Association of CXC chemokine receptor type 4 expression and clinicopathologic features in human vulvar cancer.

OBJECTIVE: Although CXC chemokine receptor type 4 (CXCR4) is known to be expressed in various solid tumors and plays an integral role in cancer invasion and metastasis, expression of CXCR4 in human vulvar cancer has not yet been investigated. We examined distribution and expression of this chemokine receptor in specimens of invasive and noninvasive human vulvar neoplasms to elucidate its clinical significance. METHODS: Study patients were 38 consecutive patients (31 with primary vulvar cancers and 7 with intraepithelial neoplasms) treated at one of our hospitals. Sections of all specimens were evaluated for CXCR4 expression by means of immunohistochemistry. Relations between CXCR4 expression and clinicopathologic features including prognosis were investigated. RESULTS: None of the 7 vulvar intraepithelial lesions expressed CXCR4. Of the 31 invasive vulvar tumor samples examined, 19 (61%) stained positively for CXCR4; 15 (68%) of 22 squamous cell carcinomas and 2 (29%) of 7 Paget tumors were CXCR4 positive. The difference in expression between invasive cancers and intraepithelial neoplasms was significant (P = 0.003). FIGO (International Federation of Gynecology and Obstetrics) stage III-IV cancers, in comparison to FIGO stage I-II cancers, were more likely to be positive for CXCR4 (82% vs 50%, P = 0.08). In terms of disease-free survival, prognosis of cancers that expressed CXCR4 was poorer than that of CXCR4-negative cancers (P = 0.013), but in terms of disease-specific survival, prognosis did not differ significantly between CXCR4-positive and -negative cancers (P = 0.111). CONCLUSIONS: More than half of invasive squamous cell vulvar cancers can be expected to express CXCR4, and CXCR4 expression correlates with poor disease prognosis.

Preoperative management of patients with gynecologic malignancy complicated by existing venous thromboembolism.

OBJECTIVES: In treating gynecologic malignancies, we sometimes encounter patients in whom venous thromboembolism (VTE) has developed before surgery. Few reports exist on preoperative management of VTE. We conducted a study to determine the optimum preoperative management strategy for patients with gynecologic malignancy and existing VTE. STUDY DESIGN: We reviewed the clinical records of patients treated between April 2004 and March 2010 in the Department of Obstetrics and Gynecology at Mie University Hospital. During this period, 654 exploratory or therapeutic laparotomies were performed for gynecologic malignancy. All patients were assessed by ultrasound for VTE before and after surgery. Twenty-five of the 654 patients (3.8%) had preoperative VTE. We reviewed the 25 cases and evaluated the management method and outcomes in terms of VTE. RESULTS: Most preoperative VTEs were located in a crural vein (23 cases; 92%); only 2 (8%) were in a pelvic vein. Three patients were excluded from the study because they had only a small organized thrombus and were treated with VTE prophylaxis according to American College of Chest Physicians (ACCP) guidelines. The other 22 patients were given graduated compression stockings and began anticoagulation therapy with heparin (unfractionated heparin or heparin calcium) immediately after the VTE diagnosis. Anticoagulation therapy was continued until a mean 8.5h before surgery and then restarted 10h (mean) after surgery. Sixteen of the 22 patients were treated by intermittent pneumatic compression during and after surgery. This management strategy resulted in six cases (27%) of diminished VTE, 10 cases (46%) without remarkable change, and six cases (27%) of deterioration. Clinical deterioration occurred in two of the 22 cases (9%), i.e., PE or pelvic VTE developed. CONCLUSIONS: Our preoperative management of existing VTE appears to be insufficient. Shorter or no interruption of antithrombotic therapy and/or another intervention such as inferior vena cava filter placement may be necessary in patients with preoperative VTE.

A case of usual (basaloid)-type vulvar intraepithelial neoplasia that failed to respond to imiquimod cream: clinical implications.

