World Journal of Gastrointestinal Pharmacology and Therapeutics最新文献

Background: In order to improve risk stratification and clinical management of the pancreatic ductal adenocarcinoma (PDAC), the American Joint Committee on Cancer (AJCC) has published its eighth edition staging manual. Some major changes have been introduced in the new staging system for both T and N categories. Given the rarity of resectable disease, distal pancreatic cancer is likely underrepresented in the published clinical studies, and how the impact of the staging system actually reflects on to clinical outcomes remain unclear.

Aim: To validate the AJCC 8^th edition of TNM staging in distal PDAC.

Methods: A retrospective cohort study was performed in seven academic medical centers in the United States. Clinicopathological prognostic factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated through univariate and multivariate analyses.

Results: Overall, 454 patients were enrolled in the study, and were divided into 2 subgroups: Invasive intraductal papillary mucinous neoplasms (IPMN) (115 cases) and non-IPMN associated adenocarcinoma (339 cases). Compared to invasive IPMN, non-IPMN associated adenocarcinomas are more common in relatively younger patients, have larger tumor size, are more likely to have positive lymph nodes, and are associated with a higher tumor (T) stage and nodal (N) stage, lymphovascular invasion, perineural invasion, tumor recurrence, and a worse PFS and OS. The cohort was predominantly categorized as stage 3 per AJCC 7^th edition staging manual, and it's more evenly distributed based on 8^th edition staging manual. T and N staging of both 7^th and 8^th edition sufficiently stratify PFS and OS in the entire cohort, although dividing into N1 and N2 according to the 8^th edition does not show additional stratification. For PDAC arising in IPMN, T staging of the 7^th edition and N1/N2 staging of the 8^th edition appear to further stratify PFS and OS. For PDAC without an IPMN component, T staging from both versions fails to stratify PFS and OS.

Conclusion: The AJCC 8^th edition TNM staging system provides even distribution for the T staging, however, it does not provide better risk stratification than previous staging system for distal pancreatic cancer.

Background: Acromegaly is a chronic disease caused by a pituitary somatotroph adenoma resulting in excess secretion of growth hormone, which leads to excess secretion of Insulin like growth factor 1 from the liver, causing abnormal soft tissue growth. There is increasing awareness that diseases affecting connective tissue are associated with an increase in functional gastrointestinal symptoms. Data was collected from patients with a confirmed diagnosis of acromegaly to evaluate the intensity, variety and impact of abdominal symptoms in comparison with a control group who were healthy participants recruited from the local fracture clinic.

Aim: To evaluate the frequency type and burden of abdominal symptoms in acromegaly in comparison with a control group.

Methods: Medical documentation of patients with a diagnosis of acromegaly treated in one tertiary medical centre between 2010 and 2017 has been analysed. Data was collected from patients with confirmed acromegaly, using the Short Form Health Survey (SF36) and Rome IV Diagnostic questionnaire for Functional Gastrointestinal Disorders in Adults (R4DQ) and compared to a sex- and age-matched control group, to assess the burden of abdominal symptoms. Microsoft Excel and IBM SPSS v 25 were used for data analysis.

Results: Fifty patients with acromegaly (24 male and 26 females; age range 23-64 years, mean 43) and 200 controls (96 male and 104 females; age range 18-84, mean 42.4) were recruited. 92% (46 out of 50) of patients with acromegaly reported abdominal symptoms and 78% (39 out of 50) had at least one functional gastrointestinal disorder according to the Rome IV diagnostic criteria, compared to 16% of controls (OR > 1, P < 0.0001). The most commonly reported symptom was constipation (69% acromegaly vs 21% of controls OR > 1, P < 0.0001, 95%CI: 4.4-15.8). 34 out of 50 (68%) respondents met the criteria for functional constipation according to Rome IV. Upper gastrointestinal disorders were also more prevalent in the acromegaly group. There was no statistically significant difference in the prevalence of biliary and anorectal symptoms between the two groups. Patients in acromegaly group scored lower on the mean scores of the eight parameters of SF36 Quality of Life questionnaire (mean scores 60.04 vs 71.23, 95%CI: -13.6829 to -8.6971, OR > 1, P < 0.001) as compared to the control group.

Conclusion: Upper and lower functional gastrointestinal tract disorders (defined by Rome IV diagnostic criteria) are significantly more prevalent in patients with acromegaly compared with healthy age and sex matched controls in our study. Functional constipation is the most commonly reported problem. Poorer quality of life may in part be attributable to the increased prevalence of abdominal symptoms.

Pancreatic cancer (PC) remains one of the leading causes of cancer-related death in human sowing to missed early and effective diagnosis. The inability to translate research into clinical trials and to target chemotherapy drugs to tumors is a major obstacle in PC treatment. Compared with traditional cancer detection methods, the method combining existing clinical diagnosis and detection systems with nanoscale components using novel nanomaterials shows higher sensitivity and specificity. Nanomaterials can interact with biological systems to efficiently and accurately detect and monitor biological events during diagnosis and treatment. With the advance of experimental and engineering technology, more nanomaterials will begin the transition to clinical trials for their validation. This paper describes a number of nanomaterials used in the diagnosis and treatment of PC.

