Sphincter of Oddi dysfunction: Managing the patient with chronic biliary pain

Sphincter of Oddi dysfunction （SOD） is a syndrome of chronic biliary pain or recurrent pancreatitis due to functional obstruction of pancreaticobiliary flow at the level of the sphincter of Oddi. The Milwaukee classification stratifies patients according to their clinical picture based on elevated liver enzymes, dilated common bile duct and presence of abdominal pain. Type Ⅰ patients have pain as well as abnormal liver enzymes and a dilated common bile duct. Type Ⅱ SOD consists of pain and only one objective finding, and Type Ⅲ consists of biliary pain only. This classification is useful to guide diagnosis and management of sphincter of Oddi dysfunction. The current gold standard for diagnosis is manometry to detect elevated sphincter pressure, which correlates with outcome to sphincterotomy. However, manometry is not widely available and is an invasive procedure with a risk of pancreatitis. Non-invasive testing methods, including fatty meal ultrasonography and scintigraphy, have shown limited correlation with manometric findings but may be useful in predicting outcome to sphincterotomy. Endoscopic injection of botulinum toxin appears to predict subsequent outcome to sphincterotomy, and could be useful in selection of patients for therapy, especially in the setting where manometry is unavailable.

Distance management of inflammatory bowel disease:Systematic review and meta-analysis

AIM: To review the effectiveness of distance management methods in the management of adult inflammatory bowel disease (IBD) patients.

Endoscopic ultrasound in the diagnosis and treatment of pancreatic disease

Endoscopic ultrasound(EUS)is an important part of modern gastrointestinal endoscopy and now has an integral role in the diagnostic evaluation of pancreatic diseases.Furthermore,as EUS technology has advanced,it has increasingly become a therapeutic procedure,and the prospect of multiple applications of interventional EUS for the pancreas is truly on the near horizon.However,this review focuses on the established diagnostic and therapeutic roles of EUS that are used in current clinical practice.In particular,the diagnostic evaluation of acute pancreatitis,chronic pancreatitis,cystic pancreatic lesions and solid masses of the pancreas are discussed.The newer enhanced imaging modalities of elastography and contrast enhancement are evaluated in this context.The main therapeutic aspects of pancreatic EUS are then considered,namely celiac plexus block and celiac plexus neurolysis for pain control in chronic pancreatitis and pancreas cancer,and EUS-guided drainage of pancreatic fluid collections.

Validation of the Rockall scoring system for outcomes from non-variceal upper gastrointestinal bleeding in a Canadian setting

AIM: To validate the Rockall scoring system for predicting outcomes of rebleeding, and the need for a surgical procedure and death. METHODS: We used data extracted from the Registry of Upper Gastrointestinal Bleeding and Endoscopy including information of 1869 patients with non-variceal upper gastrointestinal bleeding treated in Canadian hospitals. Risk scores were calculated and used to classify patients based on outcomes. For each outcome, we used χ2 goodness-of-fit tests to assess the degree of calibration, and built receiver operating characteristic curves and calculated the area under the curve (AUC) to evaluate the discriminative ability of the scoring system. RESULTS: For rebleeding, the χ2 goodness-of-fit test indicated an acceptable fit for the model [χ2 (8) = 12.83, P = 0.12]. For surgical procedures [χ2 (8) = 5.3, P = 0.73] and death [χ2 (8) = 3.78, P = 0.88], the tests showed solid correspondence between observed proportions and predicted probabilities. The AUC was 0.59 (95% CI: 0.55-0.62) for the outcome of rebleeding and 0.60 (95% CI: 0.54-0.67) for surgical procedures, representing apoor discriminative ability of the scoring system. For the outcome of death, the AUC was 0.73 (95% CI: 0.69-0.78), indicating an acceptable discriminative ability. CONCLUSION: The Rockall scoring system provides an acceptable tool to predict death, but performs poorly for endpoints of rebleeding and surgical procedures.

Isolated colonic neurofibroma in the setting of Lynch syndrome:A case report and review of literature

BACKGROUND Gastrointestinal neurofibromas are commonly found in patients diagnosed with neurofibromatosis type 1.However,isolated gastrointestinal neurofibromas are a rare entity and only fourteen cases of isolated colorectal neurofibromas have been documented in literature.Isolated gastrointestinal neurofibromas have not been associated with Lynch syndrome(LS).Patients with LS are at an increased risk of colorectal cancer,and are recommended to undergo screening colonoscopy.CASE SUMMARY A 33-year-old healthy female with a family history of LS was found to have unresectable polyp in the ascending colon on screening colonoscopy suspicious for malignancy.The patient was asymptomatic and had no stigmata of neurofibromatosis.A staging workup for colorectal cancer revealed no evidence of metastatic disease.A discussion with the patient resulted in the decision to undergo a segmental resection with ongoing surveillance.The patient underwent a laparoscopic right hemicolectomy.Histopathology was consistent with a gastrointestinal neurofibroma.Post-operatively,the patient recovered well.She will not require further treatment with regards to her colonic neurofibroma,but will continue to follow-up for ongoing surveillance of her LS.CONCLUSION We present the first case of an isolated colonic neurofibroma in a patient with LS.This case explores considerations for the management of isolated gastrointestinal neurofibromas given the lack of guidelines in literature.

