Early versus delayed ileocolic resection for complicated Crohn's disease: is "cooling off" necessary?

BACKGROUND: Ileal Crohn's disease (CD) complicated by intraabdominal abscess, phlegmon, fistula, and/or microperforation is commonly treated with antibiotics, bowel rest, and percutaneous drainage followed by interval ileocolic resection (ICR). This "cool off" strategy is intended to facilitate the safe completion of a one-stage resection using a minimally invasive approach and minimize perioperative complications. There is limited data evaluating the benefits of delayed versus early resection. METHODS: A retrospective review of a prospectively maintained inflammatory bowel disease (IBD) database at a tertiary center was queried from 2013-2020 to identify patients who underwent ICR for complicated ileal CD confirmed on preoperative imaging. ICR cohorts were classified as early (≤ 7 days) vs delayed (> 7 days) based on the interval from diagnostic imaging to surgery. Operative approach and 30-day postoperative morbidity were analyzed. RESULTS: Out of 474 patients who underwent ICR over the 7-year period, 112 patients had complicated ileal CD including 99 patients (88%) with intraabdominal abscess. Early ICR was performed in 52 patients (46%) at a median of 3 days (IQR 2, 5) from diagnostic imaging. Delayed ICR was performed in 60 patients (54%) following a median "cool off" period of 23 days of non-operative treatment (IQR 14, 44), including preoperative percutaneous abscess drainage in 17 patients (28%). A higher proportion of patients with intraabdominal abscess underwent delayed vs early ICR (57% vs 43%, p = 0.19). Overall, there were no significant differences in the rate of laparoscopy (96% vs 90%), conversion to open surgery (12% vs 17%), rates of extended bowel resection (8% vs 13%), additional concurrent procedures (44% vs 52%), or fecal diversion (10% vs 2%) in the early vs delayed ICR groups. The median postoperative length of stay was 5 days in both groups with an overall 25% vs 17% (p = 0.39) 30-day postoperative complication rate and a 6% vs 5% 30-day readmission rate in early vs delayed ICR groups, respectively. Overall median follow-up time was 14.3 months (IQR 1.2, 24.1) with no difference in the rate of subsequent CD-related intestinal resection (4% vs 5%) between the two groups. CONCLUSIONS: In this contemporary series, at a high-volume tertiary referral center, a "cool off" delayed resectional approach was not found to reduce perioperative complications in patients undergoing ICR for complicated ileal Crohn's disease. Laparoscopic ICR can be performed within one week of diagnosis with low rates of conversion and postoperative complications.

A Quantitative Analysis of Facial Asymmetry in Torticollis Using 3-Dimensional Photogrammetry.

OBJECTIVE: To assess whether children with torticollis have quantifiably greater facial asymmetry than their age-matched controls using 3-dimensional (3D) photogrammetry. DESIGN: We retrospectively analyzed patients diagnosed with torticollis and age-matched volunteers who underwent 3D photogrammetry of their faces. We calculated the root mean square deviation (RMSD) between native and reflected facial images, as a measure of asymmetry. Two observers independently measured RMSD values for all study participants. The Spearman correlation coefficient evaluated interobserver reliability. The Wilcoxon rank-sum test with Bonferroni adjusted P values for multiple comparisons. SETTING: Institutional. PARTICIPANTS: Twenty patients diagnosed with torticollis and 12 age-matched volunteers. Patients were analyzed on a computer database and volunteers were selected and consented in the hospital. We excluded patients with a history of facial trauma, facial operations, or other craniofacial diagnoses. INTERVENTIONS: Facial surface scans were obtained using the Canfield Vectra stereophotogrammetry system. The technology captures surface anatomy without radiation. MAIN OUTCOME MEASURES: RMSD comparisons between patients with torticollis and age-matched controls. RESULTS: Compared to controls, patients with torticollis had statistically significant greater full face, upper third, and middle third facial asymmetry. There was a trend toward greater asymmetry of the lower facial third. CONCLUSIONS: We used 3D photogrammetry to quantitate facial asymmetry from torticollis. We found greater asymmetry in patients with torticollis than in their unaffected peers. All areas of the face appeared to be affected, though the asymmetry in the lower facial third just failed to reach significance.

