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Urinary tract infection in women with gynecologic malignancy
SOCIETY OF GYNECOLOGIC breast disorders and disease. A current, long-term experience reported in the gynecology literature may serve to encourage and provide a model for residency and fellowship programs seeking to incorporate the surgical management of breast disease into their curriculum. In the 12 years, 1979 through 1990, 1181 diagnostic or treatment surgical breast procedures were performed. Included were 164 fine-needle aspirations, 7 core-needle biopsies, 471 excisional breast biopsies, 316 needle localized breast biopsies, and 131 modified radical mastectomies. In the last 10 years of the study, breast-conserving treatment of appropriate small breast cancers has been practiced. Subsequently, 92 patients have chosen lumpectomy, ipsilateral axillary lymph node sampling, and radiotherapy as treatment for their breast cancer. The indications and application of each type of surgical breast procedure, benign and malignant breast pathology detected, and complications of the procedures performed are detailed. The surgical management of breast disease has become an integral part of residency and fellowship training and the daily practice of obstetrics, gynecology, and gynecologic oncology in our institutions. 103. Detection
of Ki-ras Mutations in Endocervical Adenocarcinomas by Polymerase Chain Reaction. J. KOULOS, T. WRIGHT, M. MITCHELL, AND R. RICHART, Columbia University, New York, New York
10027; and M. D. Anderson Cancer Center, Houston, Texas 77030. Mutations and alterations of the ras family of protooncogenes are commonly detected in neoplasms from a variety of sites. Recently, mutations of the c-Ha-ras protooncogene have been reported in 11% of squamous cell carcinomas of the cervix and these mutations are more frequent in advanced stage tumors. Since mutations of c-Ki-ras are more frequently encountered in adenocarcinomas than are mutations of cHa-ras, we have analyzed 55 cases of invasive adenocarcinoma of the endocevix for the presence of c-Ki-ras mutations. c-Ki-ras mutations were detected after amplification of DNA from paraffin-embedded tissue specimens using the polymerase chain reaction (PCR) and restriction enzyme digestion of amplimers. This allows detection of aspartic acid mutations at codons 12 and 13 using restriction fragment length polymorphisms. Only 4 of 55 cases (7%) contained codon 12 mutations and no case contained codon 13 mutations. The samples were also analyzed for the presence of HPV 16 or 18 DNA using PCR. HPV 16 or 18 DNA was detected in 75% of the cases. Three of the four cases with Ki-ras mutations were negative for both HPV 16 and HPV 18 and one was HPV 16 positive. Therefore the prevalence of Ki-ras mutations is significantly (P = 0.016) greater in HPV 16/18-negative adenocarcinomas (23%) than in HPV 16/18-positive adenocarcinomas (3%). Three-year clinical follow-up on the cases will be presented. 104. Hexamethylmelamine Chemotherapy and Intraperitoneal Radioactive Chromic Phosphate for Minimal Residual Epithelial Ovarian Cancer following Second-Look Surgery. D. MOORE, M. VARIA, W. FOWLER, L. WALTON, F. VALEA, AND L. VAN LE. University of
North Carolina, Chapel Hill, North Carolina 27599. Few women with advanced epithelial ovarian cancer achieve a surgically confirmed complete response to initial treatment. The prognosis for persistent ovarian cancer found at second-look surgery is guarded, and effective therapy for even minimal residual disease is controversial. We analyzed the results of 21 consecutive patients with minimal residual ovarian adenocarcinoma following surgical reassessment, treated with intraperitoneal radioactive chromic phosphate (“P) and hexamethylmelamine (HMM). All patients previously received at least one cisplatinbased chemotherapy regimen. After lysis of adhesions, attempted resection of all gross disease, and documentation of tumor residual, 15 mCi 32P in 2 liters of warmed 0.9% NaCl were given via Tenckhoff catheters immediately postoperative. HMM chemotherapy was initiated within 6 weeks of surgery at a dose of loo-150 mg/day x 14 days. Cycles were repeated at 4-week intervals for a minimum of 1 year
101
ONCOLOGISTS-ABSTRACTS
pending disease progression or toxicity. Survival data were calculated from the time of second-look surgery. The median progression-free interval was 11 months. Median survival was 16 months with 9/21 (43%) patients alive and without evidence of recurrence (at l-106 months) and 5/21 (24%) patients alive with disease (at lo-39 months). Three patients have survived greater than 3 years without recurrence. Only one patient prematurely discontinued HMM due to toxicity. We conclude that combination ‘*P/HMM is a well-tolerated, effective treatment for minimal residual ovarian cancer. 105. Urinary Tract Infection in Women with Gynecologic Malignancy. M. M. MORADI, L. F. CARSON, L. A. KING, S. A. ELG, L. TWIGGS, AND D. BROOKER, Women’s Cancer Center, University
Minnesota, Minneapolis,
B. of
Minnesota 55455.
