Intestinal Type Research Articles

Treatment development targeting Hippo pathway for scirrhous type gastric cancer.

398 Background: Treatment outcome of gastric cancer (GC) has been improved by minimally invasive surgery, and development of new drugs including immune checkpoint inhibitors. However, survival for patients with scirrhous type (SGC, Type4) gastric cancer is dismal. Methods: We collected miRNAs form exosomes released from cancer associated fibroblasts which is developed from resected gastric cancer tissue. Pathway enrichment analysis (PEA) of top miRNAs showed that they are significantly associated with Hippo signaling pathway (Hippo pathway). The molecules relating Hippo pathway was evaluated by Western blotting in cell line, and IHC of tissue array. Results: PEA using top miRNAs showed the significant relationship to Hippo pathway. Yap is a final effector in this pathway, and we found that YAP is not expressed in MKN45 cells (diffuse type), which is supposed to be degraded in cytoplasm. On the contrary, MKN74 cells express both YAP and pYAP. IHC showed that YAP translocation to nucleus is significantly associated with CTGF expression. CTGF low expression is significantly associated with worse prognosis especially in diffuse type GC (Log rank p = 0.022). This trend is similar in the analysis of patients with SGC. Conclusions: The role of Hippo pathway is different between intestinal type and diffuse type of GC. YAP activator could be effective for the treatment of SGC, and we are focusing on the treatment development.

Increased regulatory activity of intestinal innate lymphoid cells type 3 (ILC3) prevents experimental autoimmune encephalomyelitis severity

Experimental autoimmune encephalomyelitis (EAE) induced in inbred rodents, i.e., genetically identical animals kept under identical environmental conditions, shows variable clinical outcomes. We investigated such variations of EAE in Dark Agouti rats immunized with spinal cord homogenate and identified four groups: lethal, severe, moderate, and mild, at day 28 post immunization. Higher numbers of CD4+ T cells, helper T cells type 1 (Th1) and 17 (Th17) in particular, were detected in the spinal cord of the severe group in comparison with the moderate group. In addition, increased proportion of Th1 and Th17 cells, and heightened levels of interferon (IFN)-γ and interleukin (IL)-6 were detected in the small intestine lamina propria of the severe group. A selective agonist of free fatty acid receptor type 2 (Ffar2) applied orally in the inductive phase of EAE shifted the distribution of the disease outcomes towards milder forms. This effect was paralleled with potentiation of intestinal innate lymphoid cells type 3 (ILC3) regulatory properties, and diminished Th1 and Th17 cell response in the lymph nodes draining the site of immunization. Our results suggest that different clinical outcomes in DA rats are under determinative influence of intestinal ILC3 activity during the inductive phase of EAE.

Machine learning for differentiating between pancreatobiliary-type and intestinal-type periampullary carcinomas based on CT imaging and clinical findings

PurposeTo develop a diagnostic model for distinguishing pancreatobiliary-type and intestinal-type periampullary adenocarcinomas using preoperative contrast-enhanced computed tomography (CT) findings combined with clinical characteristics.MethodsThis retrospective study included 140 patients with periampullary adenocarcinoma who underwent preoperative enhanced CT, including pancreaticobiliary (N = 100) and intestinal (N = 40) types. They were randomly assigned to the training or internal validation set in an 8:2 ratio. Additionally, an independent external cohort of 28 patients was enrolled. Various CT features of the periampullary region were evaluated and data from clinical and laboratory tests were collected. Five machine learning classifiers were developed to identify the histologic type of periampullary adenocarcinoma, including logistic regression, random forest, multi-layer perceptron, light gradient boosting, and eXtreme gradient boosting (XGBoost).ResultsAll machine learning classifiers except multi-layer perceptron used achieved good performance in distinguishing pancreatobiliary-type and intestinal-type adenocarcinomas, with the area under the curve (AUC) ranging from 0.75 to 0.98. The AUC values of the XGBoost classifier in the training set, internal validation set and external validation set are 0.98, 0.89 and 0.84 respectively. The enhancement degree of tumor, the growth pattern of tumor, and carbohydrate antigen 19–9 were the most important factors in the model.ConclusionMachine learning models combining CT with clinical features can serve as a noninvasive tool to differentiate the histological subtypes of periampullary adenocarcinoma, in particular using the XGBoost classifier.

