Gastrointest. Disord., Volume 2, Issue 4 (December 2020) – 13 articles

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

Human adrenomedullin (AM), a hypotensive peptide, also has anti-colitis activity. We prepared a polyethylene glycol (PEG) ylated form of AM through the conjugation of PEG-AM (1–15) and AM (15–52). Highly pure monomeric 20 kDa PEG-AM (20kPEG-AM) stimulated cyclic adenosine monophosphate production in HEK-293 cells stably expressing the type 1 AM receptor in a dose-dependent manner. The half-life of 20kPEG-AM was 7.4 h following subcutaneous administration in mice. We assessed the anti-colitis effect of subcutaneous 20kPEG-AM administration in the dextran sodium sulfate murine colitis model. Single and double subcutaneous injection of 20kPEG-AM significantly reduced total inflammation scores. These results suggest that 20kPEG-AM is a promising therapeutic candidate for the treatment of human inflammatory bowel diseases. Full article

Treatment for inflammatory bowel disease (IBD) deserves an informed shared decision-making process between patient and doctor. IBD spans a spectrum of phenotypes that impact each patient uniquely. While treatment has primarily consisted of medical or surgical therapy, dietary approaches have become increasingly relevant. A majority of patients with IBD use some form of dietary modification, and it is common for patients to do this without their physicians’ knowledge. Lack of medical supervision can lead to nutritional deficiencies and a worsening disease state. Some patients work with their medical team to pursue a well-defined exclusion diet as a primary therapy, such as the specific carbohydrate diet, exclusive enteral nutrition, or the Crohn’s disease exclusion diet. The motivations to use dietary therapy for IBD remain unclear and the effectiveness has not been definitively established for many approaches. It is necessary for medical providers to be knowledgeable and to foster open communication with their patients in order to ensure the highest likelihood of remission. This review provides an overview of dietary treatment options, the current knowledge about patient motivations for pursuing dietary therapy, and the roles of patient empowerment and patient activation. We outline areas of improvement for the decision-making process. Full article

Alterations in the mismatch repair (MMR) system result in genomic instability, neoantigen production, and immune response in cancer. There is evidence that gastroesophageal tumors with MMR deficiency may be susceptible to immune-checkpoint inhibitors treatment, especially in those presenting at advanced-stage disease. Although a number of biomarkers have been developed in histology-agnostic settings to assess MMR status, there is evidence that a tumor-specific testing approach would improve the selection of patients for immunotherapy. However, no testing methods have been developed specifically for gastroesophageal cancers so far. Here, we discuss the state of the art, current advances, and future perspectives of MMR-related biomarkers’ biologic and clinical role in gastroesophageal cancers. Full article

Iron supplementation and fortification are used to treat iron deficiency, which is often associated with gastrointestinal conditions, such as inflammatory bowel disease and colorectal cancer. Within the gut, commensal bacteria contribute to maintaining systemic iron homeostasis. Disturbances that lead to excess iron promote the replication and virulence of enteric pathogens. Consequently, research has been interested in better understanding the effects of iron supplementation and fortification on gut bacterial composition and overall gut health. While animal and human trials have shown seemingly conflicting results, these studies emphasize how numerous factors influence gut microbial composition. Understanding how different iron formulations and doses impact specific bacteria will improve the outcomes of iron supplementation and fortification in humans. Furthermore, discerning the nuances of iron supplementation and fortification will benefit subpopulations that currently do not respond well to treatment. Full article