-gynecologist to identify women at increased risk, contribute toward risk reduction, and facilitate early diagnosis. The Society of Gynecologic Oncology's Clinical Practice Committee has reviewed the literature through March of 2014 and created evidence-based practice recommendations for diagnosis and treatment. The level of recommendations used is based on the method used by the U.S. Preventive Services Task Force (A: There is good evidence to support the recommendation, B: There is fair evidence to support the recommendation, C: There is insufficient evidence to support the recommendation; however, the recommendation may be made on other grounds, D: There is fair evidence against the recommendation, E: There is good evidence against the recommendation.). It is not the purpose of this document to provide a complete review of the literature on all aspects of endometrial cancer. This article examines: • Adjuvant therapy, including radiation, vaginal brachytherapy, and chemotherapy • Therapy for advanced disease, including chemotherapy and radiation therapy alone and in combination as well as hormone therapy • Treatment for synchronous endometrial and ovarian cancer • Fertility-sparing treatment • Post-treatment patient surveillance • The role of hormone replacement therapy in the development of endometrial carcinoma • Novel targeted therapies.

The microculture-kinetic (MiCK) assay: the role of a drug-induced apoptosis assay in drug development and clinical care.

A drug-induced apoptosis assay, termed the microculture-kinetic (MiCK) assay, has been developed. Blinded clinical trials have shown higher response rates and longer survival in groups of patients with acute myelocytic leukemia and epithelial ovarian cancer who have been treated with drugs that show high apoptosis in the MiCK assay. Unblinded clinical trials in multiple tumor types have shown that the assay will be used frequently by clinicians to determine treatment, and when used, results in higher response rates, longer times to relapse, and longer survivals. Model economic analyses suggest possible cost savings in clinical use based on increased generic drug use and single-agent substitution for combination therapies. Two initial studies with drugs in development are promising. The assay may help reduce costs and speed time to drug approval. Correlative studies with molecular biomarkers are planned. This assay may have a role both in personalized clinical therapy and in more efficient drug development.

Correlation of pretreatment drug induced apoptosis in ovarian cancer cells with patient survival and clinical response.

BACKGROUND: This study was performed to determine if a chemotherapy-induced apoptosis assay (MiCK) could predict the best therapy for patients with ovarian cancer. METHODS: A prospective, multi-institutional and blinded trial of the assay was conducted in 104 evaluable ovarian cancer patients treated with chemotherapy. The MiCK assay was performed prior to therapy, but treating physicians were not told of the results and selected treatment only on clinical criteria. Outcomes (response, time to relapse, and survival) were compared to the drug-induced apoptosis observed in the assay. RESULTS: Overall survival in primary therapy, chemotherapy naïve patients with Stage III or IV disease was longer if patients received a chemotherapy which was best in the MiCK assay, compared to shorter survival in patients who received a chemotherapy that was not the best. (p < 0.01, hazard ratio HR 0.23). Multivariate model risk ratio showed use of the best chemotherapy in the MiCK assay was the strongest predictor of overall survival (p < 0.01) in stage III or IV patients. Standard therapy with carboplatin plus paclitaxel (C + P) was not the best chemotherapy in the MiCK assay in 44% of patients. If patients received C + P and it was the best chemotherapy in the MiCK assay, they had longer survival than those patients receiving C + P when it was not the best chemotherapy in the assay (p = 0.03). Relapse-free interval in primary therapy patients was longer if patients received the best chemotherapy from the MiCK assay (p = 0.03, HR 0.52). Response rates (CR + PR) were higher if physicians used an active chemotherapy based on the MiCK assay (p = 0.03). CONCLUSION: The MiCK assay can predict the chemotherapy associated with better outcomes in ovarian cancer patients. This study quantifies outcome benefits on which a prospective randomized trial can be developed.

Uterine sarcoma occurring in a premenopausal patient after uterine artery embolization: a case report and review of the literature.

