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Patients with small recurrent cervical carcinomas following radiation therapy may be salvaged with radical hysterectomy rather than exenteration. Between 1953 and 1993, 50 patients underwent radical hysterectomy for persistent (n = 18) or recurrent (n = 32) cervical cancer after primary radiotherapy. The mean age of the cohort was 44 years (range, 23-70). Histologic types were squamous in 46, adenocarcinoma in 3, and adenosquamous in 1. Of 37 patients with staged disease, 24 had stage IB/IIA, 7 had stage IIB, 2 had stage IIIA, and 2 had stage IIIB. Combination radiotherapy, consisting of 40-45 Gy external-beam radiation plus brachytherapy (mean 6980 mg/hr), was performed in 32 patients (64%). In the 32 patients with recurrent lesions, the median interval from definitive radiotherapy to radical hysterectomy was 16 months (4-301), with 19 of these patients (60%) presenting within the first 24 months. Patients with persistent carcinomas underwent radical hysterectomy after a median observation interval of 2 months (1-4). A class II or III radical hysterectomy was performed in 39 (78%) cases. Pelvic and para-aortic lymph node samplings were performed in 39 patients (78%), including 33 (66%) who underwent complete pelvic lymphadenectomy. Among those sampled, 5 (13%) had metastatic nodal disease. All 5 patients died of disease at a median 13 months after surgery. Severe postoperative complications occurred in 21 patients (42%). The most common site of injury was the urinary tract, with 14 patients (28%) developing vesicovaginal or rectovaginal fistulae, 11 (22%) developing ureteral injuries, and 10 (20%) developing severe long-term bladder dysfunction. There was one postoperative death from sepsis among the entire population. Patients with abnormal preoperative intravenous pyelograms (P < 0.05), patients with recurrent presurgical lesions (P < 0.05), and patients with postoperative pelvic cellulitis (P < 0.01) were more likely to develop fistulae. The 5- and 10-year actuarial survival rates for all cases was 72 and 60%, respectively. Tumor size at radical hysterectomy was significantly associated with survival. Five-year actuarial survival in 12 of 44 patients (27%) with identifiable lesion diameters less than 2 cm was 90% compared with 64% in patients with larger lesions (P < 0.01). Prolonged disease-free survival occurred in 26 of 50 patients (52%) who had known disease status at follow-up, whereas recurrence after radical hysterectomy was seen in 24 patients (48%).(ABSTRACT TRUNCATED AT 400 WORDS)

Objective: To determine whether vulvar squamous cell carcinomas associated with certain morphologic features and/or human papillomavirus (HPV) nucleic acids were more likely to be associated with other genital primary squamous neoplasms., Methods: We surveyed 169 invasive squamous cell carcinomas of the vulva and correlated associated vulvar intraepithelial neoplasia (VIN), invasive growth patterns resembling VIN (intraepithelial-like or basaloid), and the presence of HPV nucleic acids by in situ hybridization with a history of a second primary squamous neoplasm of the genital tract., Results: Twenty-two patients (13%) had a history of a second primary. An intraepithelial growth pattern or an associated VIN correlated significantly with HPV, at P = .0005 and P = .007, respectively, and with a second primary, at P = .077 and P = .009, respectively. When HPV-positive, the same histologic variables correlated with a second primary at P = .099 and P = .25, respectively. Compared with cases lacking both these histologic features and HPV, they correlated with multifocal disease at P = .01 and P = .003., Conclusions: The findings of HPV nucleic acids, tumor growth patterns, and associated VIN are interrelated and confer risk of other genital primary neoplasms in women with vulvar carcinoma. This supports the concept that subsets of vulvar carcinoma may be distinguished not only by morphology and HPV DNA, but also by a distinctly different risk of a second genital primary neoplasm.

Advanced age is frequently considered a contraindication to radical exenterative surgery. We reviewed the outcomes of 63 patients age 65 years or older who underwent pelvic exenteration between 1960-1991 at The University of Texas M. D. Anderson Cancer Center. Sixty-three percent had preexisting medical illnesses. Major or potentially life-threatening complications were noted in 38% of the patients. An additional 38% experienced minor complications. Sixty percent experienced one or more infectious complications, including pyelonephritis, wound infection, sepsis, and flap necrosis. When both major and minor complications were considered, infectious morbidity was the single largest category. Although they are not life-threatening, nonspecific infectious morbidity and transient confusion were the most frequent individual complications, occurring in 26 and 24% of patients, respectively. Twenty-four percent of the patients experienced no complications. Thirty-four percent of the postoperative survivors suffered late major morbidity. Operative mortality was 11%; multisystem failure was the most frequent cause of death. After a mean follow-up of 4 years, 22 patients were alive with no clinical evidence of disease. Twenty-one patients died of recurrent disease, with a median time to recurrence of 9.6 months. The 5-year survival rate for the group was 46%. In comparison, 363 patients younger than age 65 who underwent exenteration during the same period experienced an operative mortality rate of 8.5% and a 5-year survival rate of 45%, neither of which were significantly different from the rates found for the older group (P = .51 and .52, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

