Intestinal Type Research Articles

A tuft cell - ILC2 signaling circuit provides therapeutic targets to inhibit gastric metaplasia and tumor development

Although gastric cancer is a leading cause of cancer-related deaths, systemic treatment strategies remain scarce. Here, we report the pro-tumorigenic properties of the crosstalk between intestinal tuft cells and type 2 innate lymphoid cells (ILC2) that is evolutionarily optimized for epithelial remodeling in response to helminth infection. We demonstrate that tuft cell-derived interleukin 25 (IL25) drives ILC2 activation, inducing the release of IL13 and promoting epithelial tuft cell hyperplasia. While the resulting tuft cell - ILC2 feed-forward circuit promotes gastric metaplasia and tumor formation, genetic depletion of tuft cells or ILC2s, or therapeutic targeting of IL13 or IL25 alleviates these pathologies in mice. In gastric cancer patients, tuft cell and ILC2 gene signatures predict worsening survival in intestinal-type gastric cancer where ~40% of the corresponding cancers show enriched co-existence of tuft cells and ILC2s. Our findings suggest a role for ILC2 and tuft cells, along with their associated cytokine IL13 and IL25 as gatekeepers and enablers of metaplastic transformation and gastric tumorigenesis, thereby providing an opportunity to therapeutically inhibit early-stage gastric cancer through repurposing antibody-mediated therapies.

The central role of gastrin in gastric cancer.

The prevalence of gastric cancer has markedly declined, but due to the high mortality rates associated with gastric cancer, it is still a serious disease. The preferred classification of gastric cancer is according to Lauren into either the intestinal type, which has a glandular growth pattern, or the diffuse type, which does not have glandular structures. Both types have been classified as adenocarcinomas, with the latter type based on periodic acid-Schiff (PAS) positivity presumed to reflect mucin. However, the presence of mucin in the diffuse type, in contrast to neuroendocrine/enterochromaffin-like (ECL) cell markers, has not been confirmed by immunohistochemistry and in situ hybridization. The ECL cells are probably prone to becoming cancerous because they do not express E-cadherin. Gastric cancer is unique in that a bacterium, Helicobacter pylori, is thought to be its main cause. H. pylori predisposes infected individuals to cancer only after having caused oxyntic atrophy leading to gastric hypoacidity and hypergastrinemia. No single H. pylori factor has been convincingly proved to be carcinogenic. It is probable that gastrin is the pathogenetic factor for gastric cancer due to H. pylori, autoimmune gastritis, and long-term prolonged inhibition of gastric acid secretion. Hypergastrinemia induces ECL cell hyperplasia, which develops into neuroendocrine tumors (NETs) and then into neuroendocrine carcinomas in rodents, a sequence that has also been described in humans. During carcinogenesis, the tumor cells lose specific traits, requiring that sensitive methods be used to recognize their origin. Gastric cancer occurrence may hopefully be prevented by H. pylori eradication at a young age, and by the reduced use of inhibitors of acid secretion and use of a gastrin antagonist in those with previous long-term H. pylori infection and those with autoimmune gastritis.

Intestinal flora, intestinal metabolism, and intestinal immunity changes in complete Freud's adjuvant-rheumatoid arthritis C57BL/6 mice

Rheumatoid arthritis (RA) is an inflammatory-mediated autoimmune disease characterized by persistent joint enlargement, synovial cartilage damage, and inflammatory infiltrates. Although the pathogenesis and treatment of RA are still currently insufficient, the importance of the intestine flora, metabolism and immunity for RA has been gradually recognized, and many intestine regulatory strategies have been used to treat RA. However, the relationship between RA and intestine flora, metabolism and immunity has not been fully expounded. In this study, Complete Freund's Adjuvant (CFA) was used to establish RA model, CyTOF technology was used to study the changes of intestinal immune cell types, 16S rRNA technology was used to analyze the differences of intestinal flora, and LC-MS technology was used to explain the effects of metabolites produced by the changed intestinal flora on RA. Moreover, we systematically explored how the imbalance of intestinal flora changed the intestinal immune status through its metabolites in RA mice. Our results showed that the intestinal flora of RA mice changed significantly, and the bacteria producing short-chain fatty acids (SCFAs), indole classes and secondary bile acids were significantly reduced. The abundance of SCFAs, indole classes and secondary bile acids in the intestine were significantly decreased. The balance of immune cells in the intestine of RA mice was significantly disrupted, with an overall decrease in immune cells. This work reveals the possible relationship between intestinal flora, metabolism and immunity and RA in mice, which will provide new therapeutic strategies for RA.

