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Purpose: The aim of this study was to measure the radial occult microscopic spread of tumor in patients with invasive squamous cell carcinoma of the vulva., Materials and Methods: In the operating room the gross tumor border was marked. The pathologist took a radial section in each quadrant and measured the distance of occult lateral spread of the tumor., Results: From 7/01/93 to 6/30/96, 24 tumors from 21 patients were studied. The mean maximum tumor diameter was 3. 2 cm (0.5-7.0) and the mean depth of invasion was 9.1 mm (1.1-28.0). The gross and microscopic extent correlated in 20 tumors. Maximum lateral microscopic extent of the other 4 tumors was 3.5, 5 (to the margin), 10, and 16 mm. These 4 tumors were ulcerative and infiltrative and arose from or involved mucosa., Conclusion: The gross and microscopic periphery of most invasive squamous vulvar cancers are approximately the same. Ulcerative tumors with an infiltrative pattern of invasion which involve mucosal epithelium may be more likely to extend beyond what is grossly apparent. Measurement of the tumor-free margin should be included in future studies., (Copyright 1999 Academic Press.)

Objective: To identify sentinel lymph nodes using intraoperative lymphoscintigraphy., Methods: Technetium-99-labeled sulfur colloid was injected at the site of primary vulvar carcinoma. An intraoperative gamma counter was used to identify one or more sentinel lymph nodes., Results: Ten patients underwent bilateral inguinal and femoral lymphadenectomy. The clinical stages are as follows: T1 in 6, T2 in 2, and T3 in 2. A total of four groins (3 patients) were positive for metastases. In one patient only the sentinel node was positive for disease. In a second patient, two unilateral nodes were positive for disease and both were identified with the gamma counter as sentinel nodes. In the third patient, a single sentinel node was positive for malignancy in each groin. Multiple nonsentinel lymph nodes were positive in each groin in this patient. In no case was the sentinel node negative when other nonsentinel nodes were positive., Conclusion: Intraoperative lymphoscintigraphy quantitatively identifies one or more sentinel lymph nodes. Since sentinel lymph nodes can be localized transcutaneously, this technique may be useful for selective lymphadenectomy. Larger patient accrual is necessary to verify this technique., (Copyright 1997 Academic Press.)

Our experience with gynecologic oncology patients presenting preoperatively with a deep vein femoral thrombosis is reported. Over a 3-year period data were collected on all patients at the University of South Florida (USF) requiring surgery for a known or suspected gynecologic cancer and having a concomitant active femoral venous thrombosis. Twelve such patients were managed. Management was divided among three options: heparinization, preoperative inferior vena cava (IVC) filter, and intraoperative IVC ligation. For two patients a filter could not be placed preoperatively due to tumor compression of the IVC. Both underwent IVC ligation intraoperatively. One of the two died intraoperatively, possibly related to pulmonary embolism. One of eight with a preoperative IVC filter had obvious clot propagation postoperatively, managed with heparin. One of two managed with heparin only had severe bleeding and heparin-associated thrombocytopenia (HAT) preoperatively. Based on our experience and a review of the literature, we recommend therapeutic heparinization and a preoperatively placed IVC filter for most preoperative gynecologic oncology patients with femoral deep venous thrombosis.

Over a 13-year period, intraabdominal packing has been used to control massive hemorrhage during surgery for gynecologic malignancy in six patients. Five patients had undergone total pelvic exenteration and one total abdominal hysterectomy with bilateral salpingo-oophorectomy for endometrial cancer. Massive hemorrhage was defined as infusion of more than 10 units of blood and replacement of more than one total blood volume. Tamponade was performed using continuous Kerlex rolls (Kendall Co., Boston, MA) in a bowel bag with directed pressure over the hemorrhaging site with abdominal closure. The packs were removed in 48 to 72 hr in the operating room, transabdominally in five patients and transvaginally in one. One postoperative death occurred within 8 hr of surgery. The packing was ultimately successful in the five remaining patients. In five of six patients, tumors were removed before the packing, whereas in one, the tumor was removed concurrently with the pack. In one patient, immediate repacking was required after pack removal, with ultimate hemostasis. Morbidity included "empty pelvis syndrome" in four patients, neuropathy in three (obturator in 1, sciatic in 2), and small bowel obstruction in one. In patients with severe intraoperative hemorrhage, intraabdominal packing has been successful as a mode of treatment.

Two hundred twenty-nine patients with Stage IB cervical cancer treated with radical hysterectomy were assigned to the new FIGO substages IB1 (n = 181) and IB2 (n = 48) based on clinical tumor diameter. Our purpose was to determine the impact of the new staging system for IB1 and IB2 cervical cancer on nodal status and survival. Additionally, we analyzed the morbidity of radical hysterectomy in light of the new staging system. The complications were similar between the two groups. Para-aortic lymphadenectomy was the only independent predictor of complications (P = 0.00026). Stage IB2 patients did have a significantly worse 5-year survival (72.8%) when compared with IB1 (90.0%) (P = 0.0265). Multivariate stepwise logistical regression analysis indicated that the new staging system did not have an independent impact on survival. Stage acts through nodal status in its impact on survival. Positive lymph nodes, tumor diameter, and Ponderal Index are all independent predictors of survival (P = 0.0001). Patients with Stage IB2 carcinoma of the cervix undergoing radical hysterectomy showed no significant increase in morbidity when compared with patients with Stage IB1 disease treated with the same procedure.

