Bariatric surgery and endometrial pathology in asymptomatic morbidly obese women: a prospective, pilot study.

OBJECTIVE: To determine the prevalence of occult uterine pathology in asymptomatic, morbidly obese women before and after bariatric surgery-induced weight loss. DESIGN: Prospective, blinded, non-interventional cohort. SETTING: Urban teaching hospital. POPULATION: Morbidly obese women. METHODS: Endometrial biopsies were obtained at the time of Roux-en-Y gastric bypass and again 1 year later. Both the patient and the physician were blinded to the results of the initial biopsy until the conclusion of the study. Specimens were independently reviewed by two blinded pathologists. MAIN OUTCOME MEASURE: Effect of bariatric surgery-induced weight loss on the prevalence of endometrial pathology at 1 year. RESULTS: Fifty-nine women underwent an endometrial biopsy during bariatric surgery. The mean (range) age, weight, and body mass index (BMI) were 42 years (22-62 years), 127 kg (87-176 kg), and 46.8 kg/m(2) (36-64.3 kg/m(2) ), respectively. Four women had hyperplasia (three simple and one complex), for an overall prevalence of 6.8%. The prevalence among women not receiving some anti-estrogen therapy was 9.5%. Forty-six women (78%) underwent follow-up biopsy after a mean (range) weight loss of 42 kg (19-67 kg). Simple hyperplasia was identified in 3/46 women at the 1-year follow-up (6.5%). Two women had resolution of hyperplasia, two women had persistent, simple hyperplasia, and one had had a normal initial biopsy. No woman showed progressive pathology or cancer. At the end of the follow-up all but one patient had a documented resolution of endometrial pathology. CONCLUSIONS: Asymptomatic morbidly obese women are at relatively high risk of harbouring occult endometrial hyperplasia. Bariatric surgery-associated weight loss reduced but did not eliminate this risk for endometrial pathology.

Brain metastasis from cervical carcinoma.

The aim of this study was to describe the features of patients with brain metastasis from cervical cancer. Twelve patients with brain metastasis from cervical cancer were identified. Information regarding symptoms, treatment, and survival was analyzed. The incidence of brain metastasis in our population was 0.77%. Median patient age at initial diagnosis of cervical cancer was 43.5 years (range 29-57 years) compared with 44.5 years (range 31-58 years) at identification of brain metastasis. Six patients had FIGO stage IB disease; three had stage IIB disease; and one each had stage IIIA, IIIB, and IVB disease. The median interval from diagnosis of cervical cancer to identification of brain metastasis was 17.5 months (range 1.1-96.1 months). All but one patient presented with neurologic symptoms. Eight patients received whole-brain irradiation and steroids, three received steroids alone, and one underwent surgery, followed by irradiation. All the patients who received whole-brain irradiation experienced improvement in their symptoms. Median survival from diagnosis of brain metastasis to death was 2.3 months (range 0.3-7.9 months). Five patients who received chemotherapy after brain irradiation had a median survival of 4.4 months compared to 0.9 months for those who received no additional treatment after brain irradiation (P= .016). Most patients with brain metastasis from cervical cancer presented with neurologic sequelae. Brain irradiation improved these symptoms. Survival after diagnosis of brain metastasis was poor; however, patients who received chemotherapy after brain irradiation appeared to have improved survival.

Radiation therapy with concomitant and adjuvant cisplatin and paclitaxel in high-risk cervical cancer: long-term follow-up.

INTRODUCTION: Chemo-potentiation of radiation improves survival in women with cervical cancer. Our group has previously demonstrated the tolerability of weekly paclitaxel combined with cisplatin during radiation therapy. We sought to determine the efficacy of this regimen in patients with "high risk" cervical cancer, and to determine the short- and long-term toxicity of this approach. METHODS: We prospectively enrolled surgically staged patients with positive peritoneal cytology, resectable nodal metastases, or primary tumor > 6 cm. Patients were treated using external beam radiation with concomitant cisplatin (50 mg/m2) during weeks 1, 4, and 7, and weekly paclitaxel (50 mg/m2), followed by four courses of adjuvant cisplatin (50 mg/m2) and paclitaxel (135 mg/m2). Toxicity, overall, and disease-free survival were evaluated. RESULTS: Twenty-three patients were enrolled, and 21 were evaluable. Patient allotment by FIGO stage was: IB1 - seven, IB2 - five, IIA - two, IIB - four, IIIB - two, IV - three. Twenty patients (95%) completed radiation treatment (median dose to point A was 8278 cGy). Seventeen patients (81%) completed all chemotherapy. At a median follow-up of 58 months the overall survival was 68%. Overall survival for patients with clinical Stage I and II disease was 82% at a median of 64 months. Hematologic toxicity was common but rarely resulted in treatment delays. Late complications requiring intervention (obstruction, fistula, significant lymphocyst) occurred in 11 patients (52%). CONCLUSION: The combination of paclitaxel and cisplatin appears efficacious in "high-risk" cervical cancer patients. Hematologic toxicity was common but tolerable. Long-term survival was common in these patients, however late toxicity was significant. This regimen should be investigated in collaborative phase III trials.

