Gastrointestinal Malignancies Research Articles

The efficacy of Hemospray in managing bleeding related to gastrointestinal tumors: systematic review and meta-analysis.

Gastrointestinal (GI) bleeding stemming from malignant tumors is increasingly recognized, due to advancements in oncology and detection methods. Traditional endoscopic hemostatic techniques have shown variable success rates in managing hemorrhagic GI neoplasms. Hemospray, an emerging endoscopic hemostatic powder, offers promise in treating upper GI bleeding, potentially extending its utility to neoplastic bleeding sites. This meta-analysis aims to evaluate Hemospray's efficacy in managing bleeding related to GI tumors. We searched Embase, Scopus, Web of Science, Medline/PubMed, and Cochrane. Inclusion criteria encompassed studies focusing on malignancy-related GI bleeding and interventions utilizing Hemospray. Comparative studies contrasted Hemospray with standard endoscopic treatments (SET), while noncomparative studies assessed Hemospray's efficacy independently. The risk of bias was assessed using appropriate tools, and statistical analyses were performed using Review Manager and open Meta analyst software. We included 19 studies in our meta-analysis. Hemospray demonstrated higher rates of immediate hemostasis compared to SET (odds ratio: 17.14, 95% confidence interval: 4.27-68.86), with consistent outcomes across studies. Rebleeding rates at 14 and 30 days were comparable between Hemospray and SET groups, suggesting similar efficacy in long-term hemostasis. Hemospray showed a significantly lower need for nonendoscopic hemostasis compared to SET (odds ratio: 0.51, 95% confidence interval: 0.30-0.87), indicating a potential reduction in supplementary interventions. Safety assessments revealed no confirmed adverse events directly linked to Hemospray. This meta-analysis highlights Hemospray's efficacy in achieving immediate hemostasis in GI tumor-related bleeding, with potential benefits in reducing supplementary interventions and improving patient outcomes. Despite comparable rebleeding rates, Hemospray emerges as a valuable adjunctive therapy in managing malignant GI bleeding.

The role of cGAS in epithelial dysregulation in inflammatory bowel disease and gastrointestinal malignancies.

The gastrointestinal tract is lined by an epithelial monolayer responsible for selective permeability and absorption, as well as protection against harmful luminal contents. Recognition of foreign or aberrant DNA within these epithelial cells is, in part, regulated by pattern recognition receptors such as cyclic GMP-AMP synthase (cGAS). cGAS binds double-stranded DNA from exogenous and endogenous sources, resulting in the activation of stimulator of interferon genes (STING) and a type 1 interferon response. cGAS is also implicated in non-canonical pathways involving the suppression of DNA repair and the upregulation of autophagy via interactions with PARP1 and Beclin-1, respectively. The importance of cGAS activation in the development and progression of inflammatory bowel disease and gastrointestinal cancers has been and continues to be explored. This review delves into the intricacies of the complex role of cGAS in intestinal epithelial inflammation and gastrointestinal malignancies, as well as recent therapeutic advances targeting cGAS pathways.

Smell and Taste Alterations in Patients Receiving Curative or Palliative Chemotherapy-The CONKO 021-ChemTox Trial.

Previous data regarding chemotherapy-induced olfactory and gustatory dysfunction (CIOGD) are heterogeneous due to inconsistent study designs and small numbers of patients. To provide consistent, reliable data, we conducted a cohort study using standardized testing. Patients diagnosed with lymphoma, leukemia, or gastrointestinal malignancies were examined up to five times (T1 to T5), beginning prior to chemotherapy. We examined patients receiving temporary treatment up to 12 months post-therapy. Clinical assessment included extensive questionnaires, psychophysical tests of olfactory and gustatory function, and measurement of peripheral neuropathy. Statistical analysis included non-parametric tests to evaluate the longitudinal development of CIOGD. Our data (n = 108) showed a significant decline in olfactory and gustatory testing during chemotherapy (p-values < 0.001). CIOGD appeared stronger among patients above 60 years, while sex did not matter significantly. However, we identified distinct associations between CIOGD and reported anorexia as well as with higher neuropathy scores. Self-assessment appeared less sensitive to chemosensory dysfunction than psychophysical testing. Post-therapy, olfactory and gustatory function regenerated, though baseline levels were not attained within 6 to 12 months. In conclusion, our data highlight the wide prevalence and slow recovery of CIOGD. Understanding CIOGD as a potential neurotoxic effect may disclose new therapeutic prospects.