The role of laparoscopic surgery in repeat ileocolic resection for Crohn's disease.

AIM: Laparoscopic surgery is the preferred approach for primary uncomplicated ileocolic resection (ICR); however, its role for repeat resections is unclear. This study assessed the outcomes of primary and repeated ICRs for Crohn's disease to examine rates of laparoscopy and patient morbidity. METHODS: A retrospective review of a prospectively maintained database was conducted at a tertiary centre between 2013 and 2019. All patients undergoing ICRs for Crohn's disease were included. The cohort was divided into three groups based on number of resections-primary (1R), secondary (2R) and tertiary or more (>2R) groups. The primary outcome was 30-day postoperative morbidity. RESULTS: Over a 6-year period, 474 patients underwent ICR for Crohn's disease, including 369 primary (1R, 77.8%) and 105 repeat (≥2R, 22.2%) resections. A laparoscopic approach was less common in the ≥2R versus 1R groups (79.0% vs. 93.8%, P < 0.001), but rates of conversion to an open procedure were comparable. Morbidity was higher amongst repeat resections although this was not significant (20.0% vs. 14.1%, P = 0.18). Amongst cases approached laparoscopically (n = 429), rates of conversion and postoperative morbidity did not differ by stage of resection, although operative time was longer for repeat operations. Even in the group undergoing laparoscopy for tertiary or greater resections (>2R, n = 29), the rates of conversion (10%) and morbidity (14%) were relatively low. CONCLUSION: In this contemporary series of primary and reoperative ICR for ileal CD, a laparoscopic approach is feasible and safe for the majority of repeat ICRs when performed at a high volume centre.

Penicillin G Induces H+, K+-ATPase via a Nitric Oxide-Dependent Mechanism in the Rat Colonic Crypt.

BACKGROUND/AIMS: The colonic H+, K+ ATPase (HKA2) is a heterodimeric membrane protein that exchanges luminal K+ for intracellular H+ and is involved in maintaining potassium homeostasis. Under homeostatic conditions, the colonic HKA2 remains inactive, since most of the potassium is absorbed by the small intestine. In diarrheal states, potassium is secreted and compensatory potassium absorption becomes necessary. This study proposes a novel mechanism whereby the addition of penicillin G sodium salt (penG) to colonic crypts stimulates potassium uptake in the presence of intracellular nitric oxide (NO), under sodium-free (0-Na+) conditions. METHODS: Sprague Dawley rat colonic crypts were isolated and pHi changes were monitored through the ammonium prepulse technique. Increased proton extrusion in 0-Na+ conditions reflected heightened H+, K+ ATPase activity. Colonic crypts were exposed to penG, L-arginine (a NO precursor), and N-nitro l-arginine methyl ester (L-NAME, a NO synthase inhibitor). RESULTS: Isolated administration of penG significantly increased H+, K+ ATPase activity from baseline, p 0.0067. Co-administration of arginine and penG in 0-Na+ conditions further upregulated H+, K+ ATPase activity, p <0.0001. Crypt perfusion with L-NAME and penG demonstrated a significant reduction in H+, K+ ATPase activity, p 0.0058. CONCLUSION: Overall, acute exposure of colonic crypts to penG activates the H+, K+ ATPase in the presence of NO. This study provides new insights into colonic potassium homeostasis.

Cellular Angiofibroma Presenting as a Subepithelial Rectal Mass.

A very rare case of cellular angiofibroma arising from the rectum in a 62-year-old man with a normal colonoscopy 2 years earlier is reported. To our knowledge, this is the first such case reported in the literature. The tumor was transanally excised with clear margins, and the patient had no postoperative complications. It is key to accurately differentiate this lesion from other subepithelial rectal tumors and more aggressive genital soft tissue tumors because clinical management varies. We performed a review of clinical records and pathology as well as an extensive literature review.

Glucocorticoids and serum- and glucocorticoid-inducible kinase 1 are potent regulators of CFTR in the native intestine: implications for stress-induced diarrhea.