A matched analysis comparing 250 patients less than 35 years old with squamous cell cancer of the cervix treated between 1971 and 1981 to a randomly selected group matched on treatment who were greater than 35 years old was performed. A chart review that focused on important prognosticators for survival and progression-free interval was performed. The groups were found to be similar for the important prognosticators. Overall survival and progression-free intervals were plotted using Kaplan-Meier curves and demonstrated that for advanced stages, younger patients were less likely to survive and more likely to recur. Cox proportional-hazard analyses were performed, looking at important prognosticators of survival and progression-free interval. Age, stage, positive lymph nodes, and cervical diameter emerged as statistically significant predictors of survival, while stage, positive lymph nodes, and cervical diameter emerged as statistically significant predictors of progression-free interval. The plot of relative hazard by stage of younger versus older patients showed an interaction between age and stage that merits further exploration.

Although uncommonly performed in this setting, splenectomy is sometimes indicated in patients with gynecologic malignancies. From January 1970 through March 1989, 45 patients at The University of Texas M.D. Anderson Cancer Center underwent splenectomy during the course of gynecologic laparotomies. All procedures were performed by the gynecology staff and trainees. Twenty-seven patients (60%) had ovarian cancer; endometrial and cervical cancers were present in three patients each. The remaining 11 patients had other diseases. Splenectomy was planned preoperatively in only 9 patients (20%). Thirteen patients (29%) underwent splenectomy because of injury to the spleen. Injury was most commonly due to traction during omentectomy, resulting in capsular laceration. The injury was immediately recognized in 12 patients; 1 patient required reexploration for hemoperitoneum. In 24 patients (53%), splenectomy was performed for tumor reduction. Pathologic examination showed that 11 of 24 patients had capsular involvement by tumor, 7 had parenchymal metastases, and 6 had no direct splenic involvement. Residual tumor following cytoreduction was smaller than 2 cm in 62.5% of patients. Splenectomy is a well-tolerated procedure and the operative approach can be tailored to the clinical situation and distribution of tumor. An attempt should be made to repair splenic injury when tumor involvement is not present.

Three hundred sixty-five patients with invasive squamous cell carcinoma of the vulva have been treated at M.D. Anderson Cancer Center between 1944 and 1990. We undertook a rigorous review of the medical records, and a Cox proportional hazards model was applied to examine predictors of both failure to survive and recurrence. Significant predictors of both failure to survive and recurrence included tumor size, clinical stage, therapy aim, pelvic or inguinal nodal metastases, and positive margins. We then undertook an analysis of Stage I and II lesions treated with a curative aim to see if there was a difference in survival or in disease-free interval between those patients treated with radical vulvectomy and those treated with radical wide local excision. There was no survival advantage from the radical vulvectomy procedure. We conclude that careful selection may allow us to choose some patients for less radical procedures.

Forty-one patients with pure immature teratoma of the ovary treated at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston from 1944 to 1985 were reviewed. The median age of these patients was 17 years. The most common symptom was abdominal pain, which occurred in 39 (95%) patients. FIGO stages included 24 patients with stage I, four with stage II, 12 with stage III, and one stage IV. The tumors ranged in size from 6 to 31 cm in greatest diameter, with a median of 17 cm. Of 39 cases reexamined microscopically, four were grade 1 tumors, 22 were grade 2 tumors, and 13 were grade 3 tumors. Initial surgery included ovarian cystectomy in one patient, unilateral salpingo-oophorectomy in 27 patients, and bilateral salpingo-oophorectomy in 13 patients. Fifteen of 16 patients treated with surgery alone developed recurrent disease; 11 are surviving after further therapy. Two patients died after treatment with radiotherapy plus chemotherapy. Twenty-one patients received a combination of vincristine, actinomycin-D, and cyclophosphamide postoperatively, and 18 are alive and well. One of two patients who received other combination regimens is alive and well. Therefore, 29 of the 41 patients (71%) are alive and well. Optimal management of patients with pure immature teratoma of the ovary consists of initial surgery (with preservation of a normal contralateral ovary in most patients) followed by combination chemotherapy in all patients except those with stage I, grade 1 disease; the latter may be treated safely with surgery alone.

