Hepatocyte growth factor, hepatocyte growth factor activator and arginine in a rat fulminant colitis model

INTRODUCTION: Dextran sodium sulfate (DSS) is commonly used to induce a murine fulminant colitis model. Hepatocyte growth factor (HGF) has been shown to decrease the symptoms of inflammatory bowel disease (IBD) but the effect of its activator, HGFA, is not well characterized. Arginine reduces effects of oxidative stress but its effect on IBD is not well known. The primary aim is to determine whether HGF and HGFA, or arginine will decrease IBD symptoms such as pain and diarrhea in a DSS-induced fulminant colitis murine model. METHODS: A severe colitis was induced in young, male Fischer 344 rats with 4% (w/v) DSS oral solution for seven days; rats were sacrificed on day 10. Rats were divided into five groups of 8 animals: control, HGF (700 mcg/kg/dose), HGF and HGFA (10 mcg/dose), HGF and arginine, and high dose HGF (2800 mcg/kg/dose). Main clinical outcomes were pain, diarrhea and weight loss. Blinded pathologists scored the terminal ileum and distal colon. RESULTS: DSS reliably induced severe active colitis in 90% of animals (n = 36/40). There were no differences in injury scores between control and treatment animals. HGF led to 1.38 fewer days in pain (p = 0.036), while arginine led to 1.88 fewer days of diarrhea (P = 0.017) compared to controls. 88% of HGFA-treated rats started regaining weight (P \u3c 0.001). DISCUSSION/CONCLUSION: Although treatment was unable to reverse fulminant disease, HGF and arginine were associated with decreased days of pain and diarrhea. These clinical interventions may reduce associated symptoms for severe IBD patients, even when urgent surgical intervention remains the only viable option

Clinical and Financial Impact of Readmissions Following Colorectal Resection: An Analysis of Predictors, Outcomes, and Cost

Background: Following passage of the Affordable Care Act, 30day readmissions have come under greater scrutiny, with penalties levied for higher than expected readmission rates. We examined risk factors for 30day readmission following colorectal resection and evaluated the financial impact of readmissions on the healthcare system. Methods: The University HealthSystem Consortium Clinical Database was queried for adults undergoing colorectal surgery for cancer, diverticular disease, inflammatory bowel disease, or benign tumors from 2008-2012. Predictors of 30day readmission were assessed with multivariable logistic regression. Additional endpoints included time to readmission, readmission diagnosis, readmission length of stay (LOS), and readmission cost. Results: A total of 70,484 patients met study inclusion criteria, 13.7% (9,632) of which were readmitted within 30 days of discharge. The strongest independent predictors of readmission were: LOS ≥4 days (OR 1.44; 95% CI 1.32-1.57), stoma (OR 1.54; 95% CI 1.46-1.51), and non-home discharge (OR 1.68; 95% CI 1.57-1.81). Of those readmitted, half occurred within 7 days, 13% required ICU care, 6% had a reoperation, and 2% died during the readmission stay. The median combined total direct hospital cost was over two times higher ($26,917 v.$13,817; p\u3c0.001) than non-readmitted patients. Compared with late readmissions, those readmitted within 7 days were more likely to have a reoperation (8% v. 4%, p\u3c0.001), be admitted to the ICU (14% vs. 12%, p\u3c0.001), and had a longer median readmission LOS (5d vs. 4d, p\u3c0.001). CONCLUSIONS: 30-day readmissions following colorectal resection occur frequently and incur a significant financial burden on the healthcare system. Highest-risk patients include those with longer LOS, stoma, and non-home discharge. Future studies aimed at targeted interventions may reduce readmissions and curb escalating healthcare costs

A New Look at the Volume and Outcome Relationship in Surgery for Colorectal Cancer

Purpose: Surgeon and hospital factors have a significant impact on treatment outcomes for colorectal cancer (CRC). Limited research has been done to assess cost and quality of treatment by surgeon-volume. We aim to identify the surgeon factors impacting cost and quality of surgical care for CRC. Methods: The University HealthSystem Consortium database was queried for patients who underwent colon resection for cancer from 2008 to 2012. Patients were grouped by surgeon-volume. Outcomes of interest were postoperative complications, ICU admission, readmission rate, inpatient hospital length of stay (LOS) and direct hospital cost. Average surgeon-volume per year was categorized as high (\u3e6) or low (16) based on the distribution of surgeon-volume. Results: 29,972 patients over age 18 were identified for inclusion. 25,426 underwent resection by high-volume surgeons (HVS) and 4,547 by low-volume surgeons (LVS). LVS were more likely to admit patients to the ICU than HVS (21% v 33%, p Conclusions: Surgeons who perform greater than 6 colectomies per year for colon cancer are more likely to use laparoscopy, less likely to admit patients to the ICU, have lower complication and readmission rates, and shorter LOS. Hospital cost is significantly lower in patients operated on by high volume surgeons. As health care costs continue to escalate and health care reform efforts gain momentum, factors leading to high-quality, cost-effective care need to be identified

NOD-scidIl2rg tm1Wjl and NOD-Rag1 null Il2rg tm1Wjl : A Model for Stromal Cell–Tumor Cell Interaction for Human Colon Cancer