To evaluate infectious morbidity of the urinary tract, we undertook a retrospective, descriptive review of 1204 admissions to the Gynecology Oncology service. Of the 494 patients (pts) studied, 239 had major surgical procedures. Although 68 of the 1204 admissions were for serious infections, the most frequent infection was urinary tract infection (UTI). This was the diagnosis in 90/494 (18%) of pts and in 109/1204 (9%) of admissions. Seventy-seven of the admissions were single, whereas 13 pts had multiple admissions (MA) (32 admissions). Incidence for postsurgical pts was 39%, for chemotherapy pts 27%, and for radiation therapy pts 13%, and the risk for a combination of the above was 13%. UT1 was most frequently discovered in cervix cancer pts (47% of 90 pts) followed by ovarian cancer pts (IS%), uterine cancer pts (16%), and vulvar cancer pts (9%). The most frequently isolated organism was Escherichia coli. followed by Klebsiella, Enterococcus, Pseudomonas, Enterobacter, Citrobacter, and Candida. Eighty-four percent of the cultures revealed a single organism and 16% were multiple organisms. Seven of thirteen MA pts had the same species of organisms isolated at each admission. Catheterization and/or instrumentation occurred in 97% of admissions. Foley catheter was used in 71% and nephrostomy in 21%, and ileal conduit was the source in 4%. Emphasis is made on the high risk status of this group of pts and on the need for close surveillance and an attempt to limit urinary interventions. 106. The Biodistribution
of Technetium-99m-Labeled Monoclonal OC 125 FAB’ in Tumor-Bearing Athymic Mice. M. MUTO, S. W. TSAO, AND C. C. LAW, Brigham and Women’s Hospital, Harvard Medical
School, Boston, Massachusetts 02115. Radioimmunoconjugates (RICs) currently employed for the radioimmunoscintigraphy (RIS) of ovarian cancer have significant hepatic uptake (indium-111) or emission spectra unsuitable for RIS (iodine-131). We have evaluated the biodistribution of an RIC of OC 125 Fab’ and technitium-99m (%“Tc) in mice bearing intraperitoneal xenografts of the ovarian cancer cell line NIH: OVCAR3 in order to determine its suitability for RIS. Fab’ fragments of OC 125, a monoclonal antibody recognizing the tumor associated antigen CA 125, were radiolabeled with %“Tc (sp act 2 &i/pg) via an ester-linked chelator. Doses of 50100 &i were administered via the intraperitoneal (ip), intravenous (iv), or subcutaneous route (SC) and biodistribution was determined by necropsy at 6 hr. The iv route was further evaluated at 2, 6, 12, 18, and 24 hr. Uptake was expressed as the percentage of injected dose per gram of tissue (%ID/g) corrected for decay. Localization was expressed as a ratio of tumor to normal tissue uptake (TNT). Intraperitoneal RIC demonstrated better tumor uptake than did iv RIC (4.8 ? 3.8 %ID/g vs 2.6 2 1.2 %ID/g); however the iv route yielded more favorable TNT ratios (7.1 5 1.6-fold vs 4.6 -+ 3.5-fold). Uptake and localization via the SCroute was poor. Maximum tumor uptake for the iv route was observed early (3.8 2 1.2 %ID/g at 2 hr) whereas TNT ratios were optimal at later time points (29 ? 9-fold at 24 hr). Tumor-bearing ovaries bound 37-fold more RIC than adjacent normal uterus. Liver
of Ki-ras Mutations in Endocervical Adenocarcinomas by Polymerase Chain Reaction. J. KOULOS, T. WRIGHT, M. MITCHELL, AND R. RICHART, Columbia University, New York, New York
