c-erbB-2 oncoprotein overexpression in uterine cervix carcinoma with glandular differentiation. A frequent event but not an independent prognostic marker because it occurs late in the disease.

The c-erbB-2 proto-oncogene (HER-2/neu) codes for a transmembrane, tyrosine kinase, 185 kD oncoprotein (p185erbB2), which is related to the epidermal growth factor receptor. p185erbB2 overexpression occurs in carcinomas at many sites, including the uterine cervix, and predicts poor clinical outcome. The authors hypothesize that p185erbB2 immunohistochemistry will provide additional information in the evaluation of uterine cervix carcinomas with glandular differentiation (CCGD), a difficult and more frequent clinical problem. Paraffin sections from 82 CCGDs including 41 pure adenocarcinomas and 41 adenosquamous carcinomas (7 glassy cell predominant and 34 exhibiting a gland forming component) are immunostained with anti-p185erbB2 (CB11 monoclonal, Novacastra Laboratories, Newcastle upon Tyne, UK). Seventy-seven percent of CCGDs exhibit p185erbB2 immunoreactivity with distinct plasma membrane localization (M) in 50%, the remaining 27% show cytoplasmic staining only. Adjacent benign tissue is negative. The p185erbB2 staining intensity and distribution is as follows: 54.9% strong diffuse (SD, > or = 50% cells positive) with 40.2% M, 17.1% strong focal (SF, < 50% cells positive) with 9.8% M, and 4.9% weak with no M. Immunoreactivity occurs in both squamous and glandular areas of adenosquamous carcinomas. Endometrioid histology is associated with absence of p185erbB2 (P < .01); all other histopathologic features show no association. Follow-up information is available in 77 patients: 37 exhibit recurrent disease (8 pelvic, 15 distant and 14 both) at 1 to 144 months (mean 34, median 16) and 40 were disease free at 12 to 216 months (mean 75, median 64). Strong p185erbB2 immunoreactivity predicts recurrence at 24 months (P < .05) but not overall recurrence at longer follow-up periods. Recurrent disease is associated with nuclear grade (P < .00001); high clinical stage (P < .001); vascular space invasion (P < .001); large size on clinical exam or pathologic evaluation (P < .005); and pelvic lymph node involvement (P < .05). Considering only patients in good prognosis groups, p185erbB2 immunoreactivity does not predict recurrence. Strong p185erbB2 immunoreactivity is associated with stage 3,4 disease (P < .01). p185erbB2 expression is associated with CCGD carcinogenesis but occurs late in the disease, in patients who present at late stage, hindering its prognostic predictive value. p185erbB2 immunolocalization may have a diagnostic role in confirming CCGD in histologically challenging cases, predicting high stage at initial biopsy, and defining therapeutic strategies.

Synchronous radiation and cytotoxic chemotherapy for locally advanced or recurrent squamous cancer of the vulva.

Between July 1987 and September 1991 a program of external beam radiation and synchronous, radiopotentiating chemotherapy was employed to treat 25 women with locoregionally advanced or locoregionally recurrent squamous cancer of the vulva. Of 18 previously untreated patients, 1 was Stage II, 10 were Stage III, 6 were Stage IVA, and 1 was Stage IVB. Reasons for patient referral for nonsurgical management included the presence of initially unresectable disease (5 patients), disease extent which would have necessitated partial or total exenteration if treated surgically (9 patients), disease extent predictive of inadequate surgical margins (less than 1 cm gross margin) if treated by less than exenterative surgery (8 patients), and severe comorbid illness precluding surgical management (3 patients). Complete clinical response was obtained in 16 of 18 previously untreated patients (89%) and in 4 of 7 patients with recurrent disease following vulvar surgery (57%). Of 20 patients achieving a complete clinical response, 3 patients have relapsed within the irradiated volume at 11, 38, and 48 months following completion of treatment. Fourteen patients remain alive and continuously cancer free from 2-52 months after completion of treatment (median follow-up 24 months). This experience suggests that initial management with radiation and chemotherapy may offer some patients with locally advanced squamous cancer of the vulva an alternative to exenterative surgery and may hold curative potential for some patients with surgically unresectable or medically inoperable disease.

Total exenteration, two or one ostomy.

Total exenterations require fecal and urinary diversions, necessitating ostomies in the anterior abdominal wall. This article was done to explore the possibility of extremely low anastomoses of the intestine to the anal stump, to reduce the number of ostomies to only one for the urinary diversion. Although technically feasible, the long term follow-up evaluation of these patients resulted in us having reservations concerning function.

Formation of a vagina at the time of exenteration.

The formation of an artificial vagina at the time of exenteration has been described. Femoral gluteal flaps forming a tube suspended to the iliopectineal ligament appeared to give the most satisfactory results.

20 year follow-up on microinvasive squamous carcinoma of the cervix.

