Advances and challenges in diagnosing and managing adult autoimmune enteropathy

Autoimmune enteropathy(AIE)is a rare immune mediated disorder primarily affecting children,characterized by chronic diarrhea,malabsorption,vomiting,weight loss and villous atrophy.It has also been observed in adults presenting diagnostic and treatment challenges due to its overlap with other gastrointestinal disorders such as celiac disease.Initial diagnostic criteria for AIE include small bowel villous atrophy,lack of response to dietary restrictions,presence of anti-enterocyte antibodies,and predisposition to autoimmunity without severe immu-nodeficiency.Refined criteria emphasize characteristic histological findings and exclusion of other causes of villous atrophy.AIE is associated with various autoimmune disorders and can present with overlapping features with Celiac disease,including villous atrophy but without significant intraepithelial lympho-cytosis.Treatment primarily involves immunosuppression using corticosteroids,calcineurin inhibitors,and anti-tumor necrosis factor therapy,alongside nutri-tional support.Despite the challenges,understanding AIE’s diverse manifest-ations and improving diagnostic criteria are essential for effective management and improved patient outcome.Further research is needed to elucidate the pathogenesis,disease progression and long-term outcomes of AIE.

Anticipation for hepatic arterial infusion chemotherapy in the treatment of hepatocellular carcinoma

Hepatic arterial infusion chemotherapy (HAIC) is an advanced targeted therapeuticapproach for hepatocellular carcinoma (HCC), the most common type ofprimary liver cancer. HAIC has demonstrated significant potential in managingadvanced HCC, particularly in regions with high prevalence rates. Despite itspromise, several challenges and areas for future research remain. Clinical studieshave substantiated the efficacy of HAIC in enhancing survival outcomes forpatients with advanced hepatic carcinoma. Notably, combination therapiesinvolving immune checkpoint inhibitors, such as lenvatinib and programmeddeath-1 inhibitors, have shown substantial improvements in median overallsurvival and progression-free survival compared to systemic chemotherapy.These combination therapies have also exhibited superior response rates anddisease control, with manageable and often less severe adverse events relative tosystemic treatments. This article is based on the review by Zhou et al and aims todiscuss the current status and future directions in the treatment of HCC, emphasizingthe role of HAIC and its integration with novel therapeutic agents.

Therapeutic strategies and prognostic challenges in linitis plastica

Gastric cancer ranks fifth as the most common cancer and third as the leading cause of death worldwide.Risk factors include advancing age,low-fiber diets,high salt intake and Helicobacter pylori infection.Diagnosis relies on histological examination following endoscopic biopsy with staging accomplished through various imaging modalities.Early gastric cancer is primarily managed via endoscopic resection,while non-early operable cases typically undergo surgery.Advanced cases are addressed through sequential chemotherapy lines,with initial treatment usually comprising a platinum and fluoropyrimidine combination.Linitis plastica(LP)is a rare,aggressive form of gastric cancer characterized by diffuse infiltration of the gastric wall,resulting in poor outcomes even after curative resection.The absence of a standardized definition contributes to uncertainty regarding the precise incidence of these tumors.LP is often diagnosed at advanced stages,with a reported median survival rate of approximately 4%-29%,despite“curative resection”.Its distinctive biological behavior includes perineural invasion,nodal metastasis,and peritoneal dissemination.The bleak prognosis for LP patients partly stems from delayed diagnosis and its aggressive biological nature,posing significant challenges for clinical management.Currently,no specialized treatment strategy exists for LP,and clinical approaches typically align with those used for general gastric cancer treatment.Surgical resection is the primary treatment,but the optimal surgical approach remains contentious.Recent studies have investigated the efficacy of neoadjuvant chemotherapy and radiotherapy in improving survival outcomes for LP patients.However,controversies persist regarding the role of adjuvant chemotherapy and postoperative radiotherapy.LP requires a multidisciplinary approach and personalized treatment strategies tailored to each patient’s condition.Further research is needed to elucidate optimal therapeutic interventions and improve outcomes for LP patients.

