Gastrointestinal Disorders

Cystic Fibrosis (CF) is the commonest inherited genetic disorder in Caucasians due to a mutation in the gene CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), and it should be considered as an Inherited Colorectal Cancer (CRC) Syndrome. In the United States, physicians of CF Foundation established the “Developing Innovative Gastroenterology Speciality Training Program” to increase the research on CF in gastrointestinal and hepatobiliary diseases. The risk to develop a CRC is 5–10 times higher in CF patients than in the general population and even greater in CF patients receiving immunosuppressive therapy due to organ transplantation (30-fold increased risk relative to the general population). Colonoscopy should be considered the best screening for CRC in CF patients. The screening colonoscopy should be started at the age of 40 in CF patients and, if negative, a new colonoscopy should be performed every 5 years and every 3 years if adenomas are detected. For transplanted CF patients, the screening colonoscopy could be started at the age of 35, in transplanted patients at the age of 30 and, if before, at the age of 30. CF transplanted patients, between the age of 35 and 55, must repeat colonoscopy every 3 years. Our review draws attention towards the clinically relevant development of CRC in CF patients, and it may pave the way for further screenings and studies. Full article

Introduction: Patients with symptoms (Sx) of gastrointestinal (GI) motor disorders have limitations in physical strength and mobility. We hypothesized that physical frailty correlated with severity of GI symptoms, and that a motility frailty index (MFI) could be constructed. Patients: We conducted a prospective pilot study on 40 patients, (38 F, 2 M, mean age 39.9 years) with the following diagnoses: 10 with diabetes mellitus and 30 with non-diabetic/idiopathic disorders. Upper and lower GI Sx were quantified using an FDA-compliant, traditional patient-reported outcomes (PRO) system. Methods: Patients underwent a series of physical performance measures involving standing balance (SB), usual walk speed (UW), and chair sit-and-stands (CS). A GI motility frailty index (MFI) was constructed by fitting several models with a combination of physical performance measures and correlating with PRO. Pearson’s correlation compared the constructed index with the GI Sx PRO to construct a GI MFI. Results: The studied patients collectively showed marked limitations in mobility compared with standard performance values with mean (sd) ratios of SB = 0.87 (0.20), UW = 0.45 (0.13), and CS = 0.38 (0.17). Correlations between physical mobility and GI Sx were noted for upper GI Sx (rho = 0.47, p = 0.002) but not for lower GI Sx. Conclusions: In this pilot study of patients with GI motility disorders, we found increased physical limitations on performance-based testing, which had a statistically significant positive correlation with severity of upper GI motor Sx using a standardized PRO system. A motility frailty index has been constructed that may serve as a basis for better quantifying limitations in patient mobility. Full article

Self-management is a multi-modal approach for managing chronic conditions that encompasses a number of different elements; knowledge, adherence, self-regulation, communication, and cognitive factors. Self-management has been shown to be beneficial for adults with inflammatory bowel disease (IBD), and for children with IBD it may help them learn to take control of their complex treatment regimens and lead to positive disease outcomes. The development of self-management skills for children with IBD is vital in order to maximize their potential for health autonomy, but it is still an emergent field in this population. This review provides an over-arching view of the self-management elements specific to children with IBD, and highlights outcome measures that may be used to assess skills within each field as well as the efficacy of targeted interventions. Full article

Preoperative risk stratification in cancer surgery is important to improve treatment and outcome. Sarcopenia is defined by progressive and generalized loss of skeletal muscle mass and strength and is now getting attention as a poor prognostic factor. The purpose of this review was to explore the impact of sarcopenia on short and long-term outcomes in patients undergoing surgical resection of gastrointestinal tumors. Recent studies suggest that sarcopenia contributes to postoperative complications and overall survival. The relatively simple evaluability, as well as its modifiable nature, provides an intriguing potential for sarcopenia to be included in standard preoperative clinical evaluation. Such evaluations can provide physicians with important information to target high-risk individuals with prophylactic measures and eventually improve surgical outcomes. Full article

Median arcuate ligament syndrome (MALS), otherwise called celiac artery compression syndrome (CACS), is an uncommon disorder that results from an anatomical compression of the celiac axis and/or celiac ganglion by the MAL. Patients typically present with abdominal pain of unknown etiology exacerbated by eating along with nausea, vomiting, and weight loss. MALS is a diagnosis of exclusion that should be considered in patients with severe upper abdominal pain, which does not correlate with the objective findings. The cardinal feature which is elicited in the diagnosis of MALS relies on imaging studies of the celiac artery, demonstrating narrowing during expiration. The definitive treatment is the median arcuate ligament’s surgical release to achieve surgical decompression of the celiac plexus by division of the MAL. This article describes our experience with this entity, focusing on symptom presentation, diagnostic challenges, and management, including long-term follow-up in four cases. Full article

