Radiation therapy with concomitant and adjuvant cisplatin and paclitaxel in high-risk cervical cancer: long-term follow-up.

INTRODUCTION: Chemo-potentiation of radiation improves survival in women with cervical cancer. Our group has previously demonstrated the tolerability of weekly paclitaxel combined with cisplatin during radiation therapy. We sought to determine the efficacy of this regimen in patients with "high risk" cervical cancer, and to determine the short- and long-term toxicity of this approach. METHODS: We prospectively enrolled surgically staged patients with positive peritoneal cytology, resectable nodal metastases, or primary tumor > 6 cm. Patients were treated using external beam radiation with concomitant cisplatin (50 mg/m2) during weeks 1, 4, and 7, and weekly paclitaxel (50 mg/m2), followed by four courses of adjuvant cisplatin (50 mg/m2) and paclitaxel (135 mg/m2). Toxicity, overall, and disease-free survival were evaluated. RESULTS: Twenty-three patients were enrolled, and 21 were evaluable. Patient allotment by FIGO stage was: IB1 - seven, IB2 - five, IIA - two, IIB - four, IIIB - two, IV - three. Twenty patients (95%) completed radiation treatment (median dose to point A was 8278 cGy). Seventeen patients (81%) completed all chemotherapy. At a median follow-up of 58 months the overall survival was 68%. Overall survival for patients with clinical Stage I and II disease was 82% at a median of 64 months. Hematologic toxicity was common but rarely resulted in treatment delays. Late complications requiring intervention (obstruction, fistula, significant lymphocyst) occurred in 11 patients (52%). CONCLUSION: The combination of paclitaxel and cisplatin appears efficacious in "high-risk" cervical cancer patients. Hematologic toxicity was common but tolerable. Long-term survival was common in these patients, however late toxicity was significant. This regimen should be investigated in collaborative phase III trials.

Efficacy and tolerability of lower-dose topotecan in recurrent ovarian cancer: a retrospective case review.

Topotecan (1.5 mg/m(2)/day for 5 consecutive days of a 21-day cycle) is an established recurrent ovarian cancer treatment, but myelosuppression can be dose limiting. This study evaluates the activity and tolerability of low-dose topotecan in our clinical experience. Case records were reviewed for patients with recurrent ovarian cancer in first through third relapse. Eligible patients had received > or =2 cycles of < or =1.25 mg/m(2) topotecan. Adverse events were evaluated using laboratory and clinical evaluation data. Twenty-seven eligible patients, most with advanced disease, received a total of 209 cycles (median, six cycles). Grade 3 or 4 hematologic toxicities during 184 cycles in 24 assessed patients were neutropenia, leukopenia, thrombocytopenia, and anemia in 35%, 28%, 36%, and 11% of cycles, and 21, 19, 16, and 10 patients, respectively. Only four grade 4 toxicities occurred: anemia (one) and thrombocytopenia (three). Myelosuppression was reversible, noncumulative, and manageable. Moreover, nonhematologic toxicity was generally mild to moderate, and the only two grade 3 events were constipation and deep vein thrombosis. Low-dose topotecan was active in this setting. Lower-dose topotecan is generally well tolerated and active in patients with pretreated ovarian cancer. Prospective clinical trials of low-dose topotecan in recurrent ovarian cancer are warranted.

Using a belly board device to reduce the small bowel volume within pelvic radiation fields in women with postoperatively treated cervical carcinoma.

