Pathogenesis and clinical and economic consequences of postoperative ileus

Postoperative ileus (POI) occurs frequently in patients undergoing major abdominal surgery; and only recently has there been renewed interest in understanding the pathogenesis, etiology, clinical manifestations, and clinical and economic consequences related to POI. This interest has been spurred by the potential access to novel pharmaceutical options for the management of POI. POI has a complex and multimodal pathophysiology including neurogenic, inflammatory, hormonal, and pharmacologic components. The clinical manifestations are clinically obvious and include abdominal distention, pain, nausea, vomiting, and inability to pass stools or tolerate a solid diet. Prolonged ileus has been defined as persistence of these symptoms for more than 4 days after major abdominal surgery; however the goal should be to reduce the incidence of these symptoms immediately after surgery. Clearly, the magnitude of the surgical stress and usage of opioid analgesia are the predominant causes of POI. The unappreciated sequelae of POI include increased rates in adverse surgical wound healing, reduced ambulation, atelectasis, pneumonia, urinary infections, and deep vein thrombosis. The secondary impact of these complications includes increased hospital length of stay, resource use, and healthcare costs. POI is common and the impact is underestimated. The addition of alvimopan as the first in class μ-opioid inhibitor has demonstrated consistent benefit in reducing the incidence and impact of POI with reductions in length of hospital stay. POI is a common, and underappreciated complication of major abdominal surgery, and clinicians should be aware of the clinical care options, including novel pharmaceutical agents, that can successfully reduce the incidence of this postoperative complication

Economic Analysis of Alvimopan—A Clarification and Commentary

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98345/1/phar1193.pd

Serum Adiponectin, Resistin, and Circulating Soluble Receptor for Advanced Glycation End Products in Colectomy Patients

Aim. Surgical trauma and associated complications are frequently related to physiological stress during colectomy. This study evaluated the response of adiponectin, resistin, and circulating soluble receptor for advanced glycation end products (sRAGE) in colectomy patients with or without an enhanced recovery protocol. Method. Serum samples were collected from 44 colectomy patients at 3 timframes. The surgical procedures were laparoscopic (LAP), hand-assisted laparoscopic (HALS), or open colectomy (OPEN). Adiponectin, resistin, and sRAGE levels were determined by ELISA. Repeated measures ANOVA was applied and P values < 0.05 were considered significant. Results. A total of 132 (44 × 3) sera were used for analysis. Levels of adiponectin was significantly decreased between PREOP and POD3 (P < 0.001). Conversely, concentrations of resistin significantly increased from PREOP to POD1 and returned to baseline value by POD3 (P < 0.001). Serum sRAGE levels were significantly higher in LAP in comparison with HALS (P = 0.004) and OPEN (P < 0.001). sRAGE levels were significantly higher in sera of patients that underwent ERP (P < 0.001). Conclusions. Serum adiponectin, resistin, and sRAGE have the potential to develop into a panel of stress markers. Higher sRAGE levels in sera of LAP and ERP patients may be indicative of a protective and syngeristic role for colectomy recovery

Preoperative Rectal Cancer Management: Wide International Practice Makes Outcome Comparison Challenging: Reply

In a letter to the editor Dr. Hottenrott provides valuable comments on our survey describing international preoperative rectal cancer management. In our opinion, three key messages are derived from our survey: First, most surgeons agree to neoadjuvant treatment when there is an increased risk of finding histologically positive circumferential margins. In addition, we found more than 40 other indications for neoadjuvant treatment (see our Table 4). This emphasizes the need for an international agreement, as different indications for neoadjuvant treatment will select noncomparable groups of patients in outcome studies. Second, we have shown (see our Table 6) that multidisciplinary team (MDT) meetings significantly influence several important decisions in preoperative rectal cancer management. Interestingly, centers with regular MDT have a higher rate of using magnetic resonance imaging (MRI) (Odds Ratio [OR] = 3.62) and consider a threatened circumferential resection margin (CRM) as indication for neoadjuvant treatment (OR = 5.67). We believe that MDT improves preoperative management of rectal cancer by increasing adherence to national guidelines. Similar discussions in international rectal cancer societies are needed aiming towards an international consensus statement. Finally, our survey revealed sparse use (35% of all cases) of MRI. The goal for the radiologic examination in rectal cancer is to explore the tumor’s relation to nearby anatomical structures. This evaluation will conclude with TNM staging, important for chemoradiotheraphy, surgical treatment, and prognosis. Magnetic resonance imaging has a central role in this evaluation and should be the first choice radiologic modality. Not only is MRI crucial in detection of TNM stage but also plays a central role in determination of the tumor’s distance to the mesorectal fascia and the CRM. Magnetic resonance imaging has moderate sensitivity on T1 and T2 tumors, and should be supplemented with rectal ultrasound