Prognostic and predictive role of YKL-40 in anal squamous cell carcinoma: a serological and tissue-based analysis in a multicentric cohort.

Anal squamous cell carcinoma (ASC) is a rare gastrointestinal malignancy showing an increased incidence over the past decades. YKL-40 is an immune modulator and pro-angiogenetic factor that showed a promising prognostic and predictive potential in several malignancies, but limited data are available for ASC. This study aims to provide an extensive evaluation of the prognostic and predictive role of YKL-40 in a multicenter cohort of ASC patients. We retrospectively retrieved 72 consecutive cases of ASC diagnosed between February 2011 and March 2021. Both serum and tissue protein expression of YKL-40 were assessed, the latter in ASC tumor cells and peritumor immune cells. Increased YKL-40 serum levels at the time of diagnosis were associated with older age (p = 0.035), presence of cardiovascular/metabolic comorbidities (p = 0.007), and death for any cause (p = 0.011). In addition, high serum levels of YKL-40 were associated with a poor prognosis (HR: 2.82, 95% CI: 1.01-7.84; p = 0.047). Protein expression of YKL-40 in ASC tumor cells was significantly associated with low tumor grade (p = 0.031), while the increased expression in peritumor immune cells was associated with a worse response of patients to chemoradiotherapy (p = 0.007). However, YKL-40 protein expression in ASC tumor cells or peritumor immune cells did not significantly impact patient overall survival. In conclusion, YKL-40 resulted a relevant prognostic (serum level) and predictive (tissue protein expression in peritumor immune cells) biomarker and can considerably improve ASC patient clinical management.

Laparoscopic Gastrojejunostomy Versus Endoscopic Stenting as a Palliative Treatment for Gastric Outlet Obstruction.

Introduction: Gastric outlet obstruction (GOO) is a common complication in advanced stage upper gastrointestinal malignancies. The symptoms of severe nausea and protracted vomiting can lead to a decline in quality of life and cachexia. Symptoms of GOO can be effectively managed with either operative or nonoperative palliative interventions. In our article, we aim to compare laparoscopic gastrojejunostomy (GJ) to endoscopic stenting as palliative interventions for GOO. Methods: We retrospectively evaluated the charts of patients who underwent palliative procedure for gastric outlet obstruction. Group I included patients who underwent endoscopic stenting, and group II patients underwent Laparoscopic GJ. The groups' demographics (age, gender), length of procedure, length of stay, days to oral intake, overall survival, complications rate, and 30-day mortality rates were compared. Results: Overall, 38 patients were included in the study. Nineteen patients underwent endoscopic stenting and 19 underwent laparoscopic GJ. Comparing the groups, no significant differences were noted. Surgical time was significantly longer than the endoscopic procedures (83 minutes versus 25 minutes, P = .001). No significant differences were noted in days of oral intake initiation, overall survival and 30-day mortality rates. Five patients in the stenting group had complications (26.3%) versus none in the surgical group (P = .046). No postoperative complications were noted. Conclusion: Laparoscopic GJ is a safe and feasible treatment for GOO, demonstrating early resumption of oral intake. The relative short hospital stay, combined with an encouraging postoperative complications profile and low reintervention rate, should be kept in mind especially among patients with longer life expectancy.

Zolbetuximab: First Approval.

