Jamal Rahaman

Fallopian Tube and Primary Peritoneal Carcinomas Associated With BRCA Mutations

PURPOSE The aims of this study were to determine the incidence of BRCA mutations among Ashkenazi Jewish patients with fallopian tube carcinoma (FTC) or primary peritoneal carcinoma (PPC), to study the clinicopathologic features of these cancers, and to estimate the risks of these cancers in association with a BRCA mutation. PATIENTS AND METHODS A retrospective review at two institutions identified 29 Jewish patients with FTC and 22 Jewish patients with PPC. These patients were genotyped for the three Ashkenazi Jewish BRCA founder mutations (185delAG and 5382insC in BRCA1 and 6174delT in BRCA2). Surgical and pathologic information, family history, and survival data were obtained from hospital records. All statistical tests were two sided. RESULTS Germline BRCA mutations were identified in five of 29 patients with FTC (17%) and nine of 22 patients with PPC (41%). Mutation carriers had a younger mean age at diagnosis than patients without a mutation (60 v 70 years; P =.002). The overall median survival was 148 months for mutation carriers and 41 months for patients without a mutation (P =.04). For BRCA mutation carriers, the lifetime risks of FTC and PPC were 0.6% and 1.3%, respectively. CONCLUSION Substantial proportions of Ashkenazi Jewish patients with FTC or PPC are BRCA mutation carriers. Patients with BRCA-associated FTC or PPC are younger at diagnosis and have improved survival compared with patients without a BRCA mutation. Although the lifetime risks of FTC or PPC for patients with BRCA heterozygotes are greater than those for the general population, the absolute risks seem relatively low.

microRNA-181a has a critical role in ovarian cancer progression through the regulation of the epithelial-mesenchymal transition.

Ovarian cancer is a leading cause of cancer deaths among women. Effective targets to treat advanced epithelial ovarian cancer (EOC) and biomarkers to predict treatment response are still lacking because of the complexity of pathways involved in ovarian cancer progression. Here we show that miR-181a promotes TGF-β-mediated epithelial-to-mesenchymal transition via repression of its functional target, Smad7. miR-181a and phosphorylated Smad2 are enriched in recurrent compared with matched-primary ovarian tumours and their expression is associated with shorter time to recurrence and poor outcome in patients with EOC. Furthermore, ectopic expression of miR-181a results in increased cellular survival, migration, invasion, drug resistance and in vivo tumour burden and dissemination. In contrast, miR-181a inhibition via decoy vector suppression and Smad7 re-expression results in significant reversion of these phenotypes. Combined, our findings highlight an unappreciated role for miR-181a, Smad7, and the TGF-β signalling pathway in high-grade serous ovarian cancer.

Laparoscopic management of early ovarian and fallopian tube cancers: surgical and survival outcome

OBJECTIVE To evaluate the role of laparoscopy for staging of early ovarian cancers. STUDY DESIGN Case series conducted at the University Hospital with 36 patients who had presumed early-stage adnexal cancers. Laparoscopic staging/restaging was performed. RESULTS Cases included 20 invasive epithelial tumors, 11 borderline tumors, and 5 nonepithelial tumors. Mean number of peritoneal biopsies, paraaortic nodes, and pelvic nodes were 6, 12.23, and 14.84, respectively. Eighty-three percent of the patients had laparoscopic omentectomy. On final pathology, 7 patients were upstaged. Postoperative complications included 1 small bowel obstruction, 2 pelvic lymphoceles, and 1 lymphocele cyst. Mean duration of follow-up is 55.9 months. Three patients had recurrences. All patients are alive without evidence of the disease. CONCLUSION This represents 1 of the largest series and longest follow-ups of laparoscopic staging for early-stage adnexal tumors. Laparoscopic staging of these cancers appears to be feasible and comprehensive without compromising survival when performed by gynecologic oncologists experienced with advanced laparoscopy.

