Women with breast and uterine cancer are more likely to harbor germline mutations than women with breast or uterine cancer alone: A case for expanded gene testing.

OBJECTIVE: We explored the germline mutation spectrum and prevalence among 1650 women with breast and uterine cancer (BUC) who underwent multi-gene hereditary cancer panel testing at a single commercial laboratory. METHODS: The combined frequency of mutations in 23 BC and/or UC genes was compared between BUC cases and control groups with (1) no personal cancer history; (2) BC only; and (3) UC only using logistic regression. RESULTS: Fourteen percent (n = 231) of BUC cases tested positive for mutations in BC and/or UC genes and were significantly more likely to test positive than individuals with BC only (P < 0.001), UC only (P < 0.01), or unaffected controls (P < 0.001). Analysis of gene-specific mutation frequencies revealed that MSH6, CHEK2, BRCA1, BRCA2, ATM, PMS2, PALB2 and MSH2 were most frequently mutated among BUC cases. Compared to BC only, BRCA1, MLH1, MSH2, MSH6, PMS2 and PTEN mutations were more frequent among BUC; however, only ATM mutations were more frequent among BUC compared to UC only. All of the more commonly mutated genes have published management guidelines to guide clinical care. Of patients with a single mutation in a gene with established testing criteria (n = 152), only 81.6% met their respective criteria, and 65.8% met criteria for multiple syndromes. CONCLUSIONS: Women with BUC are more likely to carry hereditary cancer gene mutations than women with breast or uterine cancer alone, potentially warranting expanded genetic testing for these women. Most mutations found via multi-gene panel testing in women with BUC have accompanying published management guidelines and significant implications for clinical care.

Does Routine Posttreatment PET/CT Add Value to the Care of Women With Locally Advanced Cervical Cancer?

OBJECTIVES: The aim of this study was to determine the necessary reduction in recurrence rate that would make postchemoradiation positron emission tomography (PET)/computed tomography (CT) to direct completion hysterectomy for locally advanced cervical cancer (LACC) cost-effective. METHODS: A decision model evaluated costs and recurrence rates of 2 posttreatment surveillance strategies in LACC: (1) routine surveillance without PET/CT and (2) PET/CT after 3 months to triage to completion hysterectomy. Incremental cost-effectiveness ratios were expressed in dollars per additional cancer recurrence avoided. Model parameters included expected rates of recurrence using each strategy, true- and false-positive rates of posttreatment PET/CT, and major complications of completion hysterectomy. From published data, we modeled an LACC baseline recurrence rate of 32%, PET/CT false-positive rate of 33%, and false-negative rate of 19%. We assumed that PET/CT revealed persistent local cervical cancer in 16% and progressive or distant disease in 6%. Costs of PET/CT, hysterectomy, and treatment for recurrence were based on Medicare reimbursements. A 50% salvage rate with hysterectomy was assumed and varied in sensitivity analysis. RESULTS: Routine use of PET/CT to direct completion hysterectomy was associated with a higher average cost ($16,579 vs $15,450) and a lower recurrence rate (26% vs 32%). The incremental cost-effectiveness ratio of PET was $20,761 per recurrence prevented. When the probability of recurrence after hysterectomy dropped to 25% or less, PET/CT was a dominant strategy. CONCLUSIONS: Routine use of PET/CT to determine which patients may benefit from a completion hysterectomy after chemoradiation for LACC has the potential to be highly cost-effective.

Survival advantage of marriage in uterine cancer patients contrasts poor outcome for widows: a Surveillance, Epidemiology and End Results study.

BACKGROUND: Marriage confers a survival advantage for many cancers but has yet to be evaluated in uterine cancer patients. We sought to determine whether uterine cancer survival varied by self-reported relationship status. METHODS: Data were downloaded from the Surveillance, Epidemiology, and End Results program for women diagnosed with uterine cancer (between 1991 and 2010 in nine geographic regions). Patients with complete clinical data for analysis were categorized as married, single, widowed or other (divorced or separated). Differences in distributions were evaluated using Chi-square, exact and/or Mantel-Haenszel test. Uterine cancer survival was analyzed by Kaplan-Meier method with log-rank test and multivariate Cox regression analysis. RESULTS: Of 47,420 eligible patients, 56% were married, 15% were single and 19% were widows. Married vs. non-married women had a higher likelihood of having low risk (grade 1/2 endometrioid) endometrial cancer and local disease (p<0.0001), and a reduced risk of cancer death (HR=0.8, 95% CI=0.77-0.84). Multivariate evaluation of uterine cancer survival by relationship type indicated that widows consistently had significantly worse uterine cancer survival than single, married and other women in all patients and subset analyses (p<0.0001). CONCLUSION: While marital status is associated with differential uterine cancer survival, evaluation of self-reported relationship by type indicated that the poor outcome observed in widows explained most of the benefit attributed to marriage. This report identifies widows as a new high-risk subpopulation with significantly inferior outcomes potentially benefiting from personalized care and social support.

