Faculty Bibliography

When peripheral vascular injuries present in conjunction with life threatening emergencies, controlling hemorrhage from a peripheral blood vessel may take initial priority, however, sacrificing a limb to preserve life is a well-established dictum. The use of intravascular shunts has allowed arterial and venous injuries to be controlled and temporized while treating other injuries. Typically, intravascular shunts are used for short time periods while orthopedic injuries are repaired or other life threatening injuries are managed. The following case demonstrates the long-term use of an intravascular arterial shunt to treat a traumatic transection of the common femoral artery and vein in a patient with an open pelvic fracture from blunt trauma. A 20-year-old woman fell between a subway platform and an oncoming train. She sustained a crush injury to her lower extremity and pelvis as she was pinned between the train and platform. The patient presented with active hemorrhage from a groin laceration, quickly became hemodynamically unstable, and was brought to the operating room. In addition to a pelvic fracture with massive pelvic hematoma she sustained a complete transection of the bifurcation of the common femoral artery (CFA), the common femoral vein (CFV), and associated orthopedic injuries. Vascular shunts were placed in the common femoral artery and vein. The patient became hypotensive from an expanding retroperitoneal hematoma. Pelvic bleeding was controlled with angioembolization and the venous injury was repaired. At this time the patient became cold, acidotic, and coagulopathic. It was thought unsafe to proceed with the arterial repair and it was elected to keep her arterial shunts in place and perform a planned reexploration in 24 hours after correcting her physiologic status. The patient returned to the operating room for an elective repair of her CFA the following day. Her shunt had remained patent throughout this time. She underwent a reverse saphenous vein graft from her CFA to her SFA. After a prolonged hospital course she was ultimately transferred to a rehabilitation center with intact pulses in both lower extremities. This case demonstrates the effectiveness of prolonged (>6 hours) use of an intravascular shunt as part of damage control surgery for peripheral arterial and venous injuries. In a patient who would otherwise undergo an amputation for their injury, the risk of shunt thrombosis, or infection, during damage control resuscitation may not be a contraindication for placement

Citing the higher perioperative risk of redo carotid surgery, balloon angioplasty and stenting of the carotid artery (CAS) has been advocated for recurrent carotid stenosis (RCS). To examine the impact of CAS on the management and outcome of recurrent stenosis, a retrospective review of a prospectively compiled database was performed. From a registry of patients treated for carotid disease, 105 procedures were performed from 1992 to 2002 for RCS. For comparison, two study groups were examined. Time I consisted of 77 reoperations performed through 1998, before CAS was introduced at our institution. Time II included 12 reoperations and 16 CAS procedures performed for RCS from 1999 through 2002. Using perioperative stroke as a measure of outcome, the results for time II were poorer than for time I (7.2% vs. 5.2%, p = NS). Overall, the risk of perioperative stroke was the same for reoperation (5/89) and CAS (1/16) (5.6% vs. 6.3%, p = NS). Although not statistically significant, there was a trend toward a higher risk of perioperative stroke for patients treated with reoperation during the latter time period (8.3% vs. 5.2%, p = NS). This probably relates to the finding that during time II, CAS was most likely to be used in asymptomatic patients (68.6% vs. 41.7%, p = NS) with early (<3 years) RCS (87.5% vs. 41.7%, p= 0.01). No patient with asymptomatic, early RCS had a perioperative stroke with either surgery or CAS (0/35 cases, 0%). The presence of preoperative neurologic symptoms was significantly predictive of a perioperative stroke among all procedures performed for RCS (13.6% vs. 0%, p = 0.004). Contrary to suggestions that CAS might improve the management of RCS, a review of our data shows the overall risk of periprocedural stroke to be no better since CAS has become available. The bias for using CAS for asymptomatic myointimal hyperplastic lesions, and reoperation for frequently symptomatic late recurrent atherosclerotic disease, makes direct comparisons of the two techniques for treating RCS difficult. It is expected that the overall risk for redo carotid surgery will increase, as fewer low-risk patients will be receiving open procedures. However, the increased risk among symptomatic patients undergoing reoperation suggests that endovascular techniques should be investigated among this group of cases as well