OBJECTIVE: We report a case of uterine leiomyosarcoma occurring after uterine artery embolization and review the previously published cases. We estimate the incidence of sarcoma after UAE, the mean diagnostic delay in young women undergoing this procedure and review the potential and limits of preoperative procedures in diagnosing uterine sarcomas. CASE REPORT: A 35-year-old woman had an early failure after UAE. She underwent surgery 13 months after the procedure. Final pathologic report was consistent with uterine leiomyosarcoma. CONCLUSION: Incidence of uterine sarcomas after UAE is low, probably similar to that of misdiagnosed leiomyosarcomas in women undergoing surgery for presumed symptomatic leiomyomas. Therefore a relation between the procedure and the malignancy seems to be very unlikely. Diagnostic delay in menstruated women younger than 50 undergoing UAE for presumed symptomatic leiomyoma ranges between 13 and 15 months. The safest procedure for women who fail the conservative management of leiomyoma with UAE is surgical, allowing for definitive pathologic exclusion of malignancy.

Extensive fever workup produces low yield in determining infectious etiology.

OBJECTIVE: The study was undertaken to evaluate the use of a fever workup in women undergoing benign gynecologic procedures. STUDY DESIGN: A retrospective chart review was performed at Jackson Memorial Hospital between 1994 and 2000. Information was abstracted from hospital and clinic records. Fever criteria was defined as 1 temperature equal to or greater than 101.5, or 2 equal to or greater than 100.4, at least 4 hours apart within a 24-hour period. Patients undergoing additional intraoperative procedures leading to increased febrile morbidity were excluded. Data abstracted included patient demographics, procedure, complications, antibiotic use, and extent of fever workup. Statistical analysis used was 2-sample t tests, Wilcoxon rank test, chi2 test, and multivariate logistic regression. Alpha level = .05. RESULTS: The charts of 505 patients were reviewed, and 147 patients met fever criteria. All patients underwent surgery for benign conditions, abdominal hysterectomy being the most common (90%). The study population was divided into 2 groups: the noninfectious group and infectious group. These groups were determined by wound infection, pelvic abscess, blood or urine culture, ultrasound, and chest roentgen. Both groups were found to be similar with respect to demographics, surgical procedures, and postoperative complications, with the exception of body mass index (28.4 vs 31.7) and length of hospital stay (3.9 vs 5.3). Results from fever workups included positive results blood cultures (9.7%), urine culture (18.8%), and chest roentgens (14%) in this study population. We found no association between positive urine analysis and urine culture. When comparing both groups, a statistically significant difference was found with regard to maximum temperature elevation, number of days febrile, and postoperative day of maximum temperature (P < .05). CONCLUSION: The extensive fever workup was not frequently positive in this study population. Its use and cost-effectiveness should be questioned. Therefore, the fever workup should be tailored to the individual patient.

Sigmoid impaction secondary to urinary stones: case report and review of literature.

BACKGROUND: This is the first case report of a Miami pouch sigmoid fistula developing passage of urinary stones resulting in the presentation of constipation secondary to impaction. CASE REPORT: A 49-year-old woman who developed a recurrence of invasive squamous cell cervical carcinoma 1 year after pelvis radiation. She then underwent anterior pelvic exenteration and creation of a Miami pouch. Approximately 14 years after the primary radiation therapy and 13 years after the creation of the exenterative procedure, the patient developed a Miami pouch sigmoid fistula. The decision was made at this time to repair the fistula and remove the urinary stones from the sigmoid colon. Postoperatively, the patient remained continent using intermittent catheterization of the pouch and there was no evidence of recurrence of the cancer. CONCLUSION: Conservative management of urinary reservoir complications should always be considered before surgical intervention is attempted. When indicated, surgical management should not be delayed.

Laparoscopic pelvic and paraaortic lymphadenectomy in gynecologic oncology.

