Patient and Physician Preferences for Nonoperative Management for Low Rectal Cancer: Is It a Reasonable Treatment Option?

BACKGROUND: Although the body of evidence supporting nonoperative management for rectal cancer has been accumulating, there has been little systematic investigation to explore how physicians and patients value the tradeoffs between oncologic and functional outcomes after abdominal perineal resection and nonoperative management. OBJECTIVE: The purpose of this study was to elicit patient and physician preferences for nonoperative management relative to abdominal perineal resection in the setting of low rectal cancer. DESIGN: We conducted a standardized interviews of patients and a cross-sectional survey of physicians. SETTINGS: Patients from 1 tertiary care center and physicians from across Canada were included. PATIENTS: The study involved 50 patients who were previously treated for rectal cancer and 363 physicians who treat rectal cancer. INTERVENTIONS: Interventions included standardized interviews using the threshold technique with patients and surveys mailed to physicians. MAIN OUTCOMES MEASURES: We measured absolute increase risk in local regrowth and absolute decrease in overall survival that patients and physicians would accept with nonoperative management relative to abdominal perineal resection. RESULTS: Patients were willing to accept a 20% absolute increase for local regrowth (ie, from 0% to 20%) and a 20% absolute decrease in overall survival (ie, from 80% to 60%) with nonoperative management relative to abdominal perineal resection, whereas physicians were willing to accept a 5% absolute increase for local regrowth (ie, from 0% to 5%) and a 5% absolute decrease in overall survival (ie, from 80% to 75%) with nonoperative management relative to abdominal perineal resection. LIMITATIONS: Data were subject to response bias and generalizable to only a select group of patients with low rectal cancer. CONCLUSIONS: Offering nonoperative management as an option to patients, even if oncologic outcomes are not equivalent, may be more consistent with the values of patients in this setting. See Video Abstract at http://links.lww.com/DCR/A688.

Colonic Stents for Colorectal Cancer Are Seldom Used and Mainly for Palliation of Obstruction: A Population-Based Study.

Self-expandable stents for obstructing colorectal cancer (CRC) offer an alternative to operative management. The objective of the study was to determine stent utilization for CRC obstruction in the province of Ontario between April 1, 2000, and March 30, 2009. Colonic stent utilization characteristics, poststent insertion health outcomes, and health care encounters were recorded. 225 patients were identified over the study period. Median age was 69 years, 2/3 were male, and 2/3 had metastatic disease. Stent use for CRC increased over the study period and gastroenterologists inserted most stents. The median survival after stent insertion was 199 (IQR, 69-834) days. 37% of patients required an additional procedure. Patients with metastatic disease were less likely to go on to surgery (HR 0.14, 95% CI 0.06-0.32, p < 0.0001). There were 2.4/person-year emergency department visits (95% CI 2.2-2.7) and 2.3 hospital admissions/person-year (95% CI 2.1-2.5) following stent insertion. Most admissions were cancer or procedure related or for palliation. Factors associated with hospital admissions were presence of metastatic disease, lack of chemotherapy treatment, and stoma surgery. Overall the use of stents for CRC obstruction remains low. Stents are predominantly used for palliation with low rates of postinsertion health care encounters.

Small bowel fibrosis and systemic inflammatory response after ileocolonic anastomosis in IL-10 null mice.