We evaluated the therapeutic value of sequential cyclical hormonal therapy (megestrol acetate, and tamoxifen citrate) plus single-agent chemotherapy (carboplatin) in the outpatient management of advanced or recurrent endometrial cancer. Carboplatin (300 mg/m2) was administered every 4 weeks for six courses or until disease progression. In addition, patients alternated megestrol acetate (80 mg orally twice daily) with tamoxifen citrate (20 mg orally twice daily) every 3 weeks. Thirteen of 18 (72.2%) patients were considered evaluable. Four patients (30.8%) had a complete response, six (46.2%) had a partial response, one (7.7%) had stable disease, and two patients (15.4%) progressed. Six of seven patients with vaginal disease responded. The median progression-free interval was 14 months for complete responders. Two patients (15.4%) are alive with no evidence of disease at 41 and 59 months. Seven of 13 patients experienced a hematologic toxicity (six grade 2, one grade 3); all resolved within 2 weeks. Dose reduction of carboplatin to 200 mg/m2 was required in one patient. No other toxicities were encountered. The median survival for all patients is 11 months, and is 33 months for complete responders. We conclude that a regimen of carboplatin plus sequential hormonal therapy shows promise in this pilot study for the treatment of advanced or recurrent endometrial cancer.

The purpose of this study is to report our experience with weekly intramuscular methotrexate for nonmetastatic gestational trophoblastic disease. Treatment was begun at a dose of 40 mg/m2 and escalated weekly by 5-10 mg/m2, depending upon response and tolerance, to a maximum dose of 60 mg/m2. Remission was induced with weekly intramuscular methotrexate alone in 12 (60%) of 20 patients in 2-12 (median 8) weeks. The remaining 7 patients had a complete response to alternate chemotherapy. There were no major toxicities. Although the results of the present study are less favorable in terms of response, the overall published results using weekly intramuscular methotrexate for nonmetastatic gestational trophoblastic disease indicate that it is comparable in efficacy to other first-line treatments while having the advantages of convenience, low cost, and low toxicity.

Embryonated eggs were coinfected with two strains of the coronavirus avian infectious bronchitis virus (IBV), IBV-Beaudette and IBV-M41, to investigate whether recombination between the two strains would occur. Virions were isolated from the allantoic fluid of the coinfected eggs and putative hybrid RNAs were detected by polymerase chain reaction (PCR), using strain-specific oligonucleotides. PCR products, of the expected sizes, were obtained as predicted from potential recombination events between the nucleoprotein (N) gene and the 3'-untranslated region of the two IBV genomes. Sequencing confirmed that they corresponded to hybrid RNAs. Virus produced as a result of the mixed infection was treated with an M41-specific neutralizing monoclonal antibody and passaged in Vero cells, in which IBV-Beaudette, but not IBV-M41, replicated. Hybrid RNA was still detectable after three serial passages. Since no IBV-M41 was detectable this confirmed that infectious recombinant genomes had been produced in the embryonated eggs. These findings not only support the circumstantial evidence, from sequencing studies of IBV field strains, that recombination occurs during replication of IBV and contributes to the diversity of IBV, but also show that coronavirus RNA recombination is not limited to mouse hepatitis virus.

Nucleotide sequence analysis has shown previously that the genomic-length mRNA (mRNA1) of the coronavirus infectious bronchitis virus (IBV) contains two large open reading frames (ORFs), 1a and 1b, with the potential to encode polyproteins of approximately 441 and 300 kDa, respectively. We have characterized the specificity of a set of region-specific antisera raised against the 5'-portion of ORF 1a by immunoprecipitation of in vitro-synthesized, C-terminally truncated 1a polypeptides and used these antisera to detect virus-specific proteins in IBV-infected Vero cells. Two antisera, which had specificity for IBV sequences from nucleotides 710 to 2079 and 1355 to 2433, respectively, immunoprecipitated a polypeptide of approximately 87 kDa from IBV-infected Vero cells. In vitro translation of ORF 1a sequence terminating at nucleotide 5763 did not produce this protein unless the in vitro translation products were incubated with Vero cell S10 extracts prepared from either IBV-infected or mock-infected Vero cells. However, processing of the 87-kDa protein was also observed when the same region was expressed in Vero cells using the vaccinia virus/T7 expression system. This observation indicates that the 87-kDa polypeptide is encoded within the 5'-most 3000 nucleotides of mRNA 1 and that it might be cleaved from the 1a polyprotein by viral and cellular proteinases.

This study was designed to examine if interleukin-12 (IL-12) can induce cytolytic function of lymphocytes from ovarian cancer patients against either an ovarian cancer cell line or their own autologous tumor cells. Lymphocytes were obtained from the peripheral blood or ascites of ovarian cancer patients and activated with IL-12 alone or concomitantly with interleukin 2 (IL-2) for 2 to 3 days. Activation of lymphocytes and assessment of tumoricidal function by a chromium release assay were performed directly in a standard control medium (RPMI 1640 containing 2 mM glutamine, 100 micrograms/ml streptomycin, 100 units penicillin, 5% heat-inactivated human AB serum, and 5 mM 4-(2-hydroxyethyl)-1-piperazinesulfonic acid) and in 50% ascitic fluid (50% by volume filter-sterilized ascites with 50% of the above-mentioned control medium). Target cells were added directly into the medium in which the lymphocytes were activated in order to more closely mimic in vivo conditions. Lymphocytes, activated by IL-12 in 50% ascitic fluid, were able to lyse autologous tumor cells in 3 of 6 assays and were able to lyse SKOV3 cells (an ovarian cancer cell line) in 5 of 7 assays. The results were not significantly different in the control medium. When both IL-2 and IL-12 were used to activate lymphocytes in 50% ascitic fluid, significant cytotoxicity was generated in 6 of 6 autologous assays and in all 7 patient assays using SKOV3 as a target (P < 0.05). Synergy between the two cytokines was seen in all 13 patient assays in ascitic medium compared to only 5 of 13 assays in control medium. Additionally, when lymphocytes were stimulated with both IL-2 and IL-12, significantly greater cytotoxicity was seen in the ascitic fluid medium compared to the control medium in 13 of 14 assays (P < 0.05). No significant tumoricidal activity was seen by lymphocytes maintained in either medium without the addition of IL-2 or IL-12. Ascitic fluid consistently potentiates the synergy between IL-2 and IL-12 in generating cytotoxicity against ovarian cancer cells but does not increase cytotoxicity induced by IL-12 alone. IL-12 by itself activates tumoricidal activity of lymphocytes in ascitic fluid; however, the addition of IL-2 increases the degree and consistency of this effect. These data support the possibility that IL-12 may warrant further investigation as a potential therapeutic agent in the treatment of advanced ovarian cancer.