Advances and challenges in peroral endoscopic myotomy:Safety,precision,and post-procedure management

Peroral endoscopic myotomy(POEM)has revolutionized the treatment of upper gastrointestinal tract motility disorders,particularly achalasia.This editorial explores the efficacy,safety,and challenges of POEM,emphasizing its role as a primary treatment with excellent long-term outcomes and minimal adverse events.The evolution of POEM underscores the need for precision in myotomy techniques and the importance of interdisciplinary collaboration,especially regar-ding anesthetic considerations.Despite significant advances,challenges remain in standardizing safety protocols and managing complications.As POEM appli-cations expand,precision endoscopy continues to enhance therapeutic outcomes,promising a transformative impact on gastrointestinal motility disorder manage-ment.

Revolutionizing gastric cancer treatment:The potential of immunotherapy

Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.

Double role of depression in gastric cancer:As a causative factor and as consequence

In this editorial we comment on the article“Hotspots and frontiers of the rela-tionship between gastric cancer and depression:A bibliometric study”.Gastric cancer(GC)is a common malignancy in the digestive system with increased mortality and morbidity rates globally.Standard treatments,such as gastrectomy,negatively impact patients'quality of life and beyond the physical strain,GC patients face psychological challenges,including anxiety and depression.The prevalence of depression can be as high as 57%,among gastrointestinal cancer patients.Due to the advancements in treatment effectiveness and increased 5-year overall survival rates,attention has shifted to managing psychological effects.However,the significance of managing the depression doesn’t lie solely in the need for a better psychological status.Depression leads to chronic stress acti-vating the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis,leading release of catecholamines inducing tumor proliferation,migration,and metastasis,contributing to GC progression.The dysregulation of neurotrans-mitters and the involvement of various signaling pathways underscore the complex interplay between depression and GC.Comprehensive strategies are required to address the psychological aspects of GC,including region-specific interventions and increased monitoring for depression.Understanding the intricate relationship between depression and GC progression is essential for developing effective therapeutic strategies and improving overall outcomes for patients facing this complex disease.In this Editorial we delve into double role of depression in the pathogenesis of GC and as a complication of it.

Understanding autoimmune pancreatitis: Clinical features, management challenges, and association with malignancies

In this editorial we comment on the article by Jaber et al.Autoimmune pancreatitis(AIP)represents a distinct form of pancreatitis,categorized into AIP-1 and AIP-2,characterized by obstructive jaundice,lymphoplasmacytic infiltrate,and fibrosis.AIP-1,associated with elevated immunoglobulin G4(IgG4)levels,exhibits higher relapse rates,affecting older males,while AIP-2 is less common and linked to inflammatory bowel disease.AIP is considered a manifestation of IgG4-related systemic disease,sharing characteristic histological findings.Steroids are the primary treatment,with emerging biomarkers like interferon alpha and inter-leukin-33.AIP poses an increased risk of various malignancies,and the assoc-iation with pancreatic cancer is debated.Surgery is reserved for severe cases,necessitating careful evaluation due to diagnostic challenges.AIP patients may have concurrent PanINs but display favorable long-term outcomes compared to pancreatic cancer patients.Thorough diagnostic assessment,including biopsy and steroid response,is crucial for informed surgical decisions in AIP.

Immune signature of small bowel adenocarcinoma and the role of tumor microenvironment

In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.Small bowel adenocarcinoma(SBA)is a rare gastrointestinal neoplasm and despite the small intestine's significant surface area,SBA accounts for less than 3%of such tumors.Early detection is challenging and the reason arises from its asymptomatic nature,often leading to late-stage discovery and poor prognosis.Treatment involves platinum-based chemotherapy with a 5-fluorouracil combination,but the lack of effective chemotherapy contributes to a generally poor prognosis.SBAs are linked to genetic disorders and risk factors,including chronic inflammatory conditions.The unique characteristics of the small bowel,such as rapid cell renewal and an active immune system,contributes to the rarity of these tumors as well as the high intratumoral infiltration of immune cells is associated with a favorable prognosis.Programmed cell death-ligand 1(PD-L1)expression varies across different cancers,with potential discrepancies in its prognostic value.Microsatellite instability(MSI)in SBA is associated with a high tumor mutational burden,affecting the prognosis and response to immunotherapy.The presence of PD-L1 and programmed cell death 1,along with tumor-infiltrating lymphocytes,plays a crucial role in the complex microenvironment of SBA and contributes to a more favorable prognosis,especially in the context of high MSI tumors.Stromal tumor-infiltrating lymphocytes are identified as independent prognostic indicators and the association between MSI status and a favorable prognosis,emphasizes the importance of evaluating the immune status of tumors for treatment decisions.