OBJECTIVE: The purpose of this study was to attempt to reduce the small bowel volume in cervical cancer patients undergoing radiation therapy using the belly board device and a four-field technique. METHODS: From 1994 through 1997, twenty-one patients with cervical cancer were referred to the University of Minnesota Medical Center and underwent surgical staging with or without radical hysterectomy followed by postoperative external beam radiotherapy for various indications including positive nodal disease (n = 11), lymph-vascular space invasion (n = 2), poor histology (n = 3), parametrial disease (n = 4), and positive vaginal margin (n = 1). RESULTS: The median age of the 21 patients was 42 years (25-54 years) and a median external beam pelvic radiation dose of 4775 cGy (range, 4200-5075 cGy) was administered. All patients were evaluated for amount of small bowel in the field in both the supine and prone positions, with and without the belly board device (BBD), using a four-field technique. With a full bladder, abdominal radiographs with contrast were obtained to evaluate the volume of small bowel within the radiation fields. In most patients, the BBD was effective at minimizing the amount of small bowel in the lateral fields, whereas a prone position on the treatment table (without the BBD) spared the most small bowel with the AP/PA fields. Therefore over a 2-day cycle, the most small bowel sparing was obtained with the patients treated prone on the BBD for the lateral fields on Day 1 and prone on the table for the AP/PA fields on Day 2. Patients had FIGO stage IB (n = 18), IA2 (n = 1), and IIA (n = 2). The median follow-up was 37 months (24-65 months). No significant acute gastrointestinal or genitourinary toxicity was experienced and no patients have experienced a bowel obstruction to date. CONCLUSIONS: The BBD may offer a means for positioning the mobile small intestine out of the radiation field and improving the tolerance of radiotherapy. The BBD provides a noninvasive technique for reduction of acute and chronic gastrointestinal morbidity.

The implementation of critical pathways in gynecologic oncology in a managed care setting: a cost analysis.

OBJECTIVES: The aim of the study is to determine whether critical pathways can be implemented at an academic institution to limit cost, without compromising patient satisfaction and quality of care. PATIENTS AND METHODS: Patients undergoing a hysterectomy with either cervical or endometrial cancer were placed on specific critical pathways consecutively for an 18-month study period. Preoperative teaching was intensified to educate the patient regarding expectations during the postoperative period. All patients were started on early feeding and patients were also placed on separate care pathways addressing pain and deep vein thrombosis prophylaxis. Total direct costs and patient satisfaction were obtained throughout the study period. During the year prior to care pathway implementation, patient data and direct costs were obtained for the preintervention group utilized for comparison. Postintervention groups were summarized every 6 months during the study period. RESULTS: From January 1997 through June 1998, 63 patients with cervical carcinoma undergoing a radical hysterectomy (DRG 353) and 21 patients with endometrial cancer who underwent a hysterectomy and lymph node sampling (DRG 355) were utilized as the preintervention group. During the 18-month study period (July 1998-December 1999), 42 patients (DRG 353) and 25 patients (DRG 355) were accrued. The average length of stay was reduced from 5.2 (DRG 353) and 4.7 days (DRG 355) prior to implementation of pathways to 3.4 days in both groups. In addition, total direct costs were reduced by 29 (DRG 353) and 32% (DRG 355) after implementation of care pathways. Patient satisfaction data recorded during the study did not demonstrate any change throughout the study period nor were there any higher rates of readmission after implementation of the care pathways. CONCLUSIONS: Critical pathways in gynecologic oncology can be implemented in a managed care environment in order to maintain high quality of care, maintain outcomes, and help reduce costs.

Phase I trial of ifosfamide and 24-h infusional paclitaxel in pelvic malignancies: a Gynecologic Oncology Group study.