Clinicopathologic Characteristics of Trop Family Proteins (Trop-2 and EpCAM) in Gastric Carcinoma.

Trop family proteins, including epithelial cell adhesion molecule (EpCAM) and Trop-2, have garnered attention as potential therapeutic and diagnostic targets for various malignancies. This study aimed to elucidate the clinicopathological significance of these proteins in gastric carcinoma (GC) and to reinforce their potential as biomarkers for patient stratification in targeted therapies. Immunohistochemical (IHC) analyses of EpCAM and Trop-2 were performed on GC and precancerous lesions, following rigorous orthogonal validation of the antibodies to ensure specificity and sensitivity. Strong membranous staining (3+) for Trop-2 was observed in 49.3% of the GC cases, whereas EpCAM was strongly expressed in almost all cases (93.2%), indicating its widespread expression in GC. A high Trop-2 expression level, characterized by an elevated H-score, was significantly associated with intestinal type by Lauren classification, gastric mucin type, presence of lymph node metastasis, human epidermal growth factor receptor 2-positivity, and Epstein-Barr virus (EBV)-positivity. Patients with a high Trop-2 expression level exhibited poorer survival outcomes on univariate and multivariate analyses. High EpCAM expression levels were prevalent in differentiated histologic type, microsatellite instability-high, and EBV-negative cancer, and were correlated with high densities of CD3 and CD8 T cells and elevated combined positive score for programmed death-ligand 1. These results highlight the differential expression of Trop-2 and EpCAM and their prognostic implications in GC. The use of meticulously validated antibodies ensured the reliability of our IHC data, thereby offering a robust foundation for future therapeutic strategies targeting Trop family members in GC.

Intestinale Florid Glandular Cystitis in Centre Medicochirurgical De Kinindo Bujumbura

Background: Glandular cystitis is a metaplastic lesion of the bladder urothelium primarily affecting men. There are two types: typical glandular cystitis and intestinal glandular cystitis. Therefore, the definitive diagnosis relies on histopathology. The controversial theory surrounds the malignant degeneration of these lesions. Here, we present a case of florid glandulo-cystic cystitis of intestinal origin. Clinic observation: A 20-year-old man presented to the clinic with intermittent total hematuria associated with obstructive and irritative symptoms that had been ongoing for more than a year. In Histology examen, there was an absence of malignant tumor proliferation and signs indicative of typical inflammation: Florid glandulo-cystic cystitis of intestinal type. Conclusion: Intestinal glandular cystitis is a rare condition affecting primarily men and involving the bladder mucosa. Its symptoms are nonspecific and often go undiagnosed. Transurethral bladder resection remains the treatment of choice, but other therapeutic modalities, proven effective, should not be dismissed. The issue of malignant degeneration remains a controversial topic for debate, but the course of the disease is primarily marked by recurrences, necessitating cystoscopic monitoring.

Does leptin cause proximal gastric cancer in the obese? The role of serum leptin in the etiology of proximal gastric cancer.

The aim of the present study was to determine the correlation between obesity, serum levels of leptin and proximal gastric cancer. Sixty-four gastric cancer patients operated on with curative intent were included in the study. We determined the correlation between the preoperative serum levels of leptin and the tumor's location. Serum leptin levels were correlated significantly with the proximal third location (p=0.04), gastric outlet obstructing tumors (p<0.0001), CRP levels (p=0.03) and BMI (p<0.0001). Patients with high serum levels of leptin had significantly more intestinal types of gastric cancer (p=0.033) and better differentiation (p=0.009). The linear regression model determined the proximal tumor location (beta: 0.467; p=0.045), BMI (beta: 0.657; p=0.001), high preoperative serum albumin (beta: 0.563; p=0.016) and the presence of pyloric stenosis (beta: 0.525; p=0.006) as related significantly to serum leptin levels. The Cox proportional hazard model identified age (HR: 0.003; 95 % CI: 0-0.794; p=0.041), preoperative serum levels of leptin (HR: 0.125; 95 % CI: 0.018-0.887; p=0.037) and the number of extracted LNs (HR: 0.001; 95 % CI: 0-0.677; p=0.038) as independent prognostic factors. Serum levels of leptin were significantly elevated in patients with proximal gastric cancer, suggesting that the leptin's effect might be due to its systemic secretion. This might explain the higher incidence of proximal gastric cancer in obese patients. Elevated serum leptin levels were an independent prognostic factor.