During 1993, four persistent groin lymphocysts were diagnosed following inguinal lymphadenectomy for the management of gynecologic cancer. All four were successfully managed by a scheme involving active drainage combined with compression. Patient details and specifics of the suggested management scheme are outlined in the text.

Eleven patients undergoing inguinofemoral lymphadenectomy for carcinoma of the vulva had the femoral vessels covered with Dura Film (Codman, Randolph, MA); a total of 21 groins were explored. The Dura Film was sutured to the inguinal ligament, sartorius muscle fascia, and adductor longus fascia. Nine of the 21 groins became infected with 3 of these breaking down; each of these 3 required removal of the Dura Film to achieve satisfactory healing. One patient developed a unilateral inflammatory groin mass requiring surgical removal of the Dura Film. One patient developed a chronic draining sinus that required surgical intervention. Seven groins developed lymphocysts. The morbidity was high with 9 of the 11 patients experiencing complications. Coverage of the femoral vessels with Dura Film after inguinofemoral lymphadenectomy is not an effective alternative to human dura mater or sartorius muscle transplant.

This is an evaluation of our experience with colorectal reanastomosis on a gynecologic oncology service. A retrospective review was carried out on all patients who underwent colorectal resection and reanastomosis on the gynecologic oncology service from October 1, 1987 to September 30, 1992. Thirty-nine procedures were performed: Nine patients underwent sigmoidectomy alone, 20 also underwent cytoreduction, and 10 also underwent exenteration. Thirty-eight percent of the patients had undergone prior radiotherapy. The level of anastomosis above the anal verge was 3-5 cm in 9 patients, 6-9 cm in 20 patients, and 10-14 cm in 10 patients. Sixteen had a protective colostomy which included 13 of the 15 patients with prior radiotherapy. Thirteen of the protective colostomies were taken down, although three of these required a second permanent colostomy. Three other patients required colostomy at a later date, one of whom developed a rectovaginal fistula 10 days following exenteration for postradiation recurrent carcinoma of the cervix. A total of 30 of the 37 evaluable patients (81%) had an ultimately functional colorectal reanastomosis. Problems related to colorectal function included stricture (4), fistula (4), chronic diarrhea (3), tenesmus (1), and fecal incontinence (1). Colorectal anastomosis is a worthwhile endeavor in selected patients with gynecologic cancer.

The Beaudette strain of IBV was passaged 16 times in chick kidney cells. Total cellular RNA was analyzed by Northern hybridization and was probed with 32P-labeled cDNA probes corresponding to the first 2 kb of the 5' end of the genome, but excluding the leader, and to the last 1.8 kb of the 3' end of the genome. A new, defective IBV RNA species (CD-91) was detected at passage 6. The defective RNA, present in total cell extract RNA and in oligo-(dT)30-selected RNA from passage 15, was amplified by the reverse transcription-polymerase chain reaction (RT-PCR) to give four fragments. The oligonucleotides used were selected such that CD-91 RNA, but not the genomic RNA, would be amplified. Cloning and sequencing of the PCR products showed that CD-91 comprises 9.1 kb and has three regions of the genome. It contains 1133 nucleotides from the 5' end of the genome, 6322 from gene 1b corresponding to position 12,423 to 18,744 in the IBV genome, and 1626 from the 3' end of the genome. At position 749 one nucleotide, an adenine residue, was absent from CD-91 RNA. By Northern hybridization CD-91 RNA was detected in virions in higher amounts than the subgenomic mRNAs.

The pudendal thigh is a sensate fasciocutaneous flap supplied by the posterior labial artery. We report on the results of pudendal thigh flaps used for vaginal reconstruction in eight patients at the time of pelvic exenteration (6) and radical vaginectomy (2). Patients were interviewed and results were assessed 5 to 19 months after surgery. The flaps were raised in the thigh creases just lateral to the hair bearing area of the labia majora and included skin, subcutaneous tissues, deep fascia of the thigh, and the epimysium of the adductor muscles. Flap sizes varied from 9 x 4 cm to 15 x 6 cm. Bilateral flaps were used in seven patients. The flaps were technically easy to perform. Partial (apical) flap necrosis occurred in four patients. One patient developed complete necrosis of bilateral flaps, followed by an enterovaginal fistula. One patient whose flaps did not necrose developed a rectovaginal fistula at the site of rectal reanastomosis. The functional results are disappointing. The only patient having successful vaginal intercourse had a unilateral flap reconstruction following lower vaginectomy in a nonirradiated pelvis. No patient with bilateral flaps or prior pelvic irradiation has had successful coitus. Other long-term sequelae include vulvar pain (2), chronic vaginal discharge (2), hair growth (4), and protrusion of the flaps (2). These vulvovaginal symptoms discourage patients and their partners from genital contact. Breaching the integrity of the vulva to construct a neovagina that is likely to be unsuitable for sexual intercourse may deprive women of their only potential for normal genital sexual responsiveness. Techniques of vaginoplasty require continued assessment.

