Christopher A. Crisera

Risk factors for abdominal donor-site morbidity in free flap breast reconstruction.

Background: The lower abdomen is the most popular donor site for autologous tissue breast reconstruction. Several studies have reported abdominal morbidity following pedicled and free flap reconstructions using this donor site, yet few studies have compared the various types of free flaps and investigated specific operative and patient-related factors that are associated with higher rates of abdominal complications. Methods: The authors conducted a retrospective review of all free flap breast reconstructions performed at University of California Los Angeles Medical Center between July of 2002 and July of 2005. Results: A total of 279 patients underwent 211 unilateral and 68 bilateral reconstructions, totaling 347 flaps. Eleven percent were free transverse rectus abdominis myocutaneous (TRAM) flaps, 52 percent were muscle-sparing free TRAM flaps, and 37 percent were deep inferior epigastric perforator (DIEP) flaps. Mean follow-up was 29.9 months. There were 30 total abdominal complications (10.9 percent of patients), including 17 rectus bulges and five hernias. Free TRAM reconstructions had a significantly higher rate of donor-site complications than did DIEP reconstructions. Bilateral flap harvests and obesity (body mass index >30) were significant risk factors for (1) any donor-site complication and (2) rectus bulge/hernia formation. There was no significant increase in donor-site complications associated with various prior abdominal operations. Conclusions: Donor-site complications are not uncommon, but paying careful attention to patient comorbidities when selecting an operative approach (bilateral versus unilateral, free TRAM versus DIEP, and so on) can minimize postoperative abdominal complications. Furthermore, the results corroborate the recent literature suggesting there is little functional difference in patients receiving muscle-sparing free TRAM versus DIEP reconstructions.

Esophageal atresia with tracheoesophageal fistula: Suggested mechanism in faulty organogenesis

BACKGROUND/PURPOSE The organogenesis of esophageal atresia with tracheoesophageal fistula (EA-TEF) is unknown. Using an established model for EA-TEF in rats, the authors proposed to study this aberrancy of development in the hope of gaining insight into its mechanism of formation. METHODS Pregnant Sprague-Dawley rats were injected with 2.2 mg/kg of Adriamycin intraperitoneally on days 6 through 9 of gestation. Using microdissection, the trachea, blind-ending esophagus, TEF, and stomach were isolated from embryos of various gestional ages. The specimens were analyzed histologically with routine H&E staining. RESULTS The classic EA-TEF developed in the embryos, with proximal EA and distal TEF. As expected, the atresia formed as a blind-ending pouch, but the distal fistula began as an apparent equal trifurcation of the tracheal anlage into two mainstem bronchi and the fistula tract leading to the stomach. Histological analysis of the fistula tract showed respiratorylike pseudostratified columnar epithelium. CONCLUSIONS TEF develops as the middle branch of a tracheal trifurcation. EA-TEF occurs by a primary atresia of the esophagus. As a secondary phenomenon, the distal foregut anlage is switched toward the pulmonary phenotype. It trifurcates, and its middle branch grows caudally to fistulize into the stomach.

Immediate Placement of Implants in Breast Reconstruction: Patient Selection and Outcomes

Background: With the advent of skin-sparing mastectomy techniques, it became clear that immediate placement of an implant could be utilized for breast reconstruction in select patients. The authors assessed the safety, patient selection factors, and aesthetic results with this technique. Methods: Thirty-five consecutive patients (eight unilateral and 27 bilateral) who underwent immediate implant-based breast reconstruction were analyzed. Patient data and complication rates were obtained from a retrospective chart review. Postoperative photographs were evaluated by a blinded panel and scored on a four-point scale. Results: With a mean follow-up of 15 months, complications occurred in six patients (17.1 percent). There was one episode (2.9 percent) of skin necrosis resulting in implant loss, two episodes (5.7 percent) of postoperative infection, both of which resulted in implant salvage, and three patients who developed capsular contracture (8.5 percent). A total of 13 patients (37 percent) required additional surgery for revision. Revisions were necessary significantly more commonly in patients with a history of radiotherapy (p = 0.047), D-cup breast size or greater (p = 0.018), and ptosis of grade 2 or more (p = 0.017). The mean overall aesthetic score was 3.19, and upon subgroup analysis, patients with a history of radiation treatment (2.46), D-cup breast size or greater (2.64), and ptosis or grade 2 or more (2.98) had lower mean scores. Exclusion of these subgroups resulted in a mean score 3.39. Conclusions: Immediate implant-based breast reconstruction is a safe and viable option that can provide a very good aesthetic result in appropriately selected candidates. The authors recommend caution and appropriate patient counseling in patients with a history of radiotherapy, larger breasts, and/or ptotic breasts.