OBJECTIVE: The goal of this work was to develop a combination chemotherapy regimen consisting of ifosfamide and paclitaxel to be evaluated in the management of gynecologic malignancies. METHODS: The Gynecologic Oncology Group conducted a Phase I trial of the regimen, initially with paclitaxel (24-h infusion) delivered on Day 1 and ifosfamide (1 h) administered (with Mesna) over the subsequent 4 days. All patients received granulocyte colony-stimulating factor (G-CSF) starting 24 h after the Day 5 chemotherapy. Treatment was repeated on a 28-day schedule. A cohort of patients also received the alternate sequence of ifosfamide (4 days) followed by paclitaxel. RESULTS: Twenty-two patients were evaluated. Even at the lowest dose level tested (paclitaxel 135 mg/m(2) followed by ifosfamide 1 g/m(2)/day x 4 days) grade 4 neutropenia was almost universal, despite the routine use of G-CSF. The alternate drug administration sequence resulted in marrow suppression of similar severity. CONCLUSION: The combination of 24-h infusional paclitaxel with ifosfamide delivered over 4 days results in severe neutropenia, despite the administration of G-CSF, and is not recommended for further evaluation. In view of the known activity of the two agents in several malignancies, including cervix cancer, it would be reasonable to investigate the delivery of the agents employing alternative treatment schedules predicted to result in less severe marrow suppression (e.g., 3-h infusional paclitaxel).

Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group.

PURPOSE: To compare the progression-free and overall survival in small-volume residual ovarian cancer after treatment with intravenous (IV) cisplatin and paclitaxel or an experimental regimen of IV carboplatin followed by IV paclitaxel and intraperitoneal cisplatin. PATIENTS AND METHODS: Patients were randomized to receive either IV paclitaxel 135 mg/m(2) over 24 hours followed by IV cisplatin 75 mg/m(2) every 3 weeks for six courses or IV carboplatin (area under curve 9) every 28 days for two courses, then IV paclitaxel 135 mg/m(2) over 24 hours followed by intraperitoneal (IP) cisplatin 100 mg/m(2) every 3 weeks for six courses. RESULTS: Of the 523 patients who entered this trial, 462 were determined to be assessable, with prognostic factors well balanced between the treatments. Neutropenia, thrombocytopenia, and gastrointestinal and metabolic toxicities were greater in the experimental arm. As a result, 18% of the patients received < or = two courses of IP therapy. Progression-free survival was superior for patients randomized to the experimental treatment arm (median, 28 v 22 months; relative risk, 0.78; log-rank P =.01, one-tail). There was a borderline improvement in overall survival associated with this regimen (median, 63 v 52 months; relative risk, 0.81; P =.05, one-tail). CONCLUSION: An experimental regimen including moderately high-dose IV carboplatin followed by IP paclitaxel and IV cisplatin yielded a significant improvement in progression-free survival when compared with a standard regimen of IV cisplatin and paclitaxel. Because the improvement in overall survival was of borderline statistical significance and toxicity was greater, the experimental arm is not recommended for routine use. However, the results provide direction for further clinical investigation in small-volume ovarian cancer.

Expression of complement regulatory proteins-CD 35, CD 46, CD 55, and CD 59-in benign and malignant endometrial tissue.

OBJECTIVE: Complement system plays an important role in host defense mechanisms against microorganisms and tumor cells. To protect themselves from autologous complement-mediated damage, normal host tissues express cell membrane-associated complement regulatory proteins (CRPs). To investigate whether neoplastic endometrial tissues overexpress these proteins to escape complement damage, we examined the distribution of complement receptor type 1 (CR1, CD35), membrane cofactor protein (MCP, CD46), decay-accelerating factor (DAF, CD55), and protectin (MACIF, CD59) on frozen endometrial tissue samples. METHODS: A total of 54 endometrial tissue samples were collected. Cryosections were obtained of 31 benign and 23 malignant tissue specimens. Tissue sections were stained by immunohistochemical staining procedure using specific antibodies and employing the avidin-biotin technique. Quantitation of the protein content of these CRPs was determined using the Samba 4000 image analysis system. RESULTS: For all four of the CRPs studied, a statistically significant difference in protein expression between the benign and malignant endometrial tissue specimens (P < 0.0001) was observed. CONCLUSIONS: Overexpression of all the CRPs studied (CD35, CD46, CD55, CD59) was observed in the malignant as compared with the benign endometrial tissues. The upregulation of these CRPs may promote resistance of the endometrial malignant tissue to complement-mediated damage, thereby allowing the tumor cells to escape from cytolysis and thus promoting carcinogenesis.