Crohn's disease with involvement of the esophagus, stomach and duodenum has a prevalence of 0.5% to 4% in symptomatic adult patients, but some studies have shown that these results may be underestimated, since upper gastrointestinal endoscopy is not performed routinely in the initial evaluation of the disease in adult patients, as it is in the pediatric population. In general, involvement of the upper gastrointestinal tract in Crohn's disease occurs concomitantly with involvement of the lower gastrointestinal tract. The diagnosis depends on clinical, endoscopic, histological and radiological evaluation. The presence of aphthoid ulcers, longitudinal ulcers, bamboo-joint-like appearance, stenoses and fistulas are endoscopic findings suggestive of the disease, and it is important to exclude the presence of Helicobacter pylori infection. The primary histological findings, which facilitate the diagnosis, are the presence of a chronic inflammatory process with a predominance of lymphoplasmacytic cells and active focal gastritis. The presence of epithelioid granuloma, although less frequent, is highly suggestive of the disease in the absence of chronic granulomatous disease. Treatment should include the use of proton pump inhibitors associated with corticosteroids, immunomodulators and biological therapy according to the severity of the disease.

Background: Inflammatory bowel disease (IBD) presents an inflammatory picture that in the long run can lead to complications and consequently more hospitalizations compared to other diseases.

Aim: To evaluate the influence of nutritional status on the occurrence of IBD-related hospitalization.

Methods: This integrative review was conducted in the online databases PubMed and MEDLINE, using the terms "obesity" and "malnutrition" accompanied by "hospitalization", each combined with "Crohn's disease" or "ulcerative colitis". Only studies conducted with humans, adults, and published in English or Spanish were selected, and those that were not directly associated with nutritional status and hospitalization were excluded from this review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyzes guide was used as the basis for selection of studies.

Results: Of the 80 studies identified, only five met the proposal of this review. None evaluated the association of good nutritional status with the risk of hospitalization. Malnutrition had a strong correlation with the risk of hospitalization related to IBD, and there was disagreement among three studies regarding the association of obesity and hospitalization rates.

Conclusion: Few studies have evaluated nutritional status as a predictor of IBD-related hospitalization. The presence of malnutrition appears to be associated with hospitalization in these patients, but further studies are needed to elucidate the issue.

Background: Patients with ulcerative colitis (UC) may be exposed to opioids over their disease duration. The use of such medications carries significant risk, including intestinal dysmotility and potential for addiction. However, the rates of narcotic use and misuse in patients with UC have not been studied extensively. Functional gastrointestinal disorders (FGID) are prevalent in patients with UC, and have been shown to increase the risk of narcotic use and misuse in patients with Crohn's disease. We hypothesized that patients with UC and a concurrent diagnosis of FGID would have increased rates of both opioid use and misuse in our patient cohort.

Aim: To evaluate the prevalence of chronic opioid use and misuse in UC.

Methods: A retrospective chart review of UC patients seen at the University of Virginia Digestive Health Center was performed on all patients evaluated between 2006 and 2011. Patient demographics, medical, surgical, and medication histories were obtained from the electronic medical record. Concomitant diagnosis of FGID was also noted at the time. The electronic prescription monitoring program was accessed to obtain prescription opioid filling histories. Prescription opioid misuse was defined as opioid prescriptions filled from four or more prescribers and four or more different pharmacies in a 12-mo period.

Results: A total of 497 patients with UC were included. Patients with UC and FGID were more likely to be female, but no other demographic variables were associated with FGID. Of the UC patients who had FGID, a greater proportion were found to be using opioids chronically (36% with FGID vs 9% without FGID, P < 0.0001) and were misusing prescription opioids (12.8% vs 1.3%, P < 0.001). Multivariate logistic regression demonstrated a significant association with FGID and chronic opioid use (OR = 4.50; 95%CI: 1.91-10.59) and opioid misuse (OR = 5.19; 95%CI 1.04-25.76). Tobacco use (OR 2.53; 95%CI: 1.06-6.08) and anxiety (OR 3.17; 95%CI: 1.08-9.26) were other variables associated with an increased risk of chronic narcotic use.

Conclusion: FGID was associated with a 4.5-fold increase in chronic opioid use and a 5-fold increased risk of opioid misuse in this patient cohort with UC.

