Three-Dimensional Imaging of the Enteric Nervous System in Human Pediatric Colon Reveals New Features of Hirschsprung's Disease.

BACKGROUND & AIMS: Hirschsprung's disease is defined by the absence of the enteric nervous system (ENS) from the distal bowel. Primary treatment is "pull-through" surgery to remove bowel that lacks ENS, with reanastomosis of "normal" bowel near the anal verge. Problems after pull-through are common, and some may be due to retained hypoganglionic bowel (ie, low ENS density). Testing this hypothesis has been difficult because counting enteric neurons in tissue sections is unreliable, even for experts. Tissue clearing and 3-dimensional imaging provide better data about ENS structure than sectioning. METHODS: Regions from 11 human colons and 1 ileal specimen resected during Hirschsprung's disease pull-through surgery were cleared, stained with antibodies to visualize the ENS, and imaged by confocal microscopy. Control distal colon from people with no known bowel problems were similarly cleared, stained, and imaged. RESULTS: Quantitative analyses of human colon, ranging from 3 days to 60 years old, suggest age-dependent changes in the myenteric plexus area, ENS ganglion area, percentage of myenteric plexus occupied by ganglia, neurons/mm2, and neuron Feret's diameter. Neuron counting using 3-dimensional images was highly reproducible. High ENS density in neonatal colon allowed reliable neuron counts using 500-µm2 × 500-µm2 regions (36-fold smaller than in adults). Hirschsprung's samples varied 8-fold in proximal margin enteric neuron density and had diverse ENS architecture in resected bowel. CONCLUSIONS: Tissue clearing and 3-dimensional imaging provide more reliable information about ENS structure than tissue sections. ENS structure changes during childhood. Three-dimensional ENS anatomy may provide new insight into human bowel motility disorders, including Hirschsprung's disease.

Outcomes of Surgical Treatment for Sural Neuritis: A Retrospective Case Series.

BACKGROUND: Somatic nerve pain is one of the most common complications following surgery of the foot and ankle but may also arise following traumatic injury or chronic nerve compression. The sural nerve is a commonly affected nerve in the foot and ankle; it is at risk given the proximity to frequently used surgical approaches, exposure to crush injuries, and traction from severe ankle inversion injuries. The purpose of this study is to investigate the outcomes of sural nerve neurectomy with proximal implantation for sural neuromas (SN) and chronic sural neuritis (CSN). METHODS: Patients that underwent neurectomy with proximal implantation (20 muscle, 1 adipose tissue) by 2 foot and ankle specialists for isolated SN- and CSN-related pain at a single tertiary institution were included. Demographic data, baseline outcomes including 36-Item Short Form Health Survey (SF-36), Foot and Ankle Ability Measure (FAAM), and visual analog scale (VAS) were recorded. Final follow-up questionnaires using Patient Reported Outcomes Measurement Information System (PROMIS) lower extremity function, pain interference (PI), and neuropathic pain quality, FAAM, and VAS were administered using REDCap. Perioperative factors including neuropathic medications, diagnostic injections, the use of collagen wraps, and perioperative ketamine were collected from the medical record. Descriptive statistics were performed and potential changes in patient-reported outcome measure scores were evaluated using Wilcoxon signed-rank tests. RESULTS: The 21 patients meeting inclusion criteria for this study had a median age of 47 years (interquartile range [IQR], 43-49) and had median follow-up duration of 33.7 months (IQR, 4.5-47.6). Median FAAM activities of daily living score improved from 40.6 (38.7-50.7) preoperatively to 66.1 (53.6-83.3) postoperatively, P = .032. FAAM sports scores improved from 14.1 (7.8-21.9) to 41.1 (25.0-60.9) postoperatively, P = .002. VAS scores improved from a median of 9.0 (8.0-9.0) to 3.0 (3.0-6.0), P < .001. At final follow-up, patients reported PROMIS lower extremity function score median of 43.8 (35.6-54.9), PROMIS neuropathic pain quality score of 54.1 (43.6-61.6), and PROMIS PI of 57.7 (41.1-63.8). Patients with both anxiety and depression reported less improvement in pain and physical. Other perioperative factors lacked sufficient numbers for statistical analysis. CONCLUSION: Sural nerve neurectomy and proximal implantation (20 muscle, 1 adipose) provided significant improvement in pain and function for patients with sural neuromas and chronic sural neuritis at median follow-up of 33.7 months. Anxiety and depression were associated with significantly poorer outcomes following surgery. Patients with CRPS as well as recent nicotine use tended to report less improvement in pain and worse function after surgery, although this sample size was too limited for statistical analysis of these variables. Further research is needed to identify the ideal surgical candidates and perioperative factors to optimize patient outcomes. LEVEL OF EVIDENCE: Level IV, retrospective case series.

