Ozone selectively inhibits growth of human cancer cells.

The growth of human cancer cells from lung, breast, and uterine tumors was selectively inhibited in a dose-dependent manner by ozone at 0.3 to 0.8 part per million of ozone in ambient air during 8 days of culture. Human lung diploid fibroblasts served as noncancerous control cells. The presence of ozone at 0.3 to 0.5 part per million inhibited cancer cell growth 40 and 60 percent, respectively. The noncancerous lung cells were unaffected at these levels. Exposure to ozone at 0.8 part per million inhibited cancer cell growth more than 90 percent and control cell growth less than 50 percent. Evidently, the mechanisms for defense against ozone damage are impaired in human cancer cells.

In vivo growth advantage of the MOPC-315 mouse myeloma over its immunoselected variants.

Myeloma cells of the "wild type" that produce complete immunoglobulin molecules and those of the more usual variant type that display only one kind of chain [either light (L) or heavy (H)] were cocultivated ip and sc in syngeneic BALB/c mice. With each of six deliberately selected variants, a progressive increase in the proportion of wild-type cells was observed; the rate of change suggested that these variants had an approximately 10% slower growth rate than that of the wild-type tumor. In contrast, a variant that arose spontaneously overgrew the wild-type cells. The results may account for a) the stable capacity of most wild-type tumors to produce complete immunoglobulin molecules (L- plus H-chains) over many years, even though they frequently generate variant cells that produce only L- or only H-chains; and b) the occasional spontaneous change of myeloma cell populations from predominantly wild-type to variant cells.

Resistance to cytolysis by tumor necrosis factor alpha in malignant gynecological cell lines is associated with the expression of protein(s) that prevent the activation of phospholipase A2 by tumor necrosis factor alpha.

Although there are a limited number of cell lines that are sensitive to cytolysis by tumor necrosis factor alpha (TNF alpha), the vast majority are resistant. The analysis of TNF alpha-sensitive cells has shown that phospholipase A2 is activated by TNF alpha in these cells and that the activity of phospholipase A2 is required for their cytolysis. Many cell lines that are resistant to TNF alpha-mediated cytolysis are dependent on the maintenance of protein synthesis for their resistance. We have recently shown that this is also true for TNF alpha-resistant cell lines derived from cervical (ME-180 and SiHa) and ovarian (SK-OV-3 and OVCAR-3) carcinomas, in that they are sensitive to cytolysis by TNF alpha only in the presence of protein synthesis inhibitors. Here we show that the TNF alpha-mediated cytolysis of these resistant cell lines in the presence of the protein synthesis inhibitor emetine is similar to that of sensitive cells, in that cytolysis is inhibited by the inhibitors of phospholipase A2. The measurement of the release of radiolabeled material from cervical and ovarian carcinoma cell lines prelabeled with [3H]arachidonic acid showed that not only was phospholipase A2 required for the cytolysis of these cells by TNF alpha in the presence of protein synthesis inhibitors, but more importantly, phospholipase A2 was not activated by TNF alpha unless protein synthesis was inhibited. These results indicate that a protein synthesis-dependent resistance mechanism expressed by these cell lines blocks TNF alpha-mediated cytolysis by preventing the activation of phospholipase A2 by TNF alpha.

Expression of a resistance mechanism in ovarian and cervical carcinoma cells prevents their lysis by gamma-interferon.