Cirrhosis of liver is a major problem in the western world. Portal hypertension is a complication of cirrhosis and can lead to a myriad of pathology of which include the development of porto-systemic collaterals. Gastrointestinal varices are dilated submucosal veins, which often develop at sites near the formation of gastroesophageal collateral circulation. The incidence of varices is on the rise due to alcohol and obesity. The most significant complication of portal hypertension is life-threatening bleeding from gastrointestinal varices, which is associated with substantial morbidity and mortality. In addition, this can cause a significant burden on the health care facility. Gastrointestinal varices can happen in esophagus, stomach or ectopic varices. There has been considerable progress made in the understanding of the natural history, pathophysiology and etiology of portal hypertension. Despite the development of endoscopic and medical treatments, early mortality due to variceal bleeding remains high due to significant illness of the patient. Recurrent variceal bleed is common and in some cases, there is refractory variceal bleed. This article aims to provide a comprehensive review of the management of gastrointestinal varices with an emphasis on endoscopic interventions, strategies to handle refractory variceal bleed and newer endoscopic treatment modalities. Early treatment and improved endoscopic techniques can help in improving morbidity and mortality.

Background: A variety of immune-modulating drugs are becoming increasingly used for various cancers. Despite increasing indications and improved efficacy, they are often associated with a wide variety of immune mediated adverse events including colitis that may be refractory to conventional therapy. Although these drugs are being more commonly used by Hematologists and Oncologists, there are still many gastroenterologists who are not familiar with the incidence and natural history of gastrointestinal immune-mediated side effects, as well as the role of infliximab in the management of this condition.

Case summary: We report a case of a 63-year-old male with a history of metastatic renal cell carcinoma who presented to our hospital with severe diarrhea. The patient had received his third combination infusion of the anti-CTLA-4 monoclonal antibody Ipilimumab and the immune checkpoint inhibitor Nivolumab and developed severe watery non-bloody diarrhea the same day. He presented to the hospital where he was found to be severely dehydrated and in acute renal failure. An extensive workup was negative for infectious etiologies and he was initiated on high dose intravenous steroids. However, he continued to worsen. A colonoscopy was performed and revealed no endoscopic evidence of inflammation. Random biopsies for histology were obtained which showed mild colitis, and were negative for Cytomegalovirus and Herpes Simplex Virus. He was diagnosed with severe steroid-refractory colitis induced by Ipilimumab and Nivolumab and was initiated on Infliximab. He responded promptly to it and his diarrhea resolved the next day with progressive resolution of his renal impairment. On follow up his gastrointestinal side symptoms did not recur.

Conclusion: Given the increasing use of immune therapy in a variety of cancers, it is important for gastroenterologists to be familiar with their gastrointestinal side effects and comfortable with their management, including prescribing infliximab.

The modern lifestyle caters to an increase in the incidence of peptic ulcer disease, gastroesophageal reflux disease and several other acid-related conditions of the gut. The drugs to prevent these conditions work either through H2 receptor blockade or inhibition of the H⁺, K⁺ ATPase enzyme. Although proton pump inhibitors have been proven to be efficacious, they have a slow onset of action with limited resolution of symptoms in most patients. Potassium-competitive acid blockers (P-CABs) are novel drugs that bind reversibly to K⁺ ions and block the H⁺, K⁺ ATPase enzyme, thus preventing acid production. P-CABs have a fast onset of action and have dose-dependent effects on acid production. Animal studies exist that differentiate the better results of P-CABs from proton pump inhibitors; further human trials will give a comprehensive picture of the results and will help to elucidate the therapeutic benefits of this new group of drugs.

Aim: To analyze the relationships between pre-diagnosis coeliac serology, duodenal histopathology, primary presenting symptoms, coeliac-related comorbidity and response to treatment in a modern cohort with new diagnosis of coeliac disease (CD).

Methods: A retrospective cohort study including 99 participants diagnosed with CD between 1999 and 2013. All patients had the following data recorded: baseline characteristics, coeliac serology, small bowel histopathology. A subset of this cohort underwent a repeat small bowel biopsy. Independent associations were assessed with logistic regression.

Results: The mean age at diagnosis was 43 years (Interquartile range 30-53 years) and 68% of the cohort was female. At diagnosis 49 (49%) patients had total villous blunting (MS 3c), 12 (12%) had subtotal villous blunting (MS 3b), and 29 (29%) had partial villous blunting (MS 3a). The prevalence of symptoms pre diagnosis was not related to the severity of villous blunting (P = 0.490). 87 (88%) of the cohort underwent repeat small bowel biopsy after a median of 7 mo (IQR 6-11 mo). 34 (39%) patients had biopsy results ≥ MS 3a which compared to 90 (90%) at the initial biopsy. 24 (71%) of this group reported adherence to a gluten free diet (GFD). Persistent MS ≥ 3a at repeat biopsy was not associated with symptoms (P = 0.358) or persistent positive coeliac serology (P = 0.485).

Conclusion: Neither symptoms nor serology predict the severity of the small bowel mucosal lesion at CD diagnosis. Whilst a GFD was associated with histological improvement many patients with newly diagnosed CD had persistent mucosal damage despite many months of gluten restriction. Negative CD serology did not exclude ongoing mucosal injury.