Nongenomic glucocorticoid (GC) and serum- and glucocorticoid-inducible kinase 1 (SGK1) signaling regulate ion transport, but CFTR has not been investigated in the intestine. We examined GC, SGK1, and phosphatidylinositol 3-kinase (PI3K) kinase signaling of CFTR ion transport in native intestine and the role of GCs on mRNA, protein, surface expression, and cyclic guanosine monophosphate (cGMP)-elicited diarrhea. Rats were treated with dexamethasone (DEXA; 2 mg/kg ip) or DMSO for 1, 4, and 24 h. Cyclic adenosine monophosphate (cAMP)-activated ion transport was examined in the presence or absence of SGK1 and PI3K inhibitors. Phosphorylation of SGK1, phosphoinositide-dependent kinase 1, and Akt kinases was confirmed by immunoblots using phosphor-specific antibodies. Tissue lysates were analyzed by mass spectrometry. CFTR and SGK1 mRNA were measured by quantitative PCR. Changes in total and surface CFTR protein were determined. The role of GC in cGMP-activated CFTR ion transport was examined. GC synergistically increased CFTR ion transport by SGK1 and PI3K signaling and increased CFTR protein without altering SGK1 or CFTR mRNA. GC induced highest levels of CFTR protein at 4 h that were associated with marked increase in surface CFTR, phosphorylation of the ubiquitin ligase neural precursor cell expressed developmentally downregulated 4-like (Nedd4-2), and 14-3-3ε, supporting their roles in surface retention and stability. Coimmunoprecipitation of CFTR, Nedd4-2, and 14-3-3ε indicated that assembly of this complex is a likely effector of the SGK and Akt pathways. Mass spectrometry identified phosphorylated peptides in relevant proteins. GC-SGK1 potently regulates CFTR in the intestine and is implicated in diarrheal disease.NEW & NOTEWORTHY This is the first study to examine the mechanisms of glucocorticoid, serum- and glucocorticoid-inducible kinase 1, and nongenomic kinase signaling of CFTR in the native intestine. We identified unique and druggable intestine-specific factors of the pathway that are targets for treating stress-induced diarrhea.

Application of Advanced Bioinformatics to Understand and Predict Burnout Among Surgical Trainees.

OBJECTIVE: Physician burnout, including surgical trainees, is multidimensional. Input variables used to predict burnout include grit, exhaustion, and financial stress. Each instrument has intrinsic limitations of scope and strength. We hypothesize that bioinformatics methods borrowed from oncogenetics may allow meta-analysis of existing predictive tools to improve identification of subpopulations at highest risk of burnout. DESIGN: A composite survey was created using widely accepted instruments: demographic factors, burnout using the Single-Item Maslach Burnout Inventory Emotional Exhaustion Measure, grit using the Duckworth Grit Scale, occupational fatigue using the Occupational Fatigue Exhaustion/Recovery Scale, financial well-being, perceptions of physician leadership, and attitudes towards robotic surgery. Surveys were analyzed using k-means analysis and supervised/unsupervised clustering. SETTING: Yale General Surgery Residency. PARTICIPANTS: Survey participants consisted of Yale General Surgery residents. Of 70 residents, 53 responded (75.7%). Males comprised 57.1% and each postgraduate year had majority representation, 68.8% to 100%. RESULTS: Unsupervised hierarchical clustering showed heterogeneous resident answer patterns and suggested clusters of responders. To define groups of dissimilar responders, we performed k-means clustering, testing 15 iterations with 50 attempts. The analysis revealed 3 discrete clusters of responders with differential risk for burnout (p = 0.021). The highest risk group demonstrated the lowest grit score, low interest in innovation and leadership, higher financial stress, and concordantly, the highest rates of anxiety, dread, and self-reported burnout. (p = 0.0004; 0.0014; 0.1217; 0.0625; 0.021; 0.0011; 0.0224) CONCLUSIONS: The limited scope of common tools aiming to predict burnout constrains their utility. The machine-learning technique of cluster analysis organizes compound data to describe complex outcomes such as oncologic risks. We apply this analysis technique to create a composite predictor of burnout among surgical residents. Our method determines subgroups of residents sharing unique traits predictive of burnout. Residencies can use this tool to allocate resources to best support resident well-being.

Robotic cholecystectomy and cholecystoenteric fistula closure in a female with remote cholangitis.

