Posthysterectomy cytology screening: indications and clinical implications.

OBJECTIVE: To review the results of patients who were referred for posthysterectomy of abnormal cytology based on screening indications. MATERIALS AND METHODS: We performed a retrospective review of 64 patients who have been referred for posthysterectomy vaginal colposcopy to the gynecologic oncology service. Patients' demographics, clinical features, reason for screening, and final diagnosis were recorded. Patients were divided into 2 groups based on posthysterectomy screening guidelines. Group A was considered to have undergone unnecessary screening based on national guidelines, and group B had risk factors that appropriately called for continued surveillance. The number of colposcopic examinations and the incidence of neoplasia were recorded for each group. RESULTS: The mean age of the patients was 65 years (range = 35-95 y). Group A included 22 patients with history of abnormal cytology posthysterectomy for benign disease. Of the 22 abnormal cytology results, 21 were low-grade squamous intraepithelial lesion (n = 14) or atypical squamous cells of undetermined significance (n = 7) with 1 high-grade squamous intraepithelial lesion. After referral and colposcopy of this group, no neoplasia was found. Group B included 42 total patients. Of these 42 patients, 20 (48%) had a history of cervical intraepithelial neoplasia, 12 (28%) had a history of vaginal intraepithelial neoplasia, 6 (14%) had history of cervical cancer, 2 (5%) had history of diethylstilbestrol exposure, and 2 (5%) had a history of radiation therapy. In group B, 8 (9%) and 1 (2%) of the patients had vaginal intraepithelial neoplasia 2/3 and squamous cell carcinoma, respectively. CONCLUSIONS: Current national guidelines are appropriate. Adherence to these guidelines will decrease intervention and not affect the detection of vaginal neoplasia. Patients with risk factors for lower genital tract neoplasia warrant continued screening after hysterectomy.

Tumor-infiltrating dendritic cell precursors recruited by a beta-defensin contribute to vasculogenesis under the influence of Vegf-A.

The involvement of immune mechanisms in tumor angiogenesis is unclear. Here we describe a new mechanism of tumor vasculogenesis mediated by dendritic cell (DC) precursors through the cooperation of beta-defensins and vascular endothelial growth factor-A (Vegf-A). Expression of mouse beta-defensin-29 recruited DC precursors to tumors and enhanced tumor vascularization and growth in the presence of increased Vegf-A expression. A new leukocyte population expressing DC and endothelial markers was uncovered in mouse and human ovarian carcinomas coexpressing Vegf-A and beta-defensins. Tumor-infiltrating DCs migrated to tumor vessels and independently assembled neovasculature in vivo. Bone marrow-derived DCs underwent endothelial-like differentiation ex vivo, migrated to blood vessels and promoted the growth of tumors expressing high levels of Vegf-A. We show that beta-defensins and Vegf-A cooperate to promote tumor vasculogenesis by carrying out distinct tasks: beta-defensins chemoattract DC precursors through CCR6, whereas Vegf-A primarily induces their endothelial-like specialization and migration to vessels, which is mediated by Vegf receptor-2.

Reducing excessive toxicity in ovarian cancer treatment: a personalized approach.

The management of ovarian cancer is not only multifactorial, but also patient-specific. Different treatment modalities lead to varying levels of toxicity and individual patient responses, necessitating a personalized approach to each treatment plan. Surgical treatment along with first-line and salvage chemotherapies, are standard modalities but recent innovations in chemotherapy delivery and innovative therapy with mechanism of action are reviewed in this article. Extensive experience with standard chemotherapy has outlined algorithms for managing various toxicities. The focus of treatment may ultimately point towards palliative care and clinicians must be comfortable and well versed in addressing this important option. Overall, management of ovarian cancer requires a multi-faceted approach, keeping the patients' overall health, curative goals and well-being at the forefront. It is nearly impossible to detail exact management plans for every possible toxicity for every patient; formulating personalized treatment plans should be based on evidence and clinician experience, all part of the art of medicine. The objective of this article is to highlight the most frequently encountered and most limiting toxicities of current standard therapies for epithelial ovarian cancer.

Interpretability of excisional biopsies of the cervix: cone biopsy and loop excision.