A clinical case of diverticular disease in a patient with COVID-19: features of the course against the background of comorbid pathology

As a consequence of the global pandemic of the coronavirus disease (COVID‑19), cases of combination of gastroenterological pathology with endocrinopathies, associated with this pandemic, occur sporadically. Therefore, reporting about a unique clinical case of post‑covid comorbidity of these diseases seems to be advisable.&#x0D; Patient K., 68 years old, who had been suffering from diabetes insipidus for five years and received appropriate treatment (desmopressin) daily, was hospitalized for 28 days at the lung disease center of the Regional Phthisiopulmonological Center due to a severe course of COVID‑19. Two months after discharge, due to prevailed gastrointestinal complaints (pain in the bowel areas, stool frequency up to 7 times a day, dryness mouth, urination up to 3 times at night (nocturia), general weakness), which required another thorough differential diagnosis, she was hospitalized in the Gastroenterology Department of Regional Clinical Hospital. The diagnosis of severe post‑covid complications has been established, including intestinal diverticular disease and type 2 diabetes mellitus, and patient was transferred to the surgical department.&#x0D; The problems of searching and improving methods for early diagnosis of post‑covid conditions that potentiate the development of polymorbidity are urgent. A pathogenetically based approach to the administration of therapy will promote reducing morbidity and mortality in patients with comorbid diseases. The coronavirus pandemic forces the medical and scientific community to join efforts for investigation of new comorbid condition. The timely diagnosis of relatively new and understudied post‑covid diseases should become the main task of multidisciplinary teams of doctors. Investigation of the diversity of the clinical courses, the development and improvement of algorithms for the treatment and prevention of severe complications of diverticular intestinal disease in combination with diabetes insipidus and diabetes mellitus are the important prospects of scientific research.

GASTRECTOMY WITH OMENTUM PRESERVATION VS GASTRECTOMY WITH OMENTECTOMY FOR LOCALLY ADVANCED GASTRIC CANCER : A SYSTEMATIC REVIEW

Background: Gastric cancers can be divided into the intestinal type and diffuse type. The most common underlying etiology of intestinal-type carcinoma is Helicobacter pylori infection, which can develop into atrophic gastritis with intestinal metaplasia. Complete omentectomy is considered to be essential in the radical gastrectomy for gastric cancer (GC), but its clinical benefit remains unclear. The aim: This study aims to show about gastrectomy with omentum preservation vs gastrectomy with omentectomy for locally advanced gastric cancer. Methods: By comparing itself to the standards set by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study was able to show that it met all of the requirements. So, the experts were able to make sure that the study was as up-to-date as it was possible to be. For this search approach, publications that came out between 2013 and 2023 were taken into account. Several different online reference sources, like Pubmed and SagePub, were used to do this. It was decided not to take into account review pieces, works that had already been published, or works that were only half done. Result: In the PubMed database, the results of our search brought up 104 articles, whereas the results of our search on SagePub brought up 77 articles. The results of the search conducted for the last year of 2013 yielded a total 88 articles for PubMed and 48 articles for SagePub. The result from title screening, a total 7 articles for PubMed and 28 articles for SagePub. In the end, we compiled a total of 10 papers. We included five research that met the criteria. Conclusion: Laparoscopic treatment of gastric cancer with D2 lymphadenectomy and omentum preservation is safe and feasible, both for EGC and for AGC. Total omentectomy may be avoided in tumors smaller than 5.25 cm and T1/T2 tumors. However, lymph node metastasis in the greater omentum is associated with recurrence in the peritoneum, liver, ovary and death.

Hirschsprung Disease and Intestinal Neuronal Dysplasia Type B: Is There a Difference in the Clinical Presentation of These Two Diseases?

