- Email: [email protected]
Survival following exenteration for recurrent adenocarcinoma of the endometrium
92
SOCIETY OF GYNECOLOGIC
4.9 ng/mg protein) (P < 0.01). Levels of PAI- were higher in Stage II/III compared to Stage I malignancy (P < 0.01) and in cancers that had invaded 50% or more of the uterine wall compared to less invasive cancers (P < 0.01). PAI- may be useful as a prognostic marker in endometrial cancer. L. VAN LE, J. C. FOWLER, University of North Carolina, Chapel Hill, North Carolina, 27514; and Carolina Medical Center, Charlotte, North Carolina.
66. H-ras Codon 12 Mutation in Cervical Dysplasias. STOERKER,* C. A. RINEHART, S. HASKILL, AND W.
H-ras oncogene has been implicated in the pathogenesis of cervical cancers. In nude mice, injection of H-ras (codon 12 mutation)-transfected cervical cells infected with human papillomavirus (HPV) mice resulted in carcinoma formation. Although H-ras gene mutations have been studied in cervical cancers, it is unknown whether precancerous cervical lesions also contain H-ras mutations and therefore may be predicted to progress to cervical cancer. To determine if mutational activation of H-ras is an early event in carcinogenesis, we looked for the presence of codon- H-ras mutation in precancerous cervical dysplasias typed for HPV. Cervical DNA from 63 normal patients and 72 patients with biopsy-proven cervical dysplasia [CIN I (51) CIN II (9), CIN III (15)] were analyzed. HPV typing was performed on these samples by Viratype and Polymerase chain reaction (PCR). To detect H-ras codon 12 mutation, DNA was isolated and amplified by PCR with primers for H-ras. Restriction enzyme analysis with MSP I was performed on PCR products to discriminate between wild-type and mutated sequences; a unique restriction site for MSP I contained within the wild-type ras PCR product allows discrimination between unmutated and mutated sequences. To visualize cleavage products the restriction digest was electrophoresed on a polyacrylamide gel and stained with ethidium bromide. HPV testing by PCR or Viratype was positive for HPV 16 or 18 in 33% of CIN I, 56% of CIN II, and all CIN III samples. No codon 12 mutations were detected in any sample. We conclude that the codon 12 H-ras mutation is not found in dysplasias regardless of the presence of HPV. Mutation at the codon 12 location in H-ras is unlikely to be an early event in the progression of precancerous lesions to cervical carcinoma. 67. Survival
following the Endometrium. KINNEY, Mayo
Exenteration T. WILSON,
for Recurrent Adenocarcinoma M. MORRIS, R. ALVAREZ AND
of
W. Clinic, Rochester, Minnesota 55905; University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030; University of Alabama, Birmingham, Alabama 35294; and University of California, Davis, Sacramento, California 95816. The records of all patients undergoing pelvic exenteration for recurrent adenocarcinoma of the endometrium at four institutions during the years 1955 to 1988 were retrospectively reviewed. Of the 24 procedures performed, 4 were judged to be palliative in nature due to known distant metastases or widespread nodal disease, and the remainder potentially curative. This report concerns those 20 patients operated with curative intent. All patients had undergone prior pelvic radiotherapy; 14 of 20 as part of their primary treatment and 6 of 20 as part of the treatment of their recurrence. Either chemotherapy or hormonal therapy was utilized in addition in 6 of 20 patients prior to exenteration. Median patient age was 65 years (range 44-79). At most recent follow-up, 8 patients are alive and disease-free, 2 are alive with disease, 6 died of disease, and 4 died of other causes. Median follow-up of living patients is 89 months. Twelve of 20 patients experienced major complications, the most common of which was neovaginal flap necrosis. One patient of the 20 (5%) died of surgical complications (in 1963). Kaplan-Meier estimate of 5-year overall survival is 56% and 5-year disease-free survival is 45%. Pelvic exenteration can produce an acceptable rate of diseasefree survival in selected patients with local recurrence of endometrial adenocarcinoma who have exhausted other treatment modalities.