The authors report a case of usual-type (basaloid-type) vulvar intraepithelial neoplasia (VIN) 3 that failed to respond to imiquimod cream. A 51-year-old Japanese woman visited her local gynecologist complaining of vulvar itching. Atypical cells were noted in cytology smears, but nine vulvar biopsy specimens showed benign proliferation of epithelial tissue. The patient was placed under careful observation for 8 months, when the vulvar smears once again showed atypical cells and biopsy specimens revealed VIN3. The patient was then referred to our hospital where she was given a diagnosis of VIN 3, basaloid type of usual type. The biopsy specimens were positive for p16 and the lesions were confirmed to be human papilloma virus (HPV)-related. We recommended simple vulvectomy but the patient requested conservative treatment with imiquimod cream. With her written informed consent, we prescribed imiquimod cream to be self-administered 3 times a week. Colposcopy and pap smear test were performed every 2 weeks. Four weeks after the start of treatment, a fingertip-sized papule was detected at the patient's vaginal introitus. By 6 weeks, the lesion had enlarged, and biopsy specimens revealed invasive squamous cell carcinoma. At 7 weeks, we performed simple vulvectomy. The surgical specimen showed stage pT1b keratinizing-type squamous cell carcinoma. HPV-16 DNA was detected in the specimen.

Efficacy of a sodium hyaluronate-carboxycellulose membrane (seprafilm) for reducing the risk of early postoperative small bowel obstruction in patients with gynecologic malignancies.

OBJECTIVE: To evaluate the effect of a sodium hyaluronate and carboxymethylcellulose membrane (Seprafilm) on early postoperative small bowel obstruction (EPSBO) in patients with gynecologic malignancies. METHODS: One hundred forty-five patients who had Seprafilm placed during gynecological surgery between April 2002 and March 2007 (Seprafilm group) were compared with a historical control group of patients managed without Seprafilm between January 1997 and March 2002. All patients undergoing primary surgery with pelvic or combined pelvic and para-aortic lymphadenectomy for gynecological malignancies were retrospectively assessed for EPSBO and surgical infections. RESULTS: The incidence of EPSBO was significantly lower (P < 0.05) in the Seprafilm group (3.1%, 6/191) than in the control group (13.9%, 25/180). According to logistic regression analysis, the use of Seprafilm (odds ratio, 0.18; 95% confidence interval, 0.07-0.47; P < 0.0005) and the performance of pelvic lymphadenectomy alone (odds ratio, 0.27; 95% confidence interval, 0.09-0.78; P < 0.02) were independent predictors of a lower rate of EPSBO. The incidence of surgical infection showed no significant difference between the Seprafilm group (3.6%) and the control group (6.7%). CONCLUSIONS: Placement of Seprafilm helped to prevent EPSBO and had no significant adverse effect on surgical infections in patients who underwent lymphadenectomy for gynecological malignancy.

Weekly low-dose paclitaxel and carboplatin therapy in gynecological cancer patients with venous thrombosis.

BACKGROUND: To evaluate the safety and toxicity of weekly low-dose paclitaxel plus carboplatin therapy in gynecological cancer patients with venous thrombosis (VT). MATERIALS AND METHODS: Ovarian or endometrial cancer patients with VT who were scheduled to receive neoadjuvant or adjuvant chemotherapy were eligible. Each 21-day cycle of treatment consisted of carboplatin (AUC 2.0) and paclitaxel (80 mg/m2) on days 1, 8 and 15. At the end of chemotherapy, each patient's VT was checked by ultrasonography. RESULTS: Twenty-five gynecological cancer patients who received warfarin therapy with a target international normalized ratio (INR) of 1.5-2.5 were enrolled in this study. Neutropenia and peripheral neuropathy (grades 3 or 4) occurred in 26% and 4% of the patients, respectively. Chemotherapy did not cause any changes of the INR in any patient. After chemotherapy, the VT showed resolution in 19 patients (76%) and no patient developed fresh thrombosis. CONCLUSION: Weekly low-dose paclitaxel plus carboplatin therapy is a reasonable treatment option for gynecological cancer patients with VT.