In order to prevent the complications of long-term nasogastric suctioning and increase patient comfort, we have been using gastrostomy tubes (G-tubes) in gynecologic oncology patients who are deemed to be at risk for protracted postoperative bowel dysfunction. This study describes our patient selection criteria and evaluates the results with 35 MIC (Medical Innovation Corporation, Milpitas, CA) gastrostomy tubes inserted between September 1, 1992 and April 30, 1993. The procedure is technically easy and adds approximately 10 min to operating time. The tubes were well tolerated by the patients over periods ranging from 5 to 135 days. All tubes were used for postoperative gastric drainage and in addition, eight tubes were used for short-term enteral feeding. One patient with short bowel syndrome continued enteral nutritional supplementation at home. Twenty patients were discharged with their G-tubes in situ. Five of these patients required continuous gastric drainage because of obstruction of gastric emptying or small bowel by advanced tumor, and four of them were taking full liquids orally prior to discharge from the hospital. Gastrostomy tubes are convenient adjuncts to postoperative care of the gynecologic oncology patient and afford palliation with few complications to patients dying with bowel obstruction.

There have been five previous well-documented cases of metastatic vulvar basal cell cancer in the literature. We now present the sixth case-an 86-year-old patient with vulvar basal cell cancer metastatic to an ipsilateral groin node. She was treated with radical vulvectomy and bilateral inguinofemoral lymphadenectomy and remains free of disease 1 year later.

There is a demand on gynecologic oncology services for semipermanent cannulization of central veins to improve the quality of life in cancer patients by circumventing the need for frequent peripheral venous punctures. Central venous thrombosis and sepsis are the major complications with these lines. We reviewed our experience with the externalized Groshong catheters and subcutaneously implanted Hickman ports in 104 gynecologic oncology patients requiring either chemotherapy (56), hyperalimentation (5), or supportive care (43). All devices were inserted under the supervision of one primary gynecologic oncologist. Groshong catheters and Hickman ports remained in place for a median of 68.5 and 210 days, respectively (P < 0.001). Thrombosis occurred in association with 4.8% of catheters and was exclusive to the Groshong catheters. Line sepsis occurred in 32% of Groshong catheters and 16.2% of Hickman ports (P = 0.04). Infection rates were not higher in dual-lumen compared to single-lumen Groshong catheters. Staphylococcus epidermidis was the comments isolate in line infections. The majority of lines were salvaged despite infectious complications. Malfunction of the catheter was equally common in both groups (10.5-13.5%), but was complete, necessitating replacement of only 2.9% of lines. The Groshong catheters took less time to insert (P < 0.003). The externalized Groshong catheter remains a useful alternative to the subcutaneously implanted ports, especially when relatively short-term use is anticipated, but gynecologic oncologists should be aware that there is an increased frequency of complications with the externalized catheter.

Metastatic disease from nonvulvar gynecologic malignancies involving the groin lymph nodes is uncommon. The purpose of this study is to analyze the morbidity, recurrence-free interval, and survival in this group of surgically managed patients. Twenty patients underwent surgical resection of metastatic disease involving the groin lymph nodes between January 1, 1984 and December 31, 1991. Individual factors which have an impact on morbidity, recurrence, and survival were analyzed. Two patients developed wound infection and 2 had wound breakdown. Both of the patients with postoperative wound infection had clinically fixed nodes. None of the patients developed deep venous thrombosis. Long-term complications included lymphocytes in 2 patients and lymphedema in 4 patients. The median local disease progression-free interval was 10 months, with 5 of 20 patients developing local recurrence. The overall median survival was 11 months, with an adjusted 5-year survival rate of 11.5%. Patients with clinically fixed lymph nodes had a shorter median survival (3.6 months) than those with clinically mobile (median, 22.6 months) nodes (P = 0.0032). Metastatic disease from carcinoma of the ovary, fallopian tube, uterus, and cervix involving the groin lymph nodes can be managed safely and effectively with surgical resection. The acute and long-term morbidity is acceptable. Local control can be achieved in the majority of patients.

The presence of subgenomic mRNAs in virions of IBV was examined by probing Northern blots of RNA extracted from virions using as a probe a cDNA of the 3'-terminal nucleocapsid protein (N) gene. This detects all five mRNAs because of the 3'-coterminal, nested-set arrangement of coronavirus mRNAs. The mRNAs were readily detected even after extensive purification of virions and after RNase A treatment of virions. In sucrose gradients the peaks of virus particles, genomic RNA (gRNA), and mRNAs were coincident. Cellular mRNA was not detected in virions. The molar ratio of gRNA to each mRNA ranged from about 10 to 30 for IBV-Beaudette and 25 to 800 for IBV-M41. The molar ratio of genomic to intracellular viral mRNAs was also determined. From this it was estimated that the efficiency of incorporation of gRNA into virions was at least 20- to 100-fold greater, depending on the mRNA species, for IBV-Beaudette and 100- to 500-fold for IBV-M41. It is concluded that most virions contain only gRNA or contain only one species of mRNA on average in addition to gRNA.