Despite extensive evidence that recombinant human gamma-interferon (IFN-gamma) exerts antiproliferative effects on a variety of cancer cell lines, IFN-gamma has not been shown to lyse cells in vitro. In order to determine whether some cancer cells might actively resist lysis by IFN-gamma, we examined eight arbitrarily selected cell lines derived from gynecological malignancies (ME-180, MS751, HT-3, SiHa, and C-33A human cervical carcinoma lines; Caov-3, SK-OV-3, and NIH:OVCAR-3 human ovarian carcinoma cell lines) for lysis by IFN-gamma. In a 24-h assay involving release of 51Cr from cells, none of these cell lines was lysed by IFN-gamma, either alone or in combination with actinomycin-D or emetine, two inhibitors of protein synthesis. However, pretreatment of cells with 100 units/ml of IFN-gamma for 24 h, followed by inhibition of protein synthesis, led to significantly increased lysis of the cell lines ME-180, MS751, and Caov-3. These results indicate that IFN-gamma induces a lytic mechanism in some cancer cells that is opposed by a protein synthesis-dependent resistance mechanism. This suggests that a combination therapy involving IFN-gamma and inhibitors of protein synthesis may be useful in the treatment of some cancers.

Radiation therapy alone or combined with surgery in the treatment of barrel-shaped carcinoma of the uterine cervix (stages IB, IIA, IIB).

This retrospective analysis reports the results of therapy in 128 patients with carcinoma of the uterine cervix classified as barrel-shaped or expanded cervix (over 5 cm in diameter). Seventy-five percent of the patients were treated with irradiation alone and 25% with combinations of irradiation and surgery. The results of therapy are compared with those observed in 714 patients with non-barrel-shaped carcinoma of the uterine cervix treated with similar techniques during the same period of time. The distribution of histological type of tumor was similar in both groups (90% epidermoid carcinoma, 8% adenocarcinoma, and 2% adenosquamous carcinoma). Approximately 15% of the patients in both groups with Stage IB and 25% with Stage IIA and IIB had positive endometrial curettings (stromal invasion or replacement by tumor only). Thus, the aggressive behavior observed in the barrel-shaped tumors is not a result of endometrial involvement, but to the large volume of tumor present. The actuarial 5-year tumor free survival in Stage IB barrel-shaped cervix was 76% compared to 92% in the non-barrel-shaped lesions. In Stage IIA the 5-year NED survival for patients with barrel-shaped cervix was 60 compared to 80% for the patients with non-barrel-shaped cervix. In Stage IIB the survival rates were 58 and 70%, respectively. A noteworthy finding in this analysis is the high incidence of distant metastases in the patients with barrel-shaped cervix (32% in Stage IB, 40% in Stage IIA, and 32% in Stage IIB) in comparison with patients with non-barrel-shaped tumors (10% in Stage IB, 16% in Stage IIA, and 25% in Stage IIB). The incidence of pelvic failures was comparable in both groups. Higher doses of irradiation resulted in better tumor control, which was comparable to that observed with a combination of irradiation and surgery (conservative hysterectomy). The 5-year survival rate in Stage IB was similar in both the barrel-shaped and non-barrel-shaped tumors treated with irradiation alone or combination irradiation and surgery. In Stage IIA the non-barrel-shaped lesions had the same survival with either treatment technique. In the barrel-shape group, eight patients treated with irradiation alone or survival of 70%, compared to 45% in 24 patients treated with irradiation alone. However, these differences are not statistically significant (p = .50). In eight patients treated with definitive irradiation and a lymphadenectomy and four patients irradiated after an exploratory laparotomy, two major and three minor (grade 2) complications were noted.(ABSTRACT TRUNCATED AT 400 WORDS)

Hysterectomy and adjuvant irradiation for pathologic stage III adenocarcinoma of the endometrium.

Three hundred and four evaluable patients with FIGO clinical Stage I adenocarcinoma of the endometrium were treated with hysterectomy and adjuvant irradiation. At surgery, 15 patients (5%) were found to have disease outside the uterus, but within the pelvis Pathologic Stage III (PSIII). A higher grade of tumor was not associated with an increase in the frequency of PSIII, being 7/158 (4%), 5/89 (6%), and 3/57 (5%) for Grades 1, 2, and 3 respectively. Depth of myometrial invasion correlated with PSIII disease in 5/69 (7%) for less than 1/3 myometrial invasion versus 7/33 (21%) for greater than 1/3 invasion (p = .05). One patient died of intercurrent disease at 4 months with 6/14 (43%) of the remaining patients developing recurrent disease. The site of initial failure was pelvis 1/15 (7%), pelvis and distant metastasis 3/15 (20%), and distant metastasis alone 2/15 (13%). Of seven patients who received external pelvic irradiation, there was one local failure (14%), which is not statistically significant from the 3/8 (38%) local failure rate among patients not receiving external pelvic irradiation (p = .569). None of the seven patients experienced a treatment related complication as a result of adjuvant irradiation.

