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The prognostic significance of residual endometrial carcinoma in the hysterectomy specimen after preoperative radiotherapy is controversial. Sixty-two patients with stage II endometrial carcinoma were treated with a standardized program of preoperative radiotherapy, followed in six weeks by an extrafascial hysterectomy. Twenty patients (32%) had no residual carcinoma in their hysterectomy specimens and 42 (68%) had residual carcinoma. There were no significant clinical, surgical, or pathologic differences between patients with or without residual carcinoma. Patients with no residual carcinoma had a 25% recurrence rate and a 53% actuarial five-year survival rate. Patients with residual carcinoma had a 21% recurrence rate and a 78% actuarial five-year survival rate. The presence of residual endometrial carcinoma in the hysterectomy specimen does not imply a compromised prognosis in patients with stage II endometrial carcinoma treated by the described method.

Fifty-two cases of the rare entity, uterine endolymphatic stromal myosis, were evaluated in a collaborative study by gynecologic oncologists trained at the M. D. Anderson Tumor Institute. Fifty percent developed recurrent disease subsequent to initial surgical therapy. Of the surgical stage I cases, 47% developed pelvic recurrences, and 9% developed distant recurrences only after initial therapy. The five- and ten-year life-table survival of surgical stages I to IV were 88% for stage I, 66% for stage II, 100% for stage III, and 75% for stage IV. These long-term survival rates were due in part to the hormonal sensitivity of the recurrent tumors. Because of the high recurrence rate after initial therapy, a suggested plan of therapy is presented for patients with uterine endolymphatic stromal myosis.

Twenty-seven patients with Stage III epithelial ovarian carcinoma received a "third-look" celiotomy. Each patient received a minimum of an additional 12 courses of chemotherapy after persistent tumor had been documented at a "second-look" procedure. Twelve of the twenty-seven patients have died. No tumor-associated deaths occurred in patients with grade 1 neoplasms. Of the patients with microscopic disease at the second-look procedure who came to third-look laparotomy, none had died secondary to tumor growth. The survival time of patients with microscopic disease at third-look is greater than that of patients with macroscopic disease (P = 0.0009). In patients who had effective tumor reductive surgery performed at second-look, the third-look findings were highly predictive as to survival. Long-term chemotherapy had a significant incidence of related mortality. Four of the twenty-seven patients died as a direct result of the chemotherapeutic toxicity. The patients receiving melphalan for at least 24 courses appeared to be at greatest risk, with 23% dying from either aplastic bone marrow changes or leukemia. The morbidity associated with third-look laparotomy was not excessive. Many factors need careful review prior to planning a third-look laparotomy. This retrospective study demonstrates that patients with either a grade 1 neoplasm or only microscopic disease at the second-look procedure do well regardless of the third-look findings.

Over an 11-year period (1971 to 1981), 212 urinary conduit surgeries were performed by the Department of Gynecology at the University of Texas, M. D. Anderson Hospital and Tumor Institute at Houston. The urinary diversions were performed as part of the pelvic exenteration operation in 154 patients, for radiation injury in 48 patients, and for palliation of disease recurrence in ten patients. Ninety-three percent had prior pelvic radiotherapy. Various segments of the gastrointestinal tract were used, including the ileum (102), sigmoid colon (99), transverse colon (four), jejunum (four), and others (three). Fifty percent of abnormal preoperative intravenous pyelograms reverted to normal after urinary diversion. Revision of the stoma was required in 6%. Other complications included infection (18%), renal loss (17%), and urinary leaks and fistulae (3%). The overall perioperative mortality was 7%, decreasing from 11% in the first five years to 3% during the last six years. Ureteral stents were routinely used. When selecting a segment of bowel for a urinary conduit, both tissue quality and mobility are important. Mortality and morbidity of urinary conduit surgery continues to decrease with experience.

Treatment was initiated for metastatic or recurrent squamous carcinoma of the cervix with a combination of doxorubicin and methyl CCNU in 37 patients. Results after at least one full course of chemotherapy were fully evaluated in 31 of these patients. The objective response rate of 45.1 per cent obtained with this therapy compared favorably with those obtained by other authors using single or multiple agents. This chemotherapy regimen may need to be modified to improve patients' tolerance. The improved survival rate and high number of complete remissions demonstrated in this pilot study show promise for this type of chemotherapy in the future.

