Shishira Bharadwaj

Therapeutic armamentarium for stricturing Crohn's disease: Medical versus endoscopic versus surgical approaches

Abstract:One-third of patients with Crohns disease (CD) present as stricturing phenotype characterized by progressive luminal narrowing and obstructive symptoms. The diagnosis and management of these patients have been intriguing and challenging. Immunomodulators and biologics have been successfully used in treating inflammatory and fistulizing CD. There are issues of efficacy and safety of biological agents in treating strictures in CD. Rapid mucosal healing from potent biological agents may predispose patients to the development of new strictures or worsening of existing strictures. On the other hand, strictures constitute one-fifth of the reasons for surgery in patients with CD. Disease recurrence is common at or proximal to the anastomotic site with the majority of these patients developing new endoscopic lesions within 1 year of surgery. The progressive nature of the disease with repetitive cycle of inflammation and stricture formation results in repeated surgery, with a risk of small bowel syndrome. There is considerable quest for bowel conserving endoscopic and surgical strategies. Endoscopic balloon dilation and stricturoplasty have emerged as valid alternatives to resection. Endoscopic balloon dilation has been shown to be feasible, safe, and effective for the short primary or anastomotic strictures. However, repeated dilations are often needed, and long-term outcomes of endoscopic balloon dilation remain to be investigated. The introduction of stricturoplasty has added another dimension to bowel saving strategy. Although postoperative recurrence rate after stricturoplasty is comparable with surgical resection, there are concerns for increased risk of malignancy in preserved bowel. Laparoscopic surgery has widely been performed with similar outcomes to open approach with fewer complications, quicker recovery, better cosmesis, and lower cost. All of these issues should be considered by physicians involved in the management of patients with stricturing CD.

Gastrointestinal Manifestations, Malnutrition, and Role of Enteral and Parenteral Nutrition in Patients With Scleroderma.

Scleroderma (systemic sclerosis) is an autoimmune disease that can affect multiple organ systems. Gastrointestinal (GI) involvement is the most common organ system involved in scleroderma. Complications of GI involvement including gastroesophageal reflux disease, small intestinal bacterial overgrowth, and chronic intestinal pseudoobstruction secondary to extensive fibrosis may lead to nutritional deficiencies in these patients. Here, we discuss pathophysiology, progression of GI manifestations, and malnutrition secondary to scleroderma, and the use of enteral and parenteral nutrition to reverse severe nutritional deficiencies. Increased mortality in patients with concurrent malnutrition in systemic sclerosis, as well as the refractory nature of this malnutrition to pharmacologic therapies compels clinicians to provide novel and more invasive interventions in reversing these nutritional deficiencies. Enteral and parenteral nutrition have important implications for patients who are severely malnourished or have compromised GI function as they are relatively safe and have substantial retrospective evidence of success. Increased awareness of these therapeutic options is important when treating scleroderma-associated malnutrition.

Fish oil-based lipid emulsion: current updates on a promising novel therapy for the management of parenteral nutrition-associated liver disease.

Intestinal failure is characterized by loss of enteral function to absorb necessary nutrients and water to sustain life. Parenteral nutrition (PN) is a lifesaving therapeutic modality for patients with intestinal failure. Lifelong PN is also needed for patients who have short bowel syndrome due to extensive resection or a dysmotility disorder with malabsorption. However, prolonged PN is associated with short-term and long-term complications. Parenteral nutrition-associated liver disease (PNALD) is one of the long-term complications associated with the use of an intravenous lipid emulsion to prevent essential fatty acid deficiency in these patients. PNALD affects 30–60% of the adult population on long-term PN. Further, PNALD is one of the indications for isolated liver or combined liver and intestinal transplantation. There is no consensus on how to manage PNALD, but fish oil-based lipid emulsion (FOBLE) has been suggested to play an important role both in its prevention and reversal. There is significant improvement in liver function in those who received FOBLE as lipid supplement compared with those who received soy-based lipid emulsion. Studies have also demonstrated that FOBLE reverses hepatic steatosis and reduces markers of inflammation in patients on long-term PN. Future prospective studies with larger sample sizes are needed to further strengthen the positive role of FOBLE in PNALD.