10027; and M. D. Anderson Cancer Center, Houston, Texas 77030. Mutations and alterations of the ras family of protooncogenes are commonly detected in neoplasms from a variety of sites. Recently, mutations of the c-Ha-ras protooncogene have been reported in 11% of squamous cell carcinomas of the cervix and these mutations are more frequent in advanced stage tumors. Since mutations of c-Ki-ras are more frequently encountered in adenocarcinomas than are mutations of cHa-ras, we have analyzed 55 cases of invasive adenocarcinoma of the endocevix for the presence of c-Ki-ras mutations. c-Ki-ras mutations were detected after amplification of DNA from paraffin-embedded tissue specimens using the polymerase chain reaction (PCR) and restriction enzyme digestion of amplimers. This allows detection of aspartic acid mutations at codons 12 and 13 using restriction fragment length polymorphisms. Only 4 of 55 cases (7%) contained codon 12 mutations and no case contained codon 13 mutations. The samples were also analyzed for the presence of HPV 16 or 18 DNA using PCR. HPV 16 or 18 DNA was detected in 75% of the cases. Three of the four cases with Ki-ras mutations were negative for both HPV 16 and HPV 18 and one was HPV 16 positive. Therefore the prevalence of Ki-ras mutations is significantly (P = 0.016) greater in HPV 16/18-negative adenocarcinomas (23%) than in HPV 16/18-positive adenocarcinomas (3%). Three-year clinical follow-up on the cases will be presented. 104. Hexamethylmelamine Chemotherapy and Intraperitoneal Radioactive Chromic Phosphate for Minimal Residual Epithelial Ovarian Cancer following Second-Look Surgery. D. MOORE, M. VARIA, W. FOWLER, L. WALTON, F. VALEA, AND L. VAN LE. University of
North Carolina, Chapel Hill, North Carolina 27599. Few women with advanced epithelial ovarian cancer achieve a surgically confirmed complete response to initial treatment. The prognosis for persistent ovarian cancer found at second-look surgery is guarded, and effective therapy for even minimal residual disease is controversial. We analyzed the results of 21 consecutive patients with minimal residual ovarian adenocarcinoma following surgical reassessment, treated with intraperitoneal radioactive chromic phosphate (“P) and hexamethylmelamine (HMM). All patients previously received at least one cisplatinbased chemotherapy regimen. After lysis of adhesions, attempted resection of all gross disease, and documentation of tumor residual, 15 mCi 32P in 2 liters of warmed 0.9% NaCl were given via Tenckhoff catheters immediately postoperative. HMM chemotherapy was initiated within 6 weeks of surgery at a dose of loo-150 mg/day x 14 days. Cycles were repeated at 4-week intervals for a minimum of 1 year
101
ONCOLOGISTS-ABSTRACTS
pending disease progression or toxicity. Survival data were calculated from the time of second-look surgery. The median progression-free interval was 11 months. Median survival was 16 months with 9/21 (43%) patients alive and without evidence of recurrence (at l-106 months) and 5/21 (24%) patients alive with disease (at lo-39 months). Three patients have survived greater than 3 years without recurrence. Only one patient prematurely discontinued HMM due to toxicity. We conclude that combination ‘*P/HMM is a well-tolerated, effective treatment for minimal residual ovarian cancer. 105. Urinary Tract Infection in Women with Gynecologic Malignancy. M. M. MORADI, L. F. CARSON, L. A. KING, S. A. ELG, L. TWIGGS, AND D. BROOKER, Women’s Cancer Center, University
Minnesota, Minneapolis,
B. of
Minnesota 55455.