A case‐controlled study of total laparoscopic radical hysterectomy with pelvic lymphadenectomy versus radical abdominal hysterectomy in a fellowship training program

To determine whether total laparoscopic radical hysterectomy (TLRH) is a feasible alternative to an abdominal radical hysterectomy (ARH) in a gynecologic oncology fellowship training program. We prospectively collected cases of all of the patients with cervical cancer treated with TLRH and pelvic lymphadenectomy by our division from 2000 to 2006. All of the patients from the TLRH group were matched 1:1 with the patients who had ARH during the same period based on stage, age, histological subtype, and nodal status. Thirty patients were treated with TLRH with a mean age of 48.3 years (range, 29–78 years). The mean pelvic lymph node count was 31 (range, 10–61) in the TLRH group versus 21.8 (range, 8–42) (P < 0.01) in the ARH group. Mean estimated blood loss was 200 cc (range, 100–600 cc) in the TLRH with no transfusions compared to 520 cc in the ARH group (P < 0.01), in which five patients required transfusions. Mean operating time was 318.5 min (range, 200–464 min) compared to 242.5 min in the ARH group (P < 0.01), and mean hospital stay was 3.8 days (range, 2–11 days) compared to 5.6 days in the ARH group (P < 0.01). All TLRH cases were completed laparoscopically. All patients in the TLRH group are disease free at the time of this report. In conclusion, it is feasible to incorporate TLRH training into the surgical curriculum of gynecologic oncology fellows without increasing perioperative morbidity. Standardization of TLRH technique and consistent guidance by experienced faculty is imperative.

Vacuum-assisted closure in the treatment of complex gynecologic wound failures

BACKGROUND Complex wound failures are a source of significant morbidity and mortality. They are costly and time consuming to treat, and may evolve into chronic, debilitating conditions. Vacuum‐assisted closure is a novel wound healing technique applying subatmospheric pressure to wounds to expedite healing. CASES We report the successful use of vacuum‐assisted closure therapy on three patients on a gynecologic oncology service with complex wound failures of various chronicity. In all cases, vacuum‐assisted closure therapy was well tolerated and demonstrated efficacy within 48 hours of initiation. CONCLUSION We conclude that vacuum‐assisted closure therapy should be included in the armamentarium of the gynecologist addressing complex wound failures.

Minimally invasive management of an advanced abdominal pregnancy.

BACKGROUND: Advanced abdominal pregnancy is a rare, life-threatening condition that presents a number of challenges. CASE: A 29-year-old primigravida with 10 years of secondary infertility and a previous tuboplasty had a 21-week abdominal pregnancy treated with preoperative arterial embolization before laparoscopically assisted fetal delivery. Postoperatively, 4 cycles of methotrexate were administered at 50 mg/m2 intramuscularly every 3 weeks for the retained abdominal placenta. Subsequent spontaneous conception occurred, and a live, full-term infant was delivered by cesarean delivery 17 months later. No adverse sequelae were found during long-term follow-up. CONCLUSION: This report demonstrates successful minimally invasive management of an advanced abdominal pregnancy with a multimodal approach that included preoperative arterial embolization, laparoscopically assisted delivery, and judicious use of postoperative methotrexate.

Role of FDG PET/CT in Staging of Recurrent Ovarian Cancer

Ovarian cancer is the fifth leading cause of cancer death among women in the United States and has a high likelihood of recurrence despite aggressive treatment strategies. Detection and exact localization of recurrent lesions are critical for guiding management and determining the proper therapeutic approach, which may prolong survival. Because of its high sensitivity and specificity compared with those of conventional techniques such as computed tomography (CT) and magnetic resonance (MR) imaging, fluorine 18 fluorodeoxyglucose positron emission tomography (PET) combined with CT is useful for detection of recurrent or residual ovarian cancer and for monitoring response to therapy. However, PET/CT may yield false-negative results in patients with small, necrotic, mucinous, cystic, or low-grade tumors. In addition, in the posttherapy setting, inflammatory and infectious processes may lead to false-positive PET/CT results. Despite these drawbacks, PET/CT is superior to CT and MR imaging for depiction of recurrent disease.

Analysis of survival after laparoscopic management of endometrial cancer.