Cholecystocolic fistula (CCF), a connection between the gallbladder and neighboring colon, is a rare entity with little consensus as to the optimal surgical management. Existing case reports have described both open and laparoscopic repairs. We describe the first reported case of a successful robotic repair of a CCF in a 50-year-old woman diagnosed with cholangitis 5 years prior to surgery. The patient had a longitudinal follow-up by a single surgeon, allowing for early diagnosis and repair. This case also includes radiographic imaging over 5 years during the index hospitalization and preoperative workup. This allows for a glimpse into the natural pathogenesis of this disease. After robotic surgery, the patient made a complete recovery with no postoperative complications.

Activation of the Calcium Sensing Receptor Decreases Secretagogue-Induced Fluid Secretion in the Rat Small Intestine.

BACKGROUND: The calcium-sensing receptor (CaSR) has been localized and characterized in numerous tissues throughout the body. In the mammalian gastrointestinal tract, the CaSR is known to act as a nutrient sensor and has recently been found to play a role in intestinal fluid and electrolyte balance. This study aims to demonstrate the functionality of the CaSR as a modulator of fluid secretion and absorption along the small intestine. METHODS: Small intestine regions (proximal, middle, and distal) were isolated from Sprague Dawley rats and loaded into an ex vivo intestinal perfusion device that provides independent intraluminal and extraluminal (serosa/basolateral) perfusion. The regions were perfused with 5 and 7 mM of Ca2+, both in the presence and absence of forskolin (FSK), a potent secretagogue. Control experiments were conducted with intraluminal perfusate containing standard Ringer-HEPES buffer with a physiological concentration of Ca2+ (1 mM). A second set of comparison experiments was performed with intraluminal perfusates containing AC-265347, a CaSR activator and agonist, in the presence of FSK. In all experimental conditions, the intraluminal perfusate contained fluorescein isothiocyanate (FITC)-inulin, a nonabsorbable fluorescent marker of secretion and/or absorption. Intraluminal fluorescence signal was utilized as a measure of water movement at the start of the experiment and every 15 min for 90 min. RESULTS: Under physiological conditions, increasing the concentration of Ca2+ in the luminal perfusate reduced intestinal fluid secretion in all regions. At a Ca2+ concentration of 7 mM, net fluid absorption was observed in all regions. In the presence of FSK, 5 mM Ca2+ significantly decreased fluid secretion and 7 mM Ca2+ abolished FSK-induced fluid secretion. Intraluminal perfusion with 5 mM Ca2+ was as effective as AC-265347, in reducing secretagogue-induced fluid hypersecretion in the proximal and middle regions. CONCLUSION: This study concludes that apical CaSR is active along the small intestine. Its activation by Ca2+ and/or calcimimetics reduces fluid secretion in a dose-dependent manner, with higher Ca2+ concentrations, or application of a calcimimetic, leading to fluid absorption. We furthermore show that, in the presence of FSK, receptor activation abates FSK secretagogue-induced fluid secretion. This presents a new therapeutic target to address secretory diarrheal illnesses.

Design and implementation of novel nutraceuticals and derivatives for treating intestinal disorders.

Gastrointestinal illnesses pose a significant worldwide disease burden and are associated with an array of medicinal and surgical therapies. Standard pharmaceutical options have adverse effects, prompting the rise of nutraceutical or food-derivative therapies. Here, we present an overview of the current nutraceutical therapies in gastrointestinal disease. We then introduce the calcium-sensing receptor (CaSR) as a novel therapeutic target. A G-protein-coupled receptor found in apical and basal intestinal cells, the CaSR modulates intestinal fluid secretion and mucosal integrity. Applying nutraceuticals that upregulate the CaSR may alleviate symptoms seen across a spectrum of illnesses. At last, we discuss how nanoparticle technology can be implemented to effectively deliver nutraceuticals to diseased regions of the intestine, thereby minimizing systemic side effects.

Surgical Correction of Metopic Craniosynostosis: A 3-D Photogrammetric Analysis of Cranial Vault Outcomes.