BACKGROUND: Crohn's disease recurrence after an ileocecal resection is common; yet, its pathophysiology is poorly understood and available treatment is suboptimal. The purpose of this study was to examine the bacterial, local, and systemic immune changes that follow ileocolonic anastomosis in a rodent model of Crohn's disease, the interleukin-10 gene-deficient (IL-10 null) mice. MATERIALS AND METHODS: We divided wild-type and IL-10 null mice into three treatment groups: ileocolonic anastomosis, sham operation (ileo-ileal anastomosis), and control group without an operation. We sacrificed mice at 6 and 15 wks after the operation. At 6 wks, we assessed bacterial changes using the denaturing gel electrophoresis and similarity coefficient calculation. At both time points, we examined the small bowel for inflammation and fibrosis with histology. We measured the interferon gamma secretion by splenocytes stimulated with gastrointestinal bacterial antigens and splenocyte composition as a marker of systemic response. RESULTS: At 6 wks, ileocolonic anastomosis resulted in increased similarity in bacterial species between the ileum and colon. The ileocolonic anastomosis did not lead to significant inflammation in the small intestine, but it resulted in an increased collagen deposition in all animals undergoing surgery, the most pronounced fibrosis of which was present in IL-10 null mice 15 wks after ileocolonic anastomosis. Furthermore, this was associated with significantly increased interferon gamma secretion by bacterial antigen-stimulated splenocytes and a decreased number of CD11+ cells in the same experimental group. CONCLUSIONS: Ileocolonic anastomosis leads to bacterial changes in the terminal ileum. In the genetically susceptible host, it is associated with small bowel fibrosis and systemic immune alterations. The composition of immune cells in the spleen is altered and splenocytes hypersecrete proinflammatory cytokine (interferon gamma) when challenged with gastrointestinal bacterial antigens.

Predicting, treating and preventing postoperative recurrence of Crohn's disease: the state of the field.

The majority of patients diagnosed with Crohn's disease eventually require surgical intervention. Unfortunately, postsurgical remission tends to be short lived; a significant number of patients experience clinical relapse and many require additional operations. The pathogenesis of this postoperative recurrence is poorly understood and, currently, there are no reliable tools to predict when and in whom the disease will recur. Furthermore, the postoperative prophylaxis profiles of available Crohn's disease therapeutic agents such as 5-aminosalicylates, immunomodulators, steroids and probiotics have been disappointing. Recently, the combination of antibiotics and azathioprine in selected high-risk patients has demonstrated some potential for benefit. The goal of the present article is to provide a coherent summary of previous and new research to guide clinicians in managing the challenging and complex problem of postoperative Crohn's disease recurrence.

The Utility of Lighted Ureteral Stents in Laparoscopic Colorectal Resection: A Survey of Canadian Surgeons.

BACKGROUND: Establishing the exact location of the ureters is critical in preventing ureteric injury during colorectal surgery. In laparoscopic colorectal resections this identification can be facilitated by the pre-operative insertion of lighted ureteral stents (LUS). LUS may also serve as an invaluable educational aid during the teaching of colorectal surgery. However, the available evidence does not support the routine use of stents as an injury prevention measure. Furthermore, stent insertion carries inherent risks of ureteric injury. The objective of this study was to determine the frequency of use and indications for LUS in laparoscopic colorectal resections among Canadian surgeons. METHODS: A seven-question survey was administered to Canadian surgeons through the monthly Canadian Association of General Surgeons (CAGS) e-news over a period of three months. The questions focused on surgeon demographics, experience with laparoscopic colon resections and the use of stents. RESULTS: Seventy-five surgeons completed the survey. There was a wide range of experience among the surgeons in terms of years in practice. The majority (84%) reported performing laparoscopic colorectal resections and of those 65% reported performing less than 25 resections a year. Only 26% of surgeons used LUS during laparoscopic resections. Furthermore, 75% of LUS users did not have sub-specialty training, 69% performed less than 25 resections per year and 50% were in practice for less than five years. When used, LUS were inserted for diverticular disease (100%), left colon resection (88%) and low anterior resections (75%). CONCLUSION: The majority of surgeons across Canada do not use LUS for laparoscopic colorectal resections. Of those performing laparoscopic colorectal resections, there may be a preference to use LUS for complex cases and by novice operators. This data suggests that proponents of LUS deem that it may have a role in diverticular disease.

The role of probiotics in management of irritable bowel syndrome.