Forty-two patients with mixed germ cell tumors of the ovary who were treated at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston from 1944 through 1983 are retrospectively reviewed. The median age of these patients was 16 years. The most common symptom was abdominal pain, occurring in 38 patients (90%). Detailed analysis of clinical and pathologic features is presented. Twenty of 42 patients are alive and well. Current management of mixed germ cell tumors, including the roles of second-look laparotomy and monitoring of tumor markers, is discussed. Optimal treatment consists of surgery followed by combination chemotherapy.

A membrane-enriched extract of a virus-infected vulvar carcinoma cell line was evaluated as adjunctive immunotherapy in 16 patients who had vulvar carcinoma with lymph node metastases. Thirteen patients also received adjunctive radiation therapy based on individually assessed risk factors. Two patients developed progressive disease. The median disease-free survival for the group was 26+ months, as compared with nine months for a historical group that had undergone surgery alone and 16 months for a second group that had received surgery and adjunctive radiation therapy. The median disease-free survival of the immunotherapy group was longer than that of either of the two historical groups. Over 400 doses of extract, each equivalent to 1.5 mg protein, were administered without significant side effects. Evidence is presented for humoral and cellular augmented immune reactivity. The authors suggest that this approach be evaluated further to determine its efficacy in preventing recurrence in selected high-risk patients who have vulvar carcinoma.

Nine years' experience with early uterine sarcoma is reviewed. In addition to hysterectomy and radiotherapy, 34 patients received adjunctive chemotherapy; 67 patients received no adjunctive chemotherapy. Seventeen patients who received chemotherapy received combination vincristine, 1.5 mg/m2 weekly; actinomycin D, 0.5 mg intravenously on Days 1 to 5; and cyclophosphamide, 300 mg intravenously on Days 1 to 5. Seventeen other patients received adriamycin either alone at a dose of 50 mg/m2 BSA/month or in combination with vincristine and cyclophosphamide. Neither the probability of survival nor the disease-free interval was improved by the addition of adjuvant chemotherapy.

A randomized study of 59 patients with recurrent squamous carcinoma of the cervix originally treated with radiotherapy is reported. Patients were randomized on recurrence to either Hexamethylmelamine, Adriamycin, or Cytoxan as first agent. When analysis was restricted to 37 patients with easily evaluable disease, Cytoxan had a significantly greater response rate (23.1%, 3/13) than Hexamethylmelamine (0%, 0/14) (p = 0.098). The response rate of Adriamycin was 20% (2/10). There was no evidence of a significant effect of first agent on survival time taken from the start of chemotherapy. The number of months from diagnosis to the start of chemotherapy (p = 0.04) and the patients' response status (p = 0.002) did however have significant effects on survival time. There was no evidence of a significant effect of first agent on survival time after treatment change but response to first agent did have a significant effect on survival (p = 0.05). Hexamethylmelamine had a greater frequency of severe toxicity (50%, 10/20) than Adriamycin (10.5%, 2/19) (p = 0.014) and Cytoxan (10%, 2/10) (p = 0.014).

Four hundred twenty-nine patients were entered into four prospective randomized clinical studies between January 1, 1973, and July 1, 1979. The records of 395 of these were analyzed to determine the proportion of patients surviving 48 months after therapy initiation. Ninety-six patients (24%) were living at 48 months, 89 of whom had second-look laparotomies. Of the 96 living patients, 53 (55%) were clinically free of disease and 43 (45%) had disease. Combination-agent chemotherapy produced a larger proportion of 48-month survivors than single-agent therapy (P = 0.001); 70% of these survivors were clinically free of disease. Patient characteristics, such as age, International Federation of Gynaecology and Obstetrics (FIGO) stage, histologic grade of tumor, and amount of residual tumor present prior to chemotherapy exerted a strong influence on length of survival. Long-term survival was not totally dependent on a complete response to chemotherapy; in fact, persistent treatment with drug regimens induced bone marrow disorders and death due to toxicity in five patients. The continued fall in survival curves after 48 months suggests that current therapy regimens are not dramatically changing long-term survival rates.

