Search Results (14)

Background and Clinical Significance: Foreign body ingestion represents an endoscopic emergency, with a risk of organ perforation of up to 35%, where increased prevalence was noticed among people with mental disorders and institutionalized patients. Case Presentation: The patient—male, 23 years old, and institutionalized for sequelae of infantile encephalopathy—was admitted for epigastric pain and hyperemetic syndrome that began 10 days earlier. Endoscopically, 12 hard plastic foreign bodies with sharp edges and sizes of 6–7 cm were identified, followed by extraction that was successfully performed in two sessions using a polypectomy snare and a Foreign Body Hood Protector. Additionally, multiple sessile exulcerated polypoid lesions were observed, measuring around 1–3 cm each, occupying the entire antrum. Histological examination showed inflammatory/regenerative elements, with features of moderate-to-high-grade dysplasia, while a rapid urease test for Helicobacter pylori infection was positive. As a consequence, the patient was administered triple eradication therapy. In addition, the patient presented marked features of hypereosinophilia and splenomegaly. Upon endoscopic reevaluation after 3 years and 8 months, no polyps were present and the H. pylori test was negative, while a complete and spectacular remission of both the hypereosinophilia and splenomegaly was observed. Conclusions: This case illustrates that the development and progression of gastric polyposis may be caused by the coexistence of chronic mucosal irritation from foreign bodies and H. pylori infection, which is a rare association. H. pylori eradication and endoscopic removal of the foreign bodies resulted in significant mucosal improvement. Full article

Background/Objectives: Fundic gland polyps (FGPs) are the most common type of gastric polyp and have increased in prevalence in the proton pump inhibitor (PPI) era. Although traditionally considered benign, dysplasia has been described in both syndromic and sporadic FGPs; data from Asian cohorts remain limited. We evaluated the prevalence of FGPs with dysplasia (FGPD) and described associated clinical and endoscopic features in a Taiwanese tertiary-care cohort. Methods: We retrospectively searched institutional pathology archives for all gastric biopsy or polypectomy specimens diagnosed as FGP between January 2000 and December 2024 and mapped these specimens to unique patients using medical record numbers. Candidate dysplastic cases underwent slide review by gastrointestinal pathologists to confirm FGPD and grade dysplasia as low- or high-grade according to standard gastric dysplasia criteria. Cases were classified as syndromic if a hereditary polyposis syndrome was documented; otherwise, they were classified as sporadic. Clinical and endoscopic variables were abstracted from electronic medical records. Patient-level prevalence estimates among patients with FGP are reported with exact 95% confidence intervals (CIs). Results: Among 35,806 unique patients with histologically confirmed FGP, 25 FGPD cases were confirmed (21 sporadic, 4 syndromic). The patient-level prevalence of sporadic FGPD was 0.059% (21/35,806; 95% CI: 0.036–0.090%). Among sporadic cases, dysplasia was low-grade in 19 (90.5%) and high-grade in 2 (9.5%). Sporadic cases occurred at a median age of 48 years (interquartile range [IQR]: 37–63.5 years), and 57.1% were female. Documented PPI exposure before the index FGPD endoscopy was present in 33.3% of patients (median documented duration: 36 months [IQR: 12–125]). No case had documented current Helicobacter pylori infection at the index evaluation. Endoscopically, sporadic FGPDs were commonly multiple, sessile, located in the gastric body/fundus, and small (median size: 0.5 cm [IQR: 0.3–0.575]). Conclusions: Sporadic FGPD was exceedingly rare in this 25-year Taiwanese cohort and was predominantly low-grade. Although typically small and body/fundus-predominant, FGPs with erythema or surface irregularity—particularly with irregular microvascular patterns on narrow-band imaging—should prompt histologic assessment to exclude dysplasia. Full article

