Peter A. Argenta

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

ObjectiveFetal skin wounds heal without scarring. To determine the role of TGF-β1 in fetal wound healing, mRNA expression of TGF-β1 was analyzed in human fetal and adult skin wounds. MethodsHuman 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-β1 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-β1 slow release disk. ResultsTransforming growth factor-β1 mRNA expression was induced by wounding adult skin. No TGF-β1 mRNA upregulation was detected in human fetal skin after wounding. However, when exogenous TGF-β1 was added to human fetal skin, induction of TGF-β1 mRNA expression in human fetal fibroblasts occurred, an adult-like inflammatory response was detected, and the skin healed with scar formation. ConclusionsTransforming growth factor-β1 is an important modulator in scar formation. Anti-TGF-β1 strategies may promote scarless healing in adult wounds.

Fallopian Tube and Primary Peritoneal Carcinomas Associated With BRCA Mutations

PURPOSEnThe aims of this study were to determine the incidence of BRCA mutations among Ashkenazi Jewish patients with fallopian tube carcinoma (FTC) or primary peritoneal carcinoma (PPC), to study the clinicopathologic features of these cancers, and to estimate the risks of these cancers in association with a BRCA mutation.nnnPATIENTS AND METHODSnA retrospective review at two institutions identified 29 Jewish patients with FTC and 22 Jewish patients with PPC. These patients were genotyped for the three Ashkenazi Jewish BRCA founder mutations (185delAG and 5382insC in BRCA1 and 6174delT in BRCA2). Surgical and pathologic information, family history, and survival data were obtained from hospital records. All statistical tests were two sided.nnnRESULTSnGermline BRCA mutations were identified in five of 29 patients with FTC (17%) and nine of 22 patients with PPC (41%). Mutation carriers had a younger mean age at diagnosis than patients without a mutation (60 v 70 years; P =.002). The overall median survival was 148 months for mutation carriers and 41 months for patients without a mutation (P =.04). For BRCA mutation carriers, the lifetime risks of FTC and PPC were 0.6% and 1.3%, respectively.nnnCONCLUSIONnSubstantial proportions of Ashkenazi Jewish patients with FTC or PPC are BRCA mutation carriers. Patients with BRCA-associated FTC or PPC are younger at diagnosis and have improved survival compared with patients without a BRCA mutation. Although the lifetime risks of FTC or PPC for patients with BRCA heterozygotes are greater than those for the general population, the absolute risks seem relatively low.

Vacuum-assisted closure in the treatment of complex gynecologic wound failures

BACKGROUND Complex wound failures are a source of significant morbidity and mortality. They are costly and time consuming to treat, and may evolve into chronic, debilitating conditions. Vacuum‐assisted closure is a novel wound healing technique applying subatmospheric pressure to wounds to expedite healing. CASES We report the successful use of vacuum‐assisted closure therapy on three patients on a gynecologic oncology service with complex wound failures of various chronicity. In all cases, vacuum‐assisted closure therapy was well tolerated and demonstrated efficacy within 48 hours of initiation. CONCLUSION We conclude that vacuum‐assisted closure therapy should be included in the armamentarium of the gynecologist addressing complex wound failures.

On the apparent failure of adjuvant pelvic radiotherapy to improve survival for women with uterine sarcomas confined to the uterus.

Despite numerous studies documenting reduction of pelvic relapses after adjuvant pelvic radiotherapy stage I and II uterine sarcomas, improved survival remains unproven. This retrospective report analyzes patterns of failure, survival, and toxicity in 42 women with stage I and 7 patients with stage II uterine sarcomas treated from 1972 through 1998 to identify patients likely to benefit from pelvic or abdominal radiotherapy and chemotherapy. Four of these patients also received adjuvant chemotherapy. There were 20 leiomyosarcomas, 18 homologous mixed mullerian tumors, and 11 heterologous mixed mullerian tumors. Disease-free survivals for mixed mullerian tumors were 65% at 5 years and 61% at 15 years. Disease-free survivals for leiomyosarcomas were 40% at 5 years and 40% at 15 years. There were 14 distant only, 5 distant and abdominal, 1 abdominal, 1 distant and pelvic, and 2 unknown initial sites of failure. Acute toxicity was acceptable as measured by a median 1-kg weight loss from radiotherapy and a 2% rate of failure to complete therapy. Chronic toxicity consisted of 3 small bowel obstructions and 1 sigmoid colon obstruction. In conclusion, the efficacy of adjuvant pelvic radiation is demonstrated by the absence of any isolated pelvic failures. Although the frequent occurrence of peritoneal failures suggests a role for prophylactic abdominal radiation for mixed mullerian tumors, more effective systemic therapy is necessary to substantially increase the chance of cure for women with early-stage uterine sarcomas.

Hysteroscopy and cytology in endometrial cancer.

OBJECTIVE: To estimate the effect of preoperative diagnostic hysteroscopy on peritoneal cytology in patients with endometrial cancer. METHODS: A total of 256 charts were reviewed. Two cohorts were established based on diagnosis by hysteroscopy or blind endometrial sampling via either endometrial biopsy or dilatation and curettage (D&C). Malignant or suspicious peritoneal cytology was the primary outcome. Cohorts were compared using logistic regression to correct for potential confounders of stage and grade. RESULTS: A total of 204 cases were diagnosed by endometrial biopsy or D&C, whereas 52 were identified by hysteroscopy. In the endometrial biopsy or D&C arm, 14 of 204 (6.9%) patients had malignant or suspicious cytology compared with 7 of 52 (13.5%) patients in the hysteroscopy arm (P = .15). After logistic regression controlling for stage and grade, the odds ratio for positive cytology after hysteroscopy was 3.88 (95% confidence interval 1.11,13.6; P = .03). Four of the 52 (7.7%) cases diagnosed by hysteroscopy were stage IIIA due to cytology alone compared with 3 of the 204 (1.4%) cases diagnosed by endometrial biopsy or D&C (P = .03). CONCLUSION: Hysteroscopy appears to be associated with an increased rate of malignant cytology after controlling for confounders of stage and grade. Further, there appears to be an association between hysteroscopy and upstaging patients due to cytology alone. LEVEL OF EVIDENCE: II-2

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.

Scarless human fetal skin repair is intrinsic to the fetal fibroblast and occurs in the absence of an inflammatory response: in situ hybridization and immunohistochemical studies

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.

Bartholin's gland hyperplasia in a postmenopausal woman

Background Benign solid tumors of Bartholins gland are rare, with only six cases reported in the English language literature since 1966. Bartholins 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 Bartholins gland. Conclusion Hyperplasia represents a new etiology for the enlarged Bartholins gland. Whether the hyperplastic gland form in response to a stimulus is unclear. However, it appears to share some features with Bartholins 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.

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.