Search

Pirarubicin (PIRA) has been shown to have improved potency with less cardiac toxicity in several phase I and II clinical trials in Japan and Europe. Since Adriamycin (DXR) remains one of the most potent drugs in treatment of gynecologic cancers, this derivative has the potential to become an important chemotherapeutic agent. In this study, we compared the performance of these two drugs against a panel of 10 gynecologic cancer cell lines. The ATP chemosensitivity assays were used to determine dose-response curves. Flow cytometry was used to study cell kinetic response to both drugs. Using an IC50 value of 0.2 micrograms/ml as a cutoff for drug sensitivity, 4 cell lines, ECC1, HEC1B, BG1, and SKOV3, were considered resistant to DXR. By comparing IC50s, PIRA was 3.4 +/- 0.4 times more potent than DXR (P = 0.05). The other 6 cell lines, AN3, AE7, HEC1A, CAOV3, SKUT1B, and ME180, were considered sensitive to DXR. In this group of cell lines, PIRA was 1.6 +/- 0.3 times more potent than DXR (P = 0.5). Both PIRA and DXR elicited a spectrum of cell kinetics. By comparing the magnitude of G2 blocks at 0.1 micrograms/ml, PIRA was approximately 2-5 times more potent than DXR in SKUT1B, HEC1A, and BG1 cell lines. PIRA also displayed a reverse dose-response pattern of G2 block so that at high dose, cell cycle kinetics would mirror those of untreated controls. This observation supports the presence of a resistant tumor subpopulation and the concept of tumor heterogeneity.

The incidence and prognostic significance of positive intraperitoneal cytology taken during a radical hysterectomy was reviewed. A prospective study looking at intraperitoneal cytology was conducted by using 400 consecutive radical hysterectomies from January 1988 through June 1996. All selected patients had peritoneal washings performed prior to a radical hysterectomy with pelvic and para-aortic lymphadenectomy. A single pathologist reviewed all cytological and histologic specimens. A total of 400 patients were included in the study. Only 7 of 400 (1.8%) had positive intraperitoneal cytology. Four had squamous cell cancer and 3 had adenocarcinoma. Five had stage IB cervical cancer and the remainder were stage IIA. Three had positive nodes. Six of 7 had tumor size greater than 3 cm. Three of 7 had >50% invasion and 2 of 7 had lymphovascular space invasion. No other risk factors were present in these specimens. Six of 7 recurred within 18 months of surgery. Recurrences were local or retroperitoneal; none were upper abdomen or intraperitoneal. The incidence of positive peritoneal cytology during radical hysterectomy is 1.8%. The cost of these cytology specimens did not offer an advantage to the current surgical–pathological factors used to determine prognosis and adjuvant therapy.

Recurrent vulvar cancer occurs in an average of 24% of cases after primary treatment after surgery with or without radiation. The relatively few primary vulvar cancers, combined with the low proportion of recurrences, has made it difficult to perform randomized studies to document the most appropriate therapeutic modalities. Most reports are small retrospective studies and anecdotal reviews that have emphasized the importance of surgery and have led to new approaches with respect to chemoradiation. Traditionally, the most accepted treatment of vulvar cancer has been and continues to be surgery. Recently, radiation and chemotherapy have been combined with very encouraging results. The therapeutic modality used depends on the location and extent of the recurrence. Most recurrences occur locally near the original resection margins or at the ipsilateral inguinal or pelvic lymph nodes. Lateralized local vulvar recurrences treated with a wide radical local excision with inguinal lymphadectomy results in an excellent cure rate of 70%. With a central pelvic recurrence with antecedent radiotherapy involving the urethra, upper vagina, and rectum, total pelvic exenteration is indicated in a select group of patients with curative intent. Radiotherapy or chemoradiation concomitantly with wide radical local excision of an advanced vulvar has proven successful in avoiding an exenteration, with improved survival and less morbidity. Prospective and retrospective studies have shown excellent results using radiation or chemoradiation with wide radical local excision in patients with locally advanced disease in whom adequate resection margins are difficult to achieve (with a central lesion requiring exenteration) or with debilitating medical conditions that preclude surgery. In these patients, chemoradiation has shown favorable results when used before a wide local resection. In patients with advanced local disease, external beam and interstitial radiation has been used for palliative and curative intent with encouraging results. Regional recurrences to the inguinal and pelvic lymph nodes have been shown to have a poor prognosis with a high mortality rate. We recommend that inguinal recurrences without prior radiation therapy undergo excision followed by radiotherapy with chemosensitization. In patients with previous radiation to the inguinal lymph nodes, we try to avoid any excisional procedures because of the high rate of complications. We offer these patients brachytherapy for palliation. With pelvic recurrences, we recommended chemoradiation as the treatment modality. In the subset of patients with distant metastasis, chemotherapy may be offered; however, few studies have been performed to advocate any single combination. The literature supports the use of 5-fluorouracil or cisplatin as single agents or in combination to have sensitivity against squamous cells. There are few studies revealing improvement in 5-year survival, thus these patients may benefit from recruitment into research protocols.

