Critical Role of CD55 in Controlling Wound Healing.

How reparative processes are coordinated following injury is incompletely understood. In recent studies, we showed that autocrine C3a and C5a receptor (C3ar1 and C5ar1) G protein-coupled receptor signaling plays an obligate role in vascular endothelial growth factor receptor 2 growth signaling in vascular endothelial cells. We documented the same interconnection for platelet-derived growth factor receptor growth signaling in smooth muscle cells, epidermal growth factor receptor growth signaling in epidermal cells, and fibroblast growth factor receptor signaling in fibroblasts, indicative of a generalized cell growth regulatory mechanism. In this study, we examined one physiological consequence of this signaling circuit. We found that disabling CD55 (also known as decay accelerating factor), which lifts restraint on autocrine C3ar1/C5ar1 signaling, concomitantly augments the growth of each cell type. The mechanism is heightened C3ar1/C5ar1 signaling resulting from the loss of CD55's restraint jointly potentiating growth factor production by each cell type. Examination of the effect of lifted CD55 restraint in four types of injury (burn, corneal denudation, ear lobe puncture, and reengraftment of autologous skin) showed that disabled CD55 function robustly accelerated healing in all cases, whereas disabled C3ar1/C5ar1 signaling universally retarded it. In wild-type mice with burns or injured corneas, applying a mouse anti-mouse CD55 blocking Ab (against CD55's active site) to wounds accelerated the healing rate by 40-70%. To our knowledge, these results provide new insights into mechanisms that underlie wound repair and open up a new tool for accelerating healing.

Characterization of long-term prognosis in acute pancreatitis: An explorative analysis.

BACKGROUND/OBJECTIVES: Severity classification systems of acute pancreatitis (AP) assess inpatient morbidity and mortality without predicting outpatient course of AP. To provide appropriate outpatient care, determinants of long-term prognosis must also be identified. The aim of this study was to define clinical groups that carry long-term prognostic significance in AP. METHODS: A retrospective study that included patients admitted with AP was conducted. Determinants of long-term prognosis were extracted: These included Revised Atlanta and Determinant Based Classification (RAC), Charlson Comorbidity Index (CCI), Modified CT Severity Index (MCTSI), etiology, and local complications (LCs). Seven surrogates of morbidity up to 1 year after discharge were also collected and subsequently imputed into a clustering algorithm. The algorithm was set to produce three categories and multinomial regression analysis was performed. RESULTS: 281 patients were included. The incidences of morbidity endpoints were similar among the 3 RAC categories. Three clusters were identified that carried long-term prognostic significance. Each cluster was given a name to reflect prognosis. The limited AP had the best prognosis and included patients without LCs with a low co-morbidity burden. The brittle AP had a low co-morbidity burden and high MCTSI (LCs 94%). It ran a very morbid course but had excellent survival. The high-risk AP had the worst prognosis with the highest mortality rate (28%). They had a high co-morbidity burden without local complications. CONCLUSION: Categories that carry long-term prognostic significance in AP have been developed. This study could help formulate appropriate follow-up and ultimately improve AP outcomes.

Multicenter evaluation of the clinical utility of laparoscopy-assisted ERCP in patients with Roux-en-Y gastric bypass.

BACKGROUND AND AIMS: The obesity epidemic has led to increased use of Roux-en-Y gastric bypass (RYGB). These patients have an increased incidence of pancreaticobiliary diseases, yet standard ERCP is not possible because of surgically altered gastroduodenal anatomy. Laparoscopy-assisted ERCP (LA-ERCP) has been proposed as an option, but supporting data are derived from single-center small case series. Therefore, we conducted a large multicenter study to evaluate the feasibility, safety, and outcomes of LA-ERCP. METHODS: This is a retrospective cohort study of adult patients with RYGB who underwent LA-ERCP in 34 centers. Data on demographics, indications, procedure success, and adverse events were collected. Procedure success was defined when all the following were achieved: reaching the papilla, cannulating the desired duct, and providing endoscopic therapy as clinically indicated. RESULTS: A total of 579 patients (median age, 51; 84% women) were included. Indication for LA-ERCP was biliary in 89%, pancreatic in 8%, and both in 3%. Procedure success was achieved in 98%. Median total procedure time was 152 minutes (interquartile range [IQR], 109-210), with a median ERCP time of 40 minutes (IQR, 28-56). Median hospital stay was 2 days (IQR, 1-3). Adverse events were 18% (laparoscopy related, 10%; ERCP related, 7%; both, 1%) with the clear majority (92%) classified as mild/moderate, whereas 8% were severe and 1 death occurred. CONCLUSIONS: Our large multicenter study indicates that LA-ERCP in patients with RYGB is feasible with a high procedure success rate comparable with that of standard ERCP in patients with normal anatomy. The ERCP-related adverse events rate is comparable with conventional ERCP, but the overall adverse event rate was higher because of the added laparoscopy-related events.

Medial-to-Lateral Approach to the Splenic Flexure Resection and End Transverse Colostomy: A Case Report and Operative Video.