Although the signs and symptoms that comprise the clinical presentation of Hirschsprung disease (HD) and intestinal neuronal dysplasia type B (IND-B) are well established, no studies have specifically compared the clinical characteristics presented by patients with these diseases. We compared the clinical pictures of patients with HD and IND-B at the time of histopathological diagnosis. This was a single-center, retrospective, analytical, and comparative study. We included 119 patients aged 0-15 years diagnosed with HD or IND-B. Information from the medical records of these patients was retrieved to obtain demographic and clinical information at the time of diagnosis. The data were compared statistically according to the characteristics of the variables. Sixty-nine patients (58.0%) were diagnosed with HD, and 50 (42.0%) had IND-B. The HD group had significantly more individuals with symptom onset in the neonatal period (p = 0.001), delayed meconium clearance (p < 0.001), failure to thrive (p = 0.02), and acute complications, such as enterocolitis (p = 0.049) or acute abdominal obstruction (p = 0.031), more commonly requiring emergency surgery (p < 0.001). Patients with IND-B were diagnosed at a significantly older age (p = 0.002). They more commonly had chronic constipation as their main symptom (p = 0.004), with local complications, such as evacuation bleeding (p = 0.007). There were significant differences between the clinical pictures of patients with HD and IND-B. Knowledge of each disease's most common signs and symptoms can help direct diagnostic susception and initial management.

Trichinella spiralis cathepsin B bound and degraded host's intestinal type I collagen

Trichinellosis is a zoonotic parasitic disease that poses threats to human health, the meat industry, food safety, and huge financial losses. The critical stage of Trichinella spiralis (T. spiralis) infection is the invasion of intestinal larvae into the host's intestinal epithelial cells (IECs). T. spiralis Cathepsin B (TsCB) specifically interacts with IECs to facilitate the invasion of larvae. This study aims to look at how TsCB affects mouse IECs. TsCB was successfully cloned, expressed, and characterized, demonstrating its natural cysteine protease hydrolysis activity. A total of 140 proteins that interact with rTsCB were identified by GST pull-down combined with LC-MS/MS, including type I collagen, an essential component of the host's intestinal epithelial barrier system and intimately related to intestinal epithelial damage. TsCB transcription and expression levels rise, whereas type I collagen in the host's intestinal mucosa declines when the T. spiralis larvae invaded. Besides, it was discovered that TsCB bound to and degraded type I collagen of the host's intestine. This research can serve as a foundation for clarifying how T. spiralis invades the host's intestinal barrier and might provide information on potential targets for the creation of novel treatments to treat parasite illnesses.

Low incidence of microsatellite instability in gastric cancers and its association with the clinicopathological characteristics: a comparative study

Gastric cancer is a complex heterogeneous disease with different molecular subtypes that have clinical implications. It is characterized by high mortality rates and limited effective therapies. Microsatellite instability (MSI) has been recognized as a subgroup with a good prognosis based on TCGA and ACRG categorizations. Besides its prognostic and predictive value, gastric cancers with high MSI exhibit different clinical behaviors. The prevalence of high MSI has been assessed in gastric cancer worldwide, especially in East Asia, but there is a lack of such information in the Middle East. Therefore, this study aimed to investigate the incidence and status of MSI in Iranian gastric cancer patients using 53 samples collected from 2015 to 2020 at Taleghani Hospital Medical Center. DNA from tumoral and normal tissues were extracted and assessed through multiplex-PCR based on five mononucleotide repeats panel. Clinicopathological variables, including age, sex, Lauren classification, lymph node involvement, TNM stage, differentiation, localization, and tumor size, were also analyzed. With 2 males and 2 females, high microsatellite instability represented a small subgroup of almost 7.5% of the samples with a median age of 60.5 years. High microsatellite instability phenotypes were significantly associated with patients aged 68 years and older (p‑value of 0.0015) and lower lymph node involvement (p‑value of 0.0004). Microsatellite instability was also more frequent in females, with distal gastric location, bigger tumor size, and in the intestinal type of gastric cancer rather than the diffuse type.

