Development of the external genitalia in rat fetuses

Development of the external genitalia in rat fetuses was studied with special reference to the formation of the labia pudenda and the determination of the stage at which the sex difference could be recognized from changes in the external structures. The urogenital fold located on either side of the external structures. The urogenital fold located on either side of the urogenital groove gradually enlarges and begins to enclose the genital tubercle with its counter fold on day 20 of gestation. Thus, the urogenital folds, which are known to become the labia minora and the prepuce of clitoris in the human, are differentiated only into the prepuce of clitoris in the rat. The genital swellings situated caudally to the urogenital folds are not well developed and come to be inconspicuously flat in situ at the end of gestation. However, the labia majora are formed by the time of puberty when the vagina opens. Therefore, it seems that the genital swellings contribute to the formation of the labia majora after birth. Sex difference in development of the external genitalia is recognized on day 17 of gestation; a small oval urogenital orifice is larger in male than in female and the genital swellings are better developed in male than in female.     

Bilateral autogenous breast reconstruction using perforator free flaps: a single center's experience

The authors present a single center's experience in bilateral breast reconstruction using perforator free flaps. The aim of this study was to show their indications, surgical technique, and results. A series of 53 patients underwent this procedure between February of 1996 and October of 2002. The surgical procedures were performed on patients with bilateral breast cancer (11 patients), patients with unilateral breast cancer and contralateral prophylactic mastectomy (22 patients), patients who had undergone bilateral prophylactic mastectomy (18 patients), a patient with Poland's syndrome, and a patient whose aesthetic breast augmentation had failed. Primary and secondary bilateral breast reconstructions were done in 18 and four patients, respectively. Eighteen patients who had earlier undergone breast reconstruction with implants had a tertiary breast reconstruction. Combined reconstruction (primary with secondary and primary with tertiary reconstruction) was done in 13 patients. Ninety-eight deep inferior epigastric perforator flaps and eight superior gluteal artery perforator flaps were used. The average operative time was 10 hours (range, 8 to 14.5 hours) for the simultaneous bilateral reconstruction. Total flap necrosis occurred in two cases (one deep inferior epigastric perforator flap and one superior gluteal artery perforator flap). Partial flap necrosis was not encountered, and fat necrosis was found in one deep inferior epigastric perforator flap (1 percent). Two pulmonary infections, one deep vein thrombosis, and one cardiac arrhythmia occurred as postoperative complications. The mean hospital stay was 9 days (range, 6 to 20 days). Abdominal bulging was reported in one patient. There were no recurrent disease or cancer manifestations, with an average follow-up of 3.5 years. This series clearly shows that perforator flaps are reliable and useful tools for bilateral breast reconstruction. This technique decreases the donor-site morbidity and offers an excellent aesthetic and long-term outcome and high patient satisfaction.     

Bilateral vermilion flaps for lower lip repair

A more natural reconstructive procedure of the lower lip using bilateral vermilion flaps was applied in five patients with excellent results. The vermilion defects were about two-fifths to three-fifths. In three patients, the vermilion defect was repaired using bilateral vermilion flaps alone. In the remaining two patients, a narrow horizontal lip defect was repaired by bilateral vermilion flaps and a subcutaneous V-Y advancement flap of the lower lip. A single vermilion flap or bilateral vermilion flaps are considered to be of great value for vermilion reconstruction because of the inherent elasticity and common anatomic unit. The postoperative scars are not remarkable at all. A long and narrow horizontal lip defect (perhaps within 1.5 cm downward from the vermilion border) may be effectively repaired by the combination of vermilion flap(s) and a V-Y advancement flap without sacrificing any additional healthy tissue.     

Molecular mechanisms of external genitalia development

External genitalia development occurs through a combination of hormone independent, hormone dependent, and endocrine pathways. Perturbation of these pathways can lead to abnormal external genitalia development. We review human and animal mechanisms of normal and abnormal external genitalia development, and we evaluate abnormal mechanisms that lead to hypospadias. We also discuss recent laboratory findings that further our understanding of animal models of hypospadias.     

