Rosanna Fontanelli

Combined preoperative chemoradiotherapy followed by radical surgery in locally advanced vulvar carcinoma: A pilot study

Although for decades exenterative surgery has represented the standard treatment for patients with locally advanced vulvar cancer, combined approaches, including preoperative radiation with or without chemotherapy, are now considered the treatment of choice. We report the results of a pilot study on concurrent chemoradiotherapy followed by radical surgery for patients with locally advanced squamous cell carcinoma of the vulva.

13 Pelvic and para-aortic lymphadenectomy in cancer of the ovary

The role of the lymphadenectomy in ovarian carcinoma is widely discussed. The natural history of disease, its tendency to spread to peritoneal cavity and the lack of any reported series of careful node dissections undertaken during surgical exploration has made it difficult to establish the real significance of nodal metastatization and the optimal therapeutic approach for patients with positive nodes. At the Istituto Nazionale Tumori, Milan, 341 patients with ovarian carcinoma have been subjected to lymph node dissection. In 253 cases in which lymphadenectomy has been carried out during first surgery, the lymphonodal diffusion has been evaluated by stage, grading and histology. The incidence of lymphonodal metastases increased with the diffusion of the primitive tumour and this is particularly evident for the serous adenocarcinoma. From our data (as shown in our series of 173 cases Stage III with peritoneal and retroperitoneal diffusion) the lymphonodal involvement has to be considered as a negative prognostic factor, influencing survival in a statistically significant way. In the 88 patients subjected to radical lymphadenectomy during second-look surgery, after chemotherapy, a smaller percentage of positive nodes was observed as compared to untreated cases but, on the other hand, we documented a portion of positive nodes not sterilized by sistemic therapy. All this data confirm the necessity to perform radical lymphadenectomy not only as a staging procedure (because of low sensitivity of lymphangiography) but also as a therapeutic one for some patients.

Diagnostic accuracy of sentinel node in endometrial cancer by using hysteroscopic injection of radiolabeled tracer

OBJECTIVE Retrospective and perspective series have shown the feasibility of sentinel lymph-node (SLN) identification of pelvic nodes in endometrial cancer using a cervical injection of tracers. We designed a perspective study to assess the detection rate and diagnostic accuracy of the SLN procedure by means of hysteroscopic injection of a radiolabeled tracer in endometrial cancer patients. METHODS Patients with endometrial cancer underwent hysteroscopic technetium injection. SLN assessment was performed intraoperatively. A systematic pelvic and paraaortic dissection was carried out thereafter. SLNs were examined by standard and immunochemistry methods. The primary endpoint was estimation of sensitivity and negative predictive value (NPV) of sentinel-node biopsy. RESULTS From 2005 to 2010, 80 consecutive patients entered the study. No severe complications occurred during or after the injection or during surgical SLN biopsy. At least one SLN was detected in 76 of the 80 eligible patients. Fifty nine patients were evaluable according to the study protocol. Ten of these patients (17%) had node metastases. Thirty-three patients (56%) had SLN in the para-aortic area. NPV was 98% (95% CI 89.4-100) and sensitivity 90% (55.5-99.8). CONCLUSIONS SLN detection for endometrial cancer patients has a high sensitivity and NPV when injection is carried out by hysteroscopy. The occurrence of a 56% of sentinel node in paraaortic area may suggest a better sensitivity in this area using hysteroscopic injection compared to cervical injection.

Prognostic indicators in melanoma of the vulva.

Background: The aim of this study was to evaluate the prognostic significance of clinicalpathologic variables in melanoma of the vulva.Methods: From 1979 through 1995, 40 women with a diagnosis of vulvar melanoma underwent radical surgery. Patient age, tumor size and site, histologic type, ulceration, tumor thickness, lymph node status, and number of positive lymph nodes were assessed for prognostic significance by multivariate analysis.Results: Tumor thickness was a significant predictor of lymph node involvement, but not of survival. The most powerful predictors of survival by multivariate analysis were the lymph node status (P 5 .002) and the number of positive lymph nodes (P 5 .00003).Conclusions: The number of positive lymph nodes represents the strongest prognostic factor in melanoma of the vulva. Because of the lack of effective adjuvant therapies, such prognostic indicators might be used to define the timing and extent of the surgical approach.

The Role of Appendectomy in Surgical Procedures for Ovarian Cancer

To assess the role of appendectomy in the surgical procedures for ovarian cancer, we evaluated retrospectively the clinical charts of 435 patients who underwent surgery after diagnosis of ovarian cancer. The appendix was removed in 160 cases and pathological examination revealed 37 with metastatic implants (23%). All the patients with appendiceal metastases showed advanced disease (stages III-IV) with an incidence of 43%. Ninety-one percent (31/34) of the tumors with appendiceal involvement at the staging operation were of the serous cell type and grade II or III. No case with early stage, right ovary carcinoma showed appendiceal metastatic foci, denying the existence of a preferential lymphatic pathway. Microscopic involvement was found only in 4 patients with advanced disease (11.7%). No intra- or postoperative complication directly related to the appendectomy was recorded. We conclude, with these results, that appendectomy should be part of the cytoreductive operation for ovarian cancer.