Torsion of the uterine adnexa. Pathologic correlations and current management trends.

OBJECTIVE: To evaluate the clinical and pathologic correlates of specimens removed for the diagnosis of adnexal torsion and to evaluate trends in the management of torsion. STUDY DESIGN: Cases of ovarian or adnexal torsion (N = 104) were identified retrospectively over a period extending from January 1987 to March 1998 by the coding of ovarian, fallopian tube or adnexal torsion. Statistical evaluation was by chi 2 analysis using the Bonferroni inequality correction when appropriate. RESULTS: Neoplastic and functional tumors of the ovary composed > 90% of the diagnoses at microscopic evaluation, with cancer diagnosed in < 1% of cases. Laparoscopy was attempted in 47 (46%) cases, and adnexasparing procedures were performed in 20 (19%) patients. Patients treated in the latter half of the study were not less likely to undergo laparotomy than those treated in the first half; however, conversion from laparoscopy to laparotomy was significantly less common in the latter half. Patients in this study were more likely to receive an adnexa-sparing operation than historical controls, but there was no improvement in this rate from the first to the second half of this study. A history of previous abdominal surgery was the most common associated condition, but 47% of patients had no known risk factors. Ovarian hyperstimulation, previously omitted in series reports, was an antecedent factor in 9% of patients. CONCLUSIONS: Adnexal torsion is most commonly associated with a benign process. A more-conservative approach to the treatment of this process is becoming increasingly common, as seems warranted in light of the low incidence of malignancy. The need for conversion from a laparoscopic to an open approach appears to have been waning over the last decade; that may correlate with an increased comfort level in gynecologists with laparoscopic approaches.

Approaching the adnexal mass in the new millennium.

Adnexal masses are common dilemmas faced by practicing gynecologists. They affect women from before birth throughout life, yet considerable disagreement exists regarding their optimal management. Traditional management focused on avoiding undertreatment of a potentially malignant process. Advances in detection, diagnosis, and minimally invasive management make it necessary to review this practice to avoid unnecessary morbidity and mortality. The literature emphasizes a minimally invasive approach to the treatment of benign lesions without sacrificing the principles of oncologic surgery.

Cortical blindness and Anton syndrome in a patient with obstetric hemorrhage.

BACKGROUND: Cortical blindness is characterized by loss of vision in the presence of intact anterior visual pathways. Anton syndrome, a form of anosognosia, is a rare complication of cortical blindness involving compromise of the visual association centers, with resulting patient denial of blindness. Both syndromes have been associated with computed tomography findings of localized cortical ischemia. In most cases, both the clinical and radiologic features are reversible. CASE: A woman with hemorrhage from an incomplete abortion at 21 weeks experienced cortical blindness and visual anosognosia. CONCLUSION: Cortical blindness and anosognosia are unusual manifestations of severe hemorrhage but should be considered in the differential diagnosis of a patient with atypical visual symptoms.

Bartholin's gland hyperplasia in a postmenopausal woman.

BACKGROUND: Benign solid tumors of Bartholin's gland are rare, with only six cases reported in the English language literature since 1966. Bartholin's gland hyperplasia has not been described. CASE: A postmenopausal woman with painless bilateral vulvar masses underwent surgical removal of one of the masses, which revealed a well-circumscribed, nonencapsulated tumor composed of mucous glands and ducts within a dense fibrous stroma, most consistent with hyperplasia of Bartholin's gland. CONCLUSION: Hyperplasia represents a new etiology for the enlarged Bartholin's gland. Whether the hyperplastic gland forms in response to a stimulus is unclear. However, it appears to share some features with Bartholin's gland hamartoma or adenoma.

The arterial anatomy of larynx transplantation: microsurgical revascularization of the larynx.