Zolbetuximab (VYLOY™), a recombinant, chimeric, anti-claudin 18.2 (CLDN18.2) monoclonal antibody (mAb), is being developed by Astellas Pharma Inc. for the treatment of patients with HER2-negative (HER2-), CLDN18.2-positive (CLDN18.2+) advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma and CLDN18.2+ advanced pancreatic adenocarcinoma. In March 2024, zolbetuximab was approved in Japan for the treatment of patients with HER2-, CLDN18.2+ unresectable, advanced/recurrent gastric cancer (the gastric cancer indication includes GEJ cancer). Zolbetuximab is also undergoing regulatory review for HER2-, CLDN18.2+ advanced gastric or GEJ adenocarcinoma in the USA, the EU, China, Australia and several other countries. This article summarizes the milestones in the development of zolbetuximab leading to this first approval for the treatment of patients with CLDN18.2+ gastrointestinal malignancies.

Role of Endoscopic Ultrasound and Endoscopic Ultrasound Guided Fine Needle Aspiration in Endoscopic Biopsy Negative Gastrointestinal Lesion

Abstract Introduction The rapidly growing incidence of gastrointestinal malignancies, makes early detection of such lesions a mandatory issue. EUS is a very sensitive modality in diagnosis of GIT wall lesions with superiority in diagnostic yield over conventional endoscopy, and non- invasive diagnostic modalities as CT and MRI. Aim To assess the feasibility, safety and accuracy of endoscopic ultrasound and endoscopic ultrasound guided fine needle aspiration in diagnosis of endoscopic biopsy negative gastrointestinal lesions. Material and Methods We conducted this prospective study over the period of 2 years that included 245 patients with mean age 46 years. All included patients had suspected GIT lesions with repeated negative endoscopic biopsies. All patients underwent EUS examination and EUS- FNA in the same session. Results EUS diagnosis SE, SP, PVP, PVN, LR+, LR-, and, DiAc were 0.94, 0.90, 0.93, 0.91, 9.11, 14.7, and 0.92 respectively, while EUS-FNA SE, SP, PVP, PVN, LR+, LR-, and DiAc were 0.86, 0.99, 0.99, 0.83, 83.89, 7.32, and 0.91respectively, with 100% technical success. Size of the lesion, size of the needle, and number of needle passes had no impact on diagnostic yield of EUS-FNA. No procedure related complications were reported. Conclusions EUS with EUS-FNA is a safe, feasible modality with high diagnostic accuracy in diagnosis of endoscopic biopsy negative gastrointestinal lesions irrespective to anatomical location of the lesion, layer of origin, lesion size, lesion echotecture, and no impact of needle size and number of needle passes on the diagnostic yield of EUS and EUS-FNA.

Immune checkpoint inhibitors and radiotherapy in gastrointestinal cancer treatment

Background. In recent decades, immunotherapy has become a topical area of research in the complex treatment of oncological diseases. A significant achievement in the immunotherapy of oncological diseases was the discovery of immune checkpoint proteins, which are effective inhibitors of the immune response. Immune checkpoint inhibitors (ICIs) have been approved for the treatment of certain gastrointestinal malignancies. However, the clinical efficacy of ICIs monotherapy remains low. To improve the outcome of treatment, numerous studies are conducted in which immunotherapy is combined with other standard methods of anticancer treatment. Radiation therapy (RT) may enhance the antitumor immune response when combined with ICIs and is worth considering when combined with immunotherapy. The effectiveness of the combined strategy is actively being investigated in clinical trials. Purpose – to highlight the latest achievements in the field of combined use of immunotherapy with ICIs and RT in malignant neoplasms of the gastrointestinal tract. Materials and methods. Data searches for the review were conducted using PubMed, Scopus, Google Scholar, and ClinicalTrials.gov databases. The data of works published in 2013-2023 were analyzed and systematized. Results and discussion. The rationality of the combination of RT and immunotherapy was substantiated. The results of the combined use of neoadjuvant chemoradiotherapy (CRT) and immunotherapy with ICIs in patients with resectable esophageal cancer and combined treatment in patients with advanced disease are analyzed. The clinical results of the use of ICIs in combination with RT or CRT in patients with gastric cancer and the combination of ICIs and RT in patients with hepatocellular carcinoma are presented. The clinical effects of adding ICIs to neoadjuvant RT or CRT in patients with locally advanced and borderline resectable pancreatic cancer and the results of trials of a combined strategy in patients with advanced disease are characterized. The clinical efficacy of the combined approach in locally advanced rectal cancer, which is a routine area of RT application, and in metastatic disease is reviewed. The results of small studies of combined treatment involving patients with metastatic colorectal cancer are presented. Conclusions. Over the past decade, research in the field of immunotherapy for gastrointestinal tumors has increased significantly. Based on the synergistic effects of radiation therapy and immune checkpoint inhibitors, the combination of these therapeutic approaches is increasingly being tested in gastrointestinal cancer to improve treatment outcomes. Published studies have shown encouraging results with satisfactory toxicity. However, most clinical trials are retrospective, non-comparative phase I/II trials and are limited to a small number of patients. The results of these studies can serve as a basis for conducting multicenter prospective studies with large sample sizes to confirm the effectiveness of combined therapy.