Familial adenomatous polyposis (FAP) is the most common hereditary colorectal adenomatous polyposis and cancer syndrome which has historically been associated with a near absolute risk of colorectal cancer. However, the morbidity and mortality from colorectal cancer has been greatly diminished by pre-symptomatic genetic testing which identifies affected individuals and by appropriately timed, risk-reducing surgery of the colorectum. Following colorectal surgery, cancer risk beyond the retained rectum or ileal pouch includes other gastrointestinal organs, especially those of the upper gastrointestinal tract. While genotype–phenotype correlations exist for the severity of colonic polyposis, they have not been demonstrated for upper gastrointestinal tract manifestations. We reviewed the impact of ethnicity on the upper gastrointestinal manifestations of FAP by a comparison of published data in patients with FAP from Asian and Western countries. Our main findings demonstrate that following risk-reducing surgery to mitigate colorectal cancer risk, patients with FAP remain at increased risk for upper gastrointestinal polyposis and cancer. The duodenal and gastric phenotype differs between patients with FAP from the West and the East, and all should be followed in a multidisciplinary surveillance program. Following risk-reducing surgery to mitigate colorectal cancer risk, patients with familial adenomatous polyposis remain at increased risk for upper gastrointestinal polyposis and cancer. The duodenal and gastric phenotype differs between patients with FAP from the West and the East, and all should be followed in a multidisciplinary surveillance program. Full article

Background/Objectives: Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a recently discovered autosomal dominant transmission disease. Patients with this condition have a higher risk of developing gastric cancer. There are numerous questions regarding the natural history of this condition, as well as concerning the diagnostic and therapeutic management of these patients. In this systematic review, we aimed to examine the current literature to determine the role of prophylactic gastrectomy in patients diagnosed with gastric adenocarcinoma and proximal polyposis of the stomach. Additional outcomes are Helicobacter pylori (HP) infection, treatment with proton pump inhibitors (PPI), and colonoscopic examination and abdominal imaging examination, as they are important factors in the therapeutic decision. Methods: We performed a systematic review of the articles published in PubMed and Google Scholar, according to the PRISMA 2020 criteria. Results: We obtained 24 studies that included 83 patients diagnosed with GAPPS, of which 42 underwent prophylactic gastrectomy, 24 benefited from endoscopic follow-up, and 17 were diagnosed with gastric cancer at the first gastroscopic examination. In the prophylactic gastrectomy specimens, malignant gastric disease was confirmed in 10% of cases. GAPPS has been diagnosed more frequently in women. Conclusions: So far, the specialized literature includes a limited number of patients diagnosed with GAPPS. There are also no guidelines yet for the diagnosis and treatment of these patients. Prophylactic gastrectomy or endoscopic surveillance are the only options for patients diagnosed with GAPPS without gastric cancer at the initial examination. For prophylactic gastrectomy, the robotic and laparoscopic approach was preferred. For establishing appropriate lymphadenectomy in prophylactic gastrectomy, future research on gastrectomy specimens is necessary. Most of the included studies were deficient in terms of postoperative follow-up of patients. Thus, we consider it useful to include these patients in a single database. For a comprehensive examination of these and making an appropriate therapeutic decision, we consider it necessary to perform a colonoscopic evaluation, take abdominal imaging, and determine the Helicobacter pylori infection status. Full article

The Wnt signaling pathway is critical in the onset and progression of gastrointestinal (GI) cancers. Anomalies in this pathway, often stemming from mutations in critical components such as adenomatous polyposis coli (APC) or β-catenin, lead to uncontrolled cell proliferation and survival. In the case of colorectal cancer, dysregulation of the Wnt pathway drives tumor initiation and growth. Similarly, aberrant Wnt signaling contributes to tumor development, metastasis, and resistance to therapy in other GI cancers, such as gastric, pancreatic, and hepatocellular carcinomas. Targeting the Wnt pathway or its downstream effectors has emerged as a promising therapeutic strategy for combating these highly aggressive GI malignancies. Here, we review the dysregulation of the Wnt signaling pathway in the pathogenesis of GI cancers and further explore the therapeutic potential of targeting the various components of the Wnt pathway. Furthermore, we summarize and integrate the preclinical evidence supporting the therapeutic efficacy of potent Wnt pathway inhibitors with completed and ongoing clinical trials in GI cancers. Additionally, we discuss the challenges of Wnt pathway-targeted therapies in GI cancers to overcome these concerns for effective clinical translation. Full article