OBJECTIVE: To compare the results of cold knife conization (CKC) and loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia to determine if excisional method has effects on pathologic interpretation. METHODS: Retrospective review of the perioperative medical records of patients who had a CKC and electrosurgical loop excision of cervix. Patients selected had either primary treatment for cervical intraepithelial neoplasia, suspected invasion, glandular abnormalities or discordant cytology. RESULTS: Among the eligible patients, 61 had CKC and 96 had LEEP. Overall, CKC specimens had interpretable surgical margins more frequently than LEEP (95% vs 85%); however, it was not statistically significant (p=.1). Margins were less likely to be involved with neoplasia in CKC specimens (16% vs 38%; p=.005). Loop electrosurgical excision procedure specimens were less likely to yield a single intact specimen (1.1 vs 1.9; p=.000). Logistic regression showed a significant effect of specimen number (p=.04) on interpretability. CONCLUSION: Current American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines for diagnostic excisional procedure used for glandular lesions suggest that the procedure provides "an intact specimen with interpretable margins." Loop electrosurgical excision procedure in the current study was associated with an increased number of specimens that limited interpretability and an increased number of positive margins. Cold knife conization is preferred in cases where margin status is critical, such as glandular lesions and suspected microinvasion. If LEEP is performed, clinicians should attempt to obtain a single surgical specimen maximizing the pathologic interpretation and disease-free margins.

Should tumor VEGF expression influence decisions on combining low-dose chemotherapy with antiangiogenic therapy? Preclinical modeling in ovarian cancer.

Because of its low toxicity, low-dose (LD) chemotherapy is ideally suited for combination with antiangiogenic drugs. We investigated the impact of tumor vascular endothelial growth factor A (VEGF-A) expression on the efficacy of LD paclitaxel chemotherapy and its interactions with the tyrosine kinase inhibitor SU5416 in the ID8 and ID8-Vegf models of ovarian cancer. Functional linear models using weighted penalized least squares were utilized to identify interactions between Vegf, LD paclitaxel and antiangiogenic therapy. LD paclitaxel yielded additive effects with antiangiogenic therapy against tumors with low Vegf expression, while it exhibited antagonism to antiangiogenic therapy in tumors with high Vegf expression. This is the first preclinical study that models interactions of LD paclitaxel chemotherapy with antiangiogenic therapy and tumor VEGF expression and offers important lessons for the rational design of clinical trials.

Traditional management of invasive cervical cancer.

Cervical carcinoma is staged clinically by examination and simple radiological procedures. CT and MRI can, however, be used to guide management. Prognosis is best made by tumor size. depth of invasion, parametrial involvement, nodal status, LVSI, and histology. CIN III and CIS can be treated by ablative or excisional procedures. Hysterectomy should not be the primary treatment. Microinvasive (<3 mm) Stage IA cervical carcinoma can be treated conservatively with conization in patients who desire fertility, but the standard of care remains simple hysterectomy. Stages IB and IIA can be treated with either radical hysterectomy or radiation therapy dependent upon the patient's health and preference. Risk factors after radical hysterectomy (eg, bulky tumors, deep invasion, involved nodes or margins. LVSI) might warrant adjuvant radiation therapy. Chemoirradiation is the current standard of care for treatment for Stages IIB, III, and [VA. Some clinicians also use this modality in patients with Stage IB disease who are undergoing radiation as the primary treatment. Locally recurrent disease can be treated with either radiation (after radical hysterectomy) or pelvic exeteration (after primary radiation therapy). Exenteration in appropriately selected patients yields 5-year survival rates up to 82% with low complication rates. Many exenterations are aborted intraoperatively because of distant or unresectable disease, however. The incidence of glandular carcinoma of the cervix is rising, particularly in younger women. Cervical carcinoma detected during pregnancy requires the combined efforts of the gynecologic oncologist and the maternal-fetal medical specialist to determine the timing and method of treatment.

Endometrial cancer surgery costs: robot vs laparoscopy.

STUDY OBJECTIVE: To compare surgical costs for endometrial cancer staging between robotic-assisted and traditional laparoscopic methods. DESIGN: Retrospective chart review from November 2005 to July 2006 (Canadian Task Force classification II-3). SETTING: Non-university-affiliated teaching hospital. PATIENTS: Thirty-three women with diagnosed endometrial cancer undergoing hysterectomy, bilateral salpingo-oophorectomy, and pelvic and paraaortic lymph node resection. INTERVENTIONS: Patients underwent either robotic or traditional laparoscopic surgery without randomization. MEASUREMENTS AND MAIN RESULTS: Hospital cost data were obtained for operating room time, instrument use, and disposable items from hospital billing records and provided by the finance department. Separate overall hospital stay costs were also obtained. Mean operative costs were higher for robotic procedures ($3323 vs $2029; p<.001), due in part to longer operating room time ($1549 vs $1335; p=.03). The more significant cost difference was due to disposable instrumentation ($1755 vs $672; p<.001). Total hospital costs were also higher for robotic-assisted procedures ($5084 vs $ 3615; p=.002). CONCLUSION: Robotic surgery costs were significantly higher than traditional laparoscopy costs for staging of endometrial cancer in this small cohort of patients.