Eighteen patients with recurrent or advanced adenocarcinoma of the endometrium were treated with the combination of cisplatin, doxorubicin, and cyclophosphamide between January 1981 and December 1983. Sixteen of the 18 had received prior irradiation. None of the patients had received prior chemotherapy. Fifteen patients had previously received hormones without response. No patients received concurrent hormone treatments. Ten of the 18 patients (56%) achieved an objective response: five (28%) achieved complete response and five (28%) achieved partial response. Myelosuppression was present in seven patients, and two developed neurotoxicity. Combination chemotherapy using cisplatin, doxorubicin, and cyclophosphamide is active in patients with adenocarcinoma of the endometrium, including those who have received prior irradiation and have failed hormonal therapy.

One hundred and forty-nine patients with early cancer of the ovary who were suitable for postoperative radiotherapy were treated in a random study in which the efficacy of whole abdominal irradiation with additional irradiation to the pelvis was compared to that of chemotherapy with melphalan. The number of patients without evidence of disease at 2 years indicates that both treatments give similar results. However, the survivals among patients with stage I ovarian cancer showed an improvement for women treated with irradiation, survivals among patients with stage II ovarian cancer showed only a minor difference between women treated with irradiation and those treated with chemotherapy, and survivals among patients with stage III ovarian cancer improved for women treated with chemotherapy. The complications resulting from both treatments differed greatly. Melphalan was well tolerated; it caused serious bone marrow depression in only one patient. The blood counts of all patients after completing their prescribed chemotherapy promptly returned to normal levels. Seven patients treated with irradiation developed small bowel injury requiring surgery. Six of these patients, however, were treated with irradiation to the pelvis followed by strip irradiation to the entire abdomen. Since this treatment plan probably gives excessive doses of irradiation to the pelvis, it has been discontinued.

The effectiveness of melphalan, hexamethylmelamine, and 5-fluorouracil was compared in the treatment of patients with advanced ovarian cancer. Patients responded the best to hexamethylmelamine, which, however, was associated with considerable neurotoxicity. Patients responded the worst to 5-fluorouracil, which occasionally induced severe gastrointestinal toxicity. Patients treated with melphalan continued to demonstrate the response rate reported for several years in the literature. Melphalan seemed the best choice as a second-line drug. It induced not only the longest survival rate among patients, but also the only two complete responses as a second-line drug. Hexamethylmelamine has shown no activity as a third-line drug to date.

An analysis of 296 patients who had pelvic exenteration discloses a high risk of postoperative complications and death; however, the safety has been improved by technical modifications for urinary diversion and treatment of the denuded pelvic cavity. Recurrent cancer of the cervix or vagina was the main reason for the operation. Prognostic factors were sought to improve selection of patients who are able to withstand operation, tolerate postoperative complications, and remain free of cancer. The five-year survival rate for 296 patients with various types of cancer calculated by the Berkson-Gage method was 56.5 per cent after death from all causes were deducted, the rate was 42.1 per cent. The five-year survival rate for 196 patients with recurrent carcinoma of the cervix calculated by the Berkson-Gage method was 48.3 per cent; after deaths from all causes were deducted, the rate was 33.8 per cent.

Twenty-six women with advanced or recurrent endometrial cancer were treated with cisplatin at a dose of 50, 70, or 100 mg/m2 every 4 weeks. An objective response was obtained in 11 of 26 patients (42%), with 10 partial responses and 1 complete response. The median duration of remission was 5 months, with a range of 2 to 11 months. The complete response lasted 8 months. Five patients had stable disease lasting an average of 5 months. One of 6 patients (16.6%) responded to cisplatin at a dose of 50 mg/m2, 4 of 7 (57%) responded to the dose of 70 mg/m2, and 6 of 13 (46%) responded to the dose of 100 mg/m2, but the differences were not statistically significant (P = .2). In 8 of 26 cases (31%) cisplatin was discontinued because of toxicity. Three patients developed a peripheral neuropathy, 1 patient refused further therapy because of vomiting, 2 patients had nephrotoxicity, and 2 others had both nephrotoxicity and neurotoxicity. The average total cumulative dose of cisplatin administered when renal deterioration and neuropathy occurred was approximately 500 mg/m2. Cisplatin is definitely active against endometrial cancer, but toxicity precludes its prolonged administration in high doses on an outpatient basis. By maintaining a forced diuresis, toxicity can probably be decreased, thereby permitting continued administration of cisplatin. The drug may also be more useful when used at a lower dose in combination with other active agents against endometrial cancer.