Are benign cellular changes on a Papanicolaou smear really benign? A prospective cohort study.

OBJECTIVES: To determine the underlying prevalence of cervical intraepithelial neoplasia (CIN) in women with benign cellular changes on a Papanicolaou smear, and to evaluate follow-up strategies to identify women at high risk for serious underlying pathology. METHODS: Nonpregnant women aged 18 to 75 years with benign cellular changes on a Papanicolaou smear were recruited from primary care clinics of an urban teaching hospital. The subjects (N = 132) were tested at baseline for the presence of human papillomavirus using the polymerase chain reaction technique, and underwent repeated cervicovaginal smears at 3, 6, and 9 months. At 12 months colposcopy was performed. The main study outcome was the proportion of subjects with CIN as determined by colposcopic biopsy specimens. We determined the sensitivity, specificity, and predictive values of historical risk factor information, human papillomavirus testing, and repeated cervicovaginal smears for the detection of CIN. RESULTS: Cervical intraepithelial neoplasia was found in 30 of 132 women, of whom 27 (20%) had low-grade CIN (CIN I) and 3 (2%) had high-grade CIN (CIN II). Underlying CIN was significantly more common in women younger than 35 years or who had a history of Trichomonas infection or venereal warts, a positive human papillomavirus test result, or abnormal follow-up smears. However, no follow-up strategy combined high sensitivity with a low referral rate for colposcopy. CONCLUSIONS: The prevalence of underlying high-grade CIN in women with benign cellular changes is low. However, further prospective studies in other settings are needed before routine follow-up can unequivocally be recommended.

Transforming growth factor-alpha levels in the serum and ascites of patients with advanced epithelial ovarian cancer.

A variety of cytokines have been identified to play a role in ovarian cancer. In this pilot study, we sought to determine whether transforming growth factor-alpha (TGF-alpha) was detectable in the serum and ascites of women with advanced stage epithelial ovarian cancer. TGF-alpha was measured using an enzyme-linked immunosorbent assay and was present in 18 of 25 control sera. Prior to treatment for stage III or IV epithelial ovarian cancer, 18 patients had undetectable serum levels of TGF-alpha, while 18 had values ranging from 10.6 to 531.7 pg/ml. The group with undetectable levels had a 6-month greater median survival; detectable TGF-alpha might be a negative prognostic indicator. In a separate group undergoing second-look laparotomy, differences in median TGF-alpha values versus controls and the primary study group approached significance. TGF-alpha was detected in significantly more control peritoneal fluid samples than in patient ascites. A larger study is warranted.

The central response to ovarian carcinoma simulates the response to sepsis.

BACKGROUND: Animal models of stress and sepsis demonstrate increased hypophyseal gene expression of the transcription factor c-fos and the cytokines interleukin-1 and interleukin-6. Chronic central nervous system exposure to interleukin-1 results in hypermetabolism, accelerated nitrogen loss, anorexia, and cachexia. We test the hypothesis that the host response to ovarian carcinoma recapitulates the host response to sepsis regarding the elaboration of the transcription factors and cytokines in the central nervous system, liver, and lung. MATERIALS AND METHODS: Nude mice were seeded intraperitoneally with either ovarian carcinoma (MA-148) or vehicle. The animal subjects were observed for 5 weeks and sacrificed for brain, pituitary, lung, and liver mRNA. We studied the mRNA accumulation of the transcription factors c-fos, c-jun, and C/EBP alpha and the cytokines interleukin-1 and interleukin-6 using reverse-transcriptase polymerase chain reaction. RESULTS: Compared with the control, ovarian carcinoma in the mouse model resulted in the following: (1) Pituitary c-fos and c-jun mRNA increased 3-fold (P = 0.012) and 6-fold (P < 0.001), respectively; (2) pituitary IL-1 and IL-6 mRNA increased 4-fold (P < 0.001) and 8-fold (P = 0.037), respectively; (3) liver c-fos mRNA increased > 8-fold (P < 0.001); and (4) lung C/EBP alpha mRNA decreased greater than 10-fold (P < 0.001). CONCLUSIONS: We conclude that the host response to ovarian carcinoma in this animal model recapitulates many aspects of the host response to bacterial sepsis especially concerning pituitary gene expression. These data suggest that, as in sepsis, a hypothalamic-hypophyseal-mediated cytokine response in ovarian carcinoma may result in hypermetabolism, accelerated nitrogen loss, anorexia, and cachexia.