The enteric nervous system relays psychological stress to intestinal inflammation.

Mental health profoundly impacts inflammatory responses in the body. This is particularly apparent in inflammatory bowel disease (IBD), in which psychological stress is associated with exacerbated disease flares. Here, we discover a critical role for the enteric nervous system (ENS) in mediating the aggravating effect of chronic stress on intestinal inflammation. We find that chronically elevated levels of glucocorticoids drive the generation of an inflammatory subset of enteric glia that promotes monocyte- and TNF-mediated inflammation via CSF1. Additionally, glucocorticoids cause transcriptional immaturity in enteric neurons, acetylcholine deficiency, and dysmotility via TGF-ß2. We verify the connection between the psychological state, intestinal inflammation, and dysmotility in three cohorts of IBD patients. Together, these findings offer a mechanistic explanation for the impact of the brain on peripheral inflammation, define the ENS as a relay between psychological stress and gut inflammation, and suggest that stress management could serve as a valuable component of IBD care.

Cellular Fibroma of Tendon Sheath With Novel TNC-USP6 Gene Fusion Clinically Mimicking Arthritis in a 7-Year-Old Boy.

Cellular fibroma of tendon sheath (CFTS) is a rare, benign myofibroblastic neoplasm of tenosynovial soft tissues closely resembling nodular fasciitis (NF), but is histomorphologically distinct from classic fibroma of tendon sheath (FTS). We report a case of a pediatric patient with thumb swelling clinically concerning for arthritis with a biopsy demonstrating myofibroblastic proliferation with features consistent with NF/CFTS, and molecular studies confirming the presence of a USP6 gene fusion (TNC-USP6). This case highlights a unique clinical presentation of CFTS in a pediatric patient mimicking an inflammatory or reactive/non-neoplastic musculoskeletal disorder and the increasingly crucial role of molecular testing to differentiate a reactive myofibroblastic process from a neoplasm. Moreover, this report identifies TNC as a new fusion partner to USP6 fusion partner adding to our growing understanding of the USP6-rearranged family of tumors.

Preoperative Chronic Opioid Therapy Negatively Impacts Long-term Outcomes Following Cervical Fusion Surgery.