Treatment of stage I adenocarcinoma of the endometrium by hysterectomy and adjuvant irradiation: a retrospective analysis of 304 patients.

Three hundred and four evaluable patients with FIGO Stage I adenocarcinoma of the endometrium were treated with hysterectomy and irradiation. Irradiation was preoperative in 250 and postoperative in 44 patients. Ten patients had a preoperative implant and postoperative external irradiation. The 5 year actuarial survival was 94%, 80% and 76% for grades 1, 2 and 3, respectively. Within each grade and for all patients there was no difference in survival for Stage IA versus IB. The initial failure rate was 26/304 (9%) with 2% of patients having only a pelvic failure, 2% pelvic and distal failure and 4% a distal failure only. There were four distal vaginal failures and no isolated cuff recurrences. The upper abdomen was the most frequent site of extra-pelvic failure for grade 3, while the periaortic nodes and lung constituted the most common sites of distal failure for grades 1 and 2 tumors. Timing of the hysterectomy following the irradiation was of importance when evaluating the prognostic significance of residual disease or depth of myometrial invasion. The presence of residual disease or greater than 1/3 myometrial invasion had a significantly worse prognosis only among patients who received no preoperative irradiation or who underwent their hysterectomy immediately following a preoperative implant. There was no difference in survival among patients with an initial local failure only as compared to those with an initial distal metastases, as the majority of patients with an initial local failure subsequently developed distant metastases.

Stage II carcinoma of the endometrium: results of therapy and prognostic factors.

A retrospective analysis is reported of 116 patients with Stage II carcinoma of the endometrium treated definitively with combined radiation and total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO) or irradiation alone from January 1960 through December 1981. At 5 and 10 years, the overall survival for all patients was 71 and 52% and the disease-free survival was 73 and 69%, respectively. Of 90 patients in the combined therapy group, most received a preoperative intracavitary insertion (3500 mgh to the uterus and 2000 mgh to the upper vagina) and preoperative external beam pelvic irradiation (2000 cGy whole pelvis, additional 3000 cGy to parametria, with midline shield) followed in 4 to 6 weeks by a TAH-BSO. The 5 and 10 year disease-free survival for this group was 78 and 75%, respectively. The incidence of major complications was 7% for the combined therapy group. Twenty-six patients were treated with irradiation alone; most of them received two intracavitary insertions (5000 mgh to the uterus and 3000 mgh to the upper vagina) and external beam pelvic irradiation (2000 cGy whole pelvis, additional 3000 cGy to parametria). The 5 and 10 year disease-free survival was 53 and 45%, respectively. The incidence of major complications was 19%. Factors found to influence the prognosis were histologic grade of tumor, clinical and histologic degree of tumor involvement of the ectocervix, presence of residual tumor in the hysterectomy specimen and the depth of myometrial invasion.

Analysis of pelvic tumor control and impact on survival in carcinoma of the uterine cervix treated with radiation therapy alone.