Lymph Node Micrometastases in Early-Stage Cervical Cancer are Not Predictive of Survival.

Although patients with early-stage cervical cancer have in general a favorable prognosis, 10% to 40% patients still recur depending on pathologic risk factors. The objective of this study was to evaluate if the presence of lymph node micrometastasis (LNmM) had an impact on patient's survival. We performed a multi-institutional retrospective review on patients with early-stage cervical cancer, with histologically negative lymph nodes, treated with radical hysterectomy and pelvic lymphadenectomy for the study period 1994 to 2004. Tissue blocks of lymph nodes from the patient's original surgery were recut and then evaluated for the presence of micrometastases. One hundred twenty-nine patients were identified who met inclusion criteria. LNmM were found in 26 patients (20%). In an average follow-up time of 70 mo, there were 11 recurrences (8.5%). Of the 11 recurrences, 2 (18%) patients had LNmM. Patients with LNmM were more likely to have received adjuvant radiation and chemotherapy. In stratified log-rank analysis, LNmM were not associated with any other high-risk clinical or pathologic variables. Survival data analysis did not demonstrate an association between the presence of LNmM and recurrence or overall survival. The presence of LNmM was not associated with an unfavorable prognosis nor was it associated with other high-risk clinical or pathologic variables predicting recurrence. Further study is warranted to understand the role of micrometastases in cervical cancer.

Growing teratoma syndrome: Brief communication and algorithm for management.

Growing teratoma syndrome (GTS) is a rare condition among women with ovarian germ cell tumours. Women with GTS classically present during or after systemic chemotherapy with normalised tumour markers and a mass pathologically consistent with mature teratoma. Awareness of this syndrome is necessary to prevent unnecessary chemotherapy and allow optimal management. We report five cases of ovarian GTS as examples of the clinical dilemmas encountered with these women and provide recommendations and an algorithm to guide potential management.

The impact of disease distribution on survival in patients with stage III epithelial ovarian cancer cytoreduced to microscopic residual: a Gynecologic Oncology Group study.

OBJECTIVE: To assess the survival impact of initial disease distribution on patients with stage III epithelial ovarian cancer (EOC) cytoreduced to microscopic residual. METHODS: We reviewed data from 417 stage III EOC patients cytoreduced to microscopic disease and given adjuvant intravenous platinum/paclitaxel on one of three randomized Gynecologic Oncology Group (GOG) trials. We subdivided patients into three groups based on preoperative disease burden: (1) minimal disease (MD) defined by pelvic tumor and retroperitoneal metastasis (2) abdominal peritoneal disease (APD) with disease limited to the pelvis, retroperitoneum, lower abdomen and omentum; and (3) upper abdominal disease (UAD) with disease affecting the diaphragm, spleen, liver or pancreas. We assessed the survival impact of potential prognostic factors, focusing on initial disease distribution using a proportional hazards model and estimated Kaplan-Meier survival curves. RESULTS: The study groups had similar clinicopathologic characteristics. Median overall survival (OS) was not reached in MD patients compared to 80 and 56 months in the APD and UAD groups (P<0.05). The five-year survival percentages for MD, APD, and UAD were 67%, 63%, and 45%. In multivariate analysis, the UAD group had a significantly worse prognosis than MD and APD both individually and combined (Progression Free Survival (PFS) Hazards Ratio (HR) 1.44; P=0.008 and OS HR 1.77; P=0.0004 compared to MD+APD). CONCLUSION: Stage III EOC patients with initial disease in the upper abdomen have a worse prognosis despite cytoreductive surgery to microscopic residual implying that factors beyond cytoreductive effort are important in predicting survival.

Clinical decision making using ovarian cancer risk assessment.

OBJECTIVE: Although any adnexal abnormality found at imaging can be concerning for an ovarian malignancy, the clinician must perform an evaluation to decide if the actual likelihood of malignancy justifies the risk of surgery. When determining the likelihood of an asymptomatic, incidental adnexal mass being malignant, the provider must answer one important question: Do the clinical findings warrant the potential morbidity of surgery? This article will focus on the decision making that goes into such an evaluation. CONCLUSION: A patient's medical history, physical examination, CA-125 level, and imaging characteristics are all factors that impact the ultimate decision of whether a patient can be observed with repeat imaging or should proceed to surgical evaluation.

The use of acellular dermal allograft for vulvovaginal reconstruction.