Integrated impact of multiple body composition parameters on overall survival in gastrointestinal or genitourinary cancers: A descriptive cohort study.

This study aimed to evaluate if combining low muscle mass with additional body composition abnormalities, such as myosteatosis or adiposity, could improve survival prediction accuracy in a large cohort of gastrointestinal and genitourinary malignancies. In total, 2015 patients with surgically-treated gastrointestinal or genitourinary cancer were retrospectively analyzed. Skeletal muscle index, skeletal muscle radiodensity, and visceral/subcutaneous adipose tissue index were determined. The primary outcome was overall survival determined by hospital records. Multivariate Cox hazard models were used to identify independent predictors for poor survival. C-statistics were assessed to quantify the prognostic capability of the models with or without incorporating body composition parameters. Survival curves were significantly demarcated by all 4 measures. Skeletal muscle radiodensity was associated with non-cancer-related deaths but not with cancer-specific survival. The survival outcome of patients with low skeletal muscle index was poor (5-year OS; 65.2%), especially when present in combination with low skeletal muscle radiodensity (5-year overall survival; 50.2%). All examined body composition parameters were independent predictors of lower overall survival. The model for predicting overall survival without incorporating body composition parameters had a c-index of 0.68 but increased to 0.71 with the inclusion of low skeletal muscle index and 0.72 when incorporating both low skeletal muscle index and low skeletal muscle radiodensity/visceral adipose tissue index/subcutaneous adipose tissue index. Patients exhibiting both low skeletal muscle index and other body composition abnormalities, particularly low skeletal muscle radiodensity, had poorer overall survival. Models incorporating multiple body composition prove valuable for mortality prediction in oncology settings.

Mucocutaneous Manifestations among Patients with Malignancies at a Tertiary Care Center in Maharashtra: A Cross-Sectional Study

Abstract Background: Malignant disorders are a leading cause of mortality and morbidity. Cutaneous manifestations may be presenting features of internal malignancies, leading to diagnosis of occult tumors, while others may occur as adverse reactions to therapeutic modalities. Aims and Objectives: To classify cutaneous manifestations among patients with malignant disorders, document their clinical profile, and analyze them with respect to age, gender, type of malignancy, and treatment. Materials and Methods: One hundred twenty patients with proven malignancy presenting with mucocutaneous lesions were enrolled in the cross-sectional study. On the basis of history, clinical examination, investigations and skin biopsy, the lesions were classified as (1) Primary cutaneous malignancy, (2) Cutaneous metastasis, (3) Paraneoplastic syndromes, (4) Mucocutaneous manifestations not related to malignancies, (5) Adverse effects secondary to treatment modalities. Results: One hundred twenty patients comprised 70 females (58.3%) and 50 males (41.7%). They were categorized as primary cutaneous malignancy (20.2%), hematological malignancies (15%), solid organ malignancy (50.9%), and gastrointestinal malignancies (5%). HIV seropositivity was seen in two patients (1.6%). Maximum belonged to Category 5 (60, 50%), of which 52 (86.7%) were adverse effects of chemotherapy with single patient showing radiation dermatitis and one patient in Category 3 (0.8%). Eleven patients showed cutaneous metastasis (9.1%), predominantly carcinoma breast. Clinically, primary cutaneous malignancies often presented as ulceronodular growths with squamous cell carcinoma being the most common histopathological type (30%). Anagen effluvium was the most common (35%) manifestation overall and in solid organ malignancies followed by melanonychia (16, 13.33%), cutaneous xerosis (9, 7.5%), and mucocutaneous hyperpigmentation (23, 19.16%). Conclusions: Mucocutaneous manifestations need prompt attention to facilitate timely diagnosis and improved outcomes.