Pretreatment surgical staging of patients with cervical carcinoma: the case for lymph node debulking.

BACKGROUND: The routine use of extraperitoneal surgical staging prior to radiation therapy in patients with bulky or locally advanced cervical carcinoma remains controversial. METHODS: A review was performed of 266 patients with cervical carcinoma who underwent extraperitoneal pelvic and paraaortic lymphadenectomy prior to receiving radiotherapy. Patients were divided into groups based on their lymph node status. Group A had negative lymph nodes; Group B had resected, microscopic lymph node metastases; Group C had macroscopically positive lymph nodes that were resectable at the time of surgery; and Group D had unresectable lymph nodes. All patients received standard radiotherapy utilizing external beam and brachy-therapy. Patients with lymph node metastases received extended field irradiation. Survival probabilities were computed by the Kaplan-Meier product limits method with statistical significance determined by the Mantel-Cox log rank test. RESULTS: Lymph node metastases were detected in 50% of patients. Five- and 10-year disease free survival rates were similar for all patients in Groups B and C. All patients in Group D recurred. There was a 10.5% incidence of severe radiation-related morbidity and a 1.1% incidence of treatment-related deaths. CONCLUSIONS: Pretreatment extraperitoneal staging of patients with bulky or locally advanced cervical carcinoma may afford a survival benefit via the debulking of macroscopically positive lymph nodes without significantly increasing treatment-related morbidity or mortality.

Alpha-1 acid glycoprotein is an immunosuppressive factor found in ascites from ovaria carcinoma.

BACKGROUND: Although the ascites of patients with ovarian carcinoma has been reported to contain immunosuppressive factors, the identity and source of this activity has not been fully elucidated. The objective of this study was to describe the purification of a single immunosuppressive protein, alpha-1 acid glycoprotein, from ovarian carcinoma ascites, identify its site of production, and describe a possible mechanism by which it inhibits lymphocytes. METHODS: Ascites from proteins from five patients with epithelial ovarian carcinoma first were differentially precipitated by size with different concentrations of polyethylene glycol and then separated on the basis of isoelectric focusing. The protein factions then were placed in a lymphocyte proliferation assay to determine immunosuppressive activity. Western blot analysis was used to identify alpha-1 acid glycoprotein as an immunosuppressive protein in ascites. Total RNA was extracted from ovarian and hepatic cell lines as well as primary and recurrent ovarian tumor samples. Reverse-transcriptase polymerase chain reaction then was utilized to identify the site of production of this protein. Purified alpha-1 acid glycoprotein was placed in lymphocyte culture and its effects on lymphocyte interleukin-2 (IL-2) production were measured by enzyme-linked immunoadsorbent assay. RESULTS: Addition of purified alpha-1 acid glycoprotein to the lymphocyte assay resulted in a 60% decrease in lymphocyte proliferation (P < 0.05). Alpha-1 acid glycoprotein transcript was not identified in ovarian tumor cells. The addition of purified alpha-1 acid glycoprotein to the lymphocyte culture resulted in a 65% decrease in IL-2 secretion into the media (P < 0.05). CONCLUSIONS: Alpha-1 acid glycoprotein is an immunosuppressive protein purified from ovarian carcinoma ascites. It is not expressed primarily by ovarian carcinoma cells. It appears to inhibit IL-2 secretion by lymphocytes.