Exposure to benzo(a)pyrene interfered with cell composition and immune ability of common carp (Cyprinus carpio) intestine through inducing cell heterogeneous responses

The intricate heterogeneity of fish intestinal cell types response to environmental stressors has remained largely unaddressed due to previous technological limitations. Emerging single-cell sequencing technology (scRNA-seq), derived from the 2010s, may be a key breakthrough in this area, which could accurately obtain the transcriptome of each cell. In this context, common carp (Cyprinus carpio), which takes the intestine as the main immune organ, was selected as the test subject in this study. The study, mainly based on single-cell sequencing technology and supplemented by gas chromatography mass spectrometry (GC/MS), histological sectioning techniques and transcriptome analysis, revealed the detailed heterogeneity responses of intestinal cells in common carp after benzo(a)pyrene (B[a]P) exposure. Our findings showed a dose-dependent effect on B[a]P accumulation within the common carp intestine as the B[a]P concentration increased. B[a]P exposure led to mucous lamina propria edema and confluent intestinal villi. The high concentration group exhibited uneven and adherent intestinal villi, an abnormal decrease in mucosal epithelial cells, vacuolation, and an anomalously widened base thickness.In the intestinal atlas, an increased proportion of T_cells and a decreased proportion of ECs were identified as the most significant features. These changes primarily affected the intestine by impairing development processes and boosting immunocompetence. A comprehensive analysis of the heterogeneous responses of ECs and T_cells to B[a]P exposure revealed that the lysosome-phagosome pathway, strengthened by the “Lysosome” pathway in the EC1 subset and the “Phagosome” pathway in T_cell 2 subset, might be one of the most critical defense mechanisms within the common carp's intestine. In conclusion, our research presents the first description of the intestinal atlas and the heterogeneous responses in common carp following B[a]P exposure. Our findings enrich the understanding of the impact of polyaromatic hydrocarbons, exemplified by B[a]P, on cyprinidae fish.

Tuberculosis: A rare cause of acute abdomen in pediatric patients - surgical considerations

BackgroundAbdominal tuberculosis (ATB) is a rare presentation of tuberculosis (TB) in pediatric patients, and its diagnosis can be challenging. This study aimed to analyze the role of surgery in patients with ATB presenting with acute abdomen. MethodsWe conducted a retrospective analysis of pediatric patients under 18 years of age who underwent surgical intervention for acute abdomen (AA) and were diagnosed with ATB at a tertiary-care center in Latin America between June 2003 and March 2023. The diagnosis was confirmed through histopathology or bacteriological analysis. Demographics, clinical presentation, diagnostic methods, and operative findings were collected, and surgical procedures and postoperative outcomes were assessed. ResultsFifteen patients were included in the study. Symptoms and signs were nonspecific. Imaging studies revealed ascites, adenopathies, and intestinal wall thickening, among other findings. Histopathological examination with identification of caseating granulomas proved essential for diagnosis. The peritoneal form was the most frequent presentation, followed by the intestinal type. There were no differences between stoma reversal surgery performed during or after treatment. Complications were observed in 73 % of cases, with intestinal perforation being the most common one. ConclusionAccurate diagnosis of ATB in pediatric patients with acute abdomen is crucial to avoid unnecessary surgeries. Surgery in acute ATB is indicated to manage intestinal complications however surgical management should be approached cautiously. Conservative procedures, such as biopsies and drainage, are recommended when intraoperative findings reveal ATB. Level of evidenceLevel III, Retrospective study

Kinesin Family Member B18 Is Related to Gastric Mucin Phenotype and Contributes to Gastric Cancer Progression by Regulating Epithelial-Mesenchymal Transition