Upper gastrointestinal endoscopy in the surgically altered patient.

As management of upper gastrointestinal malignancies improves, and with popularization of bariatric surgery, endoscopists are likely to meet patients with altered upper gastrointestinal anatomy. Short-term, the surgery can cause complications like bleeding, leaks, and fistulas, and longer-term problems such as intestinal or biliary anastomotic strictures or biliary stones can arise, all necessitating endoscopy. In addition, the usual upper gastrointestinal pathologies can also still occur. These patients pose unique challenges. To proceed, understanding the new layout of the upper gastrointestinal tract is essential. The endoscopist, armed with a clear plan for navigation, can readily diagnose and manage most commonly occurring conditions, such as marginal ulcers and proximal anastomotic strictures with standard endoscopic instruments. With complex reconstructions involving long segments of small bowel, such as Roux-en-Y gastric bypass, utilization of balloon-assisted enteroscopy may be necessary, mandating modification of procedures such as endoscopic retrograde cholangiopancreatography. Successful endoscopic management of patients with altered anatomy will require prior planning and preparation to ensure the appropriate equipment, setting, and skill set is provided.

Histomolecular subtyping of periampullary adenocarcinoma and its correlation with pathological prognostic factors

Abstract Introduction: Periampullary adenocarcinoma (PAC) is a less frequent tumor accounting for approximately 0.5%–2% of all gastrointestinal malignancies. Histologically, PAC subtyped into intestinal and pancreaticobiliary adenocarcinoma which is further confirmed by immunohistochemistry (IHC). Subtyping of PAC has emerged as an important prognostic factor with potential therapeutic implications. Aim: The aim of the study was to assess morphology and IHC expression of CK7, CK20, and CDX2 to subtype PAC and correlate the subtype predicted on histomorphology with the immunohistochemical expression. Materials and Methods: This was a cross-sectional study done from January 2018 to July 2023. A total of 28 pancreaticoduodenectomy specimens were assessed and further classified into intestinal and pancreaticobiliary subtypes after correlating both histological and immunohistochemical features. Statistical analysis was performed using the standard statistical software. P &lt;0.05 was considered statistically significant. Results: Histomorphology and IHC (CK7, CK20, and CDX2) expression was studied in 28 cases having an age range from 41 to 74 years including 18 males. Based on histomorphological findings, they are categorized into intestinal (n = 15) and pancreaticobiliary (n = 13) subtypes. The use of only morphology showed a sensitivity, specificity, and diagnostic accuracy of 63.6%, 52.9%, and 53.16%, respectively, for the intestinal subtype and 50%, 57%, and 57%, respectively, for the pancreaticobiliary subtype. With the use of combined histomorphology and IHC the sensitivity, specificity, and diagnostic accuracy was &gt;90% with a significant reduction in false-positive diagnosis. Conclusion: The correlation of histomorphology and IHC findings can aid in better subtyping of PAC.

Role of TAP1 in the identification of immune-hot tumor microenvironment and its prognostic significance for immunotherapeutic efficacy in gastric carcinoma.