Vascular endothelial growth factor expression in early stage ovarian carcinoma.

BACKGROUND: Tumor angiogenesis is essential for solid tumor growth. Yet, the importance of any particular factor in neoplastic proliferation is poorly defined. This study examines the clinical significance of increased expression of one of the angiogenic factors, vascular endothelial growth factor (VEGF), in early stage ovarian carcinoma. METHODS: Tumor specimens from 68 patients with International Federation of Gynecology and Obstetrics Stage I and II ovarian carcinoma were evaluated for VEGF expression. Antisense and corresponding sense (control) RNA probes were transcribed from the pCRII construct (Invitrogen, San Diego, CA), which contained human VEGF cDNA. The antisense probe was designed to include a highly conserved region of the VEGF coding sequence and thus detect all known variants. After in situ hybridization, sections were assessed for overexpression of VEGF. RESULTS: Twenty-nine of the tumor samples overexpressed VEGF, whereas 39 specimens did not. In patients whose tumors demonstrated elevated VEGF expression, 25% were without evidence of disease recurrence at last follow-up. In contrast, 75% of the patients whose tumors did not overexpress VEGF were without evidence of disease at last follow-up (P < 0.001). Median disease free survival for the VEGF positive group was 22 months, compared with > 108 months for the VEGF negative group (P < 0.001). When borderline tumors were excluded from the survival analysis, median disease free survival for the VEGF positive group was 18 months, compared with >120 months for the VEGF negative group (P < 0.001). Other possible prognostic variables had minimal impact on survival; these included age, stage, grade, cytology, and tumor size (P > 0.05). Assignment to a high risk group, as defined by the Gynecologic Oncology Group of the National Cancer Institute, was somewhat predictive of a shorter relapse free interval (P = 0.056). In a multivariate analysis, however, only elevated VEGF expression was associated with poorer survival. CONCLUSIONS: In this analysis, patients with early stage ovarian carcinoma with increased VEGF expression had a poorer prognosis. Further study of VEGF may ultimately lead to identification of patients with high risk lesions whose tumor biology portends a worse prognosis and who therefore may benefit from aggressive adjuvant therapy.

Chemoprophylaxis with ciprofloxacin in ovarian cancer patients receiving paclitaxel: a randomized trial.

The objective of this study was to evaluate the efficacy of oral ciprofloxacin in preventing febrile morbidity superimposed on the neutropenia induced from a paclitaxel regimen in ovarian cancer patients. Eligible patients received paclitaxel at doses of 135 to 175 mg/m2 alone or in combination with a platinum agent. They were randomized to either an observation (control) group or a ciprofloxacin prophylaxis group. Patients in the ciprofloxacin group received 500 mg ciprofloxacin orally twice a day once the absolute neutrophil count (ANC) was less than 500/mm3 and continued until the ANC was greater than 1000/mm3. Ninety patients were enrolled between the control (n = 45) and ciprofloxacin (n = 45) groups. They received 371 cycles of a paclitaxel-based regimen with 177 and 194 cycles in the control and ciprofloxacin groups, respectively. Ciprofloxacin prophylaxis was prescribed for 138 (71%) of the cycles in the ciprofloxacin group and was given for a mean duration of 7.7 days per cycle. The groups were similar in disease status and risk factors for neutropenia. Fifteen patients in the control group developed febrile neutropenia versus 12 of those in the ciprofloxacin group (P = 0.69). The mean ANC and mean length of hospital stay for neutropenic fever were also similar between groups. There was a greater frequency of an ANC < 100 associated with those prophylaxed with ciprofloxacin (P = 0.01). Only 44% of the febrile episodes were associated with a positive culture. Staphylococcus aureus was the most frequently reported organism isolated. Considering these results, it does not appear that febrile neutropenia is reduced by ciprofloxacin during grade IV neutropenia.

The effect of prolonged cycles of chemotherapy on quality of life in gynaecologic cancer patients.