One hundred and forty-nine patients with early cancer of the ovary who were suitable for postoperative radiotherapy were treated in a random study in which whole abdominal irradiation with additional treatment to the pelvis was compared to chemotherapy with Melphalan. The number of patients without evidence of disease at 2 yr seems to show that the results of treatment are similar. When the Berkson-Gage method of projection is used, however, the survival rate in stage I is apparently improved with irradiation; there is only a minor difference in the results of the two methods in stage II, and survival rates are improved for patients with stage III disease who were treated with chemotherapy. The complications of treatment in this study were quite different. Melphalan was well tolerated, and only one patient had serious bone marrow depression as a result of this treatment. All had prompt recovery of blood counts to normal after completing the prescribed chemotherapy. Seven patients treated by radiotherapy developed a small bowel injury which required surgery. Six of these were treated with irradiation to the pelvis followed by strip irradiation to the entire abdomen. This treatment plan probably gives excessive doses of irradiation to the pelvis and has been discontinued. This type of complication is much less frequent with the other sequence of treatment--strip irradiation to the whole abdomen and subsequent treatment to the pelvis. The cost to the patient of the two treatment programs varied considerably. Patients who received irradiation had the added expense of living in Houston for the duration of treatment. Patients treated with chemotherapy were often seen a 2- or 3-mo intervals and had their chemotherapy supervised by their personal physician.

During the 11-year interval from January 1971 to January 1982, 50 of 246 patients with advanced (Stage III and IV) epithelial ovarian carcinoma at second-look laparotomy had biopsy or cytologic evidence of persistent microscopic carcinoma. The stage and grade profile include 46 Stage III and 4 Stage IV patients: 4 borderline, 9 grade 1, 20 grade 2 and 17 grade 3 patients. Following second-look laparotomy, 4 patients received no further therapy, 45 received chemotherapy, and 1 received external radiation. No patient was lost to follow-up, and the median interval off therapy was 24 months. Progressive or recurrent disease has manifest in 12 (24%). No recurrences have developed either in patients younger than age 40 or in patients with grade 1 tumors. Two patients died of leukemia, 1 died of heart disease, and 35 (70%) are alive with no evidence of disease. In patients developing recurrence, the median progression-free interval was 17.5 months, with a range of 6 to 46 months. The median interval of survival following disease progression was 7 months. There was no evidence of progression at 2 years and 5 years in 81% and 70% of patients, respectively. The uncorrected 2- and 5-year survival rates were 96% and 71%, respectively. The 5-year survival rates for grades 1, 2, and 3 were 100%, 79%, and 36%, respectively. Other variables analyzed include number of positive foci, residual tumor volume at initial surgery, cytologic findings at second-look laparotomy, type of chemotherapy, and number of courses of chemotherapy before second-look laparotomy. In summary, patients with only microscopic evidence of disease at second-look surgery have a good probability for extended survival.

Seventy-one cases of primary adenocarcinoma of the fallopian tube treated at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston were reviewed. The most common presenting symptoms were abdominal pain, abnormal uterine bleeding, and vaginal discharge. The most common physical finding was a palpable abdominal or pelvic mass. The preoperative diagnosis was correct for two patients. Initial therapy consisted of surgery alone, surgery plus radiation therapy, surgery plus chemotherapy, and a combination of surgery, chemotherapy, and radiation therapy in 10, 32, 21, and eight cases, respectively. The median survival for patients in these treatment groups was 33, 22, 27, and 22 months, respectively; the median survival for all patients was 23 months. No statistically significant differences emerged among the survival curves of patients treated with each of the above regimens.