From 7/1/85 to 6/31/92 25 colostomy closures were performed. Twenty-one of the colostomies were performed in relation to gynecologic cancer and the remaining 4 were performed for benign pelvic disease. Nineteen patients underwent simple closure of a transverse loop colostomy. The other 6 patients had their colostomy closed in association with a laparotomy. There were no intraoperative complications related to the colostomy closure. There was 1 postoperative mortality secondary to adult respiratory distress syndrome following reoperation for stricture in the early postoperative period. Three other patients also experienced significant postoperative complications for an overall complication rate of 16%. These included one subcutaneous wound dehiscence, one subcutaneous wound infection, and one anastomotic stricture. One patient required a second colostomy due to recurrence of an obstruction by ovarian cancer in the rectosigmoid area. From the results of this small study, it would appear that colostomy closure is a reasonable endeavor in a selected group of gynecologic cancer patients.

This pilot study was undertaken to correlate the patterns of lymphatic drainage demonstrated by vulvar lymphoscintigraphy with the clinical and pathologic findings of the inguino-femoral lymph nodes in patients with vulvar cancer. Ten patients were studied with the radionuclide Technetium-antimony trisulfide colloid (Tc 99m ASC) using a perilesional technique. Images were obtained at 2-4 hr postinjection. Four of the six patients with central lesions or lesions that crossed the midline had bilateral groin uptake, and two had unilateral uptake to the side on which the lesion was predominantly located. Three of these patients, each with suspicious groin nodes bilaterally, had metastatic nodal disease, two unilateral and one bilateral, in whom the uptake was bilateral and unilateral, respectively. Three of the four patients with unilateral lesions had ipsilateral groin drainage only and one had no drainage. Three underwent a bilateral lymphadenectomy and none had metastasis. The pattern of Tc 99m ASC uptake was not predictive of metastatic nodal disease. In two of the three patients with unilateral groin recurrence the side of recurrence was the same as that demonstrated on lymphoscintigraphy, and in the third case there was bilateral drainage. Further data are needed to determine the role of lymphoscintigraphy in the management of vulvar cancer.

The interaction of infectious bronchitis virus (IBV) with erythrocytes was analyzed. The binding activity of IBV was not sufficient to agglutinate chicken erythrocytes. However, it acquired hemagglutinating activity after treatment with neuraminidase to remove alpha 2,3-linked N-acetylneuraminic acid from the surface of the virion. Pretreatment of erythrocytes with neuraminidase rendered the cells resistant to agglutination by IBV. Susceptibility to agglutination was restored by resialylation of asialo-erythrocytes to contain alpha 2,3-linked sialic acid. These results indicate that IBV attaches to receptors on erythrocytes, the crucial determinant of which is sialic acid alpha 2,3-linked to galactose. In contrast to other enveloped viruses with such a binding specificity (influenza viruses and paramyxoviruses) IBV lacks a receptor-destroying enzyme.

Forty-five patients who underwent a modified radical vulvectomy for invasive squamous cell carcinoma of the vulva were compared with forty-five patients who underwent radical vulvectomy for similar lesions. Vulvar wound infection and breakdown were infrequent in both groups. Anal incontinence developed postoperatively in five of the modified radical vulvectomy patients and in none of the radical vulvectomy patients. Urinary incontinence developed postoperatively in two of the modified radical vulvectomy patients and in seven of the radical vulvectomy patients. Possible reasons for these differences are discussed. One invasive local recurrence (2.2%) developed in the modified radical vulvectomy group and two (4.4%) local recurrences developed in the radical vulvectomy group. A modified radical vulvectomy appears to be efficacious for the vulvar phase of treatment of localized invasive squamous cell carcinoma of the vulva.

From 1/1/80 to 5/31/90 111 patients underwent a colostomy on a gynecologic oncology service. Six patients developed 7 (6.3%) early colostomy-related complications, including sepsis (1), stomal retraction (1), ostomy wound infection (3), and partial stomal obstruction (2). The sepsis was felt to be related to spillage of stool upon maturing the colostomy, and this patient expired on Postoperative Day 63. There were no other mortalities attributed to the colostomies. Fourteen patients developed 17 (15.3%) delayed colostomy-related complications, including parastomal hernia (5), stomal retraction (1), stomal prolapse (3), tumor replacement (2), and site-choice problems (6). These results compare favorably with those in the literature and support the continued role of the gynecologic oncologist in gynecologic cancer-related gastrointestinal surgery.

Several biochemical properties and the sequence of the fusion glycoprotein (F) have indicated that turkey rhinotracheitis virus (TRTV) is a pneumovirus, subfamily Pneumovirinae of the Paramyxoviridae family. As TRTV was known to generate polycistronic mRNAs, cDNA was generated from TRTV strain UK/3BV/85-infected Vero cell mRNAs using an oligonucleotide primer corresponding to a region of the F gene. Sequencing of four cDNAs revealed that the gene adjacent to the beginning (3' end) of the F gene was that for the matrix (M) protein, i.e., that TRTV had the partial gene order 3'-M-F-5'. This was unexpected as human respiratory syncytial (RS) virus, the type species of the genus Pneumovirus, has the partial gene order 3'-M-SH-G-F-5', where SH and G are the small hydrophobic protein and attachment glycoprotein, respectively. Instead TRTV resembled the Morbillivirus and Paramyxovirus genera of the Paramyxoviridae (subfamily Paramyxovirinae) which have the partial gene order 3'-M-F-5'. Two further oligonucleotides, one corresponding to a sequence near the end of the M gene and the other (oligo B) to a sequence near the beginning of the F gene, with their 5' ends spaced 300 nucleotides apart on the basis of the cDNA sequence, were used in a polymerase chain reaction (PCR) using genomic RNA as template. Only a PCR product of 0.3 kb was obtained. The same sized product was also obtained using these oligonucleotides and genomic RNA from three other TRTV strains (SA/91/78, UK/8544/85, and SA/2381/88) which had been grown in chicken tracheal organ cultures. In addition PCR was performed using genomic RNA from TRTV-3BV and SA/2381/88 with oligo B and another oligonucleotide near the 5' end of the gene upstream from M, spaced 1141 nucleotides apart on the basis of the sequence data. Only a 1.14-kb PCR product was obtained. Larger products would have been expected if another gene had been situated between M and F. The absence of such larger products, plus the demonstration that infected cells contained M-F dicistronic mRNAs, supported the conclusion that in the TRTV genome the M gene is adjacent to the F gene in the order 3'-M-F-5'. The 5' termini of the M and F mRNAs were confirmed by mRNA mapping. The TRTV M gene encoded a protein of 254 amino acids, very similar to that of RS virus (256 residues; 37% amino acid identity) but very different from that of the morbilliviruses and paramyxoviruses (approximately 350 residues).(ABSTRACT TRUNCATED AT 400 WORDS)