In the early 1990s, different authors independently developed techniques for pelvic and paraaortic lymph node sampling. Since then, laparoscopic lymphadenectomy has been demonstrated to yield the same number of nodes when compared with the laparotomic approach. Only one microscopically involved lymph node was lost at laparoscopic lymphadenectomy when a laparotomic control followed immediately after. It seems bleeding, which is the most serious perioperative complication, is more common during laparoscopic lymphadenectomy than during laparotomy; however, the incidence will decrease with experience of the surgeon. The laparoscopic procedure does not seem to influence negatively the survival of patients with early stage endometrial and cervical cancer. There does not seem to be a significant reduction in overall hospital charges for laparoscopic surgery in oncology, but patients who undergo laparoscopic surgery recover significantly sooner than those who undergo laparotomy.

Conversion of an incontinent urinary conduit to a continent urinary reservoir (Miami Pouch).

OBJECTIVE: External urinary or gastrointestinal appliances can impair a patient's quality of life. We report on the feasibility of converting an incontinent colonic urinary diversion to a continent urinary reservoir (Miami Pouch). CASE: We describe the case of a 66-year-old white female with a history of stage Ib(2) cervical cancer treated by radical abdominal hysterectomy and adjuvant radiation therapy. The patient developed severe radiation cystitis with a neurogenic bladder and bilateral ureteral obstruction. After failing conservative management, a urinary diversion with a transverse colon conduit was performed. The patient remained without evidence of disease for 2 years and led an active lifestyle with regular tennis games. After 7 months of an external appliance for the urinary conduit, the patient presented to the University of Miami for conversion to a continent urinary mechanism which would not require an appliance. We performed an exploratory laparotomy, conversion of a transverse colon conduit to a continent ileo-colonic urinary reservoir (Miami Pouch). There were no postoperative complications. The patient remains disease-free and performs self-catheterization with no need for an external appliance. The patient has been able to resume an active life including sports. CONCLUSIONS: Successful conversion of an incontinent urinary conduit to a continent urinary reservoir is possible in a select case resulting in a perceived improvement of quality of life.

Optimal surgical cytoreduction in patients with Stage III and Stage IV endometrial carcinoma: a study of morbidity and survival.

OBJECTIVE: To evaluate the survival impact of residual disease at the time of primary surgery for patients with Stage III and IV endometrial carcinoma; to assess morbidity associated with surgical cytoreduction. METHOD: All patients with endometrial carcinoma who underwent primary surgical therapy at the University of Miami between January 1, 1990 and June 1, 2002 were identified. Patients meeting FIGO criteria for Stage III or IV disease were selected. Papillary serous and clear cell histology was excluded. RESULTS: Eighty-five patients were identified: 66 Stage III and 19 Stage IV. Only Stage IIIC and Stage IV were included in survival analysis: 72% (33 Stage IIIC, 9 Stage IV) had optimal cytoreduction and 28% (6 Stage IIIC, 10 Stage IV) had suboptimal cytoreduction. The median survival for Stage IIIC and IV disease was 6.7 months for patients with suboptimal cytoreduction and 17.8 months for patients with optimal cytoreduction (P = 0.001). The proportion of patients with major postoperative complications (37.50% vs. 7.25%, P = 0.005), unplanned postoperative SICU admissions (31.25% vs. 7.25%, P = 0.018), and length of hospital stay exceeding 15 days (31.25% vs. 4.35%, P = 0.005) was greater in patients with suboptimal cytoreductive surgery. CONCLUSIONS: Overall survival is lower and morbidity is higher in patients with advanced endometrial carcinoma having suboptimal cytoreduction at the time of primary surgery. Patients with suspected advanced stage endometrial carcinoma should be counseled on the potential benefits of optimal cytoreductive surgery. Alternative treatment options should be considered in those patients with surgically unresectable disease.

Continent ileocolonic urinary reservoir (Miami pouch): the University of Miami experience over 15 years.