BACKGROUND/AIMS: Stromal cells and the extracellular environment are vital to human tumors, influencing growth and response to therapy. Human tumor cell lines lack stroma and transplantation into immunodeficient mice does not allow meaningful analyses of the effects of stroma on tumor cell growth. Studies of xenografts of primary human tumor fragments in nude mice and in early scid mouse models were constrained by poor tumor growth accompanied by host-versus-graft reactivity, dramatically altering tumor architecture and tumor microenvironment. In contrast, severely immunodeficient NOD-scid and NOD-Rag1(null) strains carrying the IL2rg(null) mutation (NSG and NRG) support the growth of many types of human primary tumors. METHODS/RESULTS: We compared the take rate, growth and architectural preservation of 10 clinically distinct primary human colon cancers in NOD-scid, NOD-Rag1(null), NSG and NRG mice and determined the contribution of mouse and human cells to the stroma during tumor proliferation and expansion in secondary hosts and tumor response to treatment with 5-fluorouracil (5-FU). NSG and NRG mice more readily support growth of human primary colon tumor fragments than do NOD-scid, NOD-Rag1(null) mice and maintain tumor architectural integrity in the primary recipient and through subsequent transplant generations. The human colon tumors were responsive to treatment with 5-FU. Human stromal cells in the primary graft were replaced by mouse-derived fibroblasts in a dynamic process during subsequent passages. CONCLUSION: Human colon cancer xenografts propagated in NSG and NRG mice maintain structural fidelity while replacing human stromal cells with murine stromal cells

Ischemic Colitis

Ischemic colitis is the most common form of gastrointestinal ischemia. Patients present with either occlusive or nonocclusive vascular disease, although the latter is more common. Many causes of nonocclusive disease have been identified, but the exact pathophysiology remains unclear. Most commonly, patients develop abdominal discomfort and bloody diarrhea. Diagnosis is confirmed with colonoscopy. Treatment is contingent on the severity of disease: mucosal/nongangrenous ischemia requires only supportive measures and medical management, whereas transmural/gangrenous ischemia may require prompt surgical intervention. Ischemic colitis can also become a chronic process with persistent segmental colitis or colonic stricturing. The patient's outcome depends on the severity of disease, prompt recognition, and appropriate treatment

Operative Anesthesia and Pain Control

A comprehensive understanding of operative anesthesia and postoperative pain control is essential to the practicing colon and rectal surgeon. Most of the operations performed—particularly in the perineum—cause significant patient discomfort and often result in a lengthy recovery period. A variety of factors, including patient positioning in the operating room and patient expectations, influence the choice of operative anesthesia. Postoperatively numerous modalities and agents exist for pain control. With this variety of options at hand, surgeons should be educated and decisions should be individualized, with the ultimate goals of improving the patient experience and facilitating recovery

Colonic Diverticulosis and Diverticular Hemorrhage

Colonic diverticulosis predisposes individuals to lower gastrointestinal hemorrhage in up to 5% of cases. These sac-like protrusions are pseudodiverticula and arise due to a combination of anatomic, dietary, motility, and structural influences. In the setting of acute hemorrhage, patient stabilization takes priority, followed closely by maneuvers aimed at localizing and controlling blood loss. Through the use of an arsenal of tools including colonoscopy, angiography, and nuclear scintigraphy, most diverticular bleeds can be localized and subsequently controlled. When persistent and not controlled by colonoscopic or angiographic means, expeditious surgical resection serves as definitive therapy

Complexities in Colorectal SurgeryDecision-Making and Management /

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A simple risk score for predicting surgical site infections in inflammatory bowel disease

PURPOSE: Patients with inflammatory bowel disease are often at highest risk for surgical site infections. We sought to define the predictors of surgical site infections and to develop a risk score for predicting those at highest risk. METHODS: Patients undergoing a bowel resection for Crohn\u27s disease or ulcerative colitis were identified from National Surgical Quality Improvement Program 2008. Univariate and multivariate analyses were conducted to identify predictors of surgical site infections. Clinically relevant prediction categories were developed and the predictive behavior of the model was validated by use of National Surgical Quality Improvement Program 2007. An integer-based scoring system risk score was created proportional to the logistic regression coefficients, grouping patients into categories of similar risk. RESULTS: We identified 271,368 patients; 3981 of these patients underwent an operation for Crohn\u27s disease (n = 2895) or ulcerative colitis (n = 1086). Nine hundred (22.6%) patients developed surgical site infections. Predictors included weight loss, smoking, emergent surgery, wound class, operative time (minutes), and an ASA score \u3e2. A risk score was developed by stratifying patients into low (0-5), 15.6%; medium (6-8), 25.2%; and high (\u3e8), 36.1% risk. CONCLUSIONS: Patients with inflammatory bowel disease are at high risk for surgical site infections. Preoperative factors including weight loss, smoking, emergent surgery and an ASA score \u3e2 are strong predictors of surgical site infections. Operative time and wound class are important intraoperative predictors. A risk score, based on pre- and intraoperative variables, can be used to identify patients at highest risk of developing surgical site infections. This may allow for appropriate process measures to be implemented to prevent and lessen the impact of surgical site infections in this high-risk population