Epidermoid carcinoma of the cervix was treated in 120 patients by means of exploratory celiotomy (with semitherapeutic excision of involved lymph nodes) followed by irradiation. The size of the field used for irradiation was determined by the presence and site of lymph involvement. Of 64 patients, metastatic cancer in pelvic nodes was found in 40, and in common iliac or aortic nodes in 24. Of the 2 groups, 8 and 3 patients, respectively, survived for 2 years or more. Irradiation to extended fields (using 5500 rads at 850 rads per week) controlled the cancer satisfactorily within the treated area, but the incidence of bowel complications was high. Recurrent carcinoma usually appeared as distant metastases outside the treatment area which suggests that patients with bulky primary lesions and positive nodes actually already have systemic disease as treatment is started. A safe yet effective dosage level for radiation therapy to extended fields has not yet been established.

Two patients with metastatic dysgerminoma of the ovary were treated with a combination of etoposide, bleomycin, and cisplatin at The University of Texas M.D. Anderson Hospital and Tumor Institute at Houston. Both patients achieved a complete remission. Patient 1 developed a massive recurrence in the para-aortic lymph nodes 21 months after diagnosis and treatment with right salpingo-oophorectomy alone. She received four cycles of chemotherapy and is free of disease 21 months from the start of chemotherapy. Patient 2 had Stage III dysgerminoma and a lymphangiogram positive for tumor in the para-aortic lymph nodes. After surgery she received three cycles of chemotherapy and is free of disease 20 months from the start of chemotherapy. Both complete remissions were documented with second-look laparotomy. Chemotherapy may be an alternative to radiotherapy for the treatment of metastatic dysgerminoma and should also be considered for selected patients with Stage I disease. A literature review further supports the conclusion that additional clinical trials might expand the indications for chemotherapy in patients with this disease.

Publicity associated with recent reports of a greater frequency of adenocarcinoma of the endometrium among women who take exogenous estrogens has created confusion among physicians and fear among patients. An objective review of available data on estrogen effects and current epidemiologic evidence suggests that estrogen may play an indirect role in the development of endometrial carcinoma. Until definitive data are available, physicians should exercise caution in prescribing estrogens, monitoring the status of the endometrium at regular intervals by sampling and pathologic analysis.

Forty-one patients with pure endodermal sinus tumor of the ovary who were treated at the M. D. Anderson Hospital from 1944 to 1981 are retrospectively reviewed. The median age of these patients was 19 years. The most common presenting symptom was abdominal pain, occurring in 33 patients (80%). No bilateral ovarian involvement was noted at initial surgery. With the exception of 1 patient treated by surgery alone, only patients treated with postoperative combination chemotherapy survived. Twenty-one of the 41 patients are alive and well. Sixteen of 22 patients treated with vincristine, actinomycin-D, and cyclophosphamide have survived. The roles of second-look laparotomy and alpha-fetoprotein monitoring are discussed. Optimal treatment seems to consist of surgery followed by aggressive combination chemotherapy.

Eleven patients treated with combination chemotherapy and radiotherapy for uterine sarcoma were reexplored after an interval of therapy. In none of the eight patients who were free of persistent sarcoma at the time of reexploration, did tumor recur during the period of follow-up. Two patients had all macroscopically visible residual sarcoma resected at reexploration and remain free of disease. The second-look laparotomy after a period of therapy may provide valuable prognostic information for planning therapy for patients who have metastatic or locally recurrent sarcoma.

Although this report contains only a few cases of epithelial carcinoma of the ovary and is not complete, it does suggest several new points and confirms other points reported in the literature: 1) increasing stage of cancer correlates well with decreased survival; 2) higher histologic grade of cancer correlates with decreases survival; 3) patients with a given stage of ovarian cancer having higher grades of malignancy have poorer survival; and 4) lower grade tumors are most frequently associated with lower stages of cancer, and higher grade tumors are most frequently associated with advanced stages.

Human leukocyte interferon (IFN alpha) was administered to 15 patients with epithelial ovarian carcinoma after previous chemotherapy or therapeutic irradiation. One objective response was observed. Three patients had possible stable disease for up to 6 months, including two patients who were re-explored 6 months after commencing IFN alpha and one patient who was observed to have a less than 50% reduction in her tumor diameters. Three of seven patients demonstrated clinical responses to subsequent chemotherapy, indicating an absence of resistance to subsequent chemotherapy. Toxicity included the relatively mild symptoms of anorexia, lassitude, and diarrhea. Malabsorption was observed in one patient. Platelet depression and abnormal enzyme liver functions were also observed more frequently following IFN alpha. No life-threatening toxicity was observed.