Endoplasmic reticulum (ER) stress triggers a series of signaling and transcriptional events termed the unfolded protein response (UPR). Severe ER stress is associated with the development of fibrosis in different organs, including lung, liver, kidney, heart, and intestine. ER stress is an essential response of epithelial and immune cells in the pathogenesis of Inflammatory Bowel Disease (IBD), including Crohn’s disease (CD). Intestinal epithelial cells are susceptible to ER stress-mediated damage due to secretion of a large amount of proteins that are involved in mucosal defense. In other cells, ER stress is linked to myofibroblast activation, extracellular matrix production, macrophage polarization, and immune cell differentiation. This review focuses on the role of the UPR in the pathogenesis in IBD from an immunologic perspective. The roles of macrophage and mesenchymal cells in the UPR from in vitro and in vivo animal models are discussed. The links between ER stress and other signaling pathways, such as senescence and autophagy, are introduced. Recent advances in the understanding of the epigenetic regulation of the UPR signaling are also updated here. The future directions of development of the UPR research and therapeutic strategies to manipulate ER stress levels are also reviewed. Full article

Insufficient disease-related knowledge can be a barrier to the effective management of the unpredictable and lifelong course of inflammatory bowel disease (IBD). Patients with chronic illnesses have high non-adherence rates, with direct clinical consequences. While no single intervention strategy can improve the adherence of all patients, the success of attempts to improve patient adherence depends upon the realistic assessment of patients’ knowledge and their understanding of the regimen. The aim of this study was to assess the disease-specific knowledge of the parents and patients with IBD in the South Island of New Zealand, and identify areas of poor knowledge. Families of children diagnosed with IBD were asked to complete the IBD Knowledge Inventory Device (IBD-KID). Patients 10 years and older were asked to participate along with their parents. Of 110 families, 91 responded, with completed questionnaires received from 153 parents and 66 patients. Overall, parents scored significantly higher (13.64 ± 3.88) than their children (10.03 ± 4.07; p < 0.001). Areas of poor knowledge included aspects of treatment (both conventional and alternative), along with long-term disease outcomes. This study has shown clear areas of concern in this population’s disease-specific knowledge of their disease. This should be addressed through targeted education for both the patient and the parents to improve not only their knowledge, but also their adherence and disease self-management. Full article

Gastrointestinal (GI) tumors account for a quarter of all the cancer burden and a third of the global cancer-related mortality. Among them, some cancers retain a dismal prognosis; therefore, newer and innovative therapies are urgently needed in priority disease areas of high-unmet medical need. In this context, HER2 could be a relevant prognostic and predictive biomarker acting as a target for specific drugs. However, if the role of HER2 has been object of investigation for several years in gastric cancer, it is not well established in other GI malignancies. The aim of this narrative review was to portray the current landscape of the potential role of HER2 as a predictive biomarker for GI tumors beyond gastric cancer. In colon cancer, the benefit from anti-HER2 therapies is less clear than in gastric neoplasms for the lack of controlled studies. Pancreatic, biliary tract adenocarcinomas and hepatocarcinoma may derive a less clear clinical benefit by using anti-HER2 agents in HER2 positive tumors. Overall, the results are promising and seem to suggest that the integration of multiple modalities of therapies can optimize the cancer care. However, further prospective trials are needed to validate the use of personalized targeted therapies in this field. Full article

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and the fifth most common cancer worldwide. HCC is recognized as the fourth most common cause of cancer related deaths worldwide due to the lack of effective early diagnostic tools, which often leads to individuals going undiagnosed until the cancer has reached late stage development. The current FDA approved treatments for late stage HCC provide a minimal increase in patient survival and lack tumor specificity, resulting in toxic systemic side effects. Gene therapy techniques, such as chimeric antigen receptor (CAR)-T Cells, viral vectors, and nanoparticles, are being explored as novel treatment options in various genetic diseases. Pre-clinical studies using gene therapy to treat in vitro and in vivo models of HCC have demonstrated potential efficacy for use in human patients. This review highlights genetic targets, techniques, and current clinical trials in HCC utilizing gene therapy. Full article