Inclusion of mesh in donor-site repair of free TRAM and muscle-sparing free TRAM flaps yields rates of abdominal complications comparable to those of DIEP flap reconstruction.

Background: Pedicled and free transverse rectus abdominis musculocutaneous (TRAM) flaps remain popular for autologous breast reconstruction, but the incidence of abdominal donor-site bulge and hernia is significantly greater when compared with deep inferior epigastric artery perforator (DIEP) flap reconstruction. Mesh repair after muscle harvest, however, may reduce the complication rate to that observed with perforator flaps alone. Methods: A retrospective review of all free flap breast reconstructions at the University of California, Los Angeles Medical Center from 2002 to 2007 was performed. Abdominal bulge and hernia were noted for patients undergoing free TRAM and muscle-sparing free TRAM flap reconstructions and were compared with those observed following DIEP flap reconstructions. Results: A total of 275 free TRAM plus muscle-sparing free TRAM flaps and 200 DIEP flaps were performed. Among patients with free and muscle-sparing free TRAM flaps, 11.3 percent were found to have postoperative abdominal bulge or hernia. Only 3.5 percent of DIEP flap patients had abdominal complications. Incorporating mesh into the rectus fascia repair significantly reduced the abdominal complications reported to 5.1 percent. Of the 86 free and muscle-sparing free TRAM flaps that were bilateral, 12.8 percent had hernias/bulges. Use of mesh with bilateral free and muscle-sparing free TRAM flaps reduced the complication rate to 3.7 percent. Conclusions: Incorporating mesh into rectus fascia repair in free and muscle-sparing free TRAM flap cases significantly reduces the rate of postoperative abdominal complications to levels equivalent to those for DIEP flap reconstructions. The authors advocate deciding intraoperatively between DIEP and muscle-sparing free TRAM flap dissections based on ease of dissection and whichever offers optimal safety and flap perfusion. Routine use of mesh in donor-site repair will decrease postoperative abdominal morbidity in unilateral and bilateral cases.

Ontogeny of activin B and follistatin in developing embryonic mouse pancreas: implications for lineage selection☆☆☆

Activin, a member of the transforming growth factor-beta superfamily, has been shown to be a critical regulator in exocrine and endocrine pancreas formation. The purpose of our study was to describe the ontogeny of activin B and its inhibitor, follistatin, in developing pancreas and to elucidate potential mechanisms for exocrine and endocrine lineage selection. Mouse embryonic pancreata were dissected at various ages (day 10 [E10.5] to birth [E18.5]), sectioned, and immunostained for activin B (one of two existing isomers, A and B), follistatin, insulin, and glucagon. In addition, reverse transcriptase-polymerase chain reaction was employed to determine the messenger RNA expression of follistatin in isolated pancreatic epithelia and mesenchyme of various ages. Activin B was first detected at E12.5 in epithelial ceils coexpressing glucagon. At E16.5 th ese coexpressors appeared as clusters in close proximity to early ducts. By E18.5 activin B was localized to forming islets where cells coexpressed glucagon and were arranged in the mantle formation characteristic of mature alpha cells. Follistatin was found to be ubiquitous in pancreatic mesenchyme at early ages by immunohistochemical analysis, disappearing sometime after E12.5. Follistatin reappeared in El85 islets and remains expressed in adult islets. Follistatin messenger RNA was first detected in epithelium at E11.5, preceding its protein expression in islets later in gestation. We propose that mesenchyme-derived follistatin inhibits epithelium-derived activin at early embryonic ages allowing for unopposed exocrine differentiation and relative suppression of endocrine differentiation. At later ages the decrease in the amount of mesenchyme relative to epithelium and the subsequent drop in follistatin levels liberates epithelial activin to allow differentiation of endocrine cells to form mature islets by the time of birth.