Introduction: Gastric cancer (GC) remains a common health concern worldwide and is the third leading cause of death in Japan. It can be broadly classified into gastric and intestinal mucin phenotypes using immunohistochemistry. We previously reported numerous associations of kinesin family member (KIF) genes and mucin phenotypes with GC. However, no previous studies have reported on the importance of KIF18B in GC using immunostaining. Thus, in this study, we investigated the expression and functions of KIF18B, which is highly expressed in gastric mucin phenotype GC. Methods: We performed RNA-seq of gastric and intestinal mucin type GCs, and clinicopathological studies of the KIF18B we found were performed using 96 GC cases. We also performed functional analysis using GC-derived cell lines. Result: RNA-seq showed the upregulation of matrisome-associated genes in gastric mucin phenotype GC and a high expression of KIF18B. KIF18B was detected in 52 of the 96 GC cases (54%) through immunohistochemistry. Low KIF18B expression was significantly associated with poor overall survival (p < 0.01). Other molecules that were significantly associated with KIF18B were MUC5AC and claudin 18; these were also significantly associated with the gastric mucin phenotype. KIF18B small interfering RNA (siRNA)-transfected GC cells showed greater growth and spheroid colony formation than the negative control siRNA-transfected cells. Furthermore, expression of snail family transcriptional repressor 1 and cadherin 2 was significantly increased and that of cadherin 1 was significantly decreased in KIF18B siRNA-transfected GC cells. Conclusion: These findings not only suggest that KIF18B may be a useful prognostic marker, but also provide insight into the pathogenesis of the GC phenotype.

Pathophysiological mechanisms of adaptation of the mucosa of the gastric cardia to portal hypertension

The model of before- and intrahepatic blockage of the portal system was proposed. Modeling of before-hepatic blockage of the portal system after development of toxic liver dystrophy lead to formation of the liver cirrhosis with stable portal hypertension. Gastritis with signs of hyperplastic and atrophy processes of the mucosa, formation of erosia, inflammatory infiltration of intermediate tissue and rebuilding of the glandulae were the basis of morphological changes of gastric mucosa in rats with experimental before- and intrahepatic portal blockage. Transformation of the cardiac mucosa with expressed polymorphism occured in the patients with the portal liver cirrhosis. Dystrophic and necrobiotic changes typical of hepatic gastropathy with signs of acute or chronic gastritis, formation of inflammatory infiltrates and rebuilding of the cardial mucosa into intestinal type were established microscopically. It is possible to believe that a widening of the veins leads to venous hyperemia and stasis in the portal hypertension. Therefore the morphology of the gastric mucosa was disturbed. It was accompanied bythe indurate changes and cellular destruction with erosia formation. These erosia may be a cause of rupture of the gastric mucosa in strong vomiting in Mallory-Weiss syndrome. This hypothesis needs clinic and experimental study in the future.

1651P Comparison of surgical outcome and prognostic factors between pancreaticobiliary and intestinal types of periampullary adenocarcinoma following pancreaticoduodenectomy

1651P Comparison of surgical outcome and prognostic factors between pancreaticobiliary and intestinal types of periampullary adenocarcinoma following pancreaticoduodenectomy

Establishment of a 96-well transwell system using primary human gut organoids to capture multiple quantitative pathway readouts

Disruptions in the gut epithelial barrier can lead to the development of chronic indications such as inflammatory bowel disease (IBD). Historically, barrier function has been assessed in cancer cell lines, which do not contain all human intestinal cell types, leading to poor translatability. To bridge this gap, we adapted human primary gut organoids grown as monolayers to quantify transcription factor phosphorylation, gene expression, cytokine production, and barrier function. In this work we describe and characterize a novel 96-well human gut organoid-derived monolayer system that enables quantitative assessment of candidate therapeutics. Normal human intestine differentiation patterns and barrier function were characterized and confirmed to recapitulate key aspects of in vivo biology. Next, cellular response to TNF-α (a central driver of IBD) was determined using a diverse cadre of quantitative readouts. We showed that TNF-α pathway antagonists rescued damage caused by TNF-α in a dose-dependent manner, indicating that this system is suitable for quantitative assessment of barrier modulating factors. Taken together, we have established a robust primary cell-based 96-well system capable of interrogating questions around mucosal response. This system is well suited to provide pivotal functional data to support translational target and drug discovery efforts.