Advances in immunosuppression and selective reinnervation may soon make laryngeal transplantation a potential therapy for patients undergoing total laryngectomy. Successful transplantation requires a clear delineation of those vessels necessary to completely revascularize the larynx. Our hypothesis is that the arterial inflow provided by a single superior thyroid artery is sufficient to revascularize the entire larynx. To test this hypothesis, 8 cadavers were studied via either barium latex injection (n = 4) to assess contralateral tissue perfusion or India ink (n = 4), to determine the degree of mucosal perfusion. Following injection via a single superior thyroid artery, all larynges demonstrated either complete, bilateral tissue perfusion evidenced by x-ray visualization of the barium latex injected specimen or bilateral mucosal staining with India ink. We conclude that bilateral perfusion of the entire larynx transplant, including laryngeal and epiglottic mucosa, would occur after revascularization of a single superior thyroid artery. These findings suggest that reliable revascularization of a larynx transplant is technically possible using modern microsurgical techniques.

Exogenous transforming growth factor-beta amplifies its own expression and induces scar formation in a model of human fetal skin repair.

OBJECTIVE: Fetal skin wounds heal without scarring. To determine the role of TGF-beta 1 in fetal wound healing, mRNA expression of TGF-beta 1 was analyzed in human fetal and adult skin wounds. METHODS: Human fetal skin transplanted to a subcutaneous location on an adult athymic mouse that was subsequently wounded heals without scar, whereas human adult skin heals with scar formation in that location. In situ hybridization for TGF-beta 1 mRNA expression and species-specific immunohistochemistry for fibroblasts, macrophages, and neutrophils were performed in human adult wounds, fetal wounds, and fetal wounds treated with a TGF-beta 1 slow release disk. RESULTS: Transforming growth factor-beta 1 mRNA expression was induced by wounding adult skin. No TGF-beta 1 mRNA upregulation was detected in human fetal skin after wounding. However, when exogenous TGF-beta 1 was added to human fetal skin, induction of TGF-beta 1 mRNA expression in human fetal fibroblasts occurred, an adult-like inflammatory response was detected, and the skin healed with scar formation. CONCLUSIONS: Transforming growth factor-beta 1 is an important modulator in scar formation. Anti-TGF-beta 1 strategies may promote scarless healing in adult wounds.

T cell blastogenic responses to Toxoplasma gondii trophozoites among HIV-infected patients.

OBJECTIVE: To evaluate the cell-mediated immune response to Toxoplasma gondii (T. gondii) among HIV-infected patients. METHODS: Forty HIV-infected patients were studied. Of them, 35 had antibodies to T. gondii and 5 had not. Nine of 35 patients with detectable serum Toxoplasma antibodies were classified as group A1 (CDC 1993), 10 as group B2, 6 as group B3, and 10 as group C3. Peripheral blood mononuclear cells (PBMCs) were obtained by Ficoll-Hypaque gradient centrifugation. Living Toxoplasma gondii trophozoites, herpes simplex virus (HSV), tetanus toxoid, and phytohemoagglutinin (PHA) were used in standard proliferation assays. Toxoplasma-responding blasts were expanded and assayed for antigen specificity and HLA restriction by proliferation assays. T cell subsets were analyzed using two-color flow cytometry. RESULTS: Among patients with detectable Toxoplasma serum antibodies, significant PBMC proliferation in response to T. gondii trophozoites was observed in those classified in group A1 or B2 but not in those in groups B3 and C3. Toxoplasma-induced blasts from five of six patients after 7 days of culture and from five patients after 15 days of culture proliferated in response to T. gondii in the presence of either autologous or allogeneic PBMCs as antigen-presenting cells (APCs) and/or also proliferated in response to HSV. The surface markers of T. gondii-induced blasts showed a variable percentage of CD4 and CD8 activated cells. CONCLUSIONS: T cell proliferative response to living trophozoites of T. gondii is lost only in patients with severe depletion of CD4 cells. PBMC proliferation was observed only in patients with previous T. gondii infection, but the T cell blasts generated showed a strong alloreactivity (proliferating in response to allogeneic irradiated PBMCs) and were apparently not antigen specific (proliferating also in response to HSV).

Diagnostic and prognostic role of basic fibroblast growth factor in Wilms' tumor patients.