From January 1971 through December 1981, 246 patients with advanced (Stages III and IV) epithelial ovarian cancer underwent second-look laparotomy at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston. Eighty-five of these patients had a complete response (negative second-look laparotomy) following treatment with a variety of chemotherapeutic regimens. Three patients had also received irradiation. Patients were analyzed according to pretreatment characteristics (age, FIGO stage, ascites, pleural effusion, histologic grade, tumor type, type of surgery, residual tumor diameter, initial clinical status) and by the number of biopsy specimens taken at second-look laparotomy. The probability of recurrence and the length of survival following a negative second-look laparotomy are statistically related to these characteristics. Twenty of the 85 patients (24%) developed recurrent disease 5 to 32 months after laparotomy. The estimated 2- and 5-year survival rates are 99% and 85%, respectively. Patients who achieve a surgically determined complete response have an excellent chance for long-term survival.

Bleomycin and mitomycin-C (BLM-M) induction therapy was administered to 23 patients with recurrent squamous carcinoma of the uterine cervix. Six patients (26%) responded. Although these results are much lower than originally reported with BLM-M, there is statistical evidence that patients with disease outside the previous radiation therapy field have improved or more easily determined responses. There was no difference in survival between responders and nonresponders for patients who survived at least six weeks. Therapy was found to be relatively nontoxic with no deaths related to therapy.

This review is a retrospective analysis of 263 patients with carcinoma of the cervical stump treated at The University of Texas M. D. Anderson Hospital and Tumor Institute between 1963 and 1975. Symptomatology, stage distribution, and histology of carcinoma of the cervical stump showed no significant differences from cervical carcinoma of the intact uterus. Depending on the tumor stage, tumor volume, and distorted anatomy, treatment consisted of various combinations of intracavitary radium and transvaginal and external radiation. The 5-year survival was 100% in stage 0, 91% in stage I, 77% in stage II, 46% in stage III, and 37% in stage IV. The results achieved are similar to those in cervical cancer of the intact uterus. The complication rate was 30% and there were 9 (3.7%) deaths related to radiation complications.

Most patients with epithelial cancer of the ovary are not cured by surgery, since their cancer has spread beyond the ovaries. The majority of these patients are not suitable for postoperative irradiation therapy, since the residual tumors are too large to be effectively treated with irradiation or they have metastasized to areas that cannot be effectively irradiated. Approximately 50% of the patients with advanced ovarian cancer who are treated postoperatively with melphalan will benefit from this chemotherapy. Approximately 40% of the patients who do not respond to chemotherapy with melphalan will benefit from treatment with a combination of actinomycin D, 5-fluorouracil, and cyclophosphamide. A second-look operation after 12 or more cycles of chemotherapy is often helpful in planning future treatment of patients, and it may be curative in a few patients if all the remaining tumor can be excised.

A case of isolated leptomeningeal recurrence of an epithelial ovarian cancer was recently diagnosed and treated successfully with methotrexate placed via an Ommaya reservoir in combination with radiation therapy. A review of the literature revealed no other cases of epithelial ovarian leptomeningeal malignancy similarly treated.

From 1970 to 1985, 53 patients with malignant nondysgerminomatous germ cell tumors of the ovary underwent second-look laparotomy after initial surgery and combination chemotherapy. Twenty-two patients had immature teratoma, 15 had endodermal sinus tumor, 15 had mixed germ cell tumor, and one patient had embryonal carcinoma. Thirty-one of the neoplasms were stage I, four were stage II, 17 were stage III, and one was stage IV. Two patients received a combination of actinomycin-D, 5-fluorouracil, and cyclophosphamide; four patients received vinblastine, bleomycin, and cisplatin; 44 patients received vincristine, actinomycin-D, and cyclophosphamide; and three patients received a combination of the last two regimens. Second-look findings were negative in 52 patients and positive in one patient who was subsequently salvaged with further chemotherapy. One patient with stage I endodermal sinus tumor relapsed nine months after a negative second-look laparotomy and died. Two patients with negative findings subsequently died of leukemia. Of 53 patients undergoing second-look laparotomy, three are dead (one of cancer and two of leukemia), and 50 patients are surviving without disease. Although the precise role of second-look laparotomy in patients with malignant germ cell tumors is yet to be established, possible indications are discussed.