A total of 1054 patients with histologically confirmed invasive carcinoma of the uterine cervix were treated with radiation therapy alone between 1959 and 1982. All patients are available for a minimum of 3 years follow-up. Radiation therapy consisted of external irradiation to the whole pelvis (1000-2000 cGy) and parametria (for a total of 4000-6000 cGy) combined with two intracavitary radioactive source insertions (6000-7500 cGy to point A). Patients with Stage IIB, III, and IVA have been consistently treated with somewhat higher doses of external irradiation and intracavitary insertions. A small group of 54 patients with Stage IIB or IIIB had pelvic lymphadenectomy following the irradiation (1960-1964). There was a strong correlation between the tumor regression within 30 days from completion of radiotherapy and the incidence of pelvic recurrences or distant metastases for each of the anatomical stages. The 10-year survival rate for Stage IB was 76%, Stage IIA 60%, Stage IIB 45%, and Stage III 25%. Many of the deaths were due to intercurrent disease. Thus, the 10-year tumor-free survival was 80% for Stage IB, 60% for Stages IIA and IIB and 35% for Stage III. In Stage IB total doses of 6000 cGy or higher to point A resulted in 94% pelvic tumor control. In Stage IIA, the pelvic tumor control was 87% with doses of 6000 cGy to point A or higher. However, in Stage IIB the pelvic tumor control was 58% with doses below 6000 cGy, 78% with 6001-7500 cGy and 82% with higher doses. In Stage IIIB the pelvic tumor control was 42% with doses below 6000 cGy, 57% with 6001-7500 cGy and 68% with higher doses. Tumor control in the pelvis was correlated with the following 5 year survivals: Stage IB-95% (353 patients); Stage IIA-84% (116 patients); Stage IIB-84% (308 patients); Stage IIIB-74% (245 patients). The 5-year survival for patients that recurred in the pelvis was 30% for Stage IB, about 15% for Stages IIA-B and only 5% in Stage III. Patients with tumor control in the pelvis had a significantly lower incidence of distant metastases than patients who initially failed in the pelvis (9.3% vs. 58.6% in Stage IB, 21.6% vs 52.6% in Stage IIA, 19.8% vs 16.7% in Stage IIB, and 31.2% vs 50% in Stage III). In Stage IIB the figures were 19.8% and 16.7% because the initial pelvic recurrence was frequently concurrent with distant metastases.(ABSTRACT TRUNCATED AT 400 WORDS)

Mini-colpostats in the treatment of carcinoma of the uterine cervix.

Between 1976 and 1982, 293 patients were treated for carcinoma of the uterine cervix at Washington University by definitive radiotherapy consisting of external beam therapy and two standard Fletcher-Suit applications (tandem plus vaginal colpostats). In ninety-nine patients (34%) mini-colpostats (MC) were used for one or both of their intracavitary insertions while 194 (66%) patients were treated twice with regular Fletcher-Suit colpostats (RC). The frequency of MC use was related to the age and parity of the patients. The distribution by stage of MC and RC groups was not significantly different. Pelvic failure in the MC group was similar to that of the RC group (21% vs 24%). Five-year disease-free survival was also similar between the two groups: 86% vs 80% Stage IB, 57% vs 61% Stage IIA, 47% vs 52% Stage IIB, and 27% vs 45% Stage III for MC and RC groups, respectively. The rate of major complications (grade 3) was 15% in the MC group and 8% in the RC group (p = 0.08). Careful phantom dosimetric studies in both types of colpostats and correlations of dose distributions at various points in the pelvis with frequency of rectal and bladder complications were carried out. The bladder and rectum received a 5-10% higher mean radiation dose (Gy) in the MC group than in the RC group despite lower overall exposure (milligram-hours). Thermoluminescent dosimetry in a polystyrene phantom demonstrates that approximately 10% higher doses are delivered to the bladder, rectum, and point A with an MC system as compared to an RC system, for constant exposure in mgh. Phantom measurements of a newer MC with bladder and rectal shielding demonstrate no influence on the bladder and rectal point dose at a source separation of 3 cm; midline points of the bladder and rectum are not within the full shadow of the shields even if the colpostats are flush with the tandem. Implications for therapy are discussed.

Clinical stage I endometrial cancer: prognostic factors for local control and distant metastasis and implications of the new FIGO surgical staging system.