Mode of delivery by an ulcerative colitis mother in a case of twins: Immunological differences in cord blood and placenta

AIM To understand the effects of delivery mode on the immune cells frequency and function in cord blood and placenta.METHODS We evaluated immunological differences in cord blood and placental tissues for a case of twins one of which delivered vaginally while the other delivered by caesarian section(C-section). Cord blood mononuclear cells were isolated and placenta tissues were processed for cell isolation. Immune phenotyping was performed by flow cytometry methods following staining for T cells, natural killer(NK) cells, monocytes, neutrophils and CD71^+erythroid cells in both cord blood and placenta tissues. In addition, fetal calprotectin of twins was measured 12 wk after birth.RESULTS We found lower percentages of immune cells(e.g. T cells, monocytes and neutrophils) in the cord blood of C-section delivered compared to vaginally delivered newborn. In contrast, percentages of monocytes and neutrophils were > 2 folds higher in the placental tissues of C-section delivered newborn. More importantly, we observed lower percentages of CD71^+ erythroid cells in both cord blood and placental tissues of C-section delivered case. Lower CD71^+ erythroid cells were associated with a more pro-inflammatory milieu at the fetomaternal interface reflected by higher expression of inhibitory receptors on CD4^+ T cells, higher frequency of monocytes and neutrophils. Furthermore, type of delivery impacted the gene expression profile in CD71^+erythroid cells. Finally, we found that C-section delivered child had > 20-fold higher FCP in his fecal sample at 12 wk of age.CONCLUSION Mode of delivery impacted immune cells profile in cord blood/placenta. In particular frequency of immunosuppressive CD71^+ erythroid cells was reduced in C-section delivered newborn.

Vitamin D improves inflammatory bowel disease outcomes:Basic science and clinical review

Vitamin D deficiency is commonly diagnosed among patients with inflammatory bowel disease (IBD). Patients with IBD are at risk of low bone density and increased fractures due to low vitamin D levels, long standing disease, and frequent steroid exposures; as a result, it is well established that vitamin D supplementation in this population is important. There is increasing support for the role of vitamin D in strengthening the innate immune system by acting as an immunomodulator and reducing inflammation in experimental and human IBD. The active form of vitamin D, 1,25(OH)D3, acts on T cells to promote T helper (Th)2/regulatory T responses over Th1/Th17 responses; suppresses dendritic cell inflammatory activity; induces antibacterial activity; and regulates cytokine production in favor of an anti-inflammatory response. Murine and human IBD studies support a therapeutic role of vitamin D in IBD. Risk factors for vitamin D deficiency in this population include decreased sunlight exposure, disease duration, smoking, and genetics. Vitamin D normalization is associated with reduced risk of relapse, reduced risk of IBD-related surgeries, and improvement in quality of life. Vitamin D is an inexpensive supplement which has been shown to improve IBD outcomes. However, further research is required to determine optimal serum vitamin D levels which will achieve beneficial immune effects, and stronger evidence is needed to support the role of vitamin D in inducing disease response and remission, as well as maintaining this improvement in patients’ disease states.

Necrotizing enterocolitis: A multifactorial disease with no cure

Necrotizing enterocolitis is an inflammatory bowel disease of neonates with significant morbidity and mortality in preterm infants. Due to the multifactorial nature o the disease and limitations in disease models, early diagnosis remains challenging and the pathogenesis elusive. Although preterm birth, hypoxic-ischemic events formula feeding, and abnormal bacteria colonization are established risk factors, the role of genetics and vasoactive/inflammatory mediators is unclear Consequently, treatments do not target the specific underlying disease processes and are symptomatic and surgically invasive. Breast-feeding is the most effective preventative measure. Recent advances in the prevention of necrotizing enterocolitis have focused on bioactive nutrients and trophic factors in human milk. Developmen of new disease models including the aspect of prematurity that consistently predisposes neonates to the disease with multiple risk factors will improve our understanding of the pathogenesis and lead to discovery of innovative therapeutics.

Varicella zoster meningitis complicating combined anti-tumor necrosis factor and corticosteroid therapy in Crohn's disease

Opportunistic viral infections are a well-recognized complication of anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD). Cases of severe or atypical varicella zoster virus infection, both primary and latent reactivation, have been described in association with immunosuppression of Crohn's disease (CD) patients. However, central nervous system varicella zoster virus infections have been rarely described, and there are no previous reports of varicella zoster virus meningitis associated with anti-TNF therapy among the CD population. Here, we present the case of a 40-year-old male with severe ileocecal-CD who developed a reactivation of dermatomal herpes zoster after treatment with prednisone and adalimumab. The reactivation presented as debilitating varicella zoster virus meningitis, which was not completely resolved despite aggressive antiviral therapy with prolonged intravenous acyclovir and subsequent oral valacyclovir. This is the first reported case of opportunistic central nervous system varicella zoster infection complicating anti-TNF therapy in the CD population. This paper also reviews the literature on varicella zoster virus infections of immunosuppressed IBD patients and the importance of vaccination prior to initiation of anti-TNF therapy.