Sixty-seven patients with advanced carcinoma of the lower female genital tract (cervix, vagina, and vulva) were treated with radiation and concomitant intravenous cisplatin and/or 5-fluorouracil. Fifty-seven patients (85%) responded completely clinically. Thirty-five (61%) complete responders recurred with a median time to recurrence of 6 months. Twenty-six of the thirty-five patients who recurred had some component of local failure. The 22 complete responders who have not recurred have been followed a median of 13 months. Acute toxicity was minimal, with only 6 patients requiring interruption of therapy. Nine (13%) patients developed severe late complications and eight required surgery. The actuarial 5-year survival is 22%. This treatment regimen is disappointing in terms of both survival and local control.

Twenty-eight patients underwent pelvic exenterations for gynecologic malignancies between June 1986 and June 1989. The postoperative fluid and electrolytes were managed by one of two regimens. One group of 10 patients was given concentrated 25% albumin infusion for the first 16 hr after surgery in addition to maintenance intravenous crystalloid solution according to ideal body weight. The second group of 18 patients received only a standard crystalloid solution. The albumin infusion group was found to have a more stable postoperative course as evidenced by less fluid boluses (P less than 0.01), fewer electrolyte bolus requirements (P less than 0.01), and easier management of blood pressure and urine output. There was a 50% decrease in total fluid requirement, a higher mean right atrial pressure (P less than 0.05), and a lower maintenance intravenous fluid rate (P less than 0.01). As a consequence, central hyperalimentation was started earlier (P less than 0.01) and the albumin infusion group left the Intensive Care Unit sooner than the non-albumin infusion group. There was not a single instance of clinical fluid overload with this slow infusion technique. Thus, concentrated albumin infusion was beneficial in the acute fluid management of these difficult patients.

The third largest of the nested set of subgenomic mRNAs (mRNA3) from the coronavirus infectious bronchitis virus (IBV) contains three separate open reading frames (3a, 3b, and 3c) which are not present on the next smallest of the mRNAs, suggesting that this mRNA may be functionally polycistronic. However, although a protein product has been identified from the 3c open reading frame, to date the coding function of 3a and 3b has not been established. We present nucleotide sequence data suggesting that each of the three open reading frames is conserved in a variety of different IBV strains and further show, through the preparation of monospecific antisera against bacterial fusion proteins, that IBV-infected cells contain small amounts of the products of these ORFs. In vitro translation studies using synthetic mRNAs containing the 3a, 3b, and 3c open reading frames suggest strongly that all three proteins can be translated from a single molecular species, and expression studies carried out in intact cells support this conclusion. Thus mRNA3 of IBV appears to be functionally tricistronic.

Twenty patients undergoing inguinofemoral lymphadenectomy for vulvar malignancy had the femoral vessels covered with freeze-dried human cadaver dura mater; 5 patients had a radical vulvectomy and 15 had a modified radical vulvectomy, and a total of 38 groins were explored. The dura mater was sutured to the inguinal ligament, sartorius muscle fascia, and adductor longus muscle fascia. Three of the thirty-eight wounds had wound breakdown uncovering the dura mater; each of the groins healed satisfactorily by secondary intention without exposing the femoral vessels. Three patients developed cellulitis without wound breakdown and three patients developed lymphocysts. All groin wounds have healed completely and there have been no delayed complications. The mean follow up was 12.5 months (range, 2-30 months). Coverage of the femoral vessels with dura mater after inguinofemoral lymphadenectomy appears to be a safe and effective alternative to the technically more difficult and more time-consuming sartorius muscle transplant.

Cisplatin, bleomycin, and mitomycin-C were used to treat 25 patients with recurrent squamous cell carcinoma of the cervix. Six patients had a partial response, yielding a total response rate of 27%. Nine patients had stable disease. The median survival for the whole group was 30 weeks. The median survival for responders was 32 weeks. The median progression free interval for the whole group was 12 weeks and the median progression-free free interval for responders was 14 weeks. The toxicities noted were primarily nausea, vomiting, and myelosuppression. The combination of cisplatin, bleomycin, and mitomycin-C has modest effectiveness in the treatment of recurrent squamous cell carcinoma of the cervix, but represents no improvement over single-agent chemotherapy.

A case of gonadoblastoma associated with metastatic embryonal carcinoma occurring in a phenotypic female with 46,XY pure gonadal dysgenesis is presented. Two years after treatment with surgery and combination chemotherapy the patient is disease free. This is the third reported case and first reported cure in the English-language literature over the past 25 years. Current management is reviewed.

