David S. Chang

Enteric Fistulas: Principles of Management

In the past decade, surgeons have seen a quiet but dramatic shift in clinical patterns of enteric fistulas. Despite advances in nutritional care, infection control, and surgical technique, an enterocutaneous fistula (ECF) remains a source of considerable morbidity and mortality. In addition, wide adoption of damage control and the open abdomen in trauma and emergency surgery have confronted surgeons with a new and especially vicious adversary: the enteroatmospheric (or exposed) fistula (EAF). These fistulas, occurring in the midst of an open abdominal wound, are very difficult to control and present a particularly lethal challenge. Such EAFs might well be the most common type of enteric fistula facing surgeons today. Yet this shift in clinical patterns from the classic ECF to the new EAF is still totally disregarded in major surgical texts. The aim of this review is to present current principles in the management of enteric fistulas. Additionally, we will demonstrate how traditional principles of managing enteric fistulas help us to better understand the physiology and natural history of EAFs and to deal effectively with this new challenge.

Adeno-associated viral vector-mediated gene transfer of VEGF normalizes skeletal muscle oxygen tension and induces arteriogenesis in ischemic rat hindlimb

Critical limb ischemia is an important clinical problem that often leads to disability and limb loss. Vascular endothelial growth factor (VEGF), delivered either as recombinant protein or as gene therapy, has been shown to promote both collateral artery formation (arteriogenesis) and capillary angiogenesis in animal models of hindlimb ischemia. However, none of the previous studies has demonstrated an improvement in tissue hypoxia, the condition that drives the molecular response to ischemia. Furthermore, the optimal vector and route of gene delivery have not been determined. Recently, adeno-associated viral (AAV) vectors, which efficiently transduce skeletal muscle and produce sustained transgene expression, have been used as gene therapy vectors. We asked whether an intra-arterial injection of AAV-VEGF(165) normalizes muscle oxygen tension by increasing skeletal muscle oxygen tension, and promotes arteriogenesis and angiogenesis in a rat model of severe hindlimb ischemia. We found that AAV-VEGF treatment normalized muscle oxygen tension in the ischemic limb. In contrast, vehicle and AAV-lacZ-treated limbs remained ischemic. Collateral arteries were more numerous in AAV-VEGF-treated rats, but, surprisingly, capillaries were not. We conclude that intra-arterial AAV-mediated gene transfer of AAV-VEGF(165) normalizes muscle oxygen tension and leads to arteriogenesis in rats with severe hindlimb ischemia.

Implantable Venous Doppler Monitoring in Head and Neck Free Flap Reconstruction Increases the Salvage Rate

BACKGROUND Free flap success depends on rapid identification and subsequent salvage of failing flaps. Conventional free flap monitoring techniques require an external component, whereas an implantable monitor readily indicates changes in free flap perfusion, especially in buried flaps used in head and neck reconstruction. METHODS This is a retrospective review of 169 consecutive head and neck free flaps reconstructed mostly for oncologic surgical defects in 155 patients from April of 2000 to December of 2006, all of which were monitored by an implantable venous Doppler device. RESULTS There were 25 buried flaps, representing 14.8 percent of 169 flaps. Flap ischemia caused by thrombosis (n = 16), hematoma (n = 2), or tight closure (n = 1) occurred in 11.2 percent of the cases. The Doppler probe detected all of the failing free flaps, and we were able to salvage 18 of 19 ischemic flaps (94.7 percent). All Doppler-detected ischemic nonburied flaps (100 percent) and three of the four buried free flaps were salvaged (75 percent). There were 33 total complications (19.5 percent), with thrombosis occurring in 9.5 percent of the flaps, whereas 12 flaps required reoperation for vascular revision (7.1 percent). The mortality rate was less than 1 percent (0.6 percent). The overall success rate using the implantable Doppler probe was 98.2 percent, which was similar to that of the most recent reported cases of all free flaps in the literature, with significant improvement in the salvage rate for both buried and nonburied head and neck free flaps. CONCLUSION The implantable Doppler probe is a useful monitoring device in buried free flaps and should be considered for use in head and neck reconstruction.

Overexpression of endothelial nitric oxide synthase increases skeletal muscle blood flow and oxygenation in severe rat hind limb ischemia