OBJECTIVE: A patient with a recurrent central pelvic malignancy after radiation will require urinary diversion as part of the reconstructive phase of the pelvic exenteration. The aim of our study was to assess the result of our 15-year experience with a continent ileocolonic urinary reservoir, which is known as the Miami pouch. STUDY DESIGN: Since 1988, all patients who received a continent ileocolonic urinary reservoir in the Division of Gynecologic Oncology, University of Miami School of Medicine, were included in the study. Parameters that were evaluated during the study period include functional outcomes, early and late perioperative complications, and their treatment. RESULTS: A total of 90 patients were identified from February 1988 to December 2002. Seventy-eight patients (87%) had a recurrent central pelvic malignancy, and 82 patients (91%) received radiation before the Miami pouch procedure. The non-reservoir-related morbidities were fever (76%), wound complication (30%), pelvic collection (12%), ileus/small bowel obstruction (12%), and postoperative death (11%). The most common reservoir-related complications were urinary infection (40%), ureteral stricture (20%), and difficulty with self-catheterization (18%). In our study, the overall complication rate that was related directly to the Miami pouch was 53%. Conservative treatment resolved>80% of these cases. The rate of urinary continence that was achieved in our patients was 93% during our 15-year experience with the Miami pouch. CONCLUSION: The Miami pouch is a good alternative for continent urinary diversion during exenteration or radiation-induced damage. The rate of major complications that require aggressive surgical intervention is acceptable. Most postoperative complications (80%) can be corrected with the use of conservative techniques that are associated with fewer deaths than reoperation and thus should be used first. The technique is simple and effective in women who are at high risk, who have undergone previous radiation therapy, and who have a high rate of functional success and is a profound advantage for a woman's psychosocial well-being.

The gastrointestinal complications of the Miami Pouch: a review of 77 cases.

OBJECTIVES: To describe the gastrointestinal (GI) complications associated with the Miami Pouch (MP), a continent ileocolonic urinary reservoir. METHODS: A retrospective chart review of patients who underwent a MP from 1988 to 1997 at the University of Miami, School of Medicine, was employed. Data was analyzed in terms of early and late (beyond 6 weeks) GI complications resulting directly from the operation. RESULTS: Seventy-seven patients underwent a MP, a form of continent urinary diversion. Seventy-two patients (93.5%) were previously radiated. The perioperative mortality rate was 11.7%. Twenty (26%) patients developed a GI complication (17 late and 3 early), and 5 (6.5%) were directly as a result of the MP. Twelve recto-vaginal and 1 recto-neo-vaginal fistulas were identified. All but one was considered as late. Three (3.9%) patients developed colo-MP fistulas (3, 5, and 14 months). All three patients failed conservative management and required reoperation. Two patients developed enterocutaneous fistulas (3 and 5 months). One patient developed breakdown of the ileotransverse colon anastomosis on postoperative day 12 and required reoperation with bowel resection and an ileostomy. She expired from intraabdominal sepsis. Finally, 1 patient developed short bowel syndrome secondary to an expanding hematoma in the small bowel mesentery. CONCLUSIONS: . The GI complication rate attributed directly to the MP is low (6.5%). Prompt recognition is the key to successful management of these complications. The majority of these complications are considered as late and do not occur in the immediate postoperative period. Conservative management of GI-MP fistulas is not successful and necessitates reoperation.

Pelvic exenteration and reconstruction.

For the past six decades, pelvic extenteration has been utilized in the treatment of localized central pelvic recurrences after chemo/radiotherapy. The radicality of the procedure that includes resection of the bladder, vulva/vagina, and rectum, although with curative intent, results in comprehensive changes for the patient. For this reason, all patients should undergo extensive psychosocial counseling to prepare them for the changes in body image and lifestyle. Extirpation of the pelvic viscera has undergone a number of modifications since Brunschwig first described it in 1948 to maximize survivability and minimized anatomical distortion. Most of the advancements have been focused on the reconstructive phase after pelvic exenteration. A few select patients can be free of any external appliances such as a colostomy bag with utilization of a low colorectal anastomosis, and can maintain sexual intimacy with creation of a neovagina. In addition, reconstruction of the pelvic floor with omental flaps, dura mater grafts and myocutaneous flaps have decreased postoperative morbidity. In this article, we provide a review of pelvic exenteration in gynecologic oncology, emphasizing preoperative evaluation, surgical techniques and their postoperative management.