Multiple gastric polyps are observed in various polyposis syndromes and conditions associated with polypoid lesion development in the stomach. Polyposis syndromes often occur concurrently with specific malignant tumors and can manifest at any point in an individual’s lifespan, thus explaining the diversity in surveillance methods. Furthermore, genetic counseling and surveillance are essential not only for the patients themselves but also for their blood relatives. Therefore, the accurate diagnosis and appropriate surveillance of multiple gastric polyps are crucial for improving patient outcomes. This review aims to provide essential information on such lesions along with representative endoscopic images of familial adenomatous polyposis, Peutz-Jeghers syndrome, Cowden syndrome, Cronkhite-Canada syndrome, juvenile polyposis syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, neuroendocrine tumors in autoimmune gastritis, proton pump inhibitor-related gastric mucosal changes, and multiple submucosal heterotopic glands. We wish for this review to serve as a valuable resource for endoscopists seeking to deepen their comprehension of gastric polyposis. Full article

Background: We evaluated the phenotype of sporadic gastric cancer based on HP status and binding of a tumor risk marker monoclonal, Adnab-9. Methods: We compared a familial GC kindred with an extremely aggressive phenotype to HP-positive (HP+) and -negative (HP−) sporadic gastric adenocarcinoma (GC) patients in the same community to determine if similar phenotypes exist. This might facilitate gene discovery to understand the pathogenesis of aggressive GC phenotypes, particularly with publications implicating immune-related gene-based signatures, and the development of techniques to gauge the stance of the innate immune system (InImS), such as the FERAD ratio (blood ferritin:fecal Adnab-9 binding OD-background binding). Resection specimens for the sporadic and familial group were stained for HP and examined for intestinal metaplasia (IM) and immunostaining for Adnab-9. Familial kindred specimens were also tested for the E-cadherin mutation and APC (adenomatous polyposis coli). Survival was evaluated. Results: Of 40 GC patients, 25% were HP+ with a greater proportion of intestinal metaplasia (IM) and gastric atrophy than the HP− group. The proband of the familial GC kindred, a 32-year-old mother with fatal GC, was survived by 13-year-old identical twins. Twin #1 was HP− with IM and Twin #2 was HP+. Both twins subsequently died of GC within two years. The twins did not have APC or E-cadherin mutations. The mean overall survival in the HP+ sporadic GC group was 2.47 ± 2.58 years and was 0.57 ± 0.60 years in the HP− group (p = 0.01). Survival in the kindred was 0.22 ± 0.24 years. Adnab-9 labeling was positive in fixed tissues of 50% of non-familial GC patients and in gastric tissue extract from Twin #2. The FERAD ratio was determined separately in six prospectively followed patient groups (n = 458) and was significantly lower in the gastric cancer patients (n = 10) and patients with stomach conditions predisposing them to GC (n = 214), compared to controls (n = 234 patients at increased risk for colorectal cancer but without cancer), suggesting a failure of the InImS. Conclusion: The HP+ sporadic GC group appears to proceed through a sequence of HP infection, IM and atrophy before cancer supervenes, and the HP− phenotype appear to omit this sequence. The familial cases may represent a subset with both features, but the natural history strongly resembles that of the HP− group. Two different paths of carcinogenesis may exist locally for sporadic GC. The InImS may also be implicated in prognosis. Identifying these patients will allow for treatment stratification and early diagnosis to improve GC survival. Full article

Familial adenomatous polyposis (FAP) is an autosomal dominant disease caused by a germline mutation in the adenomatous polyposis coli (APC) gene. Patients with FAP develop up to thousands of colorectal adenomas as well as lesions in the upper GI tract. In FAP, the upper digestive lesions include gastric fundic gland polyps (FGPs), antrum adenomas, duodenal or small intestinal adenomas, and carcinoma. Patients, after colectomy, are still at significant risk for extracolonic malignancies. Advances in endoscope resolution and optical enhancement technologies allow endoscopists to provide assessments of benign and malignant polyps. For this reason, in the past decades, endoscopic resection techniques have become the first line of treatment in patients with polyps in the upper GI, whereby polyps and even early cancers can be successfully cured. In FAP patients, endoscopic ampullectomy appears to be a safe and effective way of treating patients with ampullary tumors. According to current indications, endoscopic retrograde cholangiopancreatography (ERCP) and stenting of the main pancreatic duct follow ampullectomy. Full article