OBJECTIVE Although nitric oxide (NO) has a critical role in angiogenesis, the therapeutic potential of NO synthase overexpression in severe ischemia remains undefined. We tested the hypothesis that overexpression of endothelial NO synthase (eNOS) would improve tissue perfusion in severe hind limb ischemia. METHODS Severe hind limb ischemia was induced in 122 adult male Sprague-Dawley rats. Ten days after the induction of hind limb ischemia, vascular isolation and intraarterial delivery of an adenoviral vector encoding eNOS (AdeNOS), a control adenoviral vector (AdE1), or phosphate-buffered saline solution (PBS) was performed. Skeletal muscle blood flow, muscle oxygen tension, angiography, and immunohistochemistry for capillary counts were measured. RESULTS Gene transfer of AdeNOS increased eNOS protein expression and enzyme activity. Two weeks after gene transfer, skeletal muscle blood flow was fourfold higher in eNOS-transduced than in AdE1-transduced or PBS treated rats and was similar to exercise-induced maximal flow in nonischemic muscle. eNOS overexpression increased muscle oxygen tension in a titer-dependent fashion. This increase persisted 1 month after transduction, even though eNOS enzyme activity had declined to normal levels. Angiography and capillary counts showed that eNOS overexpression increased the size and number of collateral arteries, but did not significantly increase the capillary-muscle fiber ratio. CONCLUSIONS eNOS overexpression in an ischemic rat hind limb significantly increased skeletal muscle blood flow, muscle oxygen tension, and collateral arteries (arteriogenesis). Furthermore, eNOS overexpression did not result in capillary angiogenesis above control levels. These studies demonstrate the potential for eNOS overexpression as treatment for severe limb ischemia in human beings.

The error of omission: a simple checklist approach for improving operating room safety.

Summary: The primary goal of patient safety must go hand in hand with the goal of producing reliably good aesthetic and functional results. The implementation of a proactive checklist improves operating room communication and takes the necessary step toward reducing the often neglected errors of omission. These steps are necessary if we are to ultimately achieve our goal of improving safety comprehensively in the operating room.

Therapeutic angiogenesis for critical limb ischemia: invited commentary.

Lower extremity arterial occlusive disease results in tissue ischemia of the legs and is relatively common in the elderly. Clinically, it may be asymptomatic, cause muscle pain during exercise, or progress to a severe degree of ischemia that may result in limb loss. Although bypass surgery and angioplasty have increased the rate of limb salvage in these patients, amputation of the affected limb remains a common outcome for many patients. Therapeutic angiogenesis is the administration of angiogenic factors, or genes encoding these factors, to promote neovascularization and thereby increase blood flow to the ischemic leg. We have developed an animal model of hindlimb ischemia in which to study therapeutic angiogenesis. We chose nitric oxide as the angiogenic factor for our experiments because of its ability to induce angiogenesis, vasodilation, and inhibit inflammation. In this review, we will discuss our experience with our model of hindlimb ischemia, as well as discuss our results of gene therapy for therapeutic angiogenesis using nitric oxide.

Transcriptional landscape of epithelial and immune cell populations revealed through FACS-seq of healthy human skin

Human skin consists of multiple cell types, including epithelial, immune, and stromal cells. Transcriptomic analyses have previously been performed from bulk skin samples or from epithelial and immune cells expanded in cell culture. However, transcriptomic analysis of bulk skin tends to drown out expression signals from relatively rare cells while cell culture methods may significantly alter cellular phenotypes and gene expression profiles. To identify distinct transcriptomic profiles of multiple cell populations without substantially altering cell phenotypes, we employed a fluorescence activated cell sorting method to isolate keratinocytes, dendritic cells, CD4+ T effector cells, and CD8+ T effector cells from healthy skin samples, followed by RNA-seq of each cell population. Principal components analysis revealed distinct clustering of cell types across samples, while differential expression and coexpression network analyses revealed transcriptional profiles of individual cell populations distinct from bulk skin, most strikingly in the least abundant CD8+ T effector population. Our work provides a high resolution view of cutaneous cellular gene expression and suggests that transcriptomic profiling of bulk skin may inadequately capture the contribution of less abundant cell types.

Open Incisional Hernia Repair at an Academic Tertiary Care Medical Center

OBJECTIVE To describe the postoperative complication rates of a large consecutive series of patients who underwent open incisional ventral hernia repair. DESIGN Retrospective medical record review of an accumulated database. SETTING University tertiary care medical center. PATIENTS All patients who underwent open incisional ventral hernia repair from March 1, 2003, through February 28, 2008. INTERVENTION Open incisional ventral hernia repair. MAIN OUTCOME MEASURES Postoperative complications, including hernia recurrences. RESULTS A total of 507 cases (465 patients; female to male ratio, 1.1:1) met our criteria; median follow-up was 40 months. In 23.5% of the cases, repair had been attempted previously, and 16.4% had previously undergone organ transplant. The postoperative complication rate was 38.1%. Hernias recurred in 18.9% of cases. Perioperative mortality was 1.0%. Patients undergoing transplant were more likely than those not undergoing transplant to have a hernia recurrence (16.3% vs 32.5%; P < .001) and were equally likely to have a postoperative complication (36.9% vs 44.6%; P = .19). Patients who underwent repair of a recurrent incisional hernia were as likely to have a hernia recurrence as those who underwent initial repair (21.0% vs 18.3%; P = .52) but more likely to have an overall complication (47.9% vs 35.1%; P = .01). CONCLUSIONS In this series of incisional hernia repairs at a tertiary care center, the overall recurrence rate of 18.9% is comparable to that of other published series. Ours is the largest published series of recurrent hernias that shows a recurrence rate comparable to that for initial repairs. This outcome may be the result of greater use of more complex repair techniques.