Vascular development in the mouse embryonic pancreas and lung

PURPOSE The purpose of this study was to analyze the formation of blood vessels in the developing mouse pancreas and lung by studying two ligands, angiopoietin-1 (ang1) and angiopoietin-2 (ang2), which are thought to play a role as angiogenesis-activating factors in development. Understanding the role of vasculogenic peptides in normal embryonic development also may have important implications for common clinical problems regarding neonatal pulmonary vasculature. METHODS Reverse transcriptase-polymerase chain reaction (RT-PCR) as well as Southern blotting was used to determine the ontogeny of angiopoietin-1 and angiopoietin-2 gene expression in the embryonic mouse pancreas and lung. Immunohistochemistry was performed for von Willebrand factor, a known marker of endothelial cells, to chronicle the development of the vasculature in these organs. RESULTS The authors determined the temporal expression of angiopoietin-1 and angiopoietin-2 as a function of gestational age. RT-PCR data demonstrated expression of ang1 and ang2 in the developing mouse lung between gestational day E9.5 and postnatal day 1, and in the developing pancreas between gestational days E12.5 and E18.5. Southern blot analysis confirmed PCR data for ang2 expression in both the lung and pancreas. The authors also traced the spatial development of the vascular system by von Willebrand factor staining. For both lung and pancreas specimens, no blood vessels were identifiable by immunohistochemistry until embryonic day 12.5. With increased gestational age, the blood vessel networks grew larger. CONCLUSION The authors have demonstrated that ang1 and ang2 may be involved in the mechanisms of vascular development in the embryonic mouse lung and pancreas.

The ontogeny of TGF-β1, -β2, -β3, and TGF-β receptor-II expression in the pancreas: Implications for regulation of growth and differentiation

Abstract Background/Purpose: The transforming growth factor-β (TGF-β) cytokines are important regulators of growth and differentiation in multiple mammalian organ systems. Recent studies suggest that they may play a significant role in the regulation of pancreatic organogenesis. The authors proposed to examine the ontogeny of expression of the TGF-β cytokine isoforms (TGF-β1, β2, and β3), as well as that of the type II TGF-β receptor (TβRII), in the pancreas. We hypothesized that their patterns of expression might help to clarify the manner in which they influence the development of this organ. Methods: Embryos from pregnant CD-1 mice were harvested on gestational days 12.5, 15.5, and 18.5. Microdissection was performed on the embryos to isolate their pancreases. The pancreases were fixed, frozen embedded, and sectioned with a cryostat. Immunohistochemistry was performed using polyclonal antibodies to TGF-β1, β2, and β3, and TβRII. Results: The patterns of expression of TGF-β1, β2, and β3 were similar throughout gestation. They were all present, though weakly, early in the development of the pancreas, in the E12.5 epithelial cells. Their expression persisted and became localized to the acinar cells later in gestation. TβRII staining was present in both the E12.5 epithelial cells and the surrounding mesenchyme. As the pancreas developed, TβRII became strongly expressed in the ductal epithelial cells with only minimal staining in the acinar and endocrine cells. Conclusions: TGF-βs may play a role in regulating pancreatic organogenesis. Our data suggest that they may be required for the normal development of acini. As in other cell systems, TGF-β1 may act as a suppressor of pancreatic cellular growth and differentiation. The localization of TβRII to the mature ductal epithelium may indicate a need for ongoing regulation of growth and differentiation in the pancreatic ducts beyond the fetal period.

Fetal midgut volvulus presenting at term

This report describes a rare case of intrauterine midgut volvulus that presented at term. The pregnancy was uncomplicated. There were no signs of fetal distress or polyhydramnios, and the child was delivered vaginally. This patient had the unusual presentation in that at the time of delivery, the patient was distended and acidotic. She immediately required an extensive resection of gangrenous small bowel. Comparing this case to the 10 other cases of fetal intestinal volvulus that have been reported, it seems this child was particularly fortunate that the volvulus occurred at a point in gestation when she was mature enough to tolerate birth and surgery. This case is also the first demonstration that volvulus can present with abdominal distension in the immediate newborn period.