To evaluate infectious morbidity of the urinary tract, we undertook a retrospective, descriptive review of 1204 admissions to the Gynecology Oncology service. Of the 494 patients (pts) studied, 239 had major surgical procedures. Although 68 of the 1204 admissions were for serious infections, the most frequent infection was urinary tract infection (UTI). This was the diagnosis in 90/494 (18%) of pts and in 109/1204 (9%) of admissions. Seventy-seven of the admissions were single, whereas 13 pts had multiple admissions (MA) (32 admissions). Incidence for postsurgical pts was 39%, for chemotherapy pts 27%, and for radiation therapy pts 13%, and the risk for a combination of the above was 13%. UT1 was most frequently discovered in cervix cancer pts (47% of 90 pts) followed by ovarian cancer pts (IS%), uterine cancer pts (16%), and vulvar cancer pts (9%). The most frequently isolated organism was Escherichia coli. followed by Klebsiella, Enterococcus, Pseudomonas, Enterobacter, Citrobacter, and Candida. Eighty-four percent of the cultures revealed a single organism and 16% were multiple organisms. Seven of thirteen MA pts had the same species of organisms isolated at each admission. Catheterization and/or instrumentation occurred in 97% of admissions. Foley catheter was used in 71% and nephrostomy in 21%, and ileal conduit was the source in 4%. Emphasis is made on the high risk status of this group of pts and on the need for close surveillance and an attempt to limit urinary interventions. 106. The Biodistribution
of Technetium-99m-Labeled Monoclonal OC 125 FAB’ in Tumor-Bearing Athymic Mice. M. MUTO, S. W. TSAO, AND C. C. LAW, Brigham and Women’s Hospital, Harvard Medical
School, Boston, Massachusetts 02115. Radioimmunoconjugates (RICs) currently employed for the radioimmunoscintigraphy (RIS) of ovarian cancer have significant hepatic uptake (indium-111) or emission spectra unsuitable for RIS (iodine-131). We have evaluated the biodistribution of an RIC of OC 125 Fab’ and technitium-99m (%“Tc) in mice bearing intraperitoneal xenografts of the ovarian cancer cell line NIH: OVCAR3 in order to determine its suitability for RIS. Fab’ fragments of OC 125, a monoclonal antibody recognizing the tumor associated antigen CA 125, were radiolabeled with %“Tc (sp act 2 &i/pg) via an ester-linked chelator. Doses of 50100 &i were administered via the intraperitoneal (ip), intravenous (iv), or subcutaneous route (SC) and biodistribution was determined by necropsy at 6 hr. The iv route was further evaluated at 2, 6, 12, 18, and 24 hr. Uptake was expressed as the percentage of injected dose per gram of tissue (%ID/g) corrected for decay. Localization was expressed as a ratio of tumor to normal tissue uptake (TNT). Intraperitoneal RIC demonstrated better tumor uptake than did iv RIC (4.8 ? 3.8 %ID/g vs 2.6 2 1.2 %ID/g); however the iv route yielded more favorable TNT ratios (7.1 5 1.6-fold vs 4.6 -+ 3.5-fold). Uptake and localization via the SCroute was poor. Maximum tumor uptake for the iv route was observed early (3.8 2 1.2 %ID/g at 2 hr) whereas TNT ratios were optimal at later time points (29 ? 9-fold at 24 hr). Tumor-bearing ovaries bound 37-fold more RIC than adjacent normal uterus. Liver