Adult intussusception in the setting of inflammatory bowel disease (IBD) is a rare phenomenon. Giant pseudopolyps, while generally considered benign, may function as lead points for intussusception. Diagnosis and management of intussusception in the setting of IBD can be fraught with hazards. We report the case of a 27-year-old male, recently diagnosed with ulcerative colitis and giant pseudopolyps, who presented with colocolonic intussusception and obstruction. Diagnosis was confirmed using CT imaging and the patient underwent resection of the colocolonic intussusception without reduction. The following case underscores the challenges in managing adult intussusception in the setting of IBD and allows for a review of the literature to date. Resection of non-reduced intussusception, rather than endoscopic or enema reduction, should continue to be definitive treatment of patients presenting with this unusual problem

OBJECTIVE: Transcatheter embolization with coils and other agents has been described as a treatment method for type II endoleak after endovascular aortic aneurysm repair (EVAR). Type I endoleak has not been treated commonly with such therapies, although most investigators believe they warrant definitive intervention. The liquid adhesive n-butyl 2-cyanoacrylate (n-BCA) is often used to treat congenital arteriovenous malformations. The objective of this study is to report our initial experience in treating type I endoleak with n-BCA and with a variety of other interventions. METHODS: A retrospective review was performed of 270 patients who underwent EVAR at our institution between January 1994 and December 2002. Of these, 24 patients had type I endoleak (8.9%), diagnosed either intraoperatively (n = 13, 52%) or during follow-up (n = 12, 48%). Among these 24 patients, 17 had proximal leaks and the remaining 8 patients had distal leaks. These cases form the focus of this study. RESULTS: Twenty-two leaks required endovascular intervention, with the following success rate: n-BCA, 12 of 13 cases (92.3%); extender cuffs, 4 of 5 cases (80%); coils with or without thrombin, 3 of 4 cases (75%). In one patient with persistent endoleak despite attempted endovascular intervention the device ultimately was surgically explanted, and the patient did well. Of six patients with endoleak initially managed expectantly, two eventually underwent attempts at definitive intervention, both with n-BCA. Three sealed spontaneously before definitive intervention could be performed; and in one 97-year-old patient who refused intervention, the aneurysm subsequently ruptured and the patient died. In total, 13 patients with type I endoleak underwent n-BCA transcatheter embolotherapy. No serious complications were directly related to this therapy. Colon ischemia developed in one patient, and was believed to be a result of thromboembolism during wire and catheter manipulation rather than n-BCA treatment. Twelve of these 13 leaks remain sealed at mean follow-up of 5.9 months (range, 0-19 months). CONCLUSION: Our initial use of n-BCA occlusion suggests that it may be an effective and safe method of treatment of type I endoleak after EVAR. In particular, n-BCA embolotherapy may be especially useful in treating type I endoleak not amenable to placement of extender cuffs. Larger case series and longer follow-up are needed before this treatment is more broadly recommended. Type I endoleak after EVAR can be treated successfully with a variety of endovascular methods, and surgical explantation is rarely required

Successful endovascular aortic aneurysm repair (EVAR) is often defined as complete exclusion of blood flow within the aneurysm sac. Perigraft flow, also known as endoleak, is the most common complication following EVAR. Attachment site related endoleaks (type I) are generally considered to warrant some form of intervention due to the belief that they represent a risk for future rupture. Management of type II endoleaks, also known as branch or collateral endoleaks, is more controversial. Some advocate a policy of watchful-waiting whereas others treat all type II endoleaks as soon as they are discovered. The following review explores the controversies pertaining to the management, diagnosis and surveillance imaging, and treatment of type II endoleaks