Background. Malignant peripheral nerve sheath tumors (MPNSTs) are rare in the gynecological population and have a high risk for local and distant failures. Multimodal management of a patient with MPNST of the vulva and review of the literature are outlined. Case. A 34-year-old woman presented with a complaint of a rapidly increasing pelvic mass, pain, and difficulty ambulating. A disfiguring 20 × 20-cm vulvar mass was identified and a recurrent MPNST diagnosed. Therapy included external-beam radiation, anterior pelvic exenteration with pelvic reconstruction, and adjuvant chemotherapy without complication. Conclusion. It is recommended that for malignant peripheral nerve sheath tumors of the vulva, complete surgical resection be performed with adjuvant radiation and chemotherapy in selected cases.

BACKGROUND Cancer cell growth is an energy-related process supported by an increased glucose metabolism. The objective of this study was to investigate the association of GLUT-1 with response to chemotherapy and outcome in patients with ovarian carcinoma. METHODS Histologic sections of formalin fixed, paraffin embedded specimens from 113 primary ovarian carcinomas were stained for GLUT-1 by using polyclonal GLUT-1 antibody (Dako Co., Carpinteria, CA) and the labeled streptavidin biotin procedure. Intensity of GLUT-1 staining was compared with disease free survival (DFS), chemotherapy response, and other clinicopathologic characteristics. RESULTS GLUT-1 cytoplasmic membrane staining was observed in 89 of 104 (85.6%) malignant tumors. Poorly differentiated tumors showed a trend to overexpress the GLUT-1 protein compared with the more differentiated counterparts (27.6% vs. 8.7%; P = 0.08). Patients who experienced a complete clinical response to chemotherapy were more frequently GLUT-1 positive than GLUT-1 negative (80% vs. 51.5%; P = 0.036). In multivariate analysis of advanced stage disease, residual tumor (P = 0.0001) and high GLUT-1 expression levels (P = 0.028) were the only independent variables that maintained a significant association with response to chemotherapy (P = 0.0001; chi-square = 38.13). In the subgroup of Stage III–IV (International Federation of Gynecology and Obstetrics patients showing a complete clinical response, GLUT-1 overexpression was associated with a shorter DFS. The median time to progression was 30 months in GLUT-1 strongly positive cases (> 50% of cancer cells positive) versus 60 months in GLUT-1 weakly positive cases (≤ 50% of cancer cells positive; P = 0.024). CONCLUSIONS GLUT-1 status is an independent prognostic factor of response to chemotherapy in advanced stage ovarian carcinoma. Moreover, patients overexpressing GLUT-1 show a significantly shorter DFS. These results suggest that the assessment of GLUT-1 status may provide clinically useful prognostic information in patients with ovarian carcinoma. Cancer 2001;92:1144–50. © 2001 American Cancer Society.

From 1965 to 1995, at the University of Miami/Jackson Memorial Medical Center, 1223 patients with stage IA2, IB, or IIA cervical cancer have undergone a radical hysterectomy. The charts of these patients were reviewed retrospectively for pathology reports showing positive or close surgical margins. Fifty-one of these cases had final pathology results interpreted as close vaginal margins (CVM), which we define as tumor less than or equal to 0.5 cm from the vaginal margins of resection. All slides of blocks with close vaginal margins were found and reviewed by a single pathologist. Twenty-eight (54.9%) had parametrial involvement or positive lymph nodes and received adjuvant radiation therapy (RT). Of the remaining 23 cases, only 6 had other high risk factors, tumor greater than 4 cm, poorly differentiated, greater than 50% invasion, or lymphovascular space involvement. Sixteen of 23 received radiation. The 5-year survival was significantly greater with RT, 81.3%, than without RT, 28.6% (P < 0.05). The recurrence rate was also decreased from 85.7 to 12.5% (P < 0.01). Although present in less than 2% of radical hysterectomy specimens, CVM without other high risk factors may be an important prognostic variable that should be considered when making adjuvant therapy decisions.

Pelvic exenteration is a salvage procedure used primarily for recurrent gynecologic carcinoma. Up to the present time, an ileal or colon conduit has been used for urinary diversion and the patient remains incontinent of urine. This is a preliminary report of nine patients with gynecologic carcinoma in whom a continent urinary diversion procedure was performed. A segment of distal ileum, the ascending colon, and part of the transverse colon are used to create the colonic reservoir. The segment of colon is opened along the tenia and folded onto itself. The walls of the ascending and transverse colon are anastomosed to detubularize this segment of bowel and eliminate the transient high pressure of the colon. Surgical staples are used for the anastomosis. The segment of ileum is tapered and three purse-string sutures (2-O silk) are placed at the level of the ileocecal valve to achieve continence. The short segment of ileum is then exteriorized as a stoma through which the patient catheterizes. Antirefluxing, non-tunneled ureterocolonic anastomoses are performed. The anterior wall of the reservoir is closed with absorbable staples. Postoperative urodynamic studies have shown maximum capacity of 750 ml and the area of continence to be at the ileocecal valve where the purse-string sutures are placed. All patients are continent and postoperative radiographs were negative for reflux. Follow-up was 6 to 12 months. The colonic reservoir is a capacious low-pressure system and warrants further clinical trials in patients with gynecologic cancer.