Gemcitabine Combined with Oxaliplatin (GEMOX) as Second-Line Chemotherapy in Patients with Advanced Ovarian Cancer Refractory or Resistant to Platinum and Taxane

Objectives: The aimof this multicenter feasibility study was to determine the toxicity profile and antitumor activity of the gemcitabine plus oxaliplatin combination as second-line treatment in platinum plus paclitaxel resistant/refractory advanced ovarian cancer. Methods: Twenty patients received a 30–60-min infusion of gemcitabine a week for 2 weeks, followed by 120–180 min infusion of oxaliplatin every 3 weeks. The doses used were 1,000 and 130 mg/m2, respectively. Seventeen cases (85% of the total) were platinum resistant and 3 (15%) were platinum refractory. Results: Grade 3/4 thrombocytopenia occurred in 14/20 of cases (70%); there were no symptomatic cases. 2 patients required platelet transfusion and 8 patients received hydrocortisone. The dose- limiting toxicity was thrombocytopenia. Combined grade 3/4 neutropenia was observed in 8/20 (40%) of cases (no sepsis was registered). Five patients were treated with recombinant erythropoietin because of grade 3 anemia and 4 cases received G-CSF prophylactically from the first cycle. The overall response rate of the combination in terms of antitumor activity was 26% (95% CI = 9–51%). Conclusion: A combination of gemcitabine and oxaliplatin using this schedule gave rise to a moderate/severe toxicity profile and would be feasible only if growth factors were used and/or gemcitabine were administered at lower doses. The antitumor activity of the combination was insufficient reward for the resultant toxicity profile. However, equivalent to that of other drugs used in platinum refractory and resistant patients.

Adult granulosa cell tumor of the ovary: a clinico pathologic study of 35 cases.

Aims and background Adult granulosa cell tumor has a low malignant potential but requires an extensive follow-up of more than 5 years to accurately assess tumor activity. The aim of the present study was to evaluate the clinical characteristics, the treatment and the outcome of this rare ovarian tumor. Study design A retrospective review of 35 cases treated at primary onset of disease during a 23-year period from 1971 to 1993. Results The disease-free survival rate for stages IA-B-C at 5 and 10 years was 90% and 84%, respectively; for stages III-IV the 5-year freedom from progression rate was 16%. Conclusions The most important prognostic factor appears to be the extent of tumor involvement outside of the ovary.

Nondysgerminomatous tumors of the ovary treated with cisplatin, vinblastine, and bleomycin: Long-term results

Twenty-four consecutive patients with nondysgerminomatous germ cell tumor of the ovary were treated after surgery with cisplatin, vinblastine, and bleomycin (PVB regimen). The cycle was repeated every 3 weeks for three to five courses. Fourteen patients had endodermal sinus tumor, and 10 had mixed germ cell tumors. Stage of disease (FIGO, 1986) was as follows: stage I, 6; stage IIc-IV, 17; and recurrence, 1 patient. All patients were monitored by alpha-fetoprotein and human chorionic gonadotropin. Only 1 patient had received previous chemotherapy. All 5 patients without residual disease and with negative marker levels in which PVB was used as adjuvant treatment were free of disease for a median duration of 59 months from the start of PVB. Of the 19 patients with measurable disease (evident disease or positive marker levels), complete remission was obtained in 16 (84%), but 5 of these relapsed. Therefore, treatment with PVB failed in 8 out of 19 patients (42%) with measurable disease. Toxicity was evident, but no patient died of it. Menses were regular in 11 patients whose initial surgery was conservative. PVB regimen is an effective but not a satisfactory treatment. The considerable failure rate of PVB treatment suggests the investigation of other regimens.

The Role of Secondary Surgery in Recurrent Ovarian Cancer

Despite optimal treatment (complete cytoreduction and adjuvant chemotherapy), 5-year survival for advanced ovarian cancer is approximately 30% and most patients succumb to their disease. Cytoreductive surgery is accepted as a major treatment of primary ovarian cancer but its role in recurrent disease is controversial and remains a field of discussion mainly owing to missing data from prospective randomized trials. A critical review of literature evidence on secondary surgery in recurrent ovarian cancer will be described.

Surgical staging for epithelial ovarian tumors of low malignant potential

From January 1975 to December 1991, 34 patients with a diagnosis of epithelial ovarian tumors of low malignant potential (LMP) were admitted to the Istituto Nazionale Tumori of Milan. Eighteen of them (group 1) underwent complete staging laparotomy and retroperitoneal para-aortic and pelvic lymphadenectomy, as for ovarian cancer. In the remaining 16 cases (group 2), the surgical treatment ranged from unilateral oophorectomy to incomplete staging procedure. In group 1, nine patients (50%) were found to have retroperitoneal nodal involvement. In group 2, all patients had stage I disease. Patients were followed up for 20–222 months (mean 108, median 86). There were two recurrences in group 2 (after 5 years) and none in group 1 (NS). Currently all patients are alive and disease free. Nine of 18 group 1 patients were upstaged to stage III on the basis of lymph node involvement only. However, at least in this retrospective series, lymph node metastases did not affect prognosis or survival.