The authors previously established an in vitro palate nonfusion model on the basis of a spatial separation between prefusion embryonic day 13.5 mouse palates (term gestation, 19.5 days). They found that an interpalatal separation distance of 0.48 mm or greater would consistently result in nonfusion after 4 days in organ culture. In the present study, they interposed embryonic palatal mesenchymal tissue between embryonic day 13.5 mouse palatal shelves with interpalatal separation distances greater than 0.48 mm in an attempt to 'rescue' this in vitro palate nonfusion phenotype. Because no medial epithelial bilayer (i.e., medial epithelial seam) could potentially form, palatal fusion in vitro was defined as intershelf mesenchymal continuity with resolution of the medial edge epithelia bilaterally. Forty-two (n = 42) palatal shelf pairs from embryonic day 13.5 CD-1 mouse embryos were isolated and placed on cell culture inserts at precisely graded distances (0, 0.67, and 0.95 mm). Positive controls consisted of shelves placed in contact (n = 6). Negative controls consisted of shelves placed at interpalatal separation distances of 0.67 mm (n = 6) and 0.95 mm (n = 7) with no interposed mesenchyme. Experimental groups consisted of embryonic day 13.5 palatal shelves separated by 0.67 mm (n = 11) and 0.95 mm (n = 12) with interposed lateral palatal mesenchyme isolated at the time of palatal shelf harvest. Specimens were cultured for 4 days (n = 19) or 10 days (n = 23), harvested, and evaluated histologically. All positive controls at 4 and 10 days in culture showed complete histologic palatal fusion. All negative controls at 4 days and 10 days in culture remained unfused. Five of six palatal shelves separated at 0.67 mm interpalatal separation distance with interposed mesenchyme were fused at 4 days, and all five were fused at 10 days. At an interpalatal separation distance of 0.95 mm with interposed mesenchyme (n = 12), no palates (zero of four) were fused at 4 days, but seven of eight were fused at 10 days. These data suggest that nonfused palatal shelves can be 'rescued' with an interposed graft of endogenous embryonic mesenchyme to induce fusion in vitro

It is unclear whether cleft palate formation is attributable to intrinsic biomolecular defects in the embryonic elevating palatal shelves or to an inability of the shelves to overcome a mechanical obstruction (such as the tongue in Pierre Robin sequence) to normal fusion. Regardless of the specific mechanism, presumably embryonic palatal shelves are ultimately unable to bridge a critical distance and remain unapproximated, resulting in a clefting defect at birth. We propose to use a palate organ culture system to determine the critical distance beyond which embryonic palatal shelves fail to fuse (i.e., the minimal critical intershelf distance). In doing so, we hope to establish an in vitro cleft palate model that could then be used to investigate the contributions of various signaling pathways to cleft formation and to study novel in utero treatment strategies.Palatal shelves from CD-1 mouse embryos were microdissected on day 13.5 of gestation (E13.5; term = 19.5 days), before fusion. Using a standardized microscope ocular grid, paired palatal shelves were placed on a filter insert at precisely graded distances ranging from 0 (in contact) to 1.9 mm (0, 0.095, 0.19, 0.26, 0.38, 0.48, 0.57, 0.76, 0.95, and 1.9 mm). A total of 68 paired palatal shelves were placed in serum-free organ culture for 96 hours (n = 68). Sample sizes of 10 were used for each intershelf distance up to and including 0.48 mm (n = 60). For intershelf distances of 0.57 mm and greater, two-paired palatal shelves were cultured (n = 8). All specimens were assessed grossly and histologically for palatal fusion.Palatal fusion occurred in our model only when intershelf distances were 0.38 mm or less. At 0.38 mm, eight of 10 palates appeared grossly adherent, whereas six of 10 demonstrated clear fusion histologically with resolution of the medial epithelial seam and continuity of the palatal mesenchyme. None of the 18 palates fused when placed at intershelf distances of 0.48 mm or greater.Using our selected intershelf distances as a guideline, we have established an approximate minimal critical intershelf distance (0.48 mm) at which we can reliably expect no palatal fusion. Culturing palatal shelves at intershelf distances of 0.48 mm or greater results in nonfusion or clefting in vitro. This model will allow us to study biomolecular characteristics of unfused or cleft palatal shelves in comparison with fused shelves. Furthermore, we plan to study the efficacy of grafting with exogenous embryonic mesenchyme or candidate factors to overcome clefting in vitro as a first step toward future in utero treatment strategies

