FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy.

Gene copy number alterations, tumor cell stemness, and the development of platinum chemotherapy resistance contribute to high-grade serous ovarian cancer (HGSOC) recurrence. Stem phenotypes involving Wnt-ß-catenin, aldehyde dehydrogenase activities, intrinsic platinum resistance, and tumorsphere formation are here associated with spontaneous gains in Kras, Myc and FAK (KMF) genes in a new aggressive murine model of ovarian cancer. Adhesion-independent FAK signaling sustained KMF and human tumorsphere proliferation as well as resistance to cisplatin cytotoxicity. Platinum-resistant tumorspheres can acquire a dependence on FAK for growth. Accordingly, increased FAK tyrosine phosphorylation was observed within HGSOC patient tumors surviving neo-adjuvant chemotherapy. Combining a FAK inhibitor with platinum overcame chemoresistance and triggered cell apoptosis. FAK transcriptomic analyses across knockout and reconstituted cells identified 135 targets, elevated in HGSOC, that were regulated by FAK activity and ß-catenin including Myc, pluripotency and DNA repair genes. These studies reveal an oncogenic FAK signaling role supporting chemoresistance.

Survival of women with microinvasive adenocarcinoma of the cervix is not improved by radical surgery.

BACKGROUND: Treatment for early-invasive adenocarcinoma of the cervix remains controversial. Although data have shown similar survival rates to those seen with squamous cell carcinoma, conservative options for patients with microinvasive adenocarcinoma have not been as widely accepted. Despite comparable survival outcomes, patients with early-invasive adenocarcinoma are still routinely subjected to more radical surgical techniques than their equivalently staged squamous cell counterparts. OBJECTIVE: The objective of the study was to evaluate how less radical surgery has an impact on 5 year survival in patients with microinvasive adenocarcinoma of the cervix. STUDY DESIGN: The Surveillance, Epidemiology, and End Results database was queried from 1988 through 2010 to perform a retrospective analysis of women with International Federation of Gynecology and Obstetrics stage IA1 or IA2 cervical carcinoma. Five year survival by procedure type (local excision, simple hysterectomy, or radical hysterectomy) was determined for each cell type (squamous or adenocarcinoma), as was lymph node status. RESULTS: Among 1567 patients with cervical adenocarcinoma, 5 year survival was 97.3% (confidence interval, 95.8-98.2%) for stage IA1 disease and 98.3% (confidence interval, 96.5%, 99.2%) for stage IA2. For comparison, the 5-year survival rates for 5,749 patients with stage IAI or lA2 squamous cell carcinoma were 96.7% (confidence interval, 96.0-97.3%) and 95.6% (confidence interval, 94.4-96.5%), respectively. For stage IA1 ACA, survival was 96.6%, 98.4% and 96.5% following excision, hysterectomy and radical hysterectomy, respectively. For stage IA2 ACA, survival rates were 100%, 96.9% and 99.4%, respectively. There was no statistical difference in survival between patients having either cell type undergoing local excision (P = .26), simple hysterectomy (P = .08), or radical hysterectomy (P = .87). We also found no statistically significant difference in survival among patients with adenocarcinoma compared by treatment type (local excision compared with simple hysterectomy [P = .64]; local excision compared with radical hysterectomy [P = .82]; or simple hysterectomy compared with radical hysterectomy [P = .70]). Among patients with adenocarcinoma, 0.97% had positive pelvic lymph nodes, none had positive aortic lymph nodes, and 91.85% had confirmed negative lymph nodes. For squamous cell carcinoma, 0.72% of patients had positive pelvic lymph nodes and 0.10% had positive aortic lymph nodes. CONCLUSION: There was no significant difference in survival when patients were compared by cell type or procedure, suggesting that survival of patients with microinvasive adenocarcinoma is not improved by utilizing more invasive surgical methods. Regardless of histology, the frequency of nodal involvement was very low among both groups, supporting an overall excellent prognosis for all patients with microinvasive disease. We submit these data as evidence that preoperative planning of more conservative techniques is appropriate, not just for those with squamous histology or who desire future fertility, but for all patients with microinvasive cervical disease.

Squamous Cell Carcinoma of the Vulva Presenting as an Isolated Inguinal Lymph Node Metastasis: A Case Report.

Background: Vulvar carcinoma is usually diagnosed after a patient notices bleeding, pruritis, or a lesion. We describe a case of vulvar carcinoma presenting as an isolated lymph node metastasis in the setting of negative pelvic examinations, with interval development of a vulvar lesion. Case: A 45-year-old woman presented with a left groin mass, and a biopsy revealed squamous cell carcinoma of unknown primary. She underwent an extensive work-up including several evaluations by gynecologic oncologists, all with negative results. Only after 11 months of clinical monitoring did a vulvar lesion appear and the primary tumor was diagnosed. Conclusion: Cancers of unknown primary site presenting in an inguinal lymph node are relatively rare. Vulvar carcinoma should remain in the differential diagnosis even in the setting of a previously negative pelvic examination.

Intra-amniotic fluconazole therapy for Candida albicans intra-amniotic infection.

BACKGROUND: The consequences of intra-amniotic Candida infection can be devastating. Currently, standard management includes delivery. We identified only one previous case reporting intrauterine antifungal therapy, which used transcervical amphotericin B. We present two cases of intra-amniotic Candida infection treated with intra-amniotic fluconazole instilled before membrane rupture. CASES: Two patients presented with intra-amniotic Candida albicans infection that was diagnosed during previability. Both underwent cerclage placement before culture results were available. Aggressive antifungal therapy was instituted using oral, vaginal, and intra-amniotic fluconazole instilled through serial amniocenteses. Both fetuses survived without sequelae. CONCLUSION: Intra-amniotic Candida infection is associated with preterm rupture of membranes, preterm labor, severe neonatal infection, and fetal death. Early diagnosis and treatment is essential.