BACKGROUND: Many different techniques that require the surgeon to harvest autologous tissue to create a neovagina have been described in the literature. TECHNIQUE: We describe a technique for creating a neovagina with the use of an acellular dermal allograft as a replacement for split-thickness skin graft. Three patients are presented who had a successful creation of a neovagina with this technique. The indications for vaginoplasty include vaginal agglutination from lichen planus, squamous cell carcinoma of the vagina, and vaginal agenesis. CONCLUSION: The creation of a neovagina using an acellular dermal allograft can be successfully accomplished in patients undergoing constructive and exenterative procedures. The use of an acellular dermal allograft decreases operative time and decreases the incidence of postoperative morbidity because harvesting autologous tissue for the neovagina is not required.

Gemcitabine-associated large vessel vasculitis presenting as fever of unknown origin.

Gemcitabine is a nucleoside analogue used for treatment of multiple cancers. Recent reports describe small to medium vessel vasculitis as a rare complication of therapy. We report a case of significant large vessel vasculitis presenting as fever of unknown origin in a patient treated adjuvantly with docetaxel and gemcitabine for uterine leiomyosarcoma.The patient presented after her first and second exposure to chemotherapy with fever of unknown origin and worsening subsequent chest and neck discomfort. Extensive workup revealed radiographic and laboratory evidence of aortic vasculitis. We initiated treatment with high-dose corticosteroids, and the patient's condition resolved without complication over the next several weeks.To our knowledge, this represents the first case of gemcitabine-induced large vessel vasculitis which presented in our case as fever of unknown origin. Awareness of this potential complication is essential as discontinuing the inciting drug and initiating corticosteroid treatment can be life-saving.

Dedifferentiated endometrioid adenocarcinoma with trophoblastic components: Prolonged remission after treatment with bleomycin, etoposide, and cisplatin.

Dedifferentiated endometrial adenocarcinoma (DEAC) with trophoblastic components is a rare neoplasm with an aggressive behavior and a poor prognosis. Only seven cases have been reported in the literature. We present a 61-year-old patient who was diagnosed with Stage IB dedifferentiated endometrioid adenocarcinoma with trophoblastic elements. A post-operative ß-hCG was elevated at 1877 mIU/mL. The patient received 6 cycles of carboplatin and paclitaxel with normalization of ß-hCG; however, three months after completion of chemotherapy, her ß-hCG increased to 39 mIU/mL and a mass overlaying the psoas muscle was noted on imaging. The mass was resected and confirmed to be recurrent disease. Four cycles of bleomycin, etoposide, and cisplatin were administered, and the patient remains without evidence of disease 3 years after completing treatment. Due to the small number of reported cases of DEAC with trophoblastic components, there is limited information regarding the appropriate first-line adjuvant chemotherapy regimen.

Incidental gynecological findings on computed tomographic colonography: prevalence and outcomes.

OBJECTIVES: Computed tomographic colonography (CTC) is an investigational method for detecting colorectal polyps. Our objectives were to determine the prevalence of gynecologic findings found incidentally on CTC, and to determine the incidence of additional radiological studies and surgical procedures. METHODS: An electronic database identified female patients who underwent CTC at Walter Reed Army Medical Center from January 2002 to July 2005. CTC reports were pared down using gynecologic keywords. Subsequent radiological studies and pathology reports were evaluated for women with gynecological findings. RESULTS: Gynecologic extracolonic findings (ECF) were identified in 71 (9.5%) of the 749 women who underwent CTC. Of these 71 women, 14 (20%) underwent additional radiological and/or surgical evaluation. Nine (13%) of these women underwent surgical evaluation; all pathologic diagnoses were benign. CONCLUSION: Gynecologic extracolonic findings are common in women undergoing CTC. These gynecologic ECF identified on CTC may lead to additional investigative studies and procedures.

Prospective Validation of an Ex Vivo, Patient-Derived 3D Spheroid Model for Response Predictions in Newly Diagnosed Ovarian Cancer.

Although 70-80% of newly diagnosed ovarian cancer patients respond to first-line therapy, almost all relapse and five-year survival remains below 50%. One strategy to increase five-year survival is prolonging time to relapse by improving first-line therapy response. However, no biomarker today can accurately predict individual response to therapy. In this study, we present analytical and prospective clinical validation of a new test that utilizes primary patient tissue in 3D cell culture to make patient-specific response predictions prior to initiation of treatment in the clinic. Test results were generated within seven days of tissue receipt from newly diagnosed ovarian cancer patients obtained at standard surgical debulking or laparoscopic biopsy. Patients were followed for clinical response to chemotherapy. In a study population of 44, the 32 test-predicted Responders had a clinical response rate of 100% across both adjuvant and neoadjuvant treated populations with an overall prediction accuracy of 89% (39 of 44, p < 0.0001). The test also functioned as a prognostic readout with test-predicted Responders having a significantly increased progression-free survival compared to test-predicted Non-Responders, p = 0.01. This correlative accuracy establishes the test's potential to benefit ovarian cancer patients through accurate prediction of patient-specific response before treatment.