STUDY DESIGN: Retrospective, observational. OBJECTIVE: The aim of this study was to define the impact of preoperative chronic opioid therapy (COT) on outcomes following cervical spine fusions. SUMMARY OF BACKGROUND DATA: Opioid therapy is a commonly practiced method to control acute postoperative pain. However, concerns exist relating to use of prescription opioids, including inherent risk of abuse, tolerance, and inferior outcomes following major surgery. METHODS: A commercial dataset was queried from 2007 to 2015 for patients undergoing primary cervical spine arthrodesis [ICD-9 codes 81.01-81.03]. Primary outcome measures were 1-year and 2-year reoperation rates, emergency department (ED) visits, adverse events, and prolonged postoperative opioid use. Secondary outcomes included short-term outcomes including 90-day complications (cardiac, renal, neurologic, infectious, etc.). COT was defined as a history of opioid prescription filling within 3 months before surgery and was the primary exposure variable of interest. Generalized linear models investigated the association of preoperative COT on primary/secondary endpoints following risk-adjustment. RESULTS: Overall, 20,730 patients (51.3% female; 85.9% >50 years) underwent primary cervical spine arthrodesis. Of these, 10,539 (n = 50.8%) met criteria for COT. Postoperatively, 75.3% and 29.8% remained on opioids at 3 months and 1 year. Multivariable models identified an association between COT and an increased risk of 90-day ED visit [odds ratio (OR): 1.25; P < 0.001] and wound complications (OR: 1.24; P = 0.036). At 1 year, COT was strongly associated with reoperations (OR: 1.17; P = 0.043), ED visits (OR: 1.31; P < 0.001), and adverse events including wound complications (OR: 1.32; P < 0.001), infections (OR: 1.34; P = 0.042), constipation (OR: 1.11; P = 0.032), neurological complications (OR: 1.44; P = 0.01), acute renal failure (OR: 1.24; P = 0.004), and venous thromboembolism (OR: 1.20; P = 0.008). At 2 years, COT remained a significant risk factor for additional long-term negative outcomes such as reoperations, including adjacent segment disc disease (OR: 1.21; P = 0.005), ED visits (OR: 1.32; P < 0.001), and other adverse events. Preoperative COT was associated with prolonged postoperative narcotic use at 3 months (OR: 1.30; P < 0.001), 1 year (OR: 5.17; P < 0.001), and at 2 years (OR: 5.75; P < 0.001) after cervical arthrodesis. CONCLUSION: Preoperative COT is a modifiable risk factor that is strongly associated with prolonged postoperative opioid use. In addition, COT was associated with inferior short-term and long-term outcomes after cervical spine fusion. LEVEL OF EVIDENCE: 3.

A Review of Tertiary Referrals for Management of Pediatric Esophageal Eosinophilia.

Background: Eosinophilic esophagitis is a chronic, immune-mediated disease characterized by symptoms of esophageal dysfunction and ≥15 eosinophils/high-powered field (eos/hpf). Proton pump inhibitor responsive esophageal eosinophilia (1) is an entity of esophageal eosinophilia that responds to PPI therapy and is thought to be clinically and histologically similar to EoE. Current guidelines suggest therapy with PPI prior to endoscopy and use of PPI as first line for esophageal eosinophilia. In order to gain a better understanding of community practice patterns and to try differentiate between these two entities, we sought to evaluate the clinical presentations, treatment and final diagnoses of patients presenting to our institution for second opinions of esophageal eosinophilia. Methods: A search of our electronic medical record yielded a list of patients presenting for a second opinion of esophageal eosinophilia. Charts were reviewed for clinical information. Results: A total of 187 charts were included. Patients ranged from 1-19 years old with 75% being male and 74% being Caucasian. Of the patients who had documentation of their medications at the time of initial endoscopy, 70% were not on any PPI prior to their endoscopy, and 94% were on <2 mg/kg/day. Of the 19 patients who had full response to PPI therapy and were diagnosed with PPI-REE, close to half had previously been treated with diet, steroids, or both. Patients with final diagnosis of EoE had significantly higher eos/hpf on initial endoscopy compared to those with diagnosis of PPI-REE (51.9 ± 30.6 v. 35.8 ± 16.4. p = 0.027), as well as higher likelihood of having IgE-mediated food allergy (79 v. 47%, p = 0.003). Conclusions: Diagnostic and therapeutic algorithms are needed for esophageal eosinophilia to prevent misdiagnosis and unnecessary procedures and therapies.

Effects of Episodic Alcohol Exposure on BMP2 Signaling During Tibia Fracture Healing.

OBJECTIVES: To explore how alcohol affects the BMP-2 signaling pathway, which is known to play a critical role in bone and cartilage formation during fracture healing. METHODS: A rat model was used to demonstrate the detrimental effects of alcohol exposure on tibia fracture healing. Specific components of the BMP-2 pathway were analyzed in fracture callus on days 3, 7, 14, and 21 after fracture via western immunoassays and enzyme-linked immunosorbent assay. RESULTS: Alcohol exposure before tibia fracture demonstrated attenuation of downstream BMP-2 signaling. The BMP-2 antagonist, Chordin, may be the central component of the BMP-2-related changes demonstrated in this study. Although alcohol affected BMP-related proteins at all time points, it seems that day 14 after fracture is a critical time point for alcohol-related modulation of callus formation in our model. CONCLUSIONS: This study may provide the scientific basis for further studies addressing whether the application of exogenous BMP-2 in patients with a history of alcohol abuse who sustain long bone fractures may or may not be of benefit.