Paclitaxel and carboplatin chemotherapy administered during pregnancy for advanced epithelial ovarian cancer.

BACKGROUND: Ovarian cancer diagnosed during pregnancy is uncommon. Most chemotherapy use reported has been in combination with cisplatinum. Paclitaxel in combination with carboplatin during pregnancy has not yet been reported. CASE: A right adnexal mass was diagnosed during pregnancy at 5 weeks' gestational age in a 30-year-old woman. A laparotomy was performed 2 1/2 weeks later because of the worsening nature of her symptoms and the possibility of ovarian torsion. At surgery, the patient was diagnosed with stage IIIC ovarian papillary serous cystadenocarcinoma. She was treated with six cycles of paclitaxel and carboplatin beginning at 16-17 weeks' gestation. At 35.5 weeks' gestation, a cesarean hysterectomy, left salpingo-oophorectomy, and pelvic and paraaortic nodal sampling with multiple peritoneal biopsies was performed without incident. However, the patient had refractory disease present in the remaining ovary. She was treated with further chemotherapy and is currently doing well. The patient experienced no adverse reactions during her treatment, and the infant has normal growth and development at 15 months of age. CONCLUSION: Paclitaxel used in combination with carboplatin for the treatment of ovarian cancer during pregnancy caused no adverse effects in the infant.

The safety of incidental appendectomy at the time of abdominal hysterectomy.

OBJECTIVE: The purpose of this study was to assess the complication rates of incidental appendectomies in women who undergo benign gynecologic procedures. STUDY DESIGN: This was a retrospective case-controlled study of patients who did (n=100 women) or did not (n=100 women) undergo incidental appendectomies at the time of an abdominal hysterectomy between June 1995 and January 2001. Information was abstracted from hospital and clinic records and a gynecologic oncology database. Data were obtained about age, body mass index, hypertension, diabetes mellitus, the number of days with nothing by mouth, the length of hospital stay, and postoperative complications (cellulitis, fever, ileus, pneumonia, thromboembolic disease). Data were analyzed with the use of two-sample t tests, Wilcoxon Rank sum tests, chi(2) tests, and multiple logistic regressions. RESULTS: There was no difference in preoperative diagnosis or operative procedure for either group. The number of patients in the group that did have incidental appendectomy versus the group that did not have incidental appendectomy with additional procedures at the time of abdominal hysterectomy was bilateral salpingo-oophorectomy (66 vs 61 women), unilateral oophorectomy (19 vs 19 women), lysis of adhesions (9 vs 8 women), and others (12 vs 8 women). Compared with the group that did not have incidental appendectomy, the group that did have incidental appendectomy was younger (mean age+/-SD: 44+/-9.6 years vs 48+/-13.6 years, P=.02) and had a lower mean body mass index (26.1+/-6.0 kg/m(2) vs 29.8+/-8.9 kg/m(2), P=.0009). No significant differences were found between the two groups (the group that did have incidental appendectomy vs the group that did not have incidental appendectomy, respectively) with respect to the following postoperative complications: fever (40 vs 27 women), cellulitis (1 vs 2 women), wound collection (4 vs 6 women), wound dehiscence (1 vs 5 women), wound abscess (7 vs 6 women), ileus (3 vs 2 women), and urinary tract infection (4 vs 10 women). The mean length of hospital stay was significantly longer in the group that did have incidental appendectomy than in the group that did not have incidental appendectomy (3.6+/-1.52 days vs 3.1+/-1.1 days, P=.006). However, the difference was no longer significant when patients who were fed electively on the postoperative day 2 were excluded from the analysis (3.16+/-1.13 days vs 3.04+/-1.13 days, P=.507). Thirty-one percent of the histologic specimens were abnormal, with fibrous obliteration being most common, and there was one case of acute appendicitis. CONCLUSION: An incidental appendectomy at the time of benign gynecologic procedures does not increase postoperative complication rates or length of hospital stay. The inclusion of incidental appendectomies in all abdominal hysterectomies could potentially decrease the morbidity and mortality rates because of appendicitis in elderly women.