Toll-like receptors 1, 2, 4, 5, and 6 in gastric cancer.

Toll-like receptors (TLRs) are expressed on both immune cells and tumor cells, triggering both anti-tumor and pro-tumor responses. Therefore, TLRs have potential as prognostic biomarkers and immunotherapeutic targets. The aim of this study was to investigate TLR1, TLR2, TLR4, TLR5, and TLR6 expression and association with clinicopathological variables and survival in gastric cancer. Immunohistochemical study on cancer specimens from 564 resected gastric cancer patients was performed using tissue microarrays. The association between patient survival and TLR expression was calculated with Cox regression adjusted for confounding factors. Patients with high cytoplasmic TLR2 expression had significantly poorer 5-year survival than the low cytoplasmic TLR2 expression group in multivariate analysis (adjusted HR 1.38, 95% CI 1.11-1.71), and this estimate was similar in intestinal type (adjusted HR 1.33, 95% CI 0.98-1.80) and diffuse type (adjusted HR 1.48, 95% CI 1.06-2.05) histology subgroups. Patients with high cytoplasmic TLR6 expression group had significantly better 5-year survival compared with low cytoplasmic TLR6 expression group in multivariate analysis (adjusted HR 0.74, 95% CI 0.60-0.91). In the subgroup analysis of diffuse type of histology, the 5-year survival was better in high cytoplasmic TLR6 expression group in multivariable analysis (HR 0.62, 95% CI 0.46-0.83). In the intestinal type of histology subgroup, no significant differences between the groups were present. TLR1, TLR4, and TLR5 expression were not associated with 5-year survival. In conclusion, cytoplasmic TLR2 and TLR6 expression seem to have independent prognostic impact in gastric cancer, while TLR1, TLR4, and TLR5 do not.

Gut barrier defects, intestinal immune hyperactivation and enhanced lipid catabolism drive lethality in NGLY1-deficient Drosophila

Intestinal barrier dysfunction leads to inflammation and associated metabolic changes. However, the relative impact of gut bacteria versus non-bacterial insults on animal health in the context of barrier dysfunction is not well understood. Here, we establish that loss of Drosophila N-glycanase 1 (Pngl) in a specific intestinal cell type leads to gut barrier defects, causing starvation and JNK overactivation. These abnormalities, along with loss of Pngl in enterocytes and fat body, result in Foxo overactivation, leading to hyperactive innate immune response and lipid catabolism and thereby contributing to lethality. Germ-free rearing of Pngl mutants rescued their developmental delay but not lethality. However, raising Pngl mutants on isocaloric, fat-rich diets partially rescued lethality. Our data indicate that Pngl functions in Drosophila larvae to establish the gut barrier, and that the lethality caused by loss of Pngl is primarily mediated through non-bacterial induction of immune and metabolic abnormalities.

Comparison of human epidermal growth factor receptor 2 and cancer stem cell markers like CD44 and CD133 expressions with clinicopathological parameters in gastric cancer

Objectives: Gastric carcinoma (GC) is the fourth most common cause of cancer-related tumor deaths worldwide. The prognostic significance of CD44, CD133 and human epidermal growth factor receptor 2 (HER2) expression in GC remains controversial. Therefore, we aimed to investigate the relationship of CD44, CD133 and HER2 expression with clinicopathological features in metastatic and non-metastatic GC patients. Methods: A total of 139 patients with GC (68 with metastasis, 71 without metastasis) diagnosed were retrospectively analyzed. CD44 and CD133 expression were determined by immunohistochemical method in all cases. In addition, HER2 overexpression of the tumor was evaluated in patients with metastatic GC. Results: The CD133 positivity rate was 90.6% (n = 126) when all cases were considered, and that for CD44 was 84.9% (n = 118). There was no difference in CD133 and CD44 positivity (intensity or density) rates and between the total scores of metastatic and non-metastatic patients with GC (p &amp;gt; 0.05). HER2 positivity in metastatic cases was detected in 49 (70.1%) patients by immunohistochemical method. No correlation was found between CD133 total score and age, tumor size or depth, and HER2 scores in metastatic or non-metastatic cases (p &amp;gt; 0.05). In the correlation analyzes performed with CD44 scores, only a borderline significant correlation was found between CD44 scores and tumor size (r:0.175; p = 0.047) in non-metastatic cases. Conclusions: We demonstrated associations between CD44/CD133 expression and histological grade in all patients, between CD44 and tumor size in non-metastatic patients, and between HER2 and intestinal type (Lauren) in metastatic patients. The results of this study need to be confirmed by multicenter studies including large case series.