ONCOLOGISTS-ABSTRACTS and Follow-up of the Continent Real CoM. PENALVER, D. DONATO, B.-U. SEVIN, University of Miami School of Medicine,
68. Functional Characteristics ionic Urinary Reservoir. AND H. E. AVERETTE,
Miami, Florida 33101. A total of 33 patients underwent continent urinary diversion with pelvic exenteration. A detubularized right colonic segment served as a urinary reservoir and the distal ileum as a continent catheterizable efferent system. A direct nontunneled mucosa to mucosa ureterocolonic anastomosis was used. In this series 25 patients were followed for 6 to 46 months (average 17 months). Twenty-three patients are completely continent with intermittent catheterization at 4- to 8-hr intervals. Two patients suffer nighttime incontinence. Urodynamic studies demonstrate a mean reservoir volume of 650 ml. Mean and maximal contraction pressures were 25 and 49 cm of water, respectively, in the reservoir and 36 and 155 cm of water, respectively, in the plicated ileal segment (P = 0.043 and less than 0.001, respectively). The highest reservoir contractions occurred in the 2 patients with nocturnal incontinence. Of the 50 ureterocolonic anastomosis, 4 ureters developed partial obstmction and 1 required reoperation. The overall success rate (absence of reflux and obstruction) was 88.6%. Renal function deteriorated in 1 patient (4%). Three patients (12%) had diarrhea initially but all were controlled medically. One patient died of ARDS. Medical and surgical complications occurred at a rate comparable to previous series with ileal conduits. Our ongoing satisfactory experience with these patients warrants further study of this technique to achieve continent urinary diversion. of HPV Lesions to Interferon in Human Xenograjk W. A. JENSON, C. JOHNSON, R. HOLLOWAY, G. DELGADO, J. R. POTKUL, AND W. LANCASTER, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Georgetown University, Washington, D.C. 20007.
69. Response BARNES, BARTER,
Efforts to develop a systemically active therapeutic agent for HPV lesions have been hampered by the lack of a suitable experimental model; however, Kreider has induced condylomatous transformation of human epithelial xenografts exposed to HPV 11 and hosted in athymic mice. In this study interferon, a clinically active agent for the treatment of condyloma, is utilized to determine the reliability of this in vivo model for the basis of future developmental studies, as well as to test the effects of interferon on condyloma in an immunocompromised host. Animals were prepared with subrenal capsule grafts of HPV-infected epithelium. Half of the animals received daily injections of one million units (0.1 cc) of interferon a-Nl. Control animals received 0.1 cc of saline. The resulting cysts were analyzed in a blinded fashion using in situ hybridization and H&E staining. In situ positivity was graded from 0 to 4, and histology was classified as normal, intermediate, or condylomatous. The majority of control animals showed highly positive in sifu hybridization and condylomatous histology. The treated group in general showed weaker in situ hybridization positivity and normal to intermediate histologies: Histology
In situ
o-2 +
3-4 +
Normal
Intermediate
T
7
6
2
3 6
4
c
1
1
Condylomatous 0 6
The difference between condylomatous and normal to intermediate histology is statistically significant (P = 0.002); the in situ hybridization positivity shows a trend toward weaker positivity in the treated group (P = 0.08). These data demonstrate interferon activity against HPV lesions in the athymic mouse/xenograft system which correlates with previous clinical human trials, suggesting that this animal model is suit-
SOCIETY OF GYNECOLOGIC
4.9 ng/mg protein) (P < 0.01). Levels of PAI- were higher in Stage II/III compared to Stage I malignancy (P < 0.01) and in cancers that had invaded 50% or more of the uterine wall compared to less invasive cancers (P < 0.01). PAI- may be useful as a prognostic marker in endometrial cancer. L. VAN LE, J. C. FOWLER, University of North Carolina, Chapel Hill, North Carolina, 27514; and Carolina Medical Center, Charlotte, North Carolina.
66. H-ras Codon 12 Mutation in Cervical Dysplasias. STOERKER,* C. A. RINEHART, S. HASKILL, AND W.
H-ras oncogene has been implicated in the pathogenesis of cervical cancers. In nude mice, injection of H-ras (codon 12 mutation)-transfected cervical cells infected with human papillomavirus (HPV) mice resulted in carcinoma formation. Although H-ras gene mutations have been studied in cervical cancers, it is unknown whether precancerous cervical lesions also contain H-ras mutations and therefore may be predicted to progress to cervical cancer. To determine if mutational activation of H-ras is an early event in carcinogenesis, we looked for the presence of codon- H-ras mutation in precancerous cervical dysplasias typed for HPV. Cervical DNA from 63 normal patients and 72 patients with biopsy-proven cervical dysplasia [CIN I (51) CIN II (9), CIN III (15)] were analyzed. HPV typing was performed on these samples by Viratype and Polymerase chain reaction (PCR). To detect H-ras codon 12 mutation, DNA was isolated and amplified by PCR with primers for H-ras. Restriction enzyme analysis with MSP I was performed on PCR products to discriminate between wild-type and mutated sequences; a unique restriction site for MSP I contained within the wild-type ras PCR product allows discrimination between unmutated and mutated sequences. To visualize cleavage products the restriction digest was electrophoresed on a polyacrylamide gel and stained with ethidium bromide. HPV testing by PCR or Viratype was positive for HPV 16 or 18 in 33% of CIN I, 56% of CIN II, and all CIN III samples. No codon 12 mutations were detected in any sample. We conclude that the codon 12 H-ras mutation is not found in dysplasias regardless of the presence of HPV. Mutation at the codon 12 location in H-ras is unlikely to be an early event in the progression of precancerous lesions to cervical carcinoma. 67. Survival