A predictive marker for the development of synchronous/metachronous gastric cancer (GC) would be highly desirable in order to establish an effective strategy for endoscopic surveillance. Herein, we examine the significance of gastric xanthelasma (GX) and molecular abnormalities for the prediction of synchronous/metachronous GC. Patients (n = 115) were followed up (range, 12–122; median, 55 months) in whom the presence of GX and molecular alterations, including microsatellite instability (MSI) and methylation of human mutL homolog 1 (hMLH1), cyclin-dependent kinase inhibitor 2A (CDKN2A) and adenomatous polyposis coli (APC) genes, had been confirmed in non-neoplastic gastric mucosa when undergoing endoscopic submucosal dissection (ESD) for early GC. At the start of surveillance, the numbers of positive subjects were as follows: GX, 59 (51.3%); MSI, 48 (41.7%); hMLH1, 37 (32.2%); CDKN2A, 7 (6.1%); APC, 18 (15.7%). After ESD treatment, synchronous/metachronous GCs occurred in patients with the following positive factors: GX, 16 (27.1%); MSI, 7 (14.6%); hMLH1, 6 (16.2%); CDKN2A, 3 (42.9%); APC, 3 (16.7%). The presence of GX had no significant relationship to positivity for MSI or methylation of hMLH1, CDKN2A or APC. GX was significantly (p = 0.0059) and independently (hazard ratio, 3.275; 95% confidence interval, 1.134–9.346) predictive for the development of synchronous/metachronous GC, whereas those genetic alterations were not predictive. GX is a simple and powerful marker for predicting the development of synchronous or metachronous GC. Full article

Laparoscopic–endoscopic “rendezvous” procedures were introduced in surgery for common bile duct stone treatment but are now widely used in other fields of abdominal surgery. An endoscopist navigates a surgeon during the same operative procedure and, thus, enables a better visualization of the location, resection margins, bleeding control, less thermal damage, etc. Here, we present case series of 11 patients that were treated using a “rendezvous” procedure for gastrointestinal lesions on different parts of the gastrointestinal tract such as juvenile polyps on the colon (transversum, ascendens, cecum, sigma), leiomyomatosis of the stomach, Peutz–Jeghers intestinal polyposis, hyperplastic gastric polyp, ectopic pancreatic tissue in the stomach, gastric trichobezoar, and gastric schwannoma. “Rendezvous” procedures are suitable for intestinal lesions that could not be resected endoscopically due to their size, morphology and/or location. In our experience this procedure should be used for endoscopically unresectable lesions as it decreases the time of surgery, possibility of iatrogenic injury, bleeding and technical inability. Furthermore, this procedure has been shown to better navigate the surgeon during laparoscopic surgery, especially in treating polyps in particularly difficult locations such as the duodenum or cecum, and it decreases conversion rates. However, conversion is sometimes necessary, in order to assure all oncological principals are respected, and the best option in some cases. Full article

The wider use of gastrointestinal endoscopic procedures has led to an increased detection of small intestinal preneoplastic and neoplastic epithelial lesions, most of which are identified in the duodenum and ampullary region. Like their malignant counterparts, small intestinal glandular precursor lesions, which include adenomas and hamartomas, may arise sporadically or be associated with hereditary tumor syndromes, such as familial adenomatous polyposis, MUTYH-associated polyposis, Lynch syndrome, Peutz-Jeghers syndrome, juvenile polyposis syndrome, and Cowden syndrome. In addition, dysplastic, preinvasive lesions have been observed adjacent to small bowel adenocarcinomas complicating immune-related disorders, such as celiac or Crohn’s disease. Adenomatous lesions may exhibit an intestinal-type, gastric-type, or, very rarely, serrated differentiation, related to different molecular pathogenetic mechanisms. Finally, in the background of multiple endocrine neoplasia 1 syndrome, precursor neuroendocrine growths have been described. In this review we offer a comprehensive description on the histo-molecular features of the main histotypes of small bowel epithelial precursors lesions, including: (i) sporadic adenomas (intestinal-type and gastric-type; non-ampullary and ampullary); (ii) syndromic adenomas; (iii) small bowel dysplasia in celiac and Crohn’s disease; (iv) serrated lesions; (v) hamartomatous lesions; and (vi) neuroendocrine precursor lesions. Full article