MISC of the cervix is a potentially fatal disease if not properly classified and treated. Strict criteria for diagnosis are required to provide appropriate therapy. It is recommended that a radical approach be considered for those patients in whom the depth of invasion of the carcinoma is greater than 3 mm on cone biopsy and in all cases where vascular invasion is demonstrated. Confluency may not of itself be a reason for more radical therapy but is an indicator of the aggressiveness of the tumor. Vascular invasion is seen more frequently with increased depth of invasion but may be found with minimal infiltration and has a serious connotation. Further refinement of the definition of MISC of the cervix appears to be needed.

Ten-year prospective study in a management change of vulvar carcinoma.

A prospective study involving 71 cases in which operation for vulvar carcinoma was performed during a 10-year period is presented. Primary closure of the vulvar defect with the use of full-thickness transposition flaps reduced hospitalization without jeopardizing survival. This technique tends to increase the radical nature of the operation. Although complications involving groin breakdown were reduced, such complications remain a formidable challenge for newer techniques. The postoperative results have been superior to those of older methods.

Preparation of amniotic membranes for surgical use with antibiotic solutions.

A comparative study was conducted to investigate the effectiveness of antibiotic solutions for disinfecting vaginally delivered amniotic membranes. The microbial flora of eight amniotic membranes was defined and six antibiotic solutions were tested for their effectiveness in eliminating aerobic and anaerobic organisms. A solution containing 600 micrograms lincomycin HCl/ml, 500 micrograms neomycin sulfate/ml, 25 micrograms polymyxin B sulfate/ml, and 25 micrograms amphotericin B sulfate/ml in 0.5N saline was found to be capable of disinfecting amniotic membranes stored at 4 degrees C for 24 hours. This solution is now being used to disinfect surgically used amniotic membranes at our institution.

The use of amniotic membrane in acute massive full-thickness loss of the abdominal wall from clostridial myonecrosis.

A patient who developed clostridial infection of the abdominal wall following laparotomy for small bowel perforation is described. Immediate debridement resulted in the loss of the entire abdominal wall. Dressing of the exposed viscera during the period of stabilization and prior to reconstruction was achieved using amniotic membranes.

The amnion in surgery, past and present.

The clinical application of the fetal membarnes has been under study for many years. An attempt is made to bring the reader up to date in this fascinating subject and to indicate practical employment of the membrane in modern medicine. The amnion and chorion are detailed separately where possible, particularly in the field of surgery.

Use of allograft amniotic membrane for control of intra-abdominal adhesions.

The authors have studied 60 rabbits to determine the effect and fate of allograft amniotic membranes (devoid of chorion) used in the intra-peritoneal cavity to control adhesions secondary to bowel perforation and bacterial contamination. The experimental animals revealed dramatic differences when compared to the control with major reduction in adhesions. Abscesses remained localized and contained. No untoward reactions were noted in the host. Violent immunologic rejection did not occur. The membranes gradually disintegrated and left little or no evidence of its presence. Important clinical applications are obvious.

Replacement of the peritoneum with amnion following pelvic exenteration.

An analysis was made of 24 patients undergoing pelvic exenteration. By chance, the patients are divided into two groups, 12 having the pelvic floor treated by the traditional means and 12 in whom amniotic membranes have been used. A statistically significant shortening of the hospital stay was experienced by those in the amnion group with a total lack of intestinal complications being related to the raw surface of the pelvis. A large number of recurrent or de novo carcinomas of the vagina following carcinoma of the cervix treated with radiation are identified. Two deaths in this series were related to complications of the small intestine.

Complications following operation in the previously irradiated abdominopelvic cavity.

Twenty-three patients underwent 32 operations in a previously irradiated abdominopelvic cavity. The overall postoperative morbidity rate was 62% and the mortality rate was 6.2%. The data from this series do not support small bowel bypass as the only acceptable method of management of surgical radiation enteritis. Wide resection with primary anastomosis reduces the long-term morbidity of the "blind-loop syndrome", perforation and fistulization of the isolated loop, and does not have an increased mortality.

The effect of immunizing female rats with modified rat pituitary extract.

Immune reactions to a number of hormones have been induced, but information is lacking on the feasibility of inducing immune reactions to homologous gonadotropins. Female rats immunized with diazotized and tyrosylated rat pituitary extract containing gonadotropic activity and emulsified in complete Freund's adjuvant expressed various reproductive disturbances such as increased cycle length (7.0 days), increased number of sterile matings, reduced implantation in animals becoming pregnant, and reduced ability to carry fetuses to term. These effects were not exhibited by rats immunized similarly with diazotized or tyrosylated rat pituitary extract containing no detectable gonadotropic activity. Rats not becoming pregnant had a significantly higher antibody level to rat luteinizing hormone than did rats becoming pregnant. No significant elevation of rat follicle-stimulating hormone antibodies was noted. It is concluded that auto-immune reactions to gonadotropins can be induced and that very low levels of antibodies have a significant effect on reproduction.