Immediate Free Flap Reconstruction for Advanced-Stage Breast Cancer: Is It Safe?

Background: Numerous studies have demonstrated that immediate breast reconstruction following mastectomy is associated with improvements in quality of life and body image. However, immediate breast reconstruction for advanced-stage breast cancer remains controversial. This study evaluates its safety in patients with advanced-stage breast cancer. Methods: Over a 10-year period, patients diagnosed with stage IIB or greater breast cancer treated with mastectomy followed by immediate breast reconstruction were identified and analyzed. Complication rates and reconstructive aesthetics were determined. Results: One hundred seventy patients were identified who underwent 157 unilateral and 13 bilateral reconstructions (183 flaps) predominantly by means of free transverse rectus abdominis musculocutaneous flaps (n = 162). The average age was 47 years and the average hospital stay was 5.1 days. There were 15 major complications (8.8 percent), but adjuvant postoperative therapy was delayed in only eight patients (4.7 percent), with the maximum delay lasting 3 weeks in one patient. Although some degree of flap shrinkage was noted in 30 percent of patients treated with postoperative radiotherapy, only 10 percent of patients experienced severe breast distortion. Importantly, the overall cosmetic outcome in patients who underwent postoperative irradiation was comparable to that of those who did not. Conclusions: The authors have shown that immediate breast reconstruction in the setting of advanced-stage breast cancer is safe and well tolerated by patients, and is not associated with significant delays in adjuvant therapy. These findings make a strong argument for immediate reconstruction regardless of cancer stage. The authors found the changes caused by radiation to the reconstructed breast to be less significant than previously reported and readily addressed to complete an ultimate reconstruction that is aesthetically acceptable to both surgeon and patient. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. Figure. No caption available.

Immunolocalization of fibroblast growth factor receptors 1 and 2 in mouse palate development

Recent evidence has implicated mutations of fibroblast growth factor receptors (FGF-R) in the pathogenesis of craniosynostotic syndromes. Cleft palate can be a component of such syndromes. The expression of FGF-R1 and FGF-R2 has been delineated in normally developing cranium, where they seem to regulate cellular differentiation and proliferation, respectively. The specific role of fibroblast growth factor signaling in mammalian palate development is unclear. The authors investigated the patterns of expression of FGF-R1 and FGF-R2 throughout mouse palatal development in the embryo. Time-dated CD-1 mouse heads (n = 135) were harvested at embryonic ages 12.5, 13.5, 14.5, 15.5, and 16.5 days (term gestation = 19.5 days), fixed in paraformaldehyde, embedded in paraffin, and sectioned. In addition, paired palatal shelves (n = 30) were isolated by means of microdissection from embryonic day--13.5 embryos, grown on Millipore filters in serum-free medium in vitro for 24, 48, 72, or 96 hours and processed for histological analysis. Immunohistochemical analysis for FGF-R1 and FGF-R2 was performed on the in vivo and in vitro specimens. FGF-R1 and FGF-R2 were found to be specifically expressed in the epithelium of the developing palatal shelves from the time of their outgrowth from the maxillary processes through completion of fusion in vivo and in vitro. Expression of both receptors was particularly strong during the phases of medial epithelial-medial epithelial contact between the individual shelves, through the formation of the medial epithelial seam, to the ultimate dissolution of the seam. Such a pattern of expression seems to implicate fibroblast growth factor signaling in the regulation of the critical phase of fusion of the bilateral shelves. The expression of both FGF-R1 and FGF-R2 in the lateral palatal mesenchyme, where such secondary structures as tooth primordia and bone begin to appear, also suggests a role for fibroblast growth factor signaling in the induction of ongoing differentiation and maturation of the palate after fusion. These data suggest that fibroblast growth factor signaling may play a role in the epithelial-mesenchymal interactions that dictate fusion and maturation of the developing palate. Furthermore, the data are consistent with the correlation of cleft palate formation with aberrant fibroblast growth factor signaling.