OBJECTIVE: To evaluate 3-dimensional (3-D) photogrammetry as a tool for assessing the postoperative head shape of patients who had undergone cranial vault remodeling for metopic synostosis. DESIGN: We prospectively analyzed images of patients with metopic craniosynostosis who had undergone anterior cranial vault remodeling and age-matched controls. To ensure standardized facial orientation, each 3-D image was positioned to "best fit" the preoperative face by aligning 6 soft tissue landmarks. Forehead measurements were taken from a standardized position behind the surface of the face to landmarks placed in a ray configuration across the forehead. SETTING: Academic teaching hospital. PATIENTS, PARTICIPANTS: Thirteen pediatric patients with metopic craniosynostosis who had undergone anterior cranial vault remodeling and age-matched controls. INTERVENTIONS: Images were taken preoperatively, immediately postoperatively, and over 1-year postoperatively. MAIN OUTCOME MEASURES: Forehead contours preoperatively and postoperatively, with statistics performed using a multivariate analysis of variance shape analysis. RESULTS: Mean postoperative follow-up was 1.8 (0.6) years. The average distance from the origin to forehead landmarks was 55.1 (3.4) mm preoperatively, 59.3 (0.7) mm immediate postoperatively, 59.1 (1.0) mm 1-year postoperatively, and 59.4 (0.6) mm in controls. Postoperative metopic forehead contours varied significantly from preoperative contours ( P < .01), while there was no statistical difference between the 2 postoperative time points ( P = .70). One-year postoperative patients were not significantly different from their age-matched controls ( P > .99). CONCLUSIONS: Preoperative metopic forehead contours varied significantly from postoperative contours. Cranial reconstructions approximated the foreheads of normal controls, and reconstructions were stable at more than 1-year follow-up.

In Pursuit of the Parietal Cell - An Evolution of Scientific Methodology and Techniques.

The stomach has unique embryologic and anatomic properties, making the study of the parietal cell technically challenging. Numerous individuals have devoted decades of research to unraveling the pathophysiological basis of this cell type. Here, we perform a scoping review of novel in vitro and in vivo methodology pertaining to the parietal cell. First, we evaluate early in vitro methods of parietal cell analysis. This section focuses on three major techniques: gastric gland isolation, parietal cell isolation, and parietal cell culture. We also discuss parietal cell physiology and pathophysiology. Second, we discuss more contemporary efforts involving confocal microscopy and gastric organoids, a new technique that holds much promise in unveiling the temporal-spatial dynamics of the cell. Finally, we will discuss findings from our laboratory where we identified an active gastric vacuolar H+-ATPase as a putative mechanism for refractory GERD. Overall, this review aims to highlight the major milestones in understanding an elusive yet important cell. Though in no way comprehensive, we hope to provide a birds-eye view to the study of this unique cell type in the gastrointestinal tract.

Lobectomy for Lung Cancer at Veterans Administration Medical Center Versus Academic Medical Center.

BACKGROUND: Hospital and surgeon volume each have an association with postoperative outcomes. The volume of lung cancer surgery at our Veterans Administration Medical Center (VAMC) is lower than at our academic medical center (AMC). We compared the outcomes after lobectomy at VAMC versus AMC to identify specific areas of clinical care requiring quality improvement. METHODS: To keep surgeon experience constant, data were derived from a prospective database from a single surgeon. Included were all male patients undergoing lobectomy for non-small cell lung cancer. Postoperative morbidity, mortality, and overall survival were compared after propensity score matching. RESULTS: From 2004 to 2013, 419 patients were evaluated (338 AMC, 81 VAMC). Outcomes comparison after propensity score matching of 81 AMC patients with 81 VAMC patients found a higher rate of major complications (12% versus 27%, p = 0.02) and longer hospital stay (median 6.0 versus 7.5 days, p < 0.001) for VAMC, but no difference in 90-day mortality (AMC 5% versus VAMC 6%, p > 0.99). Pneumonia was the specific complication found to be higher at VAMC (11% versus AMC 1.2%, p = 0.01). There was no difference in 5-year overall survival for stage I disease (AMC 68% versus VAMC 69%, p = 0.95). CONCLUSIONS: Keeping surgeon experience constant, and after adjusting for patient factors, the rate of major complication after lobectomy is higher at VAMC. The difference is largely attributable to a higher rate of postoperative pneumonia at VAMC. Complications after pulmonary resection at VAMC could be reduced by implementing quality improvement initiatives aimed at reducing the rate of postoperative pneumonia.