Gastric cancer (GC), a multifaceted gastrointestinal malignancy, is the fourth most prevalent contributor to cancer-related fatalities globally. As a member of the ATP-binding cassette (ABC) family, transporter associated with antigen processing 1 (TAP1) is crucial for conveying antigen peptides from the cytoplasm to the lumen of the endoplasmic reticulum and subsequently loading them onto the major histocompatibility complex (MHC) class I molecules. Recent studies have established the biological significance of TAP1 in upholding tumor survival and facilitating immune evasion by remodeling the tumor microenvironment (TME) and orchestrating immune infiltration. The study was conducted to elucidate the association of TAP1 expression with immunological characteristics, and sought to exploit the value of TAP1 as a biomarker reflecting the inflamed TME and immunotherapeutic response. RNA-sequencing profiles and clinical annotations were obtained from The Cancer Genome Atlas-stomach adenocarcinoma (TCGA-STAD) cohort and Gene Expression Omnibus (GEO) portal. Preprocessing was conducting using the limma package. Weighted gene co-expression network analysis (WGCNA) was used to identify gene modules and TAP1 co-expressed genes (CEGs) based on correlation patterns. Consensus clustering and silhouette analysis determined the optimal number of TAP1-related groups. Gene expression profiles were integrated and classified using the pamr package. The Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE) algorithm and single-sample gene set enrichment analysis (ssGSEA) were used to evaluate immunological characteristics. Differential expression analysis was conducted using the limma package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Single-cell RNA sequencing (scRNA-seq) datasets were analyzed using the Seurat toolkit to characterize cell types. Within this investigation, no significant differences in TAP1 expression were observed among patients exhibiting various clinicopathological features, indicating that TAP1 expression was not specific to molecular subtypes. Subsequent analysis revealed a positive correlation between TAP1 and diverse immunological traits, encompassing immunomodulators, tumor-infiltrating immune cells, as well as immune checkpoints across multiple datasets. Besides, within a GC immunotherapy cohort, individuals displaying high TAP1 expression demonstrated an increased likelihood of achieving complete remission (CR) post-treatment, suggesting heightened sensitivity to immunotherapy. In the clinical cohort, TAP1 overexpression in GC patients was positively correlated with CD8. TAP1 appears linked to an inflamed TME and serves as a prospective biomarker for discerning immunological attributes and gauging immunotherapeutic responses in GC, particularly in identifying immune-reactive tumors.

Surgical treatment of intrahepatic and hilus cholangiocarcinoma

Cholangiocarcinoma includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point of the biliary tree. Their incidence is increasing globally, currently accounting for ~15% of all primary liver cancers and ~3% of gastrointestinal malignancies. The silent presentation of these tumours combined with their highly aggressive nature and refractoriness to chemotherapy contribute to their alarming mortality, representing ~2% of all cancer-related deaths worldwide yearly. Surgery remains the main radical method. The purpose of this review is to summarize current and modern approaches to the surgical treatment of intrahepatic and hilus cholangiocarcinoma. Key words: biliary tract cancers, intrahepatic cholangiocarcinoma, hilus cholangiocarcinoma, Klatskin tumor, surgical treatment, liver transplantatio

Impact of Neoadjuvant Treatment on Body Composition in Patients with Locally Advanced Gastric Cancer.

Neoadjuvant chemotherapy (NT) followed by radical surgery is the standard treatment for locally advanced gastric cancer (GC). The incidence of sarcopenia in upper gastrointestinal tract malignancies is very high, and it may be increased after NT. This study aimed to evaluate the impact of NT on body composition. A retrospective study of patients with locally advanced GC undergoing gastrectomy who had received NT in a tertiary hospital between 2012 and 2019 was conducted. CT measured the skeletal muscle index, total psoas area, and visceral and subcutaneous adipose tissue before and after NT. Of the 180 gastrectomies for GC, 61 patients received NT. During NT, changes in body composition were observed with a decrease in the skeletal muscle mass index (SMMI -2.5%; p < 0.001), and these changes were significantly greater in men (SMMI -10.55%). Before surgery, patients who received NT presented 15% more sarcopenia than those without NT (p = 0.048). In conclusion, patients with locally advanced gastric cancer who receive NT have significant changes in body composition during chemotherapy. These changes, which are at the expense of a loss of muscle mass, lead to an increased incidence of pre-surgical sarcopenia.

