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Long-term follow-up was obtained on 726 women with advanced ovarian carcinoma (suboptimal stage III and stage IV) who had received primary chemotherapy on two Gynecologic Oncology Group (GOG) protocols between 1976 and 1982. The first study compared melphalan alone versus melphalan plus hexamethylmelamine versus cyclophosphamide plus doxorubicin (CA). The second study evaluated the same CA regimen with or without cisplatin. Eligibility for the two studies was the same. At last contact, 76 patients were alive. In a multivariate analysis, cell type other than clear cell or mucinous, cisplatin-based treatment, good performance status, younger age, lower stage, clinically nonmeasurable disease, smaller residual tumor volume, and absence of ascites were favorable characteristics for overall survival (P less than .05). Second-look laparotomy was negative significantly more often among those with endometrioid tumors; there were no negative second-look laparotomies among those with mucinous or clear cell tumors. There were 30 patients with suboptimal stage III disease who had a negative second-look laparotomy; 18 (60%) have experienced recurrence, and 13 (43%) have died. Although cisplatin treatment was beneficial, new treatments are clearly needed.

Ovarian remnant syndrome should be considered in the differential diagnosis of pelvic pain with a mass in a patient who has had extirpative surgery. Although rarely reported in the literature, it is probably much more prevalent than is suspected. Most commonly, the initial surgery was performed for endometriosis or pelvic inflammatory disease, with incomplete excision of the ovaries. Surgical excision of the ovarian remnant, the definitive treatment, is itself difficult, and is often attended by serious complications. Medical therapy is empiric, and hormonal manipulation may help prevent recrudescence. Three cases are reported, their pathology and the literature is reviewed.

This report deals with one fellow's experience in the dog lab established to aid in the surgical training of the gynecologic oncology fellow. The first experiment was designed to train the fellow in bowel resection and end-to-end anastomosis, comparing suture and staple techniques. A second study evaluated the physical and biological properties of polyglactin 910 (Vicryl) mesh to determine its applicability in reconstructing the pelvic floor following pelvic exenteration.

Pulmonary lymphangitic carcinomatosis is a rare form of metastatic cervical cancer. A patient with persistent squamous cell carcinoma of the cervix presented with symptoms suggestive of pulmonary embolism and right heart failure. Pulmonary lymphangitic spread of the cancer was found postmortem. The pathogenesis of pulmonary lymphangitis carcinomatosis is reviewed and diagnostic evaluation discussed.

Twenty-two patients with extensive pelvic irradiation underwent supravesical urinary diversion using a transverse colon conduit. Primary diseases were most often carcinoma of the cervix and urinary bladder. Indications for diversion included original treatment planning, radiation cystitis, vesicovaginal fistula, and ureteral obstruction. Operative mortality was low (4 per cent), and most complications were managed by further surgery. Normal upper urinary tracts usually remained normal after diversion; relief of existing hydroureteronephrosis was seen in a majority of patients. Stomal problems have been minimal, and renal function has remained normal or stable. The method affords the use of nonirradiated transverse colon as well as the ureter high above the field of pelvic irradiation and is the preferred diversion in such patients.

A prospective randomized study was conducted in women with suboptimal (greater than or equal to 3 cm residual) Stage III, Stage IV, and recurrent ovarian adenocarcinoma to determine if combination chemotherapy is more effective than melphalan alone in achieving remission and improving survival. Of 233 evaluable patients with measurable disease, there were 64 treated with melphalan alone, of whom 20% achieved a clinical complete response and 17%, a partial response. Of the 97 patients receiving melphalan plus hexamethylmelamine, 28% achieved complete response compared with 32% of 72 patients given Adriamycin plus cyclophosphamide. The partial response rates for the combinations were 24% and 17%, respectively. The effect of these treatments was assessed in an additional 136 evaluable patients without measurable disease by progression-free interval and duration of survival. After statistically adjusting for distribution of cell type and grade, the clinical complete response rate for Adriamycin and cyclophosphamide (32%) in measurable cases was significantly higher (P = 0.04) than for melphalan alone. However, this combination did not improve median survival (12.3, 13.5, and 14.2 months, respectively, for M, M + H, and A + C). None of the other parameters showed a statistically significant advantage for combination chemotherapy, but the combinations caused more hematologic and gastrointestinal toxicity.

Two patients with gunshot wounds of the pregnant uterus are reported. Both were explored and delivered of stillborn infants by Cesarean section. Neither patient sustained a significant visceral injury. Expectant management with close observation is appropriate in pregnant when the entrance wound is below the level of the uterine fundus, the infant is dead, and the bullet is radiographically shown to be in the uterus.