A retrospective analysis is reported in 858 patients with clinical Stage I carcinoma of the endometrium treated definitively with combined irradiation and total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO) from January 1960 through December 1986. Most patients received a preoperative intracavitary insertion (3500-4000 mgh to the uterus and a 6500 cGy surface dose to the upper vagina) followed by a TAH-BSO within 1-2 weeks. Some patients received postoperative external beam irradiation (2000 cGy whole pelvis and an additional 3000 cGy to the parametria, with a midline stepwedge) when factors such as deep myometrial invasion were present. Occasionally patients were treated with a preoperative intracavitary insertion and preoperative external beam irradiation (2000 cGy whole pelvis). The 5-year progression-free survivals by FIGO (1988) surgical stage were 93% for IA, 90% for IB, and 91% for Stage IC. An analysis of multiple variables was performed to ascertain their prognostic significance. Factors that significantly affected the 5-year progression-free survivals by univariate analysis were grade (grade 1 = 95%, grade 2 = 88%, grade 3 = 73%; p less than 0.0001), histology (adenoacanthoma = 96%, clear cell = 89%, adenocarcinoma = 89%, papillary = 81%, adenosquamous = 80%; p = 0.04), lower uterine segment involvement (uninvolved = 89%, involved = 73%; p = 0.006), depth of myometrial invasion (no residual tumor = 91%, limited to the endometrium = 96%, less than 1/3 myometrial penetration = 92%, 1/3 - 2/3 = 100%, greater than 2/3 = 50%; p = 0.02), peritoneal cytology (negative = 92%, positive = 56%, p less than 0.0001), uterine serosal involvement (uninvolved = 89%, involved = 55%; p less than 0.0001), vascular space invasion (absent = 89%, present = 75%; p = 0.001), and the presence of extrauterine disease (absent = 90%, present = 64%; p less than 0.0001). A multivariate analysis of these prognostic variables showed that histological grade (p = 0.001), peritoneal cytology (p = 0.004), and uterine serosal involvement were prognostic for local failure and that peritoneal cytology (p less than 0.001), grade (p = 0.001), age (p = 0.002), and extrauterine disease (p = 0.02) were prognostic for the development of distant metastasis.

Impact of dose in outcome of irradiation alone in carcinoma of the uterine cervix: analysis of two different methods.

This is a retrospective analysis of 1211 patients with histologically proven invasive carcinoma of the uterine cervix with a minimum follow-up of 3 years treated with irradiation alone. The pelvic failure rates by stage were 9.6% for IB, 18.6% for IIA, 23% for IIB, 41% for III, and 75% for Stage IVA disease. External beam and intracavitary irradiation doses to point A and pelvic lymph nodes were calculated. In patients with Stage IB and IIA disease there was no significant correlation between doses to these points and pelvic tumor control. In Stage IIB doses of less than 6000 cGy to point A correlated with a high pelvic failure rate (8 of 12, 66.7%) in contrast to doses of 6000 to 9000 cGy (61 of 261, 23.4%) or higher than 9000 cGy (10 of 74, 13.5%) (p less than or equal to 0.01). In Stage III the pelvic failure rate with doses below 6000 cGy to point A was 72% (18 of 25) compared to 39% (71 of 180) for 6000 to 9000 cGy or 35% (27 of 77) with doses above 9000 cGy (p less than or equal to 0.01). TDF calculation of doses was carried out. In Stage IB and IIA there was no significant correlation between TDF to point A and probability of pelvic recurrence. In Stage IIB with TDF below 135, the pelvic recurrence rate was 41.6% (20 of 48) compared to 20% (61 of 305) with higher TDF (p less than or equal to 0.01). In Stage III the pelvic failure rate was 51% with TDF below 160 (70 of 136) in comparison with 29.5% (46 of 156) with higher TDF (p less than or equal to 0.01). Grade 2 sequelae of therapy were noted in about 10% of the patients and grade 3 in 4.7% of patients with Stage IB (18 of 384), 10.2% (12 of 128) with Stage IIA, 9.3% (33 of 353) with Stage IIB, and 8.2% (24 of 293) with Stage III disease. Doses from external beam and intracavitary irradiation to the rectum or the bladder neck were calculated. The actuarial incidence of major rectal or rectosigmoid sequelae was 2% to 4% with doses to the rectum of 6000 to 8000 cGy, 7% to 8% with 8000 to 9500 cGy, and 13% with doses higher than 9500 cGy (p less than or equal to 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Medically inoperable stage I adenocarcinoma of the endometrium treated with radiotherapy alone.