OBJECTIVE: The aim of this study was to determine if the prescription of prolonged cycles of chemotherapy to patients with a variety of gynaecologic cancers has an adverse effect on quality of life (QOL). METHODS: Patients attending a single gynaecologic oncology clinic who received greater than 6 cycles of chemotherapy were identified. Prior to each chemotherapy cycle, patients were asked to complete a modified Functional Assessment Cancer Therapy-General (FACT-G) quality of life form. QOL scores were compared to their baseline or pretreatment score (cycle 1 score), as well as to their score representing the completion of primary therapy (cycle 6 score). RESULTS: Seventeen patients were identified as having received greater than 6 cycles of systemic cytotoxic chemotherapy. The total number of chemotherapy cycles analyzed was 95. Comparing QOL scores for cycle 1 and 6 to cycles 7-16, we found no significant alteration (improvement or deterioration) in the following subscale scores: physical well being (PWB), social well being (SWB), and functional well being (FWB). Similarly, overall QOL as represented by the summed individual scores was also not affected by the prescription of up to 16 cycles of chemotherapy. Analysis of the emotional well being (EWB) subscale scores revealed a significant downward trend after the 12th cycle of therapy as compared to the 6th cycle (p = 0.04), however this trend was not significant when compared to the pretreatment or cycle 1 scores (p = 0.16). There was however a statistically significant progressive deterioration in the subscale score of the relationship with the doctor (RWD). This was most marked after the 10th cycle of therapy (p < 0.0001). When split by disease status, we again found no statistically significant alteration in PWB, SWB, RWD, EWB, FWB and overall QOL for cycle 1 and 6 as compared to cycles 7-17. However, those patients who were able to attain a complete clinical response (CCR) disease status, achieved a higher SWB (p = 0.003), RWD (p = 0.02), EWB (p = 0.03), and overall QOL scores (p = 0.04) while their PWB scores were not statistically different from patients with stable (p = 0.7) or progressive disease (p = 0.6). CONCLUSION: In conclusion, the prescription of prolonged cycles of chemotherapy to patients with gynaecologic cancers does not result in an overall deterioration of QOL. Further more an improvement in subscale and overall QOL was demonstrated in those patients able to attain a complete clinical response (CCR).

A simplified method for detubularization in the construction of a continent ileocolic reservoir (Miami pouch).

The development of continent urinary diversions was an important step forward in improving the quality of life of patients undergoing pelvic exenteration. While the technique is relatively simple, it can be very time-consuming and uses a significant portion of the patient's colon in its construction. Here a modification of the technique for construction of a continent ileocolic reservoir which results in a similar reservoir that uses less colon and requires less time to construct is presented. We also report results of the use of this technique in seven patients.

The effect of sartorius transposition on wound morbidity following inguinal-femoral lymphadenectomy.

In spite of efforts to reduce complications associated with inguinal-femoral lymphadenectomy (IFL), morbidity continues to be substantial. We sought to assess the efficacy of sartorius transposition (ST) in reducing groin wound complications following IFL, in patients with vulvar malignancy. The records of 101 patients with vulvar cancer undergoing IFL through separate incisions between March 1975 and December 1994 were examined. Sixty-two patients undergoing ST (group 1) were compared to 38 who did not (group 2). The groups were similar with respect to age, weight, tobacco/alcohol use, prior abdominal/vulvar surgery, prevalence of diabetes, hypertension, or peripheral vascular disease, and previous exposure to irradiation or chemotherapy. Additionally, there was no significant difference with respect to extent of disease, incidence of macro-/microscopic groin metastases, use of groin drains, and use of perioperative antibiotics or deep venous thrombosis prophylaxis. Groin wound complications were less frequent in patients undergoing ST (group 1). The incidence of groin cellulitis was 30% in group 1 compared with an incidence of 58% in group 2 (P = 0.011). Significant groin wound morbidity, defined as either wound breakdown or cellulitis, was seen less frequently in group 1 (41% vs 66%; P = 0.029). Employing a multivariate analysis, only patient weight < 150 lbs and performance of ST were established as independently associated with a reduction in groin morbidity following IFL (P = 0.0281 and P = 0.0075, respectively). In conclusion, despite waning enthusiasm for its performance, ST appeared to significantly reduce the incidence of wound morbidity after IFL. Our data confirmed that separate incisions, and improved perioperative antibiotics, have not eliminated the value inherent in this surgical modification. We suggest a prospective trial to further establish the benefit of sartorius transposition during IFL.