Metal complex hydrogel loaded with paclitaxel for photocatalytic and fluorescence-responsive drug control on ampullary carcinoma by modulation of HHLA2

Despite accounting for only 0.2 % of gastrointestinal malignancies, ampullary carcinoma is the second most common malignant tumor in the peripelvic area after pancreatic head cancer, highlighting the need for new drug delivery systems, as pancreaticoduodenectomy remains the primary treatment. In this study, we synthesized a novel Cd(II) coordination polymer (CP1), {[Me4N]2[Cd3(4,4′-bpdc)4]}n (4,4′-H2bpdc = 4,4′-biphenyldicarboxylic acid), under hydrothermal conditions using tetramethylammonium cations as templates. The photocatalytic performance of CP1 was investigated under UV light irradiation. Hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) were chemically synthesized to retain the biocompatibility of natural polysaccharides, resulting in HA/CMCS hydrogels with a three-dimensional porous structure, as revealed by scanning electron microscopy. This structure makes the hydrogel an excellent drug carrier. We recombined CP1 and the drug paclitaxel (PTX) within the hydrogel, constructing a HA/CMCS-CP1@PTX nanodrug platform. This platform exhibited excellent drug-loading performance and allowed effective temperature control through light sources, enabling controlled release rates. In vitro cell tests demonstrated that the system promoted apoptosis by modulating the expression of apoptosis-related factors and HHLA2, thereby inhibiting the progression of ampullary carcinoma.

Gastro Intestinal Stromal Tumor: Cases Series Report

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors of the alimentary tract. Now a day GISTs represents 0.1-3% of all gastrointestinal malignancies, making it a diagnostic challenge. Lesions are frequently located in stomach and proximal small intestine but rarely elsewhere in the abdomen. They are believed to result from mutations of protooncogenes c-Kit or platelet-derived growth factor receptor alpha polypeptide, this increase tyrosine kinase receptor activity, leading to uncontrolled proliferation of stem cells that differentiate into cells of Cajal. They can occur at any age but predominantly in middle-aged people and in elderly. We reported the cases presented to our hospital with progressively distension of the abdomen, finding in diagnostic image suggested GIST without evidence of metastasis disease, total excision was done, Cytologic and immunohistochemistry analysis confirm diagnosis of GISTs.

Comprehensive bioinformatics analysis of integrator complex subunits: expression patterns, immune infiltration, and prognostic signature, validated through experimental approaches in hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is a common gastrointestinal malignancy with a high incidence and poor prognosis. The subunits of the integrator complex (INTS1-14) play a crucial role in regulating genes dependent on RNA Polymerase II, which may be associated with cancer. However, the role of INTSs in HCC remains unclear. This study aims to comprehensively analyze the clinical value and potential role of INTS family genes in HCC through systematic bioinformatics analysis.MethodsWe employed various public databases, including UALCAN, HPA, Kaplan–Meier Plotter, GEPIA2, TNMplot, STRING, TIMER, and TISIDB, to investigate the expression levels, clinicopathological correlations, diagnostic and prognostic value, genetic alterations, co-expression network, molecular targets, and immune infiltration of INTSs in HCC. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were utilized to investigate the biological functions of genes associated with INTSs. Furthermore, Western blot, real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR), and immunohistochemistry techniques were employed to assess the expression of relevant proteins and genes. The proliferation of HCC cells was evaluated using the CCK8 assay.ResultsWe found that in HCC, there was a significant upregulation of INTSs at the transcriptional level, particularly INTS1, INTS4, INTS7, and INTS8. Additionally, the protein levels of INTS1 and INTS8 were notably elevated. The overexpression of these INTSs was strongly correlated with tumor stages in HCC patients. INTS1, INTS4, INTS7, and INTS8 exhibited significant diagnostic and prognostic value in HCC. Moreover, their expression was associated with immune infiltrations and activated status, including B cells, CD8 + T cells, CD4 + T cells, NK cells, macrophages, and dendritic cells. Functional predictions indicated that INTS1, INTS4, INTS7, and INTS8 were involved in various cancer-related signaling pathways, such as TRAIL, IFN-gamma, mTOR, CDC42, Apoptosis, and the p53 pathway. Furthermore, we observed a significant upregulation of INTS1, INTS4, INTS7, and INTS8 expression in HCC cell lines compared to normal liver cell lines. The level of INTS1 protein was higher in cancerous tissues compared to adjacent non-cancerous tissues (n = 16), and the suppression of INTS1 resulted in a significant decrease in the proliferation of Huh7 cells.ConclusionThese findings indicate the potential of INTS family genes as diagnostic biomarkers and therapeutic targets in HCC. Further research is needed to understand the underlying mechanisms and explore clinical applications.