Definitive therapy for Stage I adenocarcinoma of the endometrium consists of total abdominal hysterectomy and bilateral salpingo-oophorectomy. Pre- and/or post-operative radiotherapy (RT) is employed in selected patients with poor prognostic factors such as poorly differentiated tumors or deep myometrial invasion by tumor. The results are reported of RT alone in 69 patients with Stage I adenocarcinoma of the endometrium who presented with severe, acute, and chronic medical illnesses which prevented surgical management of their disease. Sixty-three patients (91.3%) were obese or hypertensive. Twenty-seven patients (39.1%) had diabetes mellitus, 16 (23.2%) had congestive heart failure, and the remaining patients had such conditions as stroke (17.4%), coronary artery disease (15.9%), and recent myocardial infarction (13.0%). The median age for this group of patients was 72.0 years compared to 60.0 years for a concurrent group of 304 patients with Stage I adenocarcinoma of the endometrium treated at our institution with combined surgery and RT. RT consisted of intracavitary insertions alone (11 patients), intracavitary plus low dose external beam therapy (9 patients), and intracavitary therapy plus high dose external beam therapy (49 patients, definitive RT). Younger patients and those with poorly differentiated disease were treated more aggressively. The 5- and 10-year overall survival for all patients was 76.8 and 33.3%, respectively. The 5- and 10-year disease-free survival was 88.1 and 82.4%, respectively. The 5-year overall and disease-free survival for the group of 49 patients treated with definitive RT was 85.4% and 88.7% with 15/49 (30.6%) having poorly differentiated tumors. For the definitive therapy group, the 5- and 10-year disease-free survival was 94.3, 92.3, and 78.0% for grades I, II, and III, respectively. Analysis of patterns of failure showed that none of the patients failed in the pelvis alone. Two out of 11 (18.2%) receiving intracavitary therapy alone and 3/49 (6.1%) receiving definitive RT failed in the pelvis with simultaneous distant metastasis (DM). Three patients in the definitive RT group failed with DM only. Severe complications occurred in 8 patients (16%), all of whom received definitive RT.

Clinical stage I endometrial cancer: results of adjuvant irradiation and patterns of failure.

A retrospective analysis is reported in 858 patients with clinical Stage I carcinoma of the endometrium treated definitively from January 1960 through December 1986 with combined irradiation and total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO). Most patients received a preoperative intracavitary insertion (2500-4000 mgh to the uterus with Heyman capsules and tandem and 6500 cGy surface dose to the upper vagina) followed by a TAH-BSO within 6 weeks. Some patients received postoperative external beam irradiation (2000 cGy whole pelvis and an additional 3000 cGy to the parametria, with a midline stepwedge) when deep myometrial invasion was present. Occasionally patients were treated with preoperative external beam irradiation (2000 cGy whole pelvis) and intracavitary insertion. The 5-year overall survival for all patients was 84.0% compared to an expected survival of 88.8%. The 5-year progression-free survivals were 92% for FIGO clinical Stage IA and 86% for stage IB (p = 0.12). The dose to the uterine fundus from the preoperative intracavitary insertion was found to have a significant correlation with progression-free survival in patients with grade 3 tumors. Those receiving less than 2500 mgh to the uterine cavity had a 48.9% 5-year progression-free survival compared to 62.7% for 2500-3500 mgh and 87.4% for those receiving greater than 3500 mgh. Analysis of sites of failure showed that less than 1% (7/858) failed in the pelvis alone, 3% (30/858) in the pelvis combined with distant sites, and 7% (60/858) developed distant metastasis only. The lateral pelvic sidewall was the most common site of failure within the pelvis (20/37) and intraperitoneal failures (28/90) and lung (21/90) were the most common sites of distant metastasis. The overall severe (grades 2, 3, and 4) complication rate was 2.7% (23/858).