Vascular endothelial growth factor (VEGF) expression and survival in human epithelial ovarian carcinomas.

Vascular endothelial growth factor (VEGF) expression and microvessel density were studied in cases of advanced epithelial ovarian carcinoma to evaluate their usefulness as prognostic variables. Tumor samples from 18 patients with advanced stage serous epithelial ovarian cancer were evaluated for VEGF expression by reverse-transcriptase polymerase chain reaction (RT-PCR) analysis. Immunohistochemical study of corresponding archival tissues with an antibody to von Willebrand factor (vWF; FVIII-RA) was used for tumor microvessel count determinations. The correlation of VEGF expression and mean microvessel counts was determined by an unpaired t-test. Survival analysis for known prognostic factors and VEGF expression was performed. Survival distributions were calculated by the product limit of Kaplan and Meier and significant differences between distributions were analyzed with a log rank test. From the RT-PCR analysis of tumor VEGF expression, 12 samples were found to be strongly positive, whereas six samples had low/negative VEGF expression. The median survival was 60 months for the VEGF-low/negative group and 28 months for the VEGF-positive group (P = 0.058). Other prognostic variables had minimal impact on survival, i.e. age < 65 years (P = 0.873), FIGO stage (P = 0.06), grade (P = 0.236) and debulking status (P = 0.842). Fourteen of 18 tumor specimens were suitable for microvessel counting. The mean microvessel counts of the VEGF-positive group and the VEGF-negative group were 27/hpf and 35/hpf, respectively (P = 0.16). In this preliminary analysis, high VEGF expression in epithelial ovarian carcinomas was associated with poor overall survival. Further study will be necessary to elucidate the lack of association of VEGF expression and tumor microvessel counts.

Gynecologic reconstruction with a rectus abdominis myocutaneous flap: an update.

This series reports the outcomes and significant complications associated with the rectus myocutaneous flap when used for pelvic or inguinal reconstruction in patients with gynecologic cancers. Perioperative variables were retrospectively reviewed to identify social and medical risk factors as well as intraoperative and postoperative complications that predisposed to rectus flap failure. Fifteen patients with gynecologic malignancies underwent reconstructive procedures using a vertically oriented rectus abdominis myocutaneous flap for either vaginal (n = 14) or inguinal (n = 1) reconstruction. The patients' primary cancers were cervical (n = 11), rectal (n = 1), ovarian (n = 1), vulvar (n = 1), and vaginal (n = 1). The median age was 50 years. The median follow-up was 17 months. All flaps were mobilized in conjunction with a radical salvage operation. There were no cases of vaginal prolapse and no abdominal wound infections. However, 4 patients (27%) had major postoperative morbidity in this small series. There was one wound dehiscence and three episodes of necrosis of the subcutaneous and cutaneous portions of the flap. All 4 of these patients required additional operative intervention or debridement. Eleven patients had complete healing of the flap. The rectus abdominis myocutaneous flap is a valuable option for gynecologic reconstructive procedures. Perioperative strategies for improving flap viability include the identification of risk factors that may compromise flap perfusions such as prior abdominal incisions, peripheral vascular disease, and obesity. Meticulous surgical technique is required to preserve the vascular pedicle. These strategies may be useful in preoperative counseling, the perioperative evaluation, and the intraoperative management.