From May 1976 to July 1978, 100 patients with untreated stage III or IV ovarian carcinoma were entered into a prospective randomized clinical trial comparing melphalan, cis-platinum, hexamethylmelamine and cyclophosphamide, and a combination of hexamethylmelamine, cyclophosphamide, and doxorubicin hydrochloride (Adriamycin). The 22 patients who received cis-platinum, 18 of whom ultimately received hexamethylmelamine and cyclophosphamide therapy, are analyzed, and surgical and chemotherapeutic treatments are described. Response was evaluated by either clinical or surgical methods. Eleven of the 22 patients (50%) responded to cis-platinum treatment. Survival times ranged from 2 to 24 months, with a median survival time of 21.2 months. Gastrointestinal, hematologic, renal, and neurologic toxicities are reported; peripheral neuropathy constituted the major toxicity. Methods of alleviating or preventing neurotoxicity are discussed. It is concluded that cis-platinum as a single agent possesses definite activity against ovarian cancer.

Between 1971 and 1979, 39 patients with clearly measurable metastatic or advanced recurrent sarcoma of uterine origin were treated with Adriamycin, either alone or in combination with other chemotherapeutic drugs. The median survival was 7.2 months. No patient lived beyond 32 months from the start of chemotherapy. The response rate was 10.3% (10.3% partial responses and no complete responses). The median duration of a partial response was 4 months. There was no difference between the median survival of the responders and nonresponders.

The clinical courses of 30 patients with 41 nephrostomy catheters were followed. Duration of drainage ranged from 2 days to 15 months with a mean of 3.7 months. The most common complications were hemorrhage (28%), infection (70%), and blockage of catheter (65%). No deaths occurred as a result of these complications. Renal function recovered in 14 of 20 patients (70%) who presented with elevated creatinine values. Twenty-six of 28 patients with malignant obstruction were able to receive further therapy. The only long-term survivors presented with primary advanced cervical cancer.

A retrospective review of 194 patients with stage IB cervical carcinoma treated with radical hysterectomy between January 1977 and December 1984 revealed 30 patients (15%) with pelvic node metastases. Twenty patients with pelvic node metastases received postoperative radiotherapy and ten patients did not. Five of 20 patients who received adjuvant radiotherapy had recurrence, compared with five of ten patients who did not receive radiotherapy. No pelvic recurrences occurred in the adjuvant radiotherapy group compared with two in the no radiotherapy group. Only one serious complication occurred in a patient receiving radiotherapy. Adjuvant postoperative radiotherapy may reduce pelvic recurrences and improve survival in patients with pelvic node metastases treated with radical hysterectomy and pelvic lymphadenectomy.

The members of the Felix Rutledge Society were surveyed to determine their policies concerning pelvic exenteration when regional lymph node metastasis is discovered at the outset of an operation and the resulting survival data. Survival data from the responding members are presented in a summary table. A series of 448 exenterations performed at The University of Texas M. D. Anderson Hospital and Tumor Institute from 1955 to 1984 was reviewed, and the medical records of patients with positive nodes were analyzed for factors that might influence prognosis, such as anatomical site of cancer, histologic type, and location and number of positive nodes. Of the 407 patients whose lymph nodes were studied histologically, 44 had nodal metastasis. Death from recurrent gynecologic cancer and death from all causes were used as end points, and survival rates were calculated according to primary treatment, treatment of recurrent cancer, cancer of the cervix, location of positive nodes, and number of positive nodes. For patients with positive nodes, 36.2% avoided death from recurrent cancer for 3 years, and 26.3% survived for 5 years. We conclude that although the prognosis for patients with positive nodes is poor, some longterm survivals can be achieved. The goal of pelvic exenteration is cure; however, for selected patients, the operation may be justified when it improves the quality of life and extends life.

Human placental lactogen (HPL or HCS), the beta subunit of human chorionic gonadotropin (beta-HCG), and carcinoembryonic antigen (CEA) were measured by a specific radioimmunoassay in plasma of 65 patients with ovarian cancer. Fifty-one patients had epithelial tumors, while 14 had germ cell tumors. It was found that 47 patients (72 per cent) had high levels of plasma HPL, 29 patients (45 per cent) had high levels of plasma beta-HCG, and 34 patients (52 per cent) had high levels of plasma CEA, but there was no correlation between these protein marker levels in different patients. Twenty of these patients were studied before and after operation and during chemotherapy and/or radiotherpy. There was no consistent correlation between these marker levels and the course of the disease. These data suggest that measurement of HPL, beta-HCG, and CEA in sera of patients with ovarian cancer is not of value in assessing the clinical status of the patients or in determining the effect of therapy.

Twenty patients with recurrent or metastatic squamous cell carcinoma of the cervix were treated with continuous-infusion vinblastine sulfate. Two patients (10%) had partial responses of 4 and 7 months' duration. Neutropenia was dose limiting. Vinblastine sulfate given by continuous infusion has limited activity in this malignancy.