Current status of intestinal and multivisceral transplantation

Clinical-nutritional autonomy is the ultimate goal of patients with intestinal failure (IF). Traditionally, patients with IF have been relegated to lifelong parenteral nutrition (PN) once surgical and medical rehabilitation attempts at intestinal adaptation have failed. Over the past two decades, however, outcome improvements in intestinal transplantation have added another dimension to the therapeutic armamentarium in the field of gut rehabilitation. This has become possible through relentless efforts in the standardization of surgical techniques, advancements in immunosuppressive therapies and induction protocols and improvement in postoperative patient care. Four types of intestinal transplants include isolated small bowel transplant, liver-small bowel transplant, multivisceral transplant and modified multivisceral transplant. Current guidelines restrict intestinal transplantation to patients who have had significant complications from PN including liver failure and repeated infections. From an experimental stage to the currently established therapeutic modality for patients with advanced IF, outcome improvements have also been possible due to the introduction of tacrolimus in the early 1990s. Studies have shown that intestinal transplant is cost-effective within 1–3 years of graft survival compared with PN. Improved survival and quality of life as well as resumption of an oral diet should enable intestinal transplantation to be an important option for patients with IF in addition to continued rehabilitation. Future research should focus on detecting biomarkers of early rejection, enhanced immunosuppression protocols, improved postoperative care and early referral to transplant centers.

Medical, endoscopic, and surgical management of ileal pouch strictures (with video)

The construction of ileal pouch–anal anastomosis (IPAA) is the procedure of choice for patients with ulcerative colitis or familial adenomatous polyposis who require colectomy. Furthermore, IPAA has the advantage of preserving the natural route of defecation, unlike the Brooke’s ileostomy or continent ileostomies. On the other hand, the natural history of patients with the ileal pouch can be complicated by various surgical procedure–associated mechanical adverse events as well as inflammatory and functional disorders. Pouch strictures are one of the most common adverse events after IPAA, with a reported frequency ranging from 10% to 17%. Pouch strictures may or may not be related to Crohn’s disease (CD). Pouch strictures can be primary and secondary, based on the etiology, and distal afferent limb, inlet, pouch body, and anastomotic strictures, based on the location. There are scant published data on the management of ileal pouch strictures. Medical therapy seems to be of limited value in the management of these strictures. Because of the mechanical nature of these strictures, endoscopic balloon dilation (EBD) and endoscopic stricturotomy are effective to reduce the need for surgery and the risk for pouch failure. Resection and anastomosis and stricturoplasty are 2 main surgical treatment modalities, which could be used to salvage

Intestinal Failure: Adaptation, Rehabilitation, and Transplantation.

Intestinal failure (IF) is a state in which the nutritional demands are not met by the gastrointestinal absorptive surface. A majority of IF cases are associated with short-bowel syndrome, which is a result of malabsorption after significant intestinal resection for numerous reasons, some of which include Crohn’s disease, vascular thrombosis, and radiation enteritis. IF can also be caused by obstruction, dysmotility, and congenital defects. Recognition and management of IF can be challenging, given the complex nature of this condition. This review discusses the management of IF with a focus on intestinal rehabilitation, parenteral nutrition, and transplantation.

Symptomatology of irritable bowel syndrome and inflammatory bowel disease during the menstrual cycle

Gender-related physiological variations in gastrointestinal (GI) symptomatology have been observed in women of reproductive age. Many women experience cyclical changes in GI symptomatology during their menstrual cycle, particularly alteration in their bowel habits. Physiological studies of healthy women during the menstrual cycle showed a prolonged GI transit time during the luteal phase, either in the oro-cecum route or in the colon. Worsened GI symptoms, such as abdominal pain, bloating or diarrhea are observed in patients with irritable bowel syndrome (IBS) during menses. This may be due to elevated prostaglandin levels during menses, with an enhanced perception of viscera-somatic stimuli resulting in nausea, abdominal distension and pain. Also patients with IBS or IBD demonstrate a cyclical pattern more closely related to their bowel habits than healthy controls. Women with inflammatory bowel disease (IBD) also have exacerbated symptoms during menses; however, it is unclear whether this relates to physiological variation or disease exacerbation in IBS or IBD. Studies examining the association of the menstrual cycle and GI symptomatology in patients with IBS or IBD, have not yet clarified the underlying mechanisms. Moreover medications—such as non-steroidal anti-inflammatory drugs and oral contraceptive pills used for dysmenorrhea and menstrual migraine in those patients have not well been controlled for in the previous studies, which can contribute to further bias. Understanding changes in GI symptomatology during the menstrual cycle may help to determine the true extent of disease exacerbation and proper management strategy.