Background: Malignant ureteral obstruction (MUO) is variable in presentation and there is no consensus on its management, especially when caused by gastrointestinal (GI) malignancies. Our aim was to describe our experience with this oncological complication. Methods: We retrospectively analyzed the outcomes of ureteral stent and nephrostomy tube (NT) positioning for GI-related MUO from 2010 to 2020. We performed descriptive analysis, survival analysis, and uni- and multi-variate analysis. Results: We included 51 patients. NT was mainly used when bladder involvement occurred and when MUO revealed an ex novo cancer diagnosis. Survival was poorer in patients with new diagnoses and in those receiving no treatment after decompression. Moreover, MUO caused by upper-GI tumors was related to shorter overall survival. Conclusions: GI tumors causing MUO should be considered of poor prognosis. Treatment decisions should be weighted accurately by both specialists and the patient. Full article

Eosinophilic esophagitis (EoE), an atopic disease of the esophagus, has become increasingly recognized over the last 15 years. The epidemiology of EoE has now been reported from many countries around the world. While the clinical diagnosis of this disease depends on the patient’s clinical manifestations, the final diagnosis should be made based on the histopathological examination of esophageal mucosal biopsies. In the diagnosis of EoE, to facilitate the appropriate treatment of patients, it is extremely important to precisely recognize the presence of eosinophils in biopsy specimens of the esophageal mucosa. If eosinophils are present, EoE patients should be referred to an allergist for appropriate management with dietary modification, pharmacological agents (including corticosteroids), and/or mechanical dilation of the esophagus. We herein present and recommend the use of direct fast scarlet staining for the easy and precise recognition of eosinophils in biopsy specimens of the esophageal mucosa, a technique that has been routinely used in our laboratory. Full article

The pandemic spread of obesity and type 2 diabetes is a serious health problem that cannot be contained with common therapies. At present, the most effective therapeutic tool is metabolic surgery, which substantially modifies the gastrointestinal anatomical structure. This review reflects the state of the art research in obesity and type 2 diabetes, describing the probable reason for their spread, how the various brain sectors are involved (with particular emphasis on the role of the vagal system controlling different digestive functions), and the possible mechanisms for the effectiveness of bariatric surgery. According to the writer’s interpretation, the identification of drugs that can modulate the activity of some receptor subunits of the vagal neurons and energy-controlling structures of the central nervous system (CNS), and/or specific physical treatment of cortical areas, could reproduce, non-surgically, the positive effects of metabolic surgery. Full article

Background: Gastric per oral endoscopic myotomy (GPOEM) was developed as a therapeutic option for gastroparesis after the pylorus was identified as a key target for gastroparesis management. This study includes a systematic literature review of studies in which GPOEM was utilized as therapy for gastroparesis. Methods: A literature search was conducted in three databases (MEDLINE, Scopus and Embase) of articles that included the keywords “GPOEM”, “Gastric per oral endoscopy myotomy” or “per oral pyloromyotomy” and “Gastroparesis” in the abstract or title. The search covered articles published until 29 February 2020. Results: A total of 139 articles were identified. Only 15 articles met the final inclusion criteria and were retrieved for qualitative data synthesis. Conclusion: GPOEM for gastroparesis is shown to have a high success rate among the studies but data interpretations are limited because of small sample sizes and short follow-up. Subjective and objective data prior to and post-GPOEM will be mandatory to establish credibility. The procedure is technically feasible and safe based on the limited studies available. Full article

Plummer-Vinson syndrome (PVS) is defined by the classic triad of dysphagia, esophageal web, and iron deficiency. It is a rare entity that remains poorly understood, and we describe our experience in diagnosing and management. Treatment for patients with PVS begins with aggressive dilation of the esophageal web (stricture), which has specific histopathology findings, thus helping to restore nutrition and facilitate iron absorption while also identifying other possible etiologies of iron deficiency, specifically underlying autoimmune conditions. We have reviewed the literature to place our experience in perspective and conclude that PVS now warrants a re-definition and a new perspective, which we discuss in this article. Full article