Perfusion Assessment in Laparoscopic Left-Sided/Anterior Resection (PILLAR II): A Multi-Institutional Study

BackgroundOur primary objective was to demonstrate the utility and feasibility of the intraoperative assessment of colon and rectal perfusion using fluorescence angiography (FA) during left-sided colectomy and anterior resection. Anastomotic leak (AL) after colorectal resection increases morbidity, mortality, and, in cancer cases, recurrence rates. Inadequate perfusion may contribute to AL. The PINPOINT Endoscopic Fluorescence Imaging System allows for intraoperative assessment of anastomotic perfusion.Study DesignThis is a prospective, multicenter, open-label, clinical trial that assessed the feasibility and utility of FA for intraoperative perfusion assessment during left-sided colectomy and anterior resection at 11 centers in the United States.ResultsA total of 147 patients were enrolled, of whom 139 were eligible for analysis. Diverticulitis (44%), rectal cancer (25%), and colon cancer (21%) were the most prevalent indications for surgery. The mean level of anastomosis was 10 ± 4 cm from the anal verge. Splenic-flexure mobilization was performed in 81% and high ligation of the inferior mesenteric artery in 61.9% of patients. There was a 99% success rate for FA, and FA changed surgical plans in 11 (8%) patients, with the majority of changes occurring at the time of transection of the proximal margin (7%). Overall morbidity rates were 17%. The anastomotic leak rate was 1.4% (n = 2). There were no anastomotic leaks in the 11 patients who had a change in surgical plan based on intraoperative perfusion assessment with FA.ConclusionsPINPOINT is a safe and feasible tool for intraoperative assessment of tissue perfusion during colorectal resection. There were no anastomotic leaks in patients in whom the anastomosis was revised based on inadequate perfusion with FA

Alvimopan for the Management of Postoperative Ileus After Bowel Resection: Characterization of Clinical Benefit by Pooled Responder Analysis

BACKGROUND: A pooled post hoc responder analysis was performed to assess the clinical benefit of alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist, for the management of postoperative ileus after bowel resection. METHODS: Adult patients who underwent laparotomy for bowel resection scheduled for opioid-based intravenous patient-controlled analgesia received oral alvimopan or placebo preoperatively and twice daily postoperatively until hospital discharge or for 7 postoperative days. The proportion of responders and numbers needed to treat (NNT) were examined on postoperative days (POD) 3-8 for GI-2 recovery (first bowel movement, toleration of solid food) and hospital discharge order (DCO) written. RESULTS: Alvimopan significantly increased the proportion of patients with GI-2 recovery and DCO written by each POD (P \u3c 0.001 for all). More patients who received alvimopan achieved GI-2 recovery on or before POD 5 (alvimopan, 80%; placebo, 66%) and DCO written before POD 7 (alvimopan, 87%; placebo, 72%), with corresponding NNTs equal to 7. CONCLUSIONS: On each POD analyzed, alvimopan significantly increased the proportion of patients who achieved GI-2 recovery and DCO written versus placebo and was associated with relatively low NNTs. The results of these analyses provide additional characterization and support for the overall clinical benefit of alvimopan in patients undergoing bowel resection

International Preoperative Rectal Cancer Management: Staging, Neoadjuvant Treatment, and Impact of Multidisciplinary Teams

BACKGROUND: Little is known regarding variations in preoperative treatment and practice for rectal cancer (RC) on an international level, yet practice variation may result in differences in recurrence and survival rates. METHODS: One hundred seventy-three international colorectal centers were invited to participate in a survey of preoperative management of rectal cancer. RESULTS: One hundred twenty-three (71%) responded, with a majority of respondents from North America, Europe, and Asia. Ninety-three percent have more than 5 years' experience with rectal cancer surgery. Fifty-five percent use CT scan, 35% MRI, 29% ERUS, 12% digital rectal examination and 1% PET scan in all RC cases. Seventy-four percent consider threatened circumferential margin (CRM) an indication for neoadjuvant treatment. Ninety-two percent prefer 5-FU-based long-course neoadjuvant chemoradiation therapy (CRT). A significant difference in practice exists between the US and non-US surgeons: poor histological differentiation as an indication for CRT (25% vs. 7.0%, p = 0.008), CRT for stage II and III rectal cancer (92% vs. 43%, p = 0.0001), MRI for all RC patients (20% vs. 42%, p = 0.03), and ERUS for all RC patients (43% vs. 21%, p = 0.01). Multidisciplinary team meetings significantly influence decisions for MRI (RR = 3.62), neoadjuvant treatment (threatened CRM, RR = 5.67, stage II + III RR = 2.98), quality of pathology report (RR = 4.85), and sphincter-saving surgery (RR = 3.81). CONCLUSIONS: There was little consensus on staging, neoadjuvant treatment, and preoperative management of rectal cancer. Regular multidisciplinary team meetings influence decisions about neoadjuvant treatment and staging methods