Impact of Concurrent Non-IBD Immunological Diseases on the Outcome of Primary Sclerosing Cholangitis

Background:The association between primary sclerosing cholangitis (PSC) and underlying inflammatory bowel disease (IBD) is well established. There are scant data on the association between non-IBD immunological diseases (NID) and PSC outcomes. Our objective was to investigate the impact of NID on the clinical outcomes in patients with PSC. Methods:We included 287 patients with PSC from 1985 to 2013 from our tertiary care data registry. Univariate and multivariate analyses were performed to assess the risk factors for liver transplantation. Results:Of the 287 patients with PSC, 38 (13.2%) patients had at least 1 concomitant immunological disease other than IBD; 241 patients (84.0%) had concurrent IBD. The most frequent NIDs were autoimmune thyroiditis, autoimmune hepatitis, and rheumatoid arthritis. The median follow-up time did not differ significantly between PSC patients with and without NID (10.5 years versus 7.0 years, P = 0.04). We did not find significant difference in the median time from PSC diagnosis to liver transplantation between PSC patients with and without NID (5.2 versus 6.3 years, P = 0.74). In the subgroup analysis, there was no significant difference in the median time from PSC diagnosis to liver transplantation between the PSC-only group, PSC with IBD group, and PSC with NID group (5.4 versus 6.4 versus 5.2 years, P = 0.22). Conclusions:The association of NID in patients with PSC did not seem to affect the need for liver transplantation or transplantation-free survival. The findings suggest that the increased load of autoimmunity, including the presence of IBD or NID, has a minimum impact on the disease outcome of PSC.

Association between gastro-intestinal symptoms and menstruation in patients with ileal pouches

Background and aims: Gastro-intestinal (GI) symptoms are often experienced by healthy women during menstruation. An increased frequency of GI symptoms during menses has also been reported in women with irritable bowel syndrome or inflammatory bowel disease (IBD); however, IBD patients with restorative proctocolectomy and ileal pouch-anal anastomoses (IPAA) have not been studied. We aimed to examine the association between GI symptoms before and during menses in patients with IPAA, and to assess factors for exacerbation of GI symptoms in those patients. Methods: Adult women recorded in the Pouchitis Registry were invited to participate in a mailed survey. Participants reported on GI symptoms 1–5 days prior to- (pre-menses) and during the days of their menses in recent months. Demographic and clinical variables were obtained through the survey and chart review. Results: One hundred and twenty-eight (21.3%) out of 600 women with IPAA responded to the survey questionnaire. Forty-three (33.5%) were excluded for reasons including post-menopausal (n = 25), hysterectomy (n = 14) and use of contraceptives (n = 4). Abdominal pain (P = 0.001), diarrhea (P = 0.021), and urgency (P = 0.031) were more commonly reported during menses than pre-menses by the participants. Only a history of painful menses was significantly associated with increased GI symptoms during menses for patients with ileal pouch (odds ratio = 5.67; 95% confidence interval: 1.41–22.88; P = 0.015). Conclusion: GI symptoms such as abdominal pain, diarrhea, and urgency are commonly associated with menses in patients with ileo-anal pouch. Painful menses may be associated with worsening of GI symptoms.

Management of gastroparesis-associated malnutrition.

Gastroparesis (GP) is a chronic debilitating dysmotility characterized by unrelenting nausea, vomiting, bloating, early satiety, postprandial fullness and abdominal pain. Patients with GP experience other associated conditions, including gastroesophageal reflux disease, gastric bezoars and small bowel bacterial overgrowth. Furthermore, GP is associated with poor quality of life, increased emergency room visits, hospitalizations and subsequent increased healthcare costs. Currently, the managements of GP consist of glycemic control, antiemetics, prokinetics and the use of gastric electrical stimulation. However, most GP patients are at risk for significant nutritional abnormalities. As such, it is essential to screen and diagnose malnutrition in these patients. Poor oral intake in such patients could be supplemented by enteral tube feeding. Parenteral nutrition, although a last resort, is associated with a number of complications and should be used only for the short term. In summary, a systematic approach including initial nutritional screening, diet recommendations, medical therapy, nutritional re‐evaluation and enteral and parental nutrition should be considered in complex GP patients.