following the Endometrium. KINNEY, Mayo
Exenteration T. WILSON,
for Recurrent Adenocarcinoma M. MORRIS, R. ALVAREZ AND
of
W. Clinic, Rochester, Minnesota 55905; University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030; University of Alabama, Birmingham, Alabama 35294; and University of California, Davis, Sacramento, California 95816. The records of all patients undergoing pelvic exenteration for recurrent adenocarcinoma of the endometrium at four institutions during the years 1955 to 1988 were retrospectively reviewed. Of the 24 procedures performed, 4 were judged to be palliative in nature due to known distant metastases or widespread nodal disease, and the remainder potentially curative. This report concerns those 20 patients operated with curative intent. All patients had undergone prior pelvic radiotherapy; 14 of 20 as part of their primary treatment and 6 of 20 as part of the treatment of their recurrence. Either chemotherapy or hormonal therapy was utilized in addition in 6 of 20 patients prior to exenteration. Median patient age was 65 years (range 44-79). At most recent follow-up, 8 patients are alive and disease-free, 2 are alive with disease, 6 died of disease, and 4 died of other causes. Median follow-up of living patients is 89 months. Twelve of 20 patients experienced major complications, the most common of which was neovaginal flap necrosis. One patient of the 20 (5%) died of surgical complications (in 1963). Kaplan-Meier estimate of 5-year overall survival is 56% and 5-year disease-free survival is 45%. Pelvic exenteration can produce an acceptable rate of diseasefree survival in selected patients with local recurrence of endometrial adenocarcinoma who have exhausted other treatment modalities.
ONCOLOGISTS-ABSTRACTS and Follow-up of the Continent Real CoM. PENALVER, D. DONATO, B.-U. SEVIN, University of Miami School of Medicine,
68. Functional Characteristics ionic Urinary Reservoir. AND H. E. AVERETTE,
Miami, Florida 33101. A total of 33 patients underwent continent urinary diversion with pelvic exenteration. A detubularized right colonic segment served as a urinary reservoir and the distal ileum as a continent catheterizable efferent system. A direct nontunneled mucosa to mucosa ureterocolonic anastomosis was used. In this series 25 patients were followed for 6 to 46 months (average 17 months). Twenty-three patients are completely continent with intermittent catheterization at 4- to 8-hr intervals. Two patients suffer nighttime incontinence. Urodynamic studies demonstrate a mean reservoir volume of 650 ml. Mean and maximal contraction pressures were 25 and 49 cm of water, respectively, in the reservoir and 36 and 155 cm of water, respectively, in the plicated ileal segment (P = 0.043 and less than 0.001, respectively). The highest reservoir contractions occurred in the 2 patients with nocturnal incontinence. Of the 50 ureterocolonic anastomosis, 4 ureters developed partial obstmction and 1 required reoperation. The overall success rate (absence of reflux and obstruction) was 88.6%. Renal function deteriorated in 1 patient (4%). Three patients (12%) had diarrhea initially but all were controlled medically. One patient died of ARDS. Medical and surgical complications occurred at a rate comparable to previous series with ileal conduits. Our ongoing satisfactory experience with these patients warrants further study of this technique to achieve continent urinary diversion. of HPV Lesions to Interferon in Human Xenograjk W. A. JENSON, C. JOHNSON, R. HOLLOWAY, G. DELGADO, J. R. POTKUL, AND W. LANCASTER, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Georgetown University, Washington, D.C. 20007.
69. Response BARNES, BARTER,
Efforts to develop a systemically active therapeutic agent for HPV lesions have been hampered by the lack of a suitable experimental model; however, Kreider has induced condylomatous transformation of human epithelial xenografts exposed to HPV 11 and hosted in athymic mice. In this study interferon, a clinically active agent for the treatment of condyloma, is utilized to determine the reliability of this in vivo model for the basis of future developmental studies, as well as to test the effects of interferon on condyloma in an immunocompromised host. Animals were prepared with subrenal capsule grafts of HPV-infected epithelium. Half of the animals received daily injections of one million units (0.1 cc) of interferon a-Nl. Control animals received 0.1 cc of saline. The resulting cysts were analyzed in a blinded fashion using in situ hybridization and H&E staining. In situ positivity was graded from 0 to 4, and histology was classified as normal, intermediate, or condylomatous. The majority of control animals showed highly positive in sifu hybridization and condylomatous histology. The treated group in general showed weaker in situ hybridization positivity and normal to intermediate histologies: Histology
In situ
o-2 +
3-4 +
Normal
Intermediate
T
7
6
2
3 6
4
c
1
1
Condylomatous 0 6
The difference between condylomatous and normal to intermediate histology is statistically significant (P = 0.002); the in situ hybridization positivity shows a trend toward weaker positivity in the treated group (P = 0.08). These data demonstrate interferon activity against HPV lesions in the athymic mouse/xenograft system which correlates with previous clinical human trials, suggesting that this animal model is suit-