BACKGROUND/PURPOSE: Retinoid signaling plays an important role in many differentiation pathways. Retinoid signaling has been implicated in the induction of differentiation by pancreatic ductal cancer cell lines and in patients with pancreatic cancer. The authors wished to better understand the role of retinoid signaling in pancreatic development. METHODS: Embryonic pancreas was harvested from mice at serial gestational ages and immunohistochemical analysis was performed for retinoic acid receptors (RAR-alpha, RAR-beta, RAR-gamma), and retinoid X receptors (RXR-alpha, RXR-beta, and RXR-gamma). Also, early embryonic pancreases were cultured for 7 days with exogenous 9-cis retinoic acid (9cRA) or all-trans retinoic acid (atRA) and analyzed histologically and immunohistochemically. RESULTS: Retinoid receptors were expressed in a lineage-specific distribution, with stronger expression for many in the exocrine compartment. The receptors were not often expressed until late gestation. Exogenous 9cRA induced predominantly ducts instead of acini, plus more mature endocrine (islet) architecture. Exogenous atRA induced predominantly acini instead of ducts, with no apparent endocrine effect. CONCLUSIONS: Retinoids may have an important role in pancreatic differentiation, with a particular effect on secondary lineage selection between ductal and acinar phenotype. Because the control of ductal versus acinar differentiation has been implicated strongly in the pathogenesis of pancreatic ductal carcinoma, these results may lay the groundwork for studies in the mechanism of induced differentiation of pancreatic ductal cancer by retinoids.

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

BACKGROUND/PURPOSE: The fistula tract in esophageal atresia with tracheoesophageal fistula (EA-TEF) appears to arise from a trifurcation of the embryonic lung bud. Subsequently, it does not branch like the other bronchi, which also arise from the lung bud. Previous results have implied that aberrant mesenchymal-epithelial signaling in the developing foregut, possibly involving fibroblast growth factors, may allow for the nonbranching growth of the fistula, and the ultimate development of the fistula tract in TEF. METHODS: Adriamycin injections into pregnant rat dams induced EA-TEF formation in rat embryos. Control and Adriamycin-exposed embryos were harvested on the 13th gestational day, and the developing foregut was isolated with microdissection. mRNA was isolated from the developing fistula tract, embryonic lung, and normal embryonic esophagus. Reverse transcription-polymerase chain reaction (RT-PCR) for the IIIb splice variant of the FGF2R receptor was performed. Foregut specimens also were processed for histologic analysis, and immunofluorescence for FGF1 was performed. RESULTS: FGF2R-IIIb is specifically absent from the developing fistula tract in TEF, whereas it is present in the normal developing lung and esophagus. FGF1 also is uniquely absent from the developing fistula tract, but it is present in the normal lung mesenchyme. CONCLUSIONS: FGF1, FGF7, and FGF10 are critical mesenchymal factors that mediate proliferation and branching morphogenesis by the developing respiratory epithelium. The absence of FGF2R-IIIb, the obligate common receptor for FGF7 and FGF10, from the fistula tract, and the absence of FGF1 in the fistula tract mesenchyme, collectively imply the absence of a specific FGF signaling pathway in the developing fistula tract. This absence of FGF signaling could explain the lack of branching by the developing fistula tract as it grows caudally in the abnormally developing embryo. Downregulation of these components of the FGF signaling pathways may allow for a patterned compensation by the embryo for the proximal foregut atresia in this anomaly. This compensation may then reestablish gastrointestinal continuity as the fistula tract connects to the developing stomach