Forty-three patients with advanced or recurrent endometrial carcinoma no longer amenable to management with surgery or radiotherapy were treated with adriamycin. Sixteen of the 43 patients demonstrated objective response to drug therapy with a greater than or equal to 50% reduction in the size of measurable disease. There were 11 complete responses among these 16 responders. Responders had a significantly better survival than nonresponders (P less than 0.05). Initial performance status was the only factor of demonstrable prognostic significance. Toxicity was similar to that observed in other phase II trials of adriamycin. Adriamycin, based on these data, is an active agent in the treatment of advanced or recurrent endometrial carcinoma.

Radiation-induced fistulas of the vagina are rare, occurring in only 1 of 3% of patients treated for cancer of the uterine cervix. Primary surgical repair of these fistulas is usually unsuccessful because the defect is a result of devascularization. This type of radiation injury results from endarteritis obliterans, and successful repair requires an accessory blood supply. From 1971 to 1980, the authors performed 14 Martius procedures on 12 patients with radiation-induced rectovaginal fistulas. Eleven patients had successful closure of their fistulas using this procedure, and no operative complications occurred. The Martius procedure is effective for most radiation-induced vaginal fistulas, and the operation is well tolerated by most patients.

The effect of gamma irradiation on the production of prostaglandins by human colon was investigated. Squares of tissue in organ culture dishes were irradiated with 500, 1000, or 2500 rad in single applications. Tissues that were not irradiated served as controls. After treatment the tissues were superfused and prostaglandin concentrations in the effluent fluid were determined. The rates of production of prostaglandins E2 and F2 alpha by irradiated tissues were significantly lower (p less than 0.05) than those of nonirradiated tissues. Neither the release of lactate dehydrogenase nor the rate of production of 13,14-dihydro-15-keto-prostaglandin F2 alpha were increased in the irradiated samples, suggesting that neither decreased cell viability nor increased prostaglandin metabolism accounted for the decreased prostaglandin production rates. We conclude that irradiation of the human colon in vitro results in an acute inhibition of prostaglandin synthesis. The cytoprotective nature of prostaglandins is discussed with regard to the possible pathophysiological significance of these findings.

Thirty patients with advanced stage squamous cell carcinoma of the cervix underwent exploratory celiotomy and para-aortic lymphadenectomy prior to beginning radiation therapy. Para-aortic lymph node metastases were found in 9 patients (30%), and visceral metastases in 2 patients (7%). Findings at celiotomy prior to initiation of therapy allowed patients to be divided into 3 groups: Patients with 1) visceral metastases, 2) para-aortic lymph node metastases but without visceral or scalene lymph node metastases, and 3) patients with disease confined to the pelvis. Therapy was then based on the extent of disease present in each patient. As a result of the surgical findings, 10 of 30 patients (33%) received therapy other than standard pelvic radiation therapy. The surgical technique, operative morbidity, and prognostic significance of the surgical findings are discussed.

Disturbances in the blood coagulation mechanism are seen by the obstetrician and gynecologist as rare complications of abruptio placentae, retained dead fetus syndrome, amniotic fluid embolism, toxemia, saline amnioinfusion, and septic abortion. Two cases of disseminated intravascular coagulation complicating gynecologic malignancy are presented. Laboratory studies showed thrombocytopenia, hypofibrinogenemia, and increased fibrin degradation products. Derangements of hemostasis in patients with malignancy are discussed from a clinical viewpoint.

One hundred and eighty-seven patients with stages I, II and III optimal (metastatic lesions of less than 3 centimeters) epithelial carcinoma of the ovaries were evaluated preoperatively and had standardized exploration and biopsy. The protocol called for examination and biopsy of the peritoneum, diaphragm, omentum, pelvic and para-aortic lymph nodes and aspiration of ascites or peritoneal washings for cytologic examination. Of those patients with metastases to the omentum, the clinical impression did not correlate with pathologic findings in 45 per cent. The findings were similar for diaphragmatic lymph nodes (50 per cent), pelvic lymph nodes (71 per cent) and para-aortic lymph nodes (96 per cent). Nine of 97 patients clinically thought to have stage I disease had the stage elevated to II and III based on pathologic findings. Similarly, 15 patients thought to have stage II were found to have stage III based on histopathologic findings. There were 74 complications in 54 patients, with 29 having at least one complication. Surgical exploration for early stage carcinoma of the ovary should include biopsy of the retroperitoneal pelvic and para-aortic lymph nodes, excision of the infracolic omentum, biopsies of pelvic and abdominal peritoneum, including the right diaphragm, and peritoneal cytologic studies.