Challenging differential diagnoses in small biopsies from the sinonasal tract.

Sinonasal biopsy specimens are a challenging area in anatomic pathology. The small, often fragmented or crushed nature of these biopsies can hinder morphologic assessment. Additionally, many of the tumors in this area are rare and share morphologic, and sometime immunophenotypic similarities. In many cases, immunohistochemistry is helpful if not necessary to reach a specific diagnosis. In other cases, a specific diagnosis is not possible and a differential diagnosis must be given on a biopsy specimen despite access to a well-equipped immunohistochemistry laboratory. This review article groups some of the more challenging entities in the sinonasal region based on morphologic patterns. These include low grade squamoid lesions such as sinonasal (Schneiderian) papilloma and DEK::AFF2 rearranged carcinoma, glandular neoplasms such as intestinal and non-intestinal type sinonasal adenocarcinoma, high-grade carcinomas such as HPV-related multiphenotypic sinonasal carcinoma, NUT carcinoma and SWI/SNF deficient carcinomas, small round blue cell tumors such as teratocarcinosarcoma, neuroendocrine carcinoma and olfactory neuroblastoma, and finally, low grade spindle cell neoplasms such as glomangiopericytoma, biphenotypic sinonasal sarcoma and solitary fibrous tumor.

389. DEVELOPING A PROGNOSTICALLY SIGNIFICANT MORPHOLOGICAL CLASSIFICATION SYSTEM FOR ESOPHAGEAL ADENOCARCINOMA

Abstract Background Histologically, esophageal adenocarcinoma is broadly divided into two morphological subtypes: intestinal and diffuse types, with the latter conferring a worse prognosis. However, the present classification system does not account for morphological heterogeneity and the clinical and prognostic implications of this heterogeneity remains uncertain. This study focuses on elucidating the clinical and prognostic significance of the various EAC morphological patterns. Methods We identified surgical resection cases conducted at a single center from 2008 to the present date. All tumour-containing slides were analyzed, and the percentages of each morphological pattern was calculated. The overall percentage of each morphology was determined by summing across all tumour slides per case. Cases were stratified by neoadjuvant treatment status. Results This study reviewed 106 surgical resection cases. Seventy cases (58 male, 12 female, 59.26 +/− 11.12 years) received neoadjuvant treatment prior to surgery, while 36 cases (29 male, 7 female, 66.36 +/− 11.85 years) did not. A similar average slide number was obtained from treated versus untreated cases (10.13 +/− 7.43 slides vs 9.14 +/− 8.57, p = 0.5391). Morphological heterogeneity (i.e., 3+ morphologies occupying &amp;gt;10% of the tumor) was not different between treated and untreated cases (33% versus 24.2%, p = 0.35). Subgroup analysis revealed a significant increase in tumor morphological heterogeneity with poorer neoadjuvant treatment response (score 3) (p &amp;lt; 0.05). Conclusions To our knowledge, this is the first study investigating the clinical and prognostic implications of the heterogeneous morphological patterns observed in EAC. Our results suggest that tumours with poor response to neoadjuvant therapy are more likely to exhibit significant morphological heterogeneity. We are currently exploring whether specific morphological patterns are linked to adverse prognosis and poor response to neoadjuvant therapy. These findings have the potential to guide clinical decision-making in EAC.

Sleep Duration and Stress Level in the Risk of Gastric Cancer: A Pooled Analysis of Case-Control Studies in the Stomach Cancer Pooling (StoP) Project.