Familial adenomatous polyposis (FAP) is an autosomal-dominant condition characterized by the presence of multiple colorectal adenomas, caused by germline variants in the adenomatous polyposis coli (APC) gene. More than 300 germline variants have been characterized. The detection of novel variants is important to understand the mechanisms of pathophysiology. We identified a novel pathogenic germline variant using next-generation sequencing (NGS) in a proband patient. The variant is a complex rearrangement (c.422+1123_532-577 del ins 423-1933_423-1687 inv) that generates a complete deletion of exon 5 of the APC gene. To study the variant in other family members, we designed an endpoint PCR method followed by Sanger sequencing. The variant was identified in the proband patient’s mother, one daughter, her brother, two cousins, a niece, and a second nephew. In patients where the variant was identified, we found atypical clinical symptoms, including mandibular, ovarian, breast, pancreatic, and gastric cancer. Genetic counseling and cancer prevention strategies were provided for the family. According to the American College of Medical Genetics (ACMG) guidelines, this novel variant is considered a PVS1 variant (very strong evidence of pathogenicity), and it can be useful in association with clinical data for early surveillance and suitable treatment. Full article

APC and MUTYH genes are mutated in 70–90% and 10–30% of familial adenomatous polyposis cases (FAP) respectively. An association between mutation localization and FAP clinical phenotype is reported. The aims of this study were to determine APC and MUTYH mutational status in a small cohort of FAP patients and to evaluate the genotype-phenotype correlation in mutated patients. Here, we report the identification of a novel APC germline mutation, c.510_511insA. Overall, mutational analysis showed pathogenic mutations in 6/10 patients: 5/10 in APC and 1/10 in MUTYH. Additionally, we found three variants of unknown significance in MUTYH gene that showed no evidence of possible splicing defects by in silico analysis. Molecular analysis was also extended to family members of mutated patients. A genotype-phenotype correlation was observed for colonic signs whereas a variation of disease onset age was revealed for the same mutation. Moreover, we found an intrafamilial variability of FAP onset age. Regarding extracolonic manifestations, the development of desmoid tumors was related to surgery and not to mutation position, while a genotype-phenotype correspondence was observed for the onset of thyroid or gastric cancer. These findings can be useful in association to clinical data for early surveillance and suitable treatment of FAP patients. Full article

Lynch syndrome (LS) and familial adenomatous polyposis (FAP) are autosomal dominant hereditary diseases caused by germline mutations leading to the development of colorectal cancer. Moreover, these mutations result in the development of a spectrum of different tumors, including gastric cancers (GCs). Since the clinical characteristics of GCs associated with LS and FAP are not well known, we investigated clinical and molecular features of GCs occurring in patients with LS and FAP attending our Institution. The Hereditary Tumor Registry was established in 1994 at the Department of Oncologic Gastroenterology, CRO Aviano National Cancer Institute, Italy. It includes 139 patients with LS and 86 patients with FAP. Patients were recruited locally for prospective surveillance. Out of 139 LS patients, 4 developed GC—3 in the presence of helicobacter pylori infection and 1 on the background of autoimmune diseases. All GCs displayed a high microsatellite instability (MSI-H) and loss of related mismatch repair (MMR) protein. One of the FAP patients developed a flat adenoma, displaying low-grade dysplasia at the gastric body, and another poorly differentiated adenocarcinoma with signet ring cells like Krukenberg without HP infection. LS carriers displayed a risk of GC. The recognition of HP infection and autoimmune diseases would indicate those at higher risk for an endoscopic surveillance. Regarding FAP, the data suggested the need of suitable endoscopic surveillance in long survivals with diffuse fundic gland polyps. Full article