Intestinal hormones and growth factors:Effects on the small intestine

There are various hormones and growth factors which may modify the intestinal absorption of nutrients, and which might thereby be useful in a therapeutic setting, such as in persons with short bowel syndrome. In part I, we focus first on insulin-like growth factors, epidermal and transferring growth factors, thyroid hormones and glucocorticosteroids. Part Ⅱ will detail the effects of glucagon-like peptide （GLP）-2 on intestinal absorption and adaptation, and the potential for an additive effect of GLP2 plus steroids.

Magnetic imaging-assisted colonoscopy vs conventional colonoscopy: A randomized controlled trial

AIM: To compare magnetic imaging-assisted colonoscopy (MIC) with conventional colonoscopy (CC).

Lymphoproliferative disorders in inflammatory bowel disease patients on immunosuppression: Lessons from other inflammatory disorders

Immunosuppressive agents, such as thiopurines, methotrexate, and biologics, have revolutionized the treatment of inflammatory bowel disease(IBD). However, a number of case reports, case control studies and retrospective studies over the last decade have identified a concerning link between immunosuppression and lymphoproliferative disorders(LPDs), the oncological phenomenon whereby lymphocytes divide uncontrollably. These LPDs have been associated with Epstein-Barr virus(EBV) infection in which the virus provides the impetus for malignant transformation while immunosuppression hampers the immune system's ability to detect and clear these malignant cells. As such, the use of immunosuppressive agents may come at the cost of increased risk of developing LPD. While little is known about the LPD risk in IBD, more is known about immunosuppression in the post-transplantation setting and the development of EBV associated posttransplantation lymphoproliferative disorders(PTLD). In review of the PTLD literature, evidence is available to demonstrate that certain immune suppressants such as cyclosporine and T-lymphocyte modulators in particular are associated with an increased risk of PTLD development. As well, high doses of immunosuppressive agents and multiple immunosuppressive agent use are also linked to increased PTLD development. Here,we discuss these findings in context of IBD and what future studies can be taken to understand and reduce the risk of EBV-associated LPD development from immunosuppression use in IBD.

婴幼儿胃食管反流相关性咳嗽治疗的初步研究

目的婴幼儿哮喘的诊断主要基于咳嗽及喘息等临床症状,神经系统功能正常的婴幼儿当出现过度胃食管反流时也可以出现类似症状。目前并无随机对照研究来评价单独使用质子泵抑制剂或联合促动力药在婴幼儿中应用的疗效。本研究的主要目的是证实在呼吸道症状提示哮喘的婴幼儿中的确存在过度胃食管反流。其次,通过随机空白对照试验,探讨使用氨基甲酰甲基胆碱和奥美拉唑治疗过度胃食管反流可否改善呼吸道症状。方法有慢性咳嗽或喘息病史且有病史支持、pH监测异常或胃排空扫描提示胃食管反流的婴幼儿22例,随机分为4个治疗组:安慰剂+安慰剂(PP治疗组)、奥美拉唑+氨基甲酰甲基胆碱(OB治疗组)、奥美拉唑+安慰剂(OP治疗组)、氨基甲酰甲基胆碱+安慰剂(BP治疗组)。通过临床问卷调查、检查和家庭日记以及pH监测数据评估患儿上述治疗前后及奥美拉唑+氨基甲酰甲基胆碱非盲试验后的情况。结果 19例纳入数据统计。PP治疗对胃食管反流或呼吸道症状没有作用,pH监测提示胃食管反流并无减少。然而根据pH监测及家长评估,OB治疗可减少胃食管反流,同时显著减少日间咳嗽,改善呼吸,无不良反应发生。结论对于临床表现提示慢性胃食管反流相关性咳嗽的婴幼儿,使用奥美拉唑和氨基甲酰甲基胆碱治疗是可行的选择。

Pre-emptive TIPSS in Acute Variceal Bleeding:Current Status,Controversies,and Future Directions

Acute variceal bleeding(AVB)is associated with signifi-cant short-term morbidity and mortality.Pre-emptive tran-sjugular intrahepatic portosystemic shunt(p-TIPSS)is recommended to prevent rebleeding in AVB patients with a high risk of rebleeding.Despite the benefit of prevent-ing rebleeding and de-novo ascites,the uptake of p-TIPSS remains low because logistic challenges in the real-world setting.In this review,we summarize the current evidence and controversies on p-TIPSS including patient selection for p-TIPSS,particularly in the setting of NASH cirrhosis and acute-on-chronic liver failure,the role of sarcopenia,renal impairment in the setting of p-TIPSS.Finally,we summarize both pharmacological and nonpharmacological strategies to optimize outcomes in patients undergoing p-TIPSS.