Decoding the expression pattern of MUC3A in gastric adenocarcinoma: unveiling the key to successful immunotherapy

ABSTRACT Aims Despite the promise of immunotherapy for gastric adenocarcinoma, resistance is common, necessitating the validation of new targets. Based on our previous bioinformatics analysis, the MUC3A antigen emerged as a promising candidate for immunotherapy against gastric adenocarcinoma. However, a comprehensive understanding of its expression at protein level remains elusive, despite its crucial role in determining clinical response. We also sought to establish a connection between the expression pattern and relevant clinical variables of the disease, whenever feasible. Methods Immunohistochemistry was used to determine the percentage of MUC3A-positive tumor cells in primary (PT) and metastatic tumor (MT) sites of 190 gastric adenocarcinoma patients. We also evaluated the association between MUC3A expression and variables such as Lauren classification, history of neoadjuvant chemotherapy and/or radiotherapy, and overall patient survival. Results Median MUC3A expression was 50% in PT and 70% in MT sites, exhibiting a positive correlation. MT intestinal type showed significantly higher MUC3A expression compared to other types. Neoadjuvant therapy history did not affect MUC3A expression. Higher MUC3A expression correlated with improved survival. Conclusions Based on our previous bioinformatics data and the consistently high expression of MUC3A on gastric tumor cells, we propose advancing experimental aspects of anti-MUC3A immunotherapy for gastric adenocarcinoma.

LIM-HD transcription factors control axial patterning and specify distinct neuronal and intestinal cell identities in planarians.

Adult planarians can regenerate the gut, eyes and even a functional brain. Proper identity and patterning of the newly formed structures require signals that guide and commit their adult stem cells. During embryogenesis, LIM-homeodomain (LIM-HD) transcription factors act in a combinatorial 'LIM code' to control cell fate determination and differentiation. However, our understanding about the role these genes play during regeneration and homeostasis is limited. Here, we report the full repertoire of LIM-HD genes in Schmidtea mediterranea. We found that lim homeobox (lhx) genes appear expressed in complementary patterns along the cephalic ganglia and digestive system of the planarian, with some of them being co-expressed in the same cell types. We have identified that Smed-islet1, -lhx1/5-1, -lhx2/9-3, -lhx6/8, -lmx1a/b-2 and -lmx1a/b-3 are essential to pattern and size the planarian brain as well as for correct regeneration of specific subpopulations of dopaminergic, serotonergic, GABAergic and cholinergic neurons, while Smed-lhx1/5.2 and -lhx2/9.2 are required for the proper expression of intestinal cell type markers, specifically the goblet subtype. LIM-HD are also involved in controlling axonal pathfinding (lhx6/8), axial patterning (islet1, lhx1/5-1, lmx1a/b-3), head/body proportions (islet2) and stem cell proliferation (lhx3/4, lhx2/9-3, lmx1a/b-2, lmx1a/b-3). Altogether, our results suggest that planarians might present a combinatorial LIM code that controls axial patterning and axonal growing and specifies distinct neuronal and intestinal cell identities.

The influence of Helicobacter pylori, proton pump inhibitor, and obesity on the gastric microbiome in relation to gastric cancer development

Helicobacter pylori infection is still the main risk factor for the development of gastric cancer (GC). We explore the scientific evidence for the role of the gastric microbiome beyond Helicobacter pylori (H. pylori) in gastric carcinogenesis. The composition of the gastric microbiome in healthy individuals, in presence and absence of H. pylori infection, in proton pump inhibitor (PPI)-users, obese individuals, and GC patients was investigated. Possible mechanisms for microbial involvement, limitations of available research and options for future studies are provided.A common finding amongst studies was increased levels of Streptococcus, Prevotella, Neisseria, and Actinomyces in healthy individuals or those with H. pylori-negative gastritis. In PPI-users the risk for GC increases with the treatment duration, and the gastric microbiome shifts, with the most consistent increase in the genus Streptococcus. Similarly, in obese individuals, Streptococcus was the most abundant genus, with an increased risk for cardia GC. The genera Streptococcus, Lactobacillus and Prevotella were found to be more prominent in GC patients in multiple studies. Potential mechanisms of non-H. pylori microbiota contributing to GC are linked to lipopolysaccharide production, contribution to inflammatory pathways, and the formation of N-nitroso compounds and reactive oxygen species.In conclusion, the knowledge of the gastric microbiome in GC is mainly descriptive and based on sequencing of gastric mucosal samples. For a better mechanistic understanding of microbes in GC development, longitudinal cohorts including precancerous lesions, different regions in the stomach, and subtypes of GC, and gastric organoid models for diffuse and intestinal type GC should be employed.