The association between sleep and stress and cancer is underinvestigated. We evaluated these factors in association with gastric cancer (GC). Five case-control studies from the Stomach Cancer Pooling (StoP) Project were included. We calculated the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for sleep duration and stress level in association with GC through multiple logistic regression models adjusted for several lifestyle factors. The analysis included 1293 cases and 4439 controls, 215 cardia and 919 noncardia GC, and 353 diffuse and 619 intestinal types. Sleep duration of ≥9 h was associated with GC (OR =1.57, 95% CI = 1.23-2.00) compared to 8 h. This was confirmed when stratifying by subsite (noncardia OR = 1.59, 95% CI = 1.22-2.08, and cardia OR = 1.63, 95% CI = 0.97-2.72) and histological type (diffuse OR = 1.65, 95% CI = 1.14-2.40 and intestinal OR = 1.24, 95% CI = 0.91-1.67). Stress was associated with GC (OR = 1.33, 95% CI = 1.18-1.50, continuous). This relationship was selectively related to noncardia GC (OR = 1.28, 95% 1.12-1.46, continuous). The risk of diffuse (OR = 1.32, 95% CI = 1.11-1.58) and intestinal type (OR = 1.23, 95% CI = 1.07-1.42) were higher when stress was reported. Results for the association between increasing level of stress and GC were heterogeneous by smoking and socioeconomic status (p for heterogeneity = 0.02 and <0.001, respectively). In conclusion, long sleep duration (≥9 h) was associated with GC and its subtype categories. Stress linearly increased the risk of GC and was related to noncardia GC.

The Histopathological Characteristics of Gastric Tumor at The National Oncology Center in Benghazi in the Period of 2020-2021

Background: Gastric cancer is considered globally a major health issue. Many studies have shown that adenocarcinomas represent about 90% of all gastric cancers. It is subdivided into two main histological types; intestinal and diffuse. Aim: The aim of this study is to determine the frequency and the histopathological characteristics of gastric adenocarcinoma among patients of the National Cancer Center of Benghazi in the period of 2020-2021. Subjects and methods: A retrospective study of 52 gastric cancer cases from the archive of the National Oncology Center in Benghazi and data was analyzed with SPSS. Results: In the research period between January 2020 to May 2021, the total number of patients with confirmed gastric cancer was 52 cases. The patients' ages were between 29 to 86 and the mean age was 63. Thirty-one (31) cases were male (59.6%) and twenty-one (21) were female (40.4%). Diffuse adenocarcinoma was predominant over the intestinal type (25% and 19.2 % respectively). 48% of the cases were of undetermined type and 3.8% were gastrointestinal stromal tumors. Most of the cases presented at stage IV. Conclusion: The histopathological picture of gastric cancer in our study was similar to a previously published study done in Benghazi with male predominant and diffuse adenocarcinoma as the more common cancer. Some risk factors are attributed such as infection with H pylori, smoking and anemia.

The intestine as an endocrine organ and the role of gut hormones in metabolic regulation.

Gut hormones orchestrate pivotal physiological processes in multiple metabolically active tissues, including the pancreas, liver, adipose tissue, gut and central nervous system, making them attractive therapeutic targets in the treatment of obesity and type 2 diabetes mellitus. Most gut hormones are derived from enteroendocrine cells, but bioactive peptides that are derived from other intestinal epithelial cell types have also been implicated in metabolic regulation and can be considered gut hormones. A deeper understanding of the complex inter-organ crosstalk mediated by the intestinal endocrine system is a prerequisite for designing more effective drugs that are based on or target gut hormones and their receptors, and extending their therapeutic potential beyond obesity and diabetes mellitus. In this Review, we present an overview of gut hormones that are involved in the regulation of metabolism and discuss their action in the gastrointestinal system and beyond.

Clinical significance of CD166 and HER-2 in different types of gastric cancer.