Complications of gynecologic surgery.

Complications during gynecologic surgery result from the proximity of the uterus and ovaries to other critical pelvic structures. These structures include the urinary tract, bowel, nerves, and vasculature. Knowledge of pelvic anatomy is important when performing these procedures and is critical in cases of altered anatomy from adhesive disease and during intraoperative hemorrhage. Recognition and repair of an unintended injury gives the best chance for minimizing sequelae from these complications.

Benign disorders of the ovary.

Most ovarian disorders are benign, with the majority being functional ovarian cysts and benign neoplasms. Imaging can often aid in diagnosis and risk assessment. Benign ovarian disorders are frequently incidental findings, but they may cause symptoms from hormonal overproduction, mass effects, or torsion. In addition to symptoms, any ovarian abnormality can raise the specter of malignancy. Knowledge of the cause, presentation, and natural history of these benign ovarian disorders helps providers counsel and treat patients appropriately.

Clitoral priapism due to distant clitoral metastasis of high-grade serous ovarian carcinoma: A case report and review of the literature.

•Cutaneous metastasis at the initial presentation of ovarian carcinoma is rare.•Clitoral metastasis in a gynecological malignancy can occasionally present as clitoral priapism.•Clitoral priapism can be treated with oral or intramuscular alpha blockade.

Establishing a mean postvoid residual volume in asymptomatic perimenopausal and postmenopausal women.

OBJECTIVE: To estimate mean postvoid residual (PVR) volumes among perimenopausal and postmenopausal women without significant lower urinary tract or pelvic organ prolapse symptoms. METHODS: Patients presenting for well-women encounters were offered study participation. Women with a history of urinary incontinence greater than twice per week, urinary retention, symptomatic pelvic organ prolapse, or neurologic disorders were excluded. Pelvic relaxation, if present, was characterized according to the pelvic organ prolapse quantification system. Within 10 minutes of spontaneously voiding, PVR volume was assessed with bladder ultrasonography. RESULTS: A total of 96 patients were enrolled; mean age was 60+/-11 years. The majority (80%) were postmenopausal; 30% had a previous hysterectomy. Most women (92%) had some degree of prolapse; the median stage was one, most commonly involving the anterior compartment (70%). The median PVR volume was 19 mL (range 0-145 mL); the mean PVR volume was 24+/-29 mL. Only 15% of patients had a PVR volume greater than 50 mL, and 95% had a PVR volume 100 mL or less. Only age 65 years or older was associated with a higher mean PVR volume; hormone therapy, vaginal atrophy, parity, and stage of asymptomatic prolapse did not affect PVR volumes. CONCLUSION: Most asymptomatic perimenopausal and postmenopausal women had a PVR volume less than 50 mL, which was unaffected by multiple factors that were thought to potentially affect bladder function. Establishing "normal" volumes in this population may aid in developing recommendations regarding appropriate bladder function and retention criteria for women who are symptomatic or those who have had pelvic floor surgery.

The use of acellular dermal graft for vulvovaginal reconstruction in a patient with lichen planus.

BACKGROUND: Vulvovaginal lichen planus is an inflammatory dermatosis that can progress to an erosive form with scarring of the vulva, resorption of the labia minora, vaginal synechiae, and vaginal obliteration secondary to desquamative vaginitis. Traditionally, conservative medical therapy has consisted of topical corticosteroids and immunosuppressants. CASE: A 61-year-old woman with a history of refractory erosive vulvovaginal lichen planus presented with complete obliteration of the vaginal vault. The patient failed both medical and conservative surgical management and desired definitive management. After performing a skinning vulvectomy and simple vaginectomy, acellular dermal graft was used for grafting the vulva and creating a neovagina. CONCLUSION: Acellular dermal graft is a suitable graft material for vulvar and vaginal reconstruction in select patients, and it avoids the postoperative pain associated with graft harvest sites.

Laparoscopic exposure in obese high-risk patients with mechanical displacement of the abdominal wall.

BACKGROUND: Patients with morbid obesity or pulmonary disease are at a higher risk for complications during advanced laparoscopic procedures. Higher intraperitoneal carbon dioxide pressures required to elevate the pannus can negatively impact hemodynamic and respiratory parameters. CASES: We describe a technique that uses a combination of a mechanical retractor and a Foley catheter inserted midway between the umbilicus and the pubic symphysis that assists in elevating the anterior abdominal wall. In 3 cases this technique allowed for a low-pressure pneumoperitoneum during advanced laparoscopic pelvic surgery, which resulted in improved hemodynamic parameters and pulmonary function in these high-risk patients. CONCLUSION: The Foley Lap-Lift facilitated laparoscopy through mechanical abdominal wall elevation and allowed for a lower-pressure pneumoperitoneum. This technique is an addition to traditional operative laparoscopy in select high-risk patients.