Splenic flexure cancer is relatively rare among colon cancers. We present a case of a 76-year-old female with a partially obstructing tumor in the proximal descending colon and pulmonary metastasis who underwent a laparoscopic resection of the splenic flexure with end transverse colostomy due to clinical symptoms of obstruction. This case highlights several important technical considerations in safely performing the laparoscopic resection of the splenic flexure through the medial-to-lateral approach starting at the plane below the inferior mesenteric vein (IMV), taking care to preserve the tail of the pancreas. We present a narrated video demonstrating our approach, taking care to highlight important anatomic landmarks.

Recurrent midgut volvulus in an 83-year-old female.

We present a rare case of recurrent primary midgut volvulus in an elderly female with an interesting intraoperative finding of an abnormally elongated small bowel mesentery. This patient presented with symptoms of obstruction, including nausea, vomiting and obstipation, similar to previous episodes of volvulus for which she underwent exploratory laparotomies and reduction of the volvulus. We describe a novel use for enteropexy in which we effectively shortened the small bowel mesentery in an effort to eliminate the source of recurrent volvulus. The patient's post-operative course was complicated by prolonged ileus requiring total parenteral nutrition. However, she had not developed signs or symptoms of bowel ischemia or recurrent volvulus at the time of this writing. Our findings suggest that enteropexy is an effective technique for preventing recurrent midgut volvulus primarily caused by abnormally elongated mesentery.

Outcomes of endoscopic treatment of leaks and fistulae after sleeve gastrectomy: results from a large multicenter U.S. cohort.

BACKGROUND: Sleeve gastrectomy is the most commonly performed bariatric surgery in the United States. Leaks after sleeve gastrectomy (SGL) occur in 1% to 3% of patients. Endoscopic therapies are increasingly used for treatment of SGLs, but few data exist on their outcomes. OBJECTIVES: The aim of this study was to assess technical success, leak resolution, and reoperation rates of patients undergoing endoscopic therapy for repair SGLs. SETTING: Eight high-volume academic endoscopy centers. METHODS: Patients undergoing endoscopic therapy for SGLs from 2007 to 2017 were identified. Patients were excluded if the index endoscopic therapy for SGL was performed elsewhere or if no follow-up data were available. Leaks were classified as acute (≤7 d of SG), early (1-6 wk), late (7-12 wk), and chronic (>12 wk). Leak resolution was defined as lack of extraluminal air, extravasation on oral contrast radiography, cross-sectional imaging, or resolution of percutaneous drain output. Demographic and procedural data were recorded as rates of additional therapy, adverse events, and surgical revision. RESULTS: A total of 85 patients met criteria for analysis (70 women, age 42.6 ± 10.8 yr). A total of 295 endoscopic sessions (median 3, range 1-14) were performed across the cohort. SGLs resolved after index endoscopic therapy in 43 (50.1%) patients. The primary outcome of endoscopic resolution of SGL was observed in 62 patients (72.9%). There were 34 (11.5%) PRAE (the majority occurring with self-expandable metal stents), all but 1 of which were managed endoscopically. Surgical revision was required in 23 (21.7%) patients. On univariate analyses independent variables associated with the need for surgical revision included both acute and chronic SGLs (P = .028), loculated subphrenic collections/abscesses (P = .03), and intraabdominal sepsis (P = .03). On multivariable logistic regression using statistically significant predictors from the univariate analyses, acute SGLs were significantly associated with a need for surgical revision (odds ratio 4.8, 95% confidence interval 1.2-18.9, P = .025). CONCLUSION: Endoscopic therapy for SGLs is associated with good clinical success, avoiding the need for surgical revision in 73% of patients, with an acceptable adverse event profile. Patients with acute or chronic SGLs and those with loculated abscesses or intraabdominal sepsis are more likely to undergo surgical revision. Endoscopic therapy is an appropriate first-line modality for the management of SGLs, especially those not classified as acute or chronic.

Visceral Adiposity Predicts Severity of Acute Pancreatitis.

OBJECTIVES: The aim of this study was to determine the association of visceral adiposity with severe outcomes in acute pancreatitis (AP). METHODS: This retrospective study included consecutive patients with AP admitted to a tertiary care hospital between January 2010 and January 2015 who underwent a computed tomography scan. The visceral adipose tissue (VAT) volume was estimated using the method of Linder and colleagues. Multivariable logistic regression analysis was conducted to assess VAT as a predictor of severe AP compared with other validated predictors of severity. RESULTS: Five hundred and seventy four patients were admitted during the study period, of which 252 had a computed tomography scan available. Patients with severe AP had a larger VAT area compared with those with mild or moderate AP (mean: 184.9 cm vs 79.9 cm, P = 0.006). Patients who developed multisystem organ failure or had acute necrotic collections had a larger VAT area than those who did not (150.6 cm vs 91.0 cm, P = 0.004 and 174.0 cm vs 91.9 cm, P = 0.003, respectively). Visceral adipose tissue area demonstrated superior discrimination of severe AP compared with other severity predictors. CONCLUSIONS: Increased VAT area is a strong predictor of severe pancreatitis, necrosis, and multisystem organ failure.