Arterial protocol including prophylactic distal perfusion catheter decreases limb ischemia complications in patients undergoing extracorporeal membrane oxygenation.

OBJECTIVE: Venoarterial extracorporeal membrane oxygenation (ECMO) is a salvage therapy in patients with severe cardiopulmonary failure. Owing to the large size of the cannulas inserted via the femoral vessels (≤24-F) required for adequate oxygenation, this procedure could result in significant limb ischemic complications (10%-70%). This study evaluates the results of a distal limb perfusion arterial protocol designed to reduce associated complications. METHODS: We conducted a retrospective institutional review board-approved review of consecutive patients requiring ECMO via femoral cannulation (July 2010-January 2015). To prevent arterial ischemia, a distal perfusion catheter (DPC) was placed antegrade into the superficial femoral artery and connected to the ECMO circuit. Limb perfusion was monitored via near-infrared spectroscopy (NIRS) placed on both calves. Decannulation involved open repair, patch angioplasty, and femoral thrombectomy as needed. RESULTS: A total of 91 patients were placed on ECMO via femoral arterial cannula (16-F to 24-F) for a mean duration of 9 days (range, 1-40 days). A percutaneous DPC was inserted prophylactically at the time of cannulation in 55 of 91 patients, without subsequent ischemia. Of the remaining 36 patients without initial DPC placement, 12 (33% without DPC) developed ipsilateral limb ischemia related to arterial insufficiency, as detected by NIRS and clinical findings. In these patients, the placement of a DPC (n = 7) with or without a fasciotomy, or with a fasciotomy alone (n = 4), resulted in limb salvage; only one patient required subsequent amputation. After decannulation (n = 7), no patients had further evidence of limb ischemia. Risk factors for the development of limb ischemia identified by categorical analysis included lack of DPC at time of cannulation and ECMO cannula size of less than 20-Fr. There was a trend toward younger patient age. Overall ECMO survival rate was 42%, whereas survival in patients with limb ischemia was only 25%. CONCLUSIONS: Limb ischemia complications from ECMO may be decreased by prophylactic placement of an antegrade DPC. Without DPC, continuous monitoring using NIRS may identify limb ischemia, which can be treated subsequently with DPC and or fasciotomy.

Median Arcuate Ligament Syndrome-Review of This Rare Disease.

IMPORTANCE: Median arcuate ligament (MAL) syndrome is a rare disease resulting from compression of the celiac axis by fibrous attachments of the diaphragmatic crura, the median arcuate ligament. Diagnostic workup and therapeutic intervention can be challenging. OBJECTIVE: To review the literature to define an algorithm for accurate diagnosis and successful treatment for patients with MAL syndrome. EVIDENCE REVIEW: A search of PubMed (1995-September 28, 2015) was conducted, using the key terms median arcuate ligament syndrome and celiac artery compression syndrome. FINDINGS: Typically a diagnosis of exclusion, MAL syndrome involves a vague constellation of symptoms including epigastric pain, postprandial pain, nausea, vomiting, and weight loss. Extrinsic compression of the vasculature and surrounding neural ganglion has been implicated as the cause of these symptoms. Multiple imaging techniques can be used to demonstrate celiac artery compression by the MAL including mesenteric duplex ultrasonography, computed tomography angiography, magnetic resonance angiography, gastric tonometry, and mesenteric arteriography. Surgical intervention involves open, laparoscopic, or robotic ligament release; celiac ganglionectomy; and celiac artery revascularization. There remains a limited role for angioplasty because this intervention does not address the underlying extrinsic compression resulting in symptoms, although angioplasty with stenting may be used in recalcitrant cases. CONCLUSIONS AND RELEVANCE: Median arcuate ligament syndrome is rare, and as a diagnosis of exclusion, diagnosis and treatment paradigms can be unclear. Based on previously published studies, symptom relief can be achieved with a variety of interventions including celiac ganglionectomy as well as open, laparoscopic, or robotic intervention.