Management of recurrent ovarian cancer: evidence-based decisions.

In this era of advanced medical technology, recurrent ovarian cancer continues to be a therapeutic dilemma. Most of these patients will succumb to their disease process. For this reason, it is of paramount importance for all clinicians to recognize that the primary goal of salvage therapy is to maximize disease-free survival and quality of life. With this goal in mind, they can offer patients a variety of different modalities to control disease, including second-look surgery, secondary or interval cytoreduction, second-line chemotherapy, hormonal therapy, and immunotherapy. The role of second-look surgery has yet to be delineated, but the modality can be helpful in evaluating disease status and guiding further therapy in patients receiving first-line platinum-based chemotherapy or in research protocols. Interval cytoreductive surgery has been shown to confer a survival advantage in a small subset of patients with localized resectable disease proven to be platinum sensitive. The choice of chemotherapeutic agents and the prognosis depend directly on whether the patient is a platinum-sensitive responder. Many agents are approved for the treatment of recurrent ovarian cancer, and the treatment of each patient should be individualized depending on the cumulative toxicities and performance status. Extensive ongoing research trials are underway to elucidate the best salvage therapy.

Recurrent vulvar cancer.

Recurrent vulvar cancer occurs in an average of 24% of cases after primary treatment after surgery with or without radiation. The relatively few primary vulvar cancers, combined with the low proportion of recurrences, has made it difficult to perform randomized studies to document the most appropriate therapeutic modalities. Most reports are small retrospective studies and anecdotal reviews that have emphasized the importance of surgery and have led to new approaches with respect to chemoradiation. Traditionally, the most accepted treatment of vulvar cancer has been and continues to be surgery. Recently, radiation and chemotherapy have been combined with very encouraging results. The therapeutic modality used depends on the location and extent of the recurrence. Most recurrences occur locally near the original resection margins or at the ipsilateral inguinal or pelvic lymph nodes. Lateralized local vulvar recurrences treated with a wide radical local excision with inguinal lymphadectomy results in an excellent cure rate of 70%. With a central pelvic recurrence with antecedent radiotherapy involving the urethra, upper vagina, and rectum, total pelvic exenteration is indicated in a select group of patients with curative intent. Radiotherapy or chemoradiation concomitantly with wide radical local excision of an advanced vulvar has proven successful in avoiding an exenteration, with improved survival and less morbidity. Prospective and retrospective studies have shown excellent results using radiation or chemoradiation with wide radical local excision in patients with locally advanced disease in whom adequate resection margins are difficult to achieve (with a central lesion requiring exenteration) or with debilitating medical conditions that preclude surgery. In these patients, chemoradiation has shown favorable results when used before a wide local resection. In patients with advanced local disease, external beam and interstitial radiation has been used for palliative and curative intent with encouraging results. Regional recurrences to the inguinal and pelvic lymph nodes have been shown to have a poor prognosis with a high mortality rate. We recommend that inguinal recurrences without prior radiation therapy undergo excision followed by radiotherapy with chemosensitization. In patients with previous radiation to the inguinal lymph nodes, we try to avoid any excisional procedures because of the high rate of complications. We offer these patients brachytherapy for palliation. With pelvic recurrences, we recommended chemoradiation as the treatment modality. In the subset of patients with distant metastasis, chemotherapy may be offered; however, few studies have been performed to advocate any single combination. The literature supports the use of 5-fluorouracil or cisplatin as single agents or in combination to have sensitivity against squamous cells. There are few studies revealing improvement in 5-year survival, thus these patients may benefit from recruitment into research protocols.