A descriptive analysis of gastric cancer with an immunohistochemical Study of Ki67 and p53 as prognostic factors.: Bahrain experience.

To describe the increasing number of gastric cancer cases at Bahrain Defense Force Hospital with implementation of immunohistochemistry markers as prognostic factors. This study included histologically confirmed malignant gastric tumors diagnosed at Bahrain Defense Force Hospital from January 2009 to June 2019. Various epidemiological and pathological data were abstracted and recorded with immunohistochemical analysis of the proliferation marker Ki67 and cell-cycle regulator p53 as prognostic factors. A total of 53 patients with gastric cancer were included in the study, with mean age of 59.75 ± 12.9 years. The typical histological types were signet ring cell adenocarcinoma (68%) and intestinal type adenocarcinoma (17%). Helicobacter pylori and intestinal metaplasia were significantly associated with gastric cancer (p<0.01). The studied population's mortality was 39 (74%). The Ki67 proliferation index showed a mean and standard deviation of 67.09 ± 16.338, with a higher mortality rate in patients with low Ki67 but no difference in survival time. No statistically significant association was found between clinicopathological findings with p53 immunostaining positivity. The common gastric cancers are signet ring cell adenocarcinoma and intestinal type adenocarcinoma, affecting a wide range of age groups (33-91 years), with those over 60 years at greater risk. Interestingly, low Ki67 is associated with a higher mortality rate, whereas p53 has no prognostic significance. Expression of both Ki67 and p53 showed no association with survival time.

Single-nucleus sequencing of silkworm larval midgut reveals the immune escape strategy of BmNPV in the midgut during the late stage of infection

The midgut is an important barrier against microorganism invasion and proliferation, yet is the first tissue encountered when a baculovirus naturally invades the host. However, only limited knowledge is available how different midgut cell types contribute to the immune response and the clearance or promotion of viral infection. Here, single-nucleus RNA sequencing (snRNA seq) was employed to analyze the responses of various cell subpopulations in the silkworm larval midgut to B. mori nucleopolyhedrovirus (BmNPV) infection. We identified 22 distinct clusters representing enteroendocrine cells (EEs), enterocytes (ECs), intestinal stem cells (ISCs), Goblet cell-like and muscle cell types in the BmNPV-infected and uninfected silkworm larvae midgut at 72 h post infection. Further, our results revealed that the strategies for immune escape of BmNPV in the midgut at the late stage of infection include (1) inhibiting the response of antiviral pathways; (2) inhibiting the expression of antiviral host factors; (3) stimulating expression levels of genes promoting BmNPV replication. These findings suggest that the midgut, as the first line of defense against the invasion of the baculovirus, has dual characteristics of "resistance" and "tolerance". Our single-cell dataset reveals the diversity of silkworm larval midgut cells, and the transcriptome analysis provides insights into the interaction between host and virus infection at the single-cell level.

Comparison of survival between diffuse type and intestinal type early-onset gastric cancer patients: A large population-based study.

Currently, little knowledge about the survival of early-onset gastric cancer and little evidence about the difference of survival based on Lauren type has been reported. In order to investigate the difference, we conducted a retrospective study using the Surveillance, Epidemiology, and End Results (SEER) database and compared it comprehensively. SEER database was used to extracted patients and multiple imputation was utilized to fill blank data. Multivariate cox regression analysis and competing risk model were used to identify the risk factors of survival. K-M survival curve and propensity score matching (PSM) was applied to compare the difference of survival of patients based on Lauren type. Totally, we extracted 3932 EOGC patients including 2086 diffused type and 1846 intestinal type. K-M survival curve showed patients aged 20 to 29 had worse survival compared to patients aged at 30 to 45 years. The survival of EOGC patients would be greatly improved after surgery. Multivariate cox regression analysis revealed diffused type was an independent risk factor, as well as T stage, lymph node metastasis, tumor size (>5 cm) and metastasis, while surgery treatment and examined lymph nodes were protective factors. Multivariate competing risk regression model also showed diffused type was risk factor. We performed PSM by matching 1433 diffused EOGC with 1433 intestinal EOGC patients, finding patients with diffused type had a poorer survival. our results revealed that compared to diffused type EOGC, intestinal type was characterized by a better survival. EOGC should be attached more attention by clinicians.