Brachytherapy-related complications for medically inoperable stage I endometrial carcinoma.

PURPOSE: The current study was conducted to investigate the incidence and risk factors for medical complications associated with low dose rate brachytherapy in patients with medically inoperable Stage I endometrial cancer treated with irradiation alone. METHODS AND MATERIALS: From 1965 through 1991 at Mallinckrodt Institute of Radiology, 150 implants were performed on 96 patients who were deemed medically unfit for hysterectomy because of advanced age, obesity, and various medical problems. The records of these patients were examined retrospectively to determine the incidence of medical complications that occurred in the first 30 days following the initiation of brachytherapy. The association of risk factors that precluded major surgery and the occurrence of brachytherapy-related complications was examined by logistic regression. RESULTS: Of these 96 patients, 40 patients were older than 75 years, and 31 patients were deemed morbidly obese. Medical problems included hypertension in 45 patients, and diabetes in 37; there was a history of congestive heart failure in 23, stroke in 11, myocardial infarction in 10, and thromboembolism in 8. There were concurrent malignancies in five patients. Implants were performed using intrauterine Simon-Heyman capsules, tandems, and vaginal ovoids in all patients. General anesthesia was used for 98 implants, spinal anesthesia for 26, local anesthesia for 25, and epidural anesthesia for 1. The duration of anesthesia ranged from 30 to 120 min (median, 60 min). The duration of radioisotope application ranged from 11 to 96 h (median, 46 h). Preventive measures included low dose subcutaneous heparin in 55 patients (since 1978), and intermittent pneumatic compression boots in 29 (since 1985). Four patients developed life-threatening complications including myocardial infarction (two patients), congestive heart failure (one patient), and pulmonary embolism (one patient). Two of these four patients died; one with a myocardial infarction and the other with pulmonary embolism. The morbidity rate was thus 4.2% (4 out of 96), and the mortality was 2.1% (2 out of 96). Although the four serious complications occurred within 30 days of the procedure, only one complication and one death occurred during treatment. There was no correlation between occurrence of complications and medical risk factors, type and duration of anesthesia, or type and duration of implant. CONCLUSIONS: There is a low incidence of complications associated with conventional low dose rate brachytherapy. The procedure is well tolerated in patients with medically inoperable Stage I endometrial cancer. In comparison to the predicted serious complication rate of surgery in these patients, the number of life-threatening complications from brachytherapy appears to be quite acceptable.

Proliferative serous tumors of the ovary. Histologic features and prognosis.

In reviewing all proliferative serous tumors of the ovary seen at Barnes Hospital from 1950 to 1974, we quantitated histologic characteristics and defined criteria for diagnosis in 55 borderline tumors, 13 well-differentiated cystadenocarcinomas, and 15 cystadenomas with unusual proliferative areas. This last type with focal proliferation behaved in a benign fashion and should be considered a variant of a simple cystadenoma. Stromal invasion was the only histologic feature which consistently distinguished carcinomas from the borderline tumors. The presence in some borderline tumors of severe cellular atypia, marked epithelial disorganization, frequent mitoses, and cribriform glands in the stroma neither signified carcinoma nor indicated poor prognosis. No patient with a Stage I borderline lesion died of tumor. Although the mortality of patients with Stage IIb or Stage III borderline tumors is high, tumor-related deaths rarely occurred before 5 years, and three patients lived more than 10 years. Borderline serous tumors are low-grade malignant neoplasms which differ from overt carcinomas in the excellent prognosis of Stage I lesions and in long survival even with widespread abdominal disease.