Delayed Gastric Emptying After Pancreaticoduodenectomy: an Analysis of Risk Factors and Cost.

INTRODUCTION: Delayed gastric emptying (DGE) is a common complication after pancreaticoduodenectomy (PD), yet it remains incompletely understood. The International Study Group of Pancreatic Surgery (ISGPS) in 2007 defined a three-tiered grading system to standardize studies of DGE. METHODS: In this study, 721 patients undergoing PD between 2006 and 2012 were retrospectively categorized by the ISGPS DGE criteria, as well as a modified grading system (termed primary DGE) if, on retrospective review, DGE was not believed to be a sequela of a separate complication. Predictive factors and associated outcomes were determined. RESULTS: ISGPS-defined DGE occurred in 140 (19.4%) patients. In a multivariate analysis, predictors of ISGPS-defined DGE included abdominal infection (odds ratio (OR) 5.5, p < 0.001), male gender (OR 1.92, p = 0.007), smoking history (OR 1.75 p = 0.033), and periampullary adenocarcinoma (OR 1.66, p = 0.041). Primary DGE occurred in 12.2% of patients. Predictors included abdominal infection (OR 3.15, p < 0.001) and smoking history (OR 2.04, p = 0.008). Median hospital charges increased over $10,000 with each severity grade of DGE (p < 0.001). CONCLUSION: DGE is common after PD and contributes substantially to cost. DGE is frequently a secondary complication of abdominal infection, and interventions that limit such complications may be the most effective strategy toward preventing DGE.

An interesting anatomic variant of inferior vena cava duplication: case report and review of the literature.

Congenital anomalies of the inferior vena cava (IVC) occur in roughly 4% of the population. We report an interesting case of an atypical variant of duplicated IVC. A 20-year-old man presented with orthopedic injuries and intracranial hemorrhage following a motorcycle accident. He was taken to the fluoroscopy suite for IVC filter placement; duplication of the IVC was noted. The right and left iliac veins shared a normal confluence but two IVCs drained independently into renal veins before reuniting into a single structure. Both IVC filters were placed via a single puncture in the groin. We performed a search of the PubMed database using' inferior vena cava duplication' and reviewed common anomalies of the IVC. Several variants of duplicated IVC exist; the most common of which is two distinct IVCs that arise from each iliac vein without a normal confluence. Our patient had a unique anomaly which allowed filter placements from a single puncture.

Coral reef aorta: case report and review of the literature.

Coral reef aorta (CRA) is a rare form of atherosclerosis that affects the paravisceral and pararenal aorta and its branches. Patients typically present with arterial insufficiency of the bowels, kidneys and lower extremities. The current mainstay of treatment is operative, typically involving transaortic endarterectomy. Herein, we describe a 54-year-old woman with incapacitating lower extremity claudication secondary to a paravisceral coral reef atheroma treated successfully with transaortic endarterectomy via a left retroperitoneal approach. In addition, we present a complete review of modern English literature on CRA.

Results of polytetrafluoroethylene-covered nitinol stents crossing the inguinal ligament.