OGC P27 Resection margin strategy in gastric cancer surgery: the European REMARCS (Resection MARgin for Cancer of the Stomach) survey

Abstract Background Surgery with negative resection margins and appropriate lymphadenectomy is the only curative treatment for gastric cancer. The adequate proximal resection margins length in European guidelines is between 5 to 8 centimeters depending on the histological subtype. However, these recommendations are based on outdated studies with limited data. The peri-operative treatment modalities have evolved, and the application of these resection margin cut-offs may not be as uniform as before. The aim of our study was to assess the current European practice in gastric cancer surgery with particular attention to resection margins. Methods A panel of 13 international experts composed of surgeons, pathologists, and oncologists developed a web-based survey containing 45 questions about center demographic, resection margin strategy, and post-operative care. The survey was distributed to Upper Gastrointestinal (UGI) surgeons through UGI and visceral surgical societies mailing lists and social media between February and June 2022. Participants were excluded if they did not answer a minimum of 80% completion of the questionary). Results 172 surgeons from 154 centers in 19 countries responded to the survey. The most represented countries were Germany 60 (35%), Switzerland 30 (18%) and Italy 16 (9%). The mean surgical years’ experience of the responders was 20.8 and their caseload was 23.2 cases per year. For intestinal type gastric tumor, a proximal resection margin length of a minimum of 5 centimeters was advocated by 119 (77%) of the responders. For diffuse, a resection margin of a minimum of 8 cm was applied by 98 (63%) of the surgeons. Macroscopic inspection of the specimen was routinely performed by 110 respondents (64%). Conclusions The real-world data from our questionnaire shows that the length of resection margins proposed by actual guidelines are not strictly applied in European centers. Further data from clinical research are needed to standardize resection margin cut-off. This could help European surgeons to propose more organ-sparing strategies to their patients.

Exploration of the Tumour Biological Significance of PCLO in Gastric Cancer: Results from a Large Central European Cohort

Introduction: A recent multiregional whole-exome sequencing of 48 tumour samples from 9 gastric adenocarcinomas discovered PCLO mutations in 23 (47.9%) tumour samples. Based on that unexpected high prevalence of PCLO mutations, we hypothesized a tumour biological significance of PCLO in gastric cancer (GC). Methods: Tumour samples (whole tissue sections) obtained from 466 patients resected for therapy-naive GC were stained with an anti-PCLO antibody. The histoscore for tumour cells and the presence of immunostaining of stromal cells and tumour vessels was documented for each case. An algorithm for PCLO immunopositivity was formed and correlated with clinicopathological patient characteristics. Results: 175 GCs were classified as PCLO positive within tumour cells, and 291 as negative. Stromal cells were positive for PCLO in 106 cases and tumour vessels in 84. PCLO-positive GCs more often showed an intestinal phenotype, a lower T category and were more commonly associated with Helicobacter pylori infection. A separate analysis of PCLO expression in intestinal and diffuse type GCs, respectively, showed no significant correlations. Patients with PCLO negative/low tumour cells showed a shortened overall (14.0 ± 1.4 vs. 16.0 ± 1.8 months) and tumour-specific survival (15.0 ± 1.6 months vs. 17.9 ± 3.6). Comparison of PCLOs genotype with its phenotype in 48 tumour samples obtained from nine cases showed no direct correlations with missense mutations. Conclusion: Our data provide evidence that PCLO is differentially expressed in GC and might delay tumour progression.

Intraductal papillary neoplasms of the bile ducts-what can be seen with ultrasound?

Intraductal papillary neoplasm of the bile ducts is a rare tumor. Characteristic features include bile duct dilatation, cystic lesions with communication to the bile ducts, and intraluminal solid nodules arising from the bile duct wall. As in pancreatic intraductal papillary mucinous neoplasia, intestinal, pancreaticobiliary, gastric, and oncocytic types are described. Intraductal papillary neoplasm of the bile ducts has a high potential for malignancy, and patients should be surgically resected when possible. In this review, the complex imaging diagnosis is presented. The main focus is on contrast-enhanced ultrasound, an established method for many other indications whose potential on the biliary system should be better exploited. In the present article, typical contrast-enhanced ultrasound findings in intraductal papillary neoplasm of the bile ducts are demonstrated.