Twenty patients were studied with static and cinefluoroscopic intravenous pyelograms to quantitate the morphologic and physiologic ureteral alterations following radical hysterectomy and pelvic lymphadenectomy. More than 87% of the patients in the 48-hour study had ureteral dilatation, which persisted for 7 days in most patients, proximal to the site of pelvic dissection. By 6 weeks after surgery, the dilatation had regressed and pyelograms returned to normal. Transit time from renal pelvis to bladder was doubled at 7 days. An alteration in the character of peristalsis was noted on the cinefluoroscopic studies at 48 hours and at 7 days. The distal ureter appeared as a rigid conduit, and the peristaltic activity was replaced by bolus emptying.

Wound infection and breakdown constitute the most common complication of radical vulvectomy and groin lymphadenectomy. The use of pigskin xenograft as biologic dressing when the skin edges cannot be closed primarily without tension after radical vulvectomy and groin lymphadenectomy is described. This technique allows for clean granulation tissue to develop early (within five to seven days) and seems to accelerate the healing process. Its use has been associated with early ambulation and rapid recovery as well as a shorter postoperative stay.

From July 1970 to January 1977, 23 patients with previously untreated cancer of the cervix (CA CX), mostly Stage IIIB, were included in this study. The para-aortic lymph nodes (PALN) were histologically documented to have metastatic disease in all 23 patients. External radiation treatment (RT) was delivered using a Cobalt--60 machine to a spade-shaped field to treat the pelvic cavity and para-aortic area. The majority of the patients received 4000-6000 rad to the pelvic cavity and from 5000-5500 rad to the PALN's by external RT. In addition, intracavitary radium was used in 21 patients. Five patients are alive and free of disease at 115, 110, 90, 73 and 45 months after completion of RT. One survivor had clinical Stage IB, one had Stage IIB, and three had Stage IIIB cervical carcinoma. Two of 15 patients with clinically enlarged and suspicious para-aortic nodes are alive, while 3 of 8 patients with clinically normal appearing nodes survived. Three (60%) of the survivors developed late bowel radiation damage. Eighteen patients died--10 during the first year, 3 during the second year, 2 during the third year, 1 during the fourth year and 2 during the eighth year of the follow-up. Five (27.8%) of the patients who died had developed late bowel radiation damage. Fifteen of the 18 died with disease at an average of 21 months. Three patients died of intercurrent disease. Their average survival was 40 months, double that of patients dying of disease. This report suggests that in cancer of the cervix, radiation therapy can control some PALN metastatic disease, but the risk of complications is rather high. In the absence of better methods of management, this risk of complications is justifiable because the alternative is to leave known disease untreated.

The role of radioisotopes in the treatment of ovarian carcinoma is discussed. The University of Iowa experience with prophylactic treatment of stage Ia ovarian cancer with radiogold is presented. Cumulative survival in 56 patients with epithelial cancers was 94.3%. In a prospective study, we compare the use of radiogold and total abdominal irradiation in the treatment of stage Ia ovarian carcinoma.

Two cases of lymphaticoperitoneal fistula are reported. One patient had a recurrent carcinoma of the cervix and the other had a recurrent vaginal carcinoma. A brief discussion of the pathophysiology is presented.

A new synthetic absorbable mesh made of polyglactin 910 (Vicryl) fiber was used to reconstruct the pelvic floor in seven women undergoing pelvic exenteration. The technique is described. The follow-up ranged from three to 31 months and no patient developed a bowel problem. The material seems to be appropriate for this use, is completely absorbed, and acts as a latticework for the deposition of granulation tissue. The technique can be applied in patients requiring pelvic irradiation following surgery for malignant neoplasms of the gastrointestinal or genitourinary tracts. The small bowel is effectively held out of the pelvis and the radiation field, and is spared the effects of the radiation beam.

Intestinal fistulas and obstruction are the most common and most serious complication of pelvic exenteration for gynecologic cancer. In a series of 58 patients, early intestinal fistulas developed in seven and late fistulas in 13 of the patients. Early fistulas are more commonly secondary to surgical trauma or technical errors and were noted to occur more frequently in patients who had previously undergone irradiation. Late fistulas are usually associated with intestinal obstruction and with a high incidence of recurrent malignant growth. The management of choice for intestinal fistulas following pelvic exenteration appears to be prompt surgical intervention with bypass procedures in preference to intestinal resections. Although several technical modifications have been applied to the exenterative operation with a trend toward a decrease in early obstruction and fistula formation rate, additional technical efforts will be necessary if these problems are to be solved.