The results of a pilot study employing the administration of intraarterial chemotherapy and accelerated fractionation radiotherapy for advanced gynecologic malignancies are reported. The protocol consisted of three treatment sessions every 3 to 4 weeks. Each session consisted of bilateral or unilateral catheterization of the hypogastric artery with the infusion of cisplatin 100 mg/m2 on Day 1 and 2-deoxy-5-fluorouridine (FUDR) 300 mg/m2 on Day 2. An accelerated fractionation schedule of external-beam radiation was begun on Day 1 consisting of 200 rads twice daily for 4 days (1600 rads per session). Eight patients entered the protocol, and seven completed external-beam radiotherapy. Five completed three intraarterial sessions, and three, two sessions. Five of seven evaluable patients had a complete local response. Local control was sustained fom 6 to 24 months in four patients. Complications included three sensorimotor neuropathies, one clinically insignificant catheter-related thrombosis, and three clinically significant radiation injuries. This multimodality treatment for locally advanced gynecologic tumors appears feasible with modification, and continued work exploring this approach is encouraged.

Perianal resection for neoplasia is associated with a significant risk for subsequent fecal incontinence. This report describes primary reconstruction of the anus using local skin flaps in nine patients who had undergone resection of perianal tissue for neoplasia. Seven patients had invasive cancer, and two patients had carcinoma in situ with a preoperative suspicion of invasive cancer. In all nine patients a portion of the external anal sphincter was excised during surgery. Bilateral rhomboid flaps were used in five patients, and four patients had advancement of local full-thickness skin flaps. All nine patients had a satisfactory anatomic result and were ultimately fecally continent.

Morbidity and survival patterns were reviewed in 50 patients who underwent radical hysterectomy, pelvic lymphadenectomy, and adjuvant postoperative pelvic radiotherapy for invasive cervical cancer. Ninety percent of the patients were FIGO stage IB, and 10% were clinical stage IIA or IIB. Indications for adjuvant radiotherapy included pelvic lymph node metastasis, large volume, deep stromal penetration, lower uterine segment involvement, or capillary space involvement. Seventy-two percent of the patients had multiple high-risk factors. An average of 4700 cGy of whole-pelvis radiotherapy was administered. Ten percent of the patients suffered major gastrointestinal complications, 14% minor gastrointestinal morbidity, 12% minor genitourinary complications, one patient a lymphocyst, and one patient lymphedema. Of the five patients with major gastrointestinal morbidity, all occurred within 12 months of treatment. Three patients required intestinal bypass surgery for distal ileal obstructions and all are currently doing well and free of disease. All of the patients who developed recurrent disease had multiple, high-risk factors. The median time of recurrence was 12 months. All patients recurred within the radiated field. Actuarial survival was 90% and disease-free survival 87% at 70 months. It is our opinion that the morbidity of postoperative pelvic radiotherapy is acceptable, and benefit may be gained in such a high-risk patient population.

Ovarian management at the time of radical hysterectomy for cervical cancer was reviewed retrospectively over a 7-year period. All patients had early-stage cancer except three who had stage IIB disease. Approximately 80% of patients had squamous cancer and 20% adenocarcinoma or adenosquamous carcinoma. The mean age was 44, and 24% of patients were 35 or younger. Ninety-nine patients had their ovaries removed. None of the ovaries contained metastatic disease including 22 patients with adenocarcinoma or adenosquamous carcinoma. Of the 17 patients with retained ovaries 14 had transposition into the paracolic gutters. Only one of the 14 patients with transposed ovaries developed symptoms of ovarian failure. No patients with retained ovaries developed metastatic disease or required reoperation secondary to new ovarian pathology. It is our opinion that normal ovaries can be preserved in young women at the time of radical hysterectomy for early cervical cancer regardless of histologic type.

Regional deposition patterns determine the dose of inhaled gaseous toxicant received by various areas of the respiratory tract. To study potential species differences in upper respiratory tract (URT) deposition of acetone and ethanol vapors, and to determine if deposition of these vapors could be described by a ventilation-perfusion (V-P) model, URT deposition efficiencies of these vapors were measured over a 12- to 18-min period at selected flow rates in the surgically isolated URT of urethane-anesthetized Fischer rats and Hartley guinea pigs. For both gases in both species, deposition efficiencies were significantly dependent upon inspiratory flow rate (p less than 0.0005). The V-P model predicts a linear relationship will exist between the ratio of the deposited to the nondeposited fraction and the inverse of the inspiratory flow rate. Such relationships were observed for deposition of acetone (r = 0.93, p less than 0.0005) and ethanol vapors (r = 0.95, p less than 0.0005) in the guinea pig and for deposition of acetone vapor (r = 0.95, p less than 0.0005) in the rat. In contrast, a linear relationship was not observed for ethanol in the rat suggesting that deposition mechanism(s) differ for this vapor in this species. Despite the fact that the surface area of the URT of the guinea pig is greater than that of the rat, URT deposition of these vapors was as much as twice as efficient in the rat as in the guinea pig (p less than 0.0005). This effect was not due to different blood:air partition coefficients as they were identical in both species. In toto, these results suggest there may be important anatomic and/or physiologic differences in the URT of the Hartley guinea pig and Fischer rat. Such differences may have to be considered when comparing the response(s) of these species to toxic gases or when extrapolating data obtained from these species to the human.

The combination of cisplatin, doxorubicin, and cyclophosphamide was used to treat 28 patients with recurrent and metastatic cervical cancer. Five patients had a complete response and one patient had a partial response, yielding a total response rate of 21%. Eleven patients had stable disease. The median survival for the whole group was 42 weeks. Responders had a statistically significant prolongation of survival at a median of 113 weeks (P less than 0.01). There was no statistically significant difference in progression-free interval between responders and patients with stable disease. The overall median progression-free survival was 26 weeks. The toxicities noted were primarily nausea, vomiting, and myelosuppression. The combination of cis-platin, doxorubicin, and cyclophosphamide has modest effectiveness in the treatment of metastatic or recurrent carcinoma of the cervix.