OBJECTIVE: Placement of arterial endoprostheses across the inguinal ligament is generally thought to be contraindicated for fear of device kinking, fracture, or occlusion and possible obliteration of the deep femoral artery (DFA). We present a series of selected patients who underwent insertion of polytetrafluoroethylene-covered nitinol stents (Viabahn stent grafts. W. L. Gore and Associates Inc, Flagstaff, Ariz) crossing the middle common femoral artery (CFA) on an emergency basis or who were considered high risk for open surgery. METHODS: We treated 16 patients with 17 lesions adjacent to or within the CFA with stent grafts that originated in the common iliac (two) or external iliac (15) artery and terminated in the distal CFA (12), DFA (three), or superficial femoral (two) artery. Stent grafts were placed on an elective (10) or emergency (seven) basis for arterial occlusive disease (10), bleeding (six), and aneurysmal disease (one). Comorbidities favoring endovascular treatment were high medical risk (10) previous scarring (four), morbid obesity (two), and dense arterial calcification precluding open surgical repair (one). RESULTS: The DFA was deliberately sacrificed in one of the 17 cases. No patient suffered major complications after the procedure. All grafts remained patent based on duplex ultrasound imaging during follow-up (mean, 12.3 months; range, 1-58 months). Two patients required an additional endovascular intervention to treat inflow or outflow stenoses during follow-up, yielding a 2-year primary patency rate of 93.8% and assisted primary patency rate of 100%. CONCLUSIONS: These results suggest that selective placement of Viabahn stent grafts across the inguinal ligament to treat arterial occlusive disease or bleeding may prove to be safe, effective, and associated with acceptable patency rates. This strategy helps avoid complicated open arterial surgery in high-risk patients with associated multiple medical risk factors or hostile scarred groins.

Contained rupture of a pseudoaneurysm of the descending thoracic aorta related to remnant outflow graft of left ventricular assist device after heart transplantation.

The Jarvik 2000 left ventricular assist device is inserted via a left thoracotomy with the outflow graft anastomosed to the descending thoracic aorta. Removal of the device during heart transplantation involves division of the outflow graft, resulting in a retained remnant. We describe the first reported case of a mycotic pseudoaneurysm of the descending thoracic aorta related to the remnant of a left ventricular assist device outflow graft in an immunosuppressed heart recipient complicated with systemic Pseudomonas infection. The pseudoaneurysm was temporarily treated with endovascular stent grafting followed by delayed thoracotomy, pseudoaneurysm excision, and placement of an aortic interposition graft using an aortic allograft.

Management of infected caval filter with simultaneous aortic pseudoaneurysm and retroperitoneal perforation: a case report and literature review.

Inferior vena cava (IVC) filters have been reported to have complication rates up to 35%. Penetration of surrounding retroperitoneal structures is an uncommon, but potentially serious, complication, with several reports in the literature. We present a unique case of a 34-year-old intravenous drug user with infected IVC filter struts penetrating multiple structures simultaneously. Definitive operative management was necessary for removal of filter struts from the aorta, the second part of the duodenum and the iliopsoas muscle. Drainage and debridement of an associated iliopsoas abscess was performed, followed by aortic and caval reconstruction.

Robotic-assisted median arcuate ligament release.

Median arcuate ligament syndrome results from external compression of the celiac axis by attachments of the diaphragmatic crura. It has been treated with open or laparoscopic surgical decompression of the celiac axis with neurolysis. We describe our initial experience treating three patients using a robotic-assisted technique with median arcuate ligament release and celiac neurolysis. Average operative time was 2.2 hours. No intraoperative complications occurred. At an average of 11 months postoperative (14, 11, and 8 months), two patients continue with resolution of preoperative symptoms. Our experience affirms that further study using the robotic approach appears warranted.

An unusual cause of venous hypertension after dialysis access creation.

Venous hypertension after creation of arteriovenous fistula or arteriovenous shunt occurs in approximately 10-15% of patients (Kojecky et al., Biomed Papers, 2002;146:77-79; Criado et al., Ann Vasc Surg 1994;8:530-535). Its etiology is commonly stenosis and/or thrombosis of the central venous system secondary to previous catheterization with subsequent development of venous hypertension after the arteriovenous connection is made. Treatment strategies often involve venography to determine the site of venous stenosis and/or occlusion centrally and subsequent endovascular recanalization of the stenotic or occluded veins. In this article, we report a case of venous hypertension in a 76-year-old man who presented with a swollen arm after placement of an arteriovenous fistula. In this circumstance, venography revealed extrinsic compression of the subclavian vein at the level of the first rib, the anatomic abnormality seen in venous thoracic outlet syndrome. In this report, we describe surgical and endovascular management of this patient, and review the literature on the causes of central vein stenosis discovered after creation of dialysis access.