Basic fibroblast growth factor (bFGF) is a potent angiogenic peptide implicated in the growth and metastasis of solid tumors. Elevated concentrations of bFGF have been found in the urine of patients with bladder, prostate, and renal tumors. Furthermore, urinary bFGF levels have been shown to correlate with extent of disease. In order to test the utility of urinary bFGF as a Wilms' tumor marker, we measured bFGF levels in preoperative and postoperative urine samples from 97 patients with Wilms' tumor. Preoperative urine samples (n = 97), early postoperative samples obtained from 1 to 3 weeks after surgery (n = 43), and late postoperative samples obtained from 1 to 6 months after surgery (n = 66) were collected from Wilms' tumor patients at 30 institutions between 1989 and 1993. Urine samples from age-matched controls (n = 17) were also obtained. The bFGF levels were determined in duplicate by a competitive sandwich ELISA capable of measuring bFGF at the pg/ml level. Samples were normalized for creatinine content. Urinary bFGF was elevated in 42% of preoperative samples when compared to controls (>90th percentile of normal). Patients with stage III, IV, and V disease had significantly higher preoperative levels of urinary bFGF when compared to patients with stage I and II disease (P < 0.01). Patients with relapse or persistent disease had significantly elevated late postoperative bFGF levels when compared to disease-free patients and controls (P < 0.05). Thus, in patients with Wilms' tumor, elevated preoperative urinary bFGF levels raise the suspicion of aggressive disease while elevated postoperative levels may indicate recurrence or persistence of disease. These data suggest that bFGF is a biological marker for Wilms' tumor and may have a role in the evaluation of patients with this disease.

Urinary hyaluronic acid is a Wilms' tumor marker.

Wilms' tumor is a renal neoplasm that is histologically similar to fetal kidney tissue. Both Wilms' tumor and the fetal kidney have high levels of the glycosaminoglycan hyaluronic acid (HA) in the extracellular matrix. Preliminary studies suggest that urinary HA levels are elevated in Wilms' tumor patients. To test the utility of urinary HA as a Wilms' tumor marker, the authors compared HA levels in urine specimens from 105 Wilms' tumor patients with those of 17 age-matched controls. Preoperative urine samples (n = 92), early postoperative samples, obtained from 1 to 3 weeks after surgery (n = 63), and late postoperative samples, obtained from 1 to 6 months after surgery (n = 58) were collected from patients at 30 institutions between 1989 and 1993. The HA levels were determined in triplicate by a competitive enzyme-linked immunosorbent binding assay. Seventy-four percent of the preoperative urine specimens contained elevated HA levels compared with the controls. The preoperative HA levels were significantly higher than the early postoperative (P < .01), late postoperative (P < .01), and control levels (P < .01). There was significant correlation between preoperative HA levels and clinical tumor staging. The mean preoperative HA level for patients with histological evidence of nephroblastomatosis was higher than that for patients without nephroblastomatosis. In the late postoperative period, patients with relapse or persistent disease had higher levels of urinary HA than did the disease-free patients (P < .05). In Wilms' tumor patients, urinary HA levels are elevated preoperatively and decline progressively after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Scarless human fetal skin repair is intrinsic to the fetal fibroblast and occurs in the absence of an inflammatory response.

The fetus heals skin wounds without scar formation. Human fetal skin that is transplanted to a subcutaneous location on an adult athymic mouse and subsequently wounded heals without scar formation, whereas the same skin heals with scar formation when transplanted to a cutaneous location. In situ hybridization with species-specific DNA probes and immunohistochemistry were performed to characterize the healing process of human fetal skin in these two locations. Species-specific human and mouse DNA probes were constructed and used to probe graft wounds under high stringency in situ hybridization conditions. Immunostaining for species-specific fibroblasts, macrophages, and neutrophils was also performed. We found that the cutaneous human fetal grafts healed with scar and showed an influx of mouse fibroblasts and macrophages. In contrast, subcutaneous human fetal grafts showed exclusively human fetal fibroblasts in the wound environment, an absence of inflammatory cells, and scar-free repair. We conclude that the highly organized collagen deposition in scarless human fetal wound repair appears to be intrinsic to the human fetal fibroblasts and occurs in the absence of an adult-like inflammatory response.

Herpes simplex virus and oral mucositis in children with cancer.

The relationship between herpes simplex virus (HSV) and oral mucositis was investigated in children undergoing antineoplastic chemotherapy. HSV culture was performed in 20 children with stomatitis developing after antineoplastic chemotherapy. Viral isolates were typed and susceptibility to acyclovir was investigated. The virus was isolated from oral lesions in 10 of 20 children with severe oral mucositis. Viral reactivation was the most likely explanation in most cases, since HSV was isolated in 9 of 13 seropositive patients (and in 1 patient with unknown anti-HSV serology), but in no seronegative patient. HSV type 1 was isolated more frequently than HSV type 2 (8 versus 2). Acyclovir showed standard in vitro activity against all isolates. Our results suggest that oral mucositis in children receiving antineoplastic treatment is probably multifactorial in origin and that HSV can be an important cofactor, especially in children who are seropositive for HSV. In our Centre, acyclovir remains active in vitro against this opportunistic pathogen and could be employed in prophylaxis and therapy.