The deposition of nonreactive gases in the lungs is well studied and is dependent on the ventilation-perfusion relationships of that organ. The current investigation was undertaken to determine if pulmonary ventilation-perfusion models could be successfully applied to quantitatively describe upper respiratory tract (URT) deposition of acetone and ethanol vapors. Toward this end, the deposition of these vapors was measured in the surgically isolated URT of the anesthetized rat at selected inspiratory flow rates (ranging from 70 to 500 ml/min) and exposure times (ranging from 3.3 to 13.3 min). The deposition of acetone in the URT followed apparent quasi-steady-state conditions, suggestive of a ventilation-perfusion relationship. Pulmonary ventilation-perfusion models predict the ratio of the amount deposited to the amount not deposited should be linearly related to the inverse of the inspiratory flow rate. Such a relationship was observed for URT acetone (r = 0.988, N = 16,p less than 0.0001) and ethanol (r = 0.963, N = 20, p less than 0.0001) deposition. From the deposition-flow relationships estimates of 0.31 and 0.33 ml/min were obtained for nasal blood flow in the ethanol and acetone studies, respectively. The 95% confidence limits for these estimates overlapped. The successful application of a ventilation-perfusion model to describe URT deposition suggests that acetone and ethanol vapors equilibrate between the inspired airstream and the capillary blood of the URT and that their deposition is dependent on both the URT ventilation and perfusion rates.

Twenty-three consecutive patients with advanced squamous carcinoma of the lower female genital tract were entered into a pilot study to determine the response rate and toxicity of a combination of intravenous cisplatin and 5-fluorouracil given concomitantly with radiation therapy. Twenty (87%) of the patients had a complete clinical response. Two patients (9%) had a partial response and one (4%) had stable disease. Nine (45%) of the complete responders have recurred with a median time to recurrence of 4 months. Seven (35%) had some component of local recurrence. The complete responders who have not recurred have been followed a median of 17 months. The acute toxicity was generally mild and there was no life-threatening acute complications. Three patients developed significant late complications. The response rate in this study was very high. The responses were usually prompt and dramatic, but often not sustained.

Whole-abdomen irradiation was delivered to 11 patients with persistent epithelial ovarian cancer after chemotherapy. Ten of the eleven patients have recurred and subsequently died of disease. The median time to recurrence was 5.5 months. All 10 recurrences were within the irradiated field. All 6 patients with microscopic disease at second-look laparotomy recurred. Four of the five patients with minimal residual disease (less than or equal to 5 mm) at second-look laparotomy recurred. One patient is alive with no evidence of recurrence at 14 months. Four patients developed small bowel obstruction, three of which were associated with recurrence. During therapy, 4 patients developed significant enteritis and 5 patients developed significant bone marrow suppression. All 11 patients completed radiation therapy, although in 4 there were interruptions of 1 to 3 weeks. Whole-abdomen irradiation does not appear to be an effective second-line regimen for epithelial ovarian cancer, even in the presence of microscopic or minimal residual disease.

Nine well-accepted cases of endometrial carcinoma associated with pregnancy have been reported. A 10th patient is added and the cases are briefly summarized. At the time of her definitive surgery 6 weeks postpartum, our patient was also found to have a Stage I endometrioid ovarian carcinoma. Nine of the 10 cases have been well-differentiated adenocarcinoma or adenoacanthoma and the lesions have tended to be focal with minimal or no invasion. Given the small number of patients, conclusions regarding prognosis and treatment are difficult to make. However, in younger patients with noninvasive adenocarcinoma of the endometrium, the adnexa may be spared. Endometrioid adenocarcinoma of the ovary, discovered incidentally in our patient, is associated with a concomitant adenocarcinoma of the endometrium in 5-29% of cases, but the present case in which the lesions coexisted with pregnancy appears to be the first such report in the literature.

Thirteen patients underwent reconstruction of the pelvic floor following pelvic exenteration using polyglactin 910 (Vicryl) mesh with omentum. One patient developed a conduit leak in the early postoperative period and one patient developed an enterocutaneous fistula at the time of recurrence. There were no other gastrointestinal or urinary tract complications. Six patients developed significant postoperative pelvic infections, four of which manifest as abscesses below the mesh. Vicryl mesh with omentum appears to be a reasonable method for reconstruction of the pelvic floor following exenteration. The postoperative infectious morbidity in this series is concerning, however.

Nerve injury is an infrequent complication of gynecologic surgery. We reviewed, over the previous academic year, our experience with this complication after radical pelvic surgery. Four cases are reported (1.06%) and discussed. In our experience, neuropathies are infrequently associated with radical pelvic surgery. However, they are often irreversible. Careful surgical technique and care in the methods of obtaining hemostasis are probably the most important factors in the prevention of these complications. In gynecologic operations in general, the most important factors in prevention of postoperative neuropathies include careful placement of the self-retaining retractor for abdominal operations, and careful positioning of the patient in stirrups whenever they are used.

One hundred patients underwent radical hysterectomy at the University of South Florida over a 4 1/2-year period. In all patients the anterior division of the internal iliac artery was ligated on the left, and the uterine artery was ligated at its origin from the internal iliac artery on the right. One patient developed a left ureterovaginal fistula for a urinary tract fistula rate of 1%. Preservation of the distal branches of the anterior division of the internal iliac artery may help prevent urinary tract fistulas following radical hysterectomy. This study would suggest, however, that this of minimal importance.