Irritable bowel syndrome (IBS) affects a significant proportion of the North American population; however, the etiology and pathophysiology of this disease remain poorly understood, and treatment is focused on symptom management. Over the years, research has revealed that the bacterial flora in the human gut interact with the bowel in a complex and dynamic relationship and may be responsible for the induction and progression of some of the pathophysiologic aspects of IBS. Probiotics are nonpathogenic bacteria that benefit the host, and the roles they can play in the bacterio-gut relationship provide hope of a safe treatment that would allow for modulation of IBS disease states. Probiotic treatment for IBS has undergone significant exploration, yet the exact therapeutic effects and doses of these beneficial bacteria remain unclear due to the conflicting nature of available evidence. This review discusses the evidence from randomized controlled trials on probiotic treatment of IBS and presents the current understanding of the mechanisms of action of probiotics as they apply to IBS and provides a plausible explanation for the variability in evidence documented by the various trials under review.

Cardiotrophin-1: expression in experimental myocardial infarction and potential role in post-MI wound healing.

Cardiotrophin-1 (CT-1), a member of the IL-6 family of cytokines, has been shown to be elevated in the serum of patients with ischemic heart disease and valvular heart disease, and induces cardiomyocyte hypertrophy in vitro. We investigated expression of CT-1 in post-MI rat heart and the effect of CT-1 on cultured primary adult rat cardiac fibroblasts. Elevated CT-1 expression was observed in the infarct zone at 24 h and continued through 2, 4 and 8 weeks post-MI, compared to sham-operated animals. CT-1 induced rapid phosphorylation of Jak, Jak2, STAT1, STAT3, p42/44 MAPK and Akt in cultured adult cardiac fibroblasts. CT-1 induced cardiac fibroblast protein synthesis and proliferation. Protein and DNA synthesis were dependent on activation of Jak/STAT, MEK1/2, PI3K and Src pathways as evidenced by decreased 3H-leucine and 3H-thymidine incorporation after pretreatment with AG490, PD98059, LY294002 and genistein respectively. Furthermore, CT-1 treatment increased procollagen-1-carboxypropeptide (PICP) synthesis, a marker of mature collagen synthesis. CT-1 induced cell migration of rat cardiac fibroblasts. Our results suggest that CT-1, as expressed in post-MI heart, may play an important role in infarct scar formation and ongoing remodeling of the scar. CT-1 was able to initiate each of the processes considered important in the formation of infarct scar including cardiac fibroblast migration as well as fibroblast proliferation and collagen synthesis. Further work is required to determine factors that induce CT-1 expression and interplay with other mediators of cardiac infarct wound healing in the setting of acute cardiac ischemia and chronic post-MI heart failure.

Induction of protein synthesis in cardiac fibroblasts by cardiotrophin-1: integration of multiple signaling pathways.

OBJECTIVE: Cardiotrophin-1 (CT-1) is a member of the IL-6 family of cytokines and is expressed in various cardiovascular disease states. CT-1 induces cardiomyocyte hypertrophy, and protects myocytes from ischemia reperfusion injury. We sought to elucidate CT-1 signaling in cardiac fibroblasts with respect to initiation of protein synthesis. METHODS: Cardiac fibroblasts were isolated from the ventricles of 200-g Sprague-Dawley rats and stimulated with CT-1 at specified concentrations with or without inhibitors of cell signaling pathways. Activation of intracellular signaling pathways was determined by Western analysis and immunocytochemistry. Protein synthesis was measured by incorporation of [3H]leucine. RESULTS: CT-1 treatment resulted in activation of the Jak/STAT, MAPK, and Akt pathways in addition to protein synthesis regulatory proteins with resultant increase in overall protein synthesis. Analysis with phospho-specific antibodies revealed that AG490 (Jak inhibitor), PD98059 (MEK1/2 inhibitor), SB203580 (p38 MAPK inhibitor), LY294002 (PI3-K inhibitor) and rapamycin (mTOR inhibitor) act at different levels in the signaling cascade to inhibit CT-1 induced protein synthesis. CONCLUSION: Cardiotrophin-1 activates the Jak/STAT, PI3K/Akt, p38 and p42/44 MAPK pathways in cardiac fibroblasts. Use of pharmacologic inhibitors reveals that each of these pathways play a role in CT-1 induced protein synthesis.