Tissue-specific requirements of beta-catenin in external genitalia development

External genitalia are body appendages specialized for internal fertilization. Their development can be divided into two phases, an early androgen-independent phase and a late androgen-dependent sexual differentiation phase. In the early phase, the embryonic anlage of external genitalia, the genital tubercle (GT), is morphologically identical in both sexes. Although congenital external genitalia malformations represent the second most common birth defect in humans, the genetic pathways governing early external genitalia development and urethra formation are poorly understood. Proper development of the GT requires coordinated outgrowth of the mesodermally derived mesenchyme and extension of the endodermal urethra within an ectodermal epithelial capsule. Here, we demonstrate that beta-catenin plays indispensable and distinct roles in each of the aforementioned three tissue layers in early androgen-independent GT development. WNT-beta-catenin signaling is required in the endodermal urethra to activate and maintain Fgf8 expression and direct GT outgrowth, as well as to maintain homeostasis of the urethra. Moreover, beta-catenin is required in the mesenchyme to promote cell proliferation. By contrast, beta-catenin is required in the ectoderm to maintain tissue integrity, possibly through cell-cell adhesion during GT outgrowth. The fact that both endodermal and ectodermal beta-catenin knockout animals develop severe hypospadias in both sexes raises the possibility that the deregulation of any of these functions can contribute to the etiology of congenital external genital defects in humans.     

Cost-based comparison between perforator flaps and TRAM flaps for breast reconstruction

More women than ever before are undergoing mastectomies secondary to increased awareness and screening. This increase has also caused a corresponding increase in the number of breast reconstructions requested each year. The increased demand for reconstruction has fueled recent advances in new techniques. Aside from foreign-body reconstruction such as implants, the methods now being used are related to autogenous donations and reconstruction. Transverse rectus abdominis myocutaneous (TRAM) flaps and perforator flaps are currently being used for autogenous breast reconstruction. This study will compare these two techniques on the basis of cost and length of stay. A retrospective study of 49 patients undergoing a total of 64 perforator flap breast reconstructions at Memorial Medical Center in New Orleans, Louisiana, during the 1997 calendar year was used. There were 59 deep inferior epigastric perforator and five gluteal artery perforator breast reconstructions. All patients underwent some form of breast reconstruction and differed only in respect to whether a mastectomy was performed and whether the reconstruction was unilateral or bilateral. Those patients who underwent a mastectomy with immediate perforator flap reconstruction (n = 26) were then compared with patients undergoing mastectomy with immediate TRAM flap reconstruction (n = 154) at the University of Texas M. D. Anderson Cancer Center. The data from the Anderson Study were obtained from material published in Plastic and Reconstructive Surgery in 1996. Comparison of patients was limited to those who underwent mastectomy with immediate breast reconstruction because this was the design of the M. D. Anderson study. This approach allowed a cost and length of stay comparison while keeping other variables relatively similar. Patients in the perforator flap series enjoyed a marginally shorter operating time and a much shorter length of stay. On average, the operative time for all perforator flap reconstructions was approximately 2 hours shorter than for all TRAM flaps. As for length of stay, perforator flap patients were discharged, on average, 3 days after the initial reconstruction. In contrast, TRAM flap patients remained in the hospital for an average of approximately 7 days after the initial reconstruction. The overall total, average cost for the perforator flap reconstruction in this study is $9625, whereas the average cost of all TRAM flaps performed in the Anderson study is $18,070.     

Cellular and molecular mechanisms of development of the external genitalia

The limb and external genitalia are appendages of the body wall. Development of these structures differs fundamentally in that masculine development of the external genitalia is androgen dependent, whereas development of the limb is not. Despite this fundamental difference in developmental regulation, epithelial-mesenchymal interactions play key roles in the development of both structures, and similar regulatory molecules are utilized as mediators of morphogenetic cell-cell interactions during development of both the limb and external genitalia. Given the relatively high incidence of hypospadias, a malformation of penile development, it is appropriate and timely to review the morphological, endocrine, and molecular mechanisms of development of the genital tubercle (GT), the precursor of the penis in males and the clitoris in females. Morphological observations comparing development of the GT in humans and mouse emphasize the validity of the mouse as an animal model of GT development and validate the results of experimental studies. Accordingly, the use of mutant mice provides important insights into the roles of specific regulatory molecules in development of the external genitalia. While our current understanding of the morphological and molecular mechanisms of mammalian external genitalia development is still rudimentary, this review summarizes the current state of our knowledge and whenever possible draws from the rich experimental embryology literature on other relevant organs such as the developing limb. Future research on the hormonal and molecular mechanisms of GT development may yield strategies to prevent or reduce the incidence of hypospadias and to elucidate the molecular genetic mechanisms of GT morphogenesis, especially in relation to common organogenetic pathways utilized in other organ systems.