Ovarian carcinoma is the only female genital malignancy surgically staged. Appropriate preoperative roentgenographic, isotopic, and endoscopic studies can help define the spread of disease and the extent of surgery required. At surgery, the common sites of metastases--pelvic and para-aortic lymph nodes, diaphragm, serosal surfaces and omentum--should be examined and biopsied or excised. Total hysterectomy, bilateral salpingo-oophorectomy, and appendectomy should also be performed in patients with epithelial ovarian tumors. Evidence suggests that patients who have had optimal cytoreduction of the tumor (less than 1.5 cm) have a better outcome following chemotherapy. Patients who have no clinical or CT evidence of disease after a full course of chemotherapy should be explored to confirm disease status. Peritoneoscopy can be used as an interval procedure to assess response to treatment.

Attempts to terminate a pregnancy by self-inflicted gunshot-wounds is a new mechanism whereby women sustain gunshot wounds of the pregnant uterus. Two patients with self-inflicted gunshot wounds of the gravid uterus in an attempt to induce abortion are presented. The conservative management of such wounds is discussed.

Twelve surgical specimens from radical vulvectomy and bilateral groin dissection were examined by xeroradiography to identify lymph nodes. Eight of the specimens were handled in a routine fashion, and four were chemically cleared. The xeroradiograph was not helpful in identifying small lymph nodes in the specimen, nor could any xeroradiographic characteristics specific for tumor-involved lymph nodes be identified.

Thirty-two evaluable patients with advanced epithelial ovarian cancer were treated with aminothiadiazole at a dosage of 125 mg/m2 weekly. Two patients had partial responses, 12 had stable disease, 16 had increasing disease, and two were inevaluable for response. Aminothiadiazole used in this dosage and schedule has minimal activity in ovarian carcinoma patients previously treated.

The versatility and other advantages of the transverse colon conduit for urinary diversion have been described and implemented in 50 patients. Because most patients considered for this procedure will be at high risk because of a history of significant pelvic irradiation, underlying malignancy, poor renal function, fistula, and so forth, the technical details of surgery and patient selection cannot be minimized. The transverse colon segment is indicated for primary supravesical diversion as well as for salvage of problems related to ileal conduits. Adenocarcinoma of the colon is an unlikely long-term complication of this form of diversion because the fecal stream is absent. Now that the transverse colon conduit has been used for more than 10 years, meaningful comparisons with ileal segments should soon be available.

The literature on gunshot wounds of the gravid uterus is reviewed, and three new cases reported. Clinical management is discussed, with emphasis on the condition of the abdominal wall and other connective tissue during pregnancy, the contraindications for paracentesis, the changes during pregnancy in blood volume, central venous pressure, white blood count, and GI and GU tracts, and indications for celiotomy or cesarean section.

The embryology and clinical implications of Meckel's diverticulum, the most common gastrointestinal anomaly, are presented from the viewpoint of the obstetrician-gynecologist. The complications and clinical management are discussed.

The healing of a midfibular fracture was studied in mature rats. The strength of the healing fracture was determined by a constant speed-driven tensiometer which measured the force required to separate the healing callus. The breaking strength of the healing experimental fracture was ascertained in control, estrogen-treated, and oophorectomized animals. The fracture strength was not significantly different in any of these groups.

Cholesterol metabolism was studied in cells from two established gynecologic cancer cell lines which were maintained in monolayer cultures. The cell lines were derived and established from poorly differentiated epidermoid cervical carcinoma (EC-50) and endometrial adenocarcinoma (AC-258). The specific activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting enzyme of cholesterol de novo synthesis, in AC-258 cells (1,700 pmoles x mg-1 microsomal protein x min-1) was three times higher than that found in EC-50 cells (550 pmoles x mg-1 microsomal protein x min-1). However, epidermoid cervical cancer cells (EC-50) metabolized low-density lipoprotein (LDL), the major transport vehicle for cholesterol in plasma, at a very high rate (14,000 ng x mg-1 cell protein x 6 hours). This rate is fifteen times greater than the rate observed in fetal adrenal tissue and fifty times greater than the rate observed in nonneoplastic gynecologic tissue, each in organ culture. Both cancer cells (EC-50 and AC-258) in monolayer culture were shown to have specific receptors for LDL. These cancer cells demonstrate no defect in LDL metabolism, and lysosomal degradation of LDL was blocked by chloroquine. From the results of studies of specific binding of LDL in tissues obtained from nude mice it was demonstrated that membrane fractions prepared from EC-50 cells, after propagation in the mice, contained fifteen to thirty times more specific binding capacity for [125I]iodo-LDL than vital organs of the mouse, such as the liver, heart, lung, kidney, or brain. The results of these studies are suggestive that certain tumor cells might have a higher affinity for LDL than normal tissues and cytotoxic drugs or radionucleotides ligated to the LDL macromolecule may be utilized for the specific delivery of these agents.