Adenocarcinoma of the uterine cervix: lack of evidence for a poor prognosis.

A retrospective analysis was performed to evaluate the prognostic significance of histologic type (epidermoid carcinoma versus adenocarcinoma) on local control of disease and on the development of distant metastatic disease in 1239 patients with carcinoma of the uterine cervix treated with radiation therapy alone or surgery and irradiation at the Radiation Oncology Center, Mallinckrodt Institute of Radiology (MIR), Washington University Medical Center, between 1959 and 1982. The 5-year disease-free survival (all stages combined) was 68.0% for 925 patients with epidermoid carcinoma compared to 64.9% for 79 patients with adenocarcinoma treated with irradiation alone (p = 0.34). There was no significant difference in the survival rate when epidermoid carcinoma and adenocarcinoma were compared after stratification by clinical stage except for stage III. The 5-year disease-free survival (all stages combined) was 73.4% for 213 patients with epidermoid carcinoma and 77.0% for 22 patients with adenocarcinoma treated with irradiation plus surgery (p= 0.74). Prognostic variables analyzed by multivariate analysis included age at diagnosis, histology, size of lesion, endometrial extension, lymph node status (as evaluated by lymphangiogram), dose to point A, and surgery. Prognostic variables that were significant (p less than 0.05) for the development of recurrent disease in the pelvis were size of the primary lesion and dose of irradiation to point A. Significant (p less than 0.05) factors for the development of distant metastatic disease were size of the primary lesion and metastatic lymph nodes at the time of diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Complications following parametrial radiogold treatment for cervical carcinoma.

Between January 1950 and March 1965, 382 patients with carcinoma of the uterine cervix were treated with parametrial radiogold injections. One hundred and ninety-two patients are known to have survived 5 or more years after the treatment without evidence of recurrence. Major complications with significant morbidity requiring hospitalization or additional surgery was observed in 9.4% of the patients. Parametrial radiogold injection is associated with a high incidence of major lower urinary tract complications, including an increased incidence of ureteral obstruction as a result of radiation fibrosis, Heterogenous distribution of radioactive material with localized areas of heavy irradiation is probably responsible for the development of late major complications.

Crohn's disease of the vulva.

Over the past 10 years, it has been well established that Crohn's disease may involve any segment of the gastrointestinal tract from the mouth to the anus and may also cause destructive extraintestinal lesions. Extensive cutaneous ulceration has recently been recognized as one of the rare extraintestinal complications. A case of chronic vulvar ulceration due to Crohn's disease is reported. The clinical manifestations and management of such a lesion are discussed.

Treatment of stage I adenocarcinoma of the endometrium by hysterectomy and irradiation: analysis of complications.

Twelve of 304 patients (4%) treated with surgery and adjuvant irradiation for endometrial carcinoma experienced a serious complication. The complication rate for patients whose irradiation consisted of an implant alone was only 1% (two of 199), if the implant was preoperative, but was 12% (three of 26) if the implant was postoperative. For patients who received external pelvic irradiation as part of their adjuvant therapy, the incidence of complications was 8.8% (seven of 79) and the timing (preoperative versus postoperative) had no effect. There was, however, a significant correlation of the complication rate with an increasing dose of external irradiation to the whole pelvis: For doses of 3000 rad or less, it was 2% (five of 264) but was 18% (seven of 40) for doses in excess of 3000 rad. These data suggest that the safest form of adjuvant irradiation for adenocarcinoma of the endometrium is a preoperative implant, and that adding external pelvic irradiation to the preoperative implant will significantly increase the complication rate if the external dose to the central pelvis exceeds 3000 rad.