Cluster of differentiation 166 (CD166), a cancer stem cell (CSC) marker, and human epidermal growth factor receptor 2 (HER-2) are expressed in a diversity of malignancies and is associated with tumor progression. Although studies regarding the importance of CSC markers and HER-2 in gastric cancer (GC) have rapidly developed, their clinicopathological, prognosis, and diagnosis value still remain unsatisfying in GC. Therefore, the present study aims to investigate the clinical, prognostic, and diagnostic significance of CD166 and HER-2 in different histological types of GC. Bioinformatic analysis was applied to determine the clinical importance of CD166 and HER-2 expression based on their tissue localization in primary GC tumors and the normal adjacent samples. The expression patterns, clinical significance, prognosis, and diagnosis value of CD166 and HER-2 proteins in tissue microarrays (TMAs) of 206 GC samples, including Signet Ring Cell (SRC) and intestinal types and also 28 adjacent normal tissues were evaluated using immunohistochemistry (IHC). The results indicated that the expression of CD166 (membranous and cytoplasmic) and HER-2 were significantly up-regulated in tumor cells compared to adjacent normal tissues (P = 0.010, P < 0.001, and P = 0.011, respectively). A statistically significant association was detected between a high level of membranous expression of CD166 and lymphovascular invasion (P = 0.006); We also observed a statistically significant association between high cytoplasmic expression of CD166 protein and more invasion of the subserosa (P = 0.040) in the SRC type. In contrast, there was no correlation between the expression of HER-2 and clinicopathologic characteristics. Both CD166 and HER-2 showed reasonable accuracy and high specificity as diagnostic markers. Our results confirmed that increased membranous and cytoplasmic expression of CD166 showed clinical significance in the SRC type and is associated with the progression of the disease and more aggressive tumor behaviors. These findings can be used to assist in designating subgroups of patients that require different follow-up strategies, and also, they might be utilized as the prognostic or diagnostic biomarkers in these types of GC for prospective clinical application.

A study of human epidermal growth factor receptor 2 overexpression by immunohistochemistry in patients with gastric adenocarcinoma.

Gastric cancer is one of the leading causes of cancer-related deaths across the world and in the Middle East. Human epidermal growth factor receptor 2 (HER2) overexpression has been observed in gastric cancers. Trastuzumab, a recombinant monoclonal antibody targeting HER2 protein, is being used for treatment of metastatic gastric cancer. To study the frequency and association of HER2 overexpression with age, gender, histopathological subtype and grade of differentiation in patients with gastric adenocarcinoma from Basra, Iraq. This cross-sectional single-center study collected demographic (age, gender), histopathological (histological subtype, grade of differentiation) and immunohistochemical (HER2 overexpression status) data from 100 consenting adult patients (male: 56) with histopathologically confirmed gastric adenocarcinoma from samples obtained through endoscopy or surgery. HER2 overexpression (ToGA score 3+) was observed in 6/100 (6%) of patients, with another 6 showing 'equivocal' HER2 expression (2+). Out of 20 patients with moderately differentiated gastric cancer, 4 (20%) showed HER2 overexpression (p=0.008). Other factors considered (age, gender, histological subtype) did not show statistically significant correlation with HER2 overexpression. More females showed HER2 overexpression than males (4 vs. 2), and more patients with intestinal type gastric cancer showed HER2 overexpression than diffuse gastric cancer (5 vs. 1), but the difference was not statistically significant in both variables. HER2 overexpression was 6% in this population; statistically significant correlation was found with histological grade. Statistically non-significant correlations were observed between HER2 overexpression and gender, age, and histological subtype.

A Mysterious Presentation of Small Bowel Stricture

Small bowel adenocarcinoma is a rare malignancy that accounts for a small percentage of gastrointestinal cancers. Diagnosis and management of small bowel adenocarcinoma can be challenging due to its rarity and nonspecific presentation. We present a case of a 51-year-old male with a history of intravenous drug use who presented with worsening abdominal pain and was found to have a small bowel obstruction. Exploratory laparotomy revealed a stricture in the jejunum caused by an intraluminal mass, which was resected. Pathological examination confirmed the diagnosis of intestinal type, moderately differentiated adenocarcinoma. This case highlights the importance of considering small bowel adenocarcinoma as a possible etiology in patients presenting with small bowel obstruction, particularly in high-risk individuals. Early diagnosis and complete resection remain the mainstays of treatment for improved outcomes in small bowel adenocarcinoma.