Hereditary Gastrointestinal Tumor Syndromes: When Risk Comes with Your Genes.

Despite recent campaigns for screening and the latest advances in cancer therapy and molecular biology, gastrointestinal (GI) neoplasms remain among the most frequent and lethal human tumors. Most GI neoplasms are sporadic, but there are some well-known familial syndromes associated with a significant risk of developing both benign and malignant GI tumors. Although some of these entities were described more than a century ago based on clinical grounds, the increasing molecular information obtained with high-throughput techniques has shed light on the pathogenesis of several of them. The vast amount of information gained from next-generation sequencing has led to the identification of some high-risk genetic variants, although others remain to be discovered. The opportunity for genetic assessment and counseling in these families has dramatically changed the management of these syndromes, though it has also resulted in significant psychological distress for the affected patients, especially those with indeterminate variants. Herein, we aim to summarize the most relevant hereditary cancer syndromes involving the stomach and colon, with an emphasis on new molecular findings, novel entities, and recent changes in the management of these patients.

Assessment of Intraoperative Scoring Systems for Predicting Cytoreduction Outcome in Peritoneal Metastatic Disease: A Systematic Review and Meta-analysis.

Cytoreductive surgery (CRS) is a widely acknowledged treatment approach for peritoneal metastasis, showing favorable prognosis and long-term survival. Intraoperative scoring systems quantify tumoral burden before CRS and may predict complete cytoreduction (CC). This study reviews the intraoperative scoring systems for predicting CC and optimal cytoreduction (OC)and evaluates the predictive performance of the Peritoneal Cancer Index (PCI) and Predictive Index Value (PIV). Systematic searches were conducted in Embase, MEDLINE, and Web of Science. Meta-analyses of extracted data were performed to compare the absolute predictive performances of PCI and PIV. Thirty-eight studies (5834 patients) focusing on gynecological (n = 34; 89.5%), gastrointestinal (n = 2; 5.3%) malignancies, and on tumors of various origins (n = 2; 5.3%) were identified. Seventy-seven models assessing the predictive performance of scoring systems (54 for CC and 23 for OC) were identified with PCI (n = 39/77) and PIV (n = 16/77) being the most common. Twenty models (26.0%) reinterpreted previous scoring systems of which ten (13%) used a modified version of PIV (reclassification). Meta-analyses of models predicting CC based on PCI (n = 21) and PIV (n = 8) provided an AUC estimate of 0.83 (95% confidence interval [CI] 0.79-0.86; Q = 119.6, p = 0.0001; I2 = 74.1%) and 0.74 (95% CI 0.68-0.81; Q = 7.2, p = 0.41; I2 = 11.0%), respectively. Peritoneal Cancer Index models demonstrate an excellent estimate of CC, while PIV shows an acceptable performance. There is a need for high-quality studies to address management differences, establish standardized cutoff values, and focus on non-gynecological malignancies.