Tumor regression following neoadjuvant treatment can be observed in lymph node (LN) metastases similar to the primary tumor in esophageal adenocarcinomas (EAC). We evaluated the prognostic significance of tumor regression in LN metastases of locally advanced EAC of 239 patients treated with neoadjuvant radiochemotherapy (RCTX) or chemotherapy (CTX) followed by esophagectomy. We examined retrospectively the LN for histopathologic signs of regression, i.e., nodular fibrosis and acellular mucin. LN classification was performed according to two parameters: presence (−) or absence (+) of residual tumor and regression characteristics in the LN, resulting in four categories: LN−/REG−, LN−/REG+, LN+/REG+, LN+/REG−. In total, LN metastases with residual tumor were detectable in 117/239 (49%) cases. Regression in LN were observed in 85/239 cases (35.5%). The distribution of the LN/REG categories were as follows: 97 patients (40.6%) were LN−/REG−. A total of 25 patients (10.5%) were LN−/REG+. A total of 60 (25.1%) were LN+/REG+ and 57 (23.8%) LN+/REG−. The LN/Reg categorization had a significant prognostic value in univariate analysis (p < 0.001) and multivariate analysis (HR = 1.326; p = 0.002) with similar results for the subgroups of patients treated with RCTX or CTX. The prognosis of LN−/REG+ was worse than LN−/REG− but better than both LN+ categories, which was demonstrated in the Kaplan–Meier curves but did not reach statistical significance (p = 0.104 and p = 0.090, respectively). In contrast, there was no difference between LN+/REG+ and LN+/REG− (p = 0.802). In summary, regression in LN metastases of EAC can be observed in a significant number of patients after neoadjuvant therapy. Complete regression of former LN metastases in comparison to “true” negative LN seems to be of prognostic relevance but additional studies are needed to confirm this trend seen in our study. Full article

Obesity and related metabolic disorders, including chronic inflammation and enhanced oxidative stress, are closely associated with the development and progression of colorectal cancer. Previous epidemiological studies have demonstrated that increased serum uric acid is associated with the risk for various types of cancer, including colon cancer. This study examined the effects of a xanthine oxidase inhibitor allopurinol, widely used as a uric acid lowering medicine, on colorectal tumorigenesis in obese mice. Male C57BL/KsJ-db/db mice were injected with azoxymethane (15 mg/kg body weight) and then received drinking water containing allopurinol (30 mg/kg body weight) for fourteen weeks. At the time of sacrifice, allopurinol treatment significantly inhibited the development of colonic premalignant lesions. In the allopurinol-treated group, cellular proliferation in colonic mucosa was significantly suppressed, which was evaluated by the expression of proliferating cell nuclear antigen. Allopurinol also inhibited macrophage infiltration in the adipose tissue and decreased the serum level of TNF-α. The values of oxidative stress markers were markedly decreased in the allopurinol-treated group compared to those in the control group. These findings suggest that allopurinol attenuated chronic inflammation and decreased oxidative stress, preventing the development of colonic pre-neoplastic lesions in obesity-associated colon tumorigenesis model. Full article

Background: Organ preservation in the treatment of rectal cancer has seen an increase in interest. Clinical complete response (cCR) after high-dose chemoradiotherapy (CRT) allows for non-surgical management (NSM), but the selection of patients is challenging and standard clinical staging insufficient. MicroRNA-21-5p (miR-21) is ubiquitously upregulated in cancer and has been associated with treatment response in rectal cancer treated with standard preoperative CRT. The aim of the present study was to investigate this association in low rectal cancer treated in the NSM setting. Methods: Forty-eight patients from our single-arm phase II trial (NCT00952926) were eligible for analysis. All patients had resectable T2 or T3, N0–N1 low adenocarcinoma and received intensity-modulated radiotherapy plus brachytherapy boost and oral tegafur–uracil. Patients with cCR six weeks after end of treatment assessed by clinical examination, magnetic resonance imaging, and biopsy, were referred to observation and close follow-up. The miR expression in the diagnostic biopsies was measured by qPCR. The relationship between miR-21 expression and cCR was assessed using the Wilcoxon rank-sum test. Results: Thirty-eight patients had cCR after treatment and were allocated to observation while 10 patients had incomplete response and underwent surgery. MicroRNA-21 was successfully analyzed in all samples. The median tumor expression of miR-21 was significantly higher in patients with incomplete response than in those with cCR, 24.3 (95% confidence interval (CI) 17.1–36.8) and 16.6 (95% CI 13.9–21.1), respectively, p = 0.03. Conclusions: The present study adds to the evidence of the clinical impact of miR-21 in rectal cancer treated with CRT. The findings are comparable with results seen in patients treated in the standard preoperative setting and may assist in the selection of patients for an organ preserving approach. Full article