STUDY OBJECTIVE To assess the effect of laparoscopic surgery on the survival of women with early-stage endometrial cancer and to analyze the factors that affect survival. DESIGN Retrospective cohort study (Canadian Task Force classification II-2). SETTING Tertiary teaching hospital. PATIENTS Women with clinical stage I and II endometrial cancer (International Federation of Gynecology and Obstetrics staging, 1971) from January 1993 through June 2003. INTERVENTION Demographic, surgical, perioperative, and pathologic characteristics of women treated with laparoscopy or laparotomy were compared by use of Fishers exact test or the Student t test. Recurrence-free and overall survival was calculated by use of the Kaplan-Meier method. Stratified analyses were performed with the log-rank test for factors affecting survival (surgical stage, histologic study, and grade). MEASUREMENTS AND MAIN RESULTS Sixty-seven and 127 women were treated with laparoscopy and laparotomy, respectively. Median follow-up was 36.3 months for the laparoscopy group and 29.6 months for the laparotomy group. The complication rates in the 2 groups were comparable. Women undergoing laparoscopy had shorter hospital stay and less morbidity related to infection. The 2- and 5-year estimated recurrence-free survival rates for the laparoscopy and laparotomy groups (93 % vs 91.7% and 88.5% vs 85%, respectively), as well as the overall 2- and 5-year survival rates (100% vs 99.2% and 100% vs 97%, respectively) were similar. CONCLUSIONS Laparoscopic surgery in women with early-stage endometrial carcinoma resulted in survival rates similar to laparotomy, although a small sample size precludes definitive conclusions. A larger randomized comparison of the 2 techniques is needed to validate these findings.

Survival analysis of robotic versus traditional laparoscopic surgical staging for endometrial cancer

OBJECTIVE The purpose of this study was to compare the survival of women with endometrial cancer managed by robotic- and laparoscopic-assisted surgery. STUDY DESIGN This was a retrospective study conducted at 2 academic centers. Primary outcomes were overall survival, disease-free survival (DFS), and disease recurrence. RESULTS From 2003 through 2010, 415 women met the study criteria. A total of 183 women had robotic and 232 women had laparoscopic-assisted surgery. Both groups were comparable in age, body mass index, comorbid conditions, histology, surgical stage, tumor grade, total nodes retrieved, and adjuvant therapy. With a median follow-up of 38 months (range, 4-61 months) for the robotic and 58 months (range, 4-118 months) for the traditional laparoscopic group, there were no significant differences in survival (3-year survival 93.3% and 93.6%), DFS (3-year DFS 83.3% and 88.4%), and tumor recurrence (14.8% and 12.1%) for robotic and laparoscopic groups, respectively. Univariate and multivariate analysis showed that surgery is not an independent prognostic factor of survival. CONCLUSION Robotic-assisted surgery yields equivalent oncologic outcomes when compared to traditional laparoscopic surgery for endometrial adenocarcinoma.

PET/CT Evaluation of Cervical Cancer: Spectrum of Disease

The prognosis of invasive cervical cancer is based on the stage, size, and histologic grade of the primary tumor and the status of the lymph nodes. Assessment of disease stage is essential in determining proper management in individual cases. In the posttherapy setting, the timely detection of recurrence is essential for guiding management and may lead to increased survival. However, the official clinical staging system of the International Federation of Gynecology and Obstetrics has inherent flaws that may lead to inaccurate staging and improper management. Combined positron emission tomography (PET)/computed tomography (CT) represents a major technologic advance, consisting of two integrated complementary modalities whose combined strength tends to overcome their respective weaknesses. PET/CT has higher sensitivity and specificity than do conventional anatomic modalities and is valuable in determining the extent of disease and detecting recurrent or residual tumor. The combination of 2-[fluorine-18]fluoro-2-deoxy-d-glucose PET with intravenous contrast material-enhanced high-resolution CT has proved useful for avoiding the interpretative weaknesses associated with either modality alone and in increasing the accuracy of staging or restaging. Nonetheless, accurate PET/CT interpretation requires a knowledge of the characteristics of disease spread or recurrence and an awareness of various imaging pitfalls if false interpretations are to be avoided.