Fourteen patients with refractory or metastatic adenocarcinoma of the endometrium were treated with continuous infusion vinblastine. No patient had a response. One patient had stable disease. Although well tolerated, vinblastine sulfate given by this method has no activity in this malignancy.

The rarity of Stage II endometrial carcinoma and variable treatment modalities have made the evaluation of prognostic factors difficult. Clinical, surgical, and pathologic characteristics were evaluated in 64 patients treated with whole pelvic irradiation and intracavitary radium followed by hysterectomy at The University of Texas M.D. Anderson Hospital and Tumor Institute from January 1965 to December 1983. Comparison of 5-year actuarial survival rates revealed the following statistically significant categories: age, grade, depth of myometrial invasion, disease extent at surgery including lymph node metastases, and pelvic cytology. Race, weight, and cell type were not significant prognostic factors. Evaluation of prognostic factors at surgery includes pelvic and para-aortic lymph node biopsies, omental biopsy, pelvic cytologic washings, and biopsy of any suspicious tissues. Patients with adverse prognostic factors are candidates for trials with adjuvant therapy.

Bartholin gland tumors are rare and management recommendations have been based on limited information. This report summarizes a 30-year clinical experience involving Bartholin gland carcinoma in 36 patients whose five-year survival rate was 84%. FIGO stages of the 36 tumors were stage I, nine; stage II, 15; stage III, ten; and stage IV, two. Cell types were: squamous, 27 (three nonkeratinizing with areas of a transitional component); adenomatous, six; adenoid cystic, two; and adenosquamous, one. Fourteen of 30 (47%) patients with lymph node dissections had nodal metastases and 11 remain disease-free. Disease recurred in nine patients (six local, two distant, one local and distant) and four were treated successfully. One of 14 (7%) patients receiving radiation and six of 22 (27%) patients not receiving radiation developed local recurrences. Wide excision (often necessitating a radical hemivulvectomy), ipsilateral inguinal lymphadenectomy, and adjunctive irradiation to the vulva and regional lymph nodes produced excellent results.

Between 1971 and 1979, seventy-four patients with metastatic or advanced recurrent sarcoma of uterine origin were treated with combination chemotherapy consisting of vincristine, actinomycin D, and cyclophosphamide (Cytoxan). The probability of survival at 2 and 5 years was 23 and 15%, respectively. The response rate for patients with measurable disease was 28.9% (15.6% partial responses and 13.3% complete responses). The median duration of a complete response was 16 months and that of a partial response was 5.5 months. The median survival of the complete responders was prolonged when compared to nonresponders.

The majority of patients with cancer of the cervix are treated adequately by irradiation alone, and surgery is not necessary. A role for operation developsin certain patients with Stage I-II cancer of the cervix, who are prone to develop central recurrence if treated by irradiation alone. In these patients the primary lesion is massive. The vasculature to the center of these bulky or barrel-shaped cancer is insufficient, and a population of the cancer cells, perhaps related to anoxia, is more resistant to irradiation. The postirradiation conservative hysterectomy was incorporated into the treatment plan for 212 selected patients and the number of local recurrences was reduced. Incomplete cure of the peripheral component of the disease is another mechanism of treatment failure. This may occur, even though the primary lesion is cured. Patients with cervical cancers greater than 5 cm diameter have a high incidence of node metastasis, regardless of clinical stage. In those patients with positive nodes, the standard portals for external irradiation were expanded to include nodes at higher levels. The site of metastases was established by pretreatment laparotomy and the irradiation portals were then extended to include the involved nodes. Survival rates were not improved, because recurrences were not prevented, and death from treatment complications were high.

Eight cases of clear cell adenocarcinoma treated at The M. D. Anderson Hospital are reviewed. Six such lesions were primarily vaginal carcinomas and 2 involved the cervix. Five patients with early carcinomas were treated entirely with a transvaginal cone or interstitial irradiation and 4 are living and well, 2 to 8 years after completion of therapy. We believe that this experience justifies further treatment of early clear cell carcinomas with conservative radiation. This form of therapy is particularly important since the DEX-exposed patients represent an identifiable high-risk group which should augment the chances for early diagnosis.