Unveiling the clinicopathological enigma of crawling-type gastric adenocarcinoma

In this editorial we comment on the article by Xu et al.Gastric adenocarcinoma(GA)is a malignancy which arises from the gastric mucosa and encompasses heterogenous tumors with varying characteristics.There are two main classifications:Lauren’s and the World Health Organization distinguishing the diverse types of GA depending on clinical,genetic,morphological and epidemiological features.“Crawling-type”adenocarcinoma(CRA)is a subtype characterized by irregularly fused glands with low-grade cellular atypia.Moreover,CRA represents differentiated tumor cells resembling intestinal metaplasia which results in misdiagnosis.The diagnosis is of utmost importance,as well as the subclassification and thorough pathological assessment.With regard to the symptoms of GA,these depend on the stage of the disease.Diagnostic methods play a crucial role in assessing the extent of the tumor and the stage of the disease.Nevertheless,early detection of CRA remains challenging due to its histological features.In summary,CRA is a distinct type of GA with particular clinicopathological and histological characteristics.Despite its significance,it not distinguished as a subtype,resulting in diagnostic challenges.Diagnosis is based on careful observation and thorough biopsy analysis,indicating the importance of comprehensive pathological assessment.

Prognostic nutritional index in predicting survival of patients with gastric or gastroesophageal junction adenocarcinoma: A systematic review

BACKGROUND Gastric cancer is the third most common cause of cancer related death worldwide.Surgery with or without chemotherapy is the most common approach with curative intent;however,the prognosis is poor as mortality rates remain high.Several indexes have been proposed in the past few years in order to estimate the survival of patients undergoing gastrectomy.The preoperative nutritional status of gastric cancer patients has recently gained attention as a factor that could affect the postoperative course and various indexes have been developed.The aim of this systematic review was to assess the role of the prognostic nutritional index(PNI)in predicting the survival of patients with gastric or gastroesophageal adenocarcinoma who underwent gastrectomy with curative intent.AIM To investigate the role of PNI in predicting the survival of patients with gastric or gastroesophageal junction adenocarcinoma.METHODS A thorough literature search of PubMed and the Cochrane library was performed for studies comparing the overall survival(OS)of patients with gastric or gastroesophageal cancer after surgical resection depending on the preoperative PNI value.The PRISMA algorithm was used in the screening process and finally 16 studies were included in this systematic review.The review protocol was registered in the International Prospective Register of Systematic Reviews(PRO) RESULTS Sixteen studies involving 14551 patients with gastric or esophagogastric junction adenocarcinoma undergoing open or laparoscopic or robotic gastrectomy with or without adjuvant chemotherapy were included in this systematic review.The patients were divided into high-and low-PNI groups according to cut-off values that were set according to previous reports or by using receiver operating characteristic curve analysis in each individual study.The 5-year OS of patients in the low-PNI groups ranged between 39%and 70.6%,while in the high-PNI groups,it ranged between 54.9%and 95.8%.In most of the included studies,patients with high preoperative PNI showed statistically significant better OS than the low PNI groups.In multivariate analyses,low PNI was repeatedly recognised as an independent prognostic factor for poor survival.CONCLUSION According to the present study,low preoperative PNI seems to be an indicator of poor OS of patients undergoing gastrectomy for gastric or gastroesophageal cancer.

Pembrolizumab in patients with gastric cancer and liver metastases: A paradigm shift in immunotherapy

In this editorial,we explore the impact of immunotherapy and its safety in pa-tients with advanced gastric cancer(GC)and liver involvement.GC,a formidable adversary in the oncology landscape,presents its most challenging battlefront when it reaches stage IV,often characterized by liver metastases.The prognosis for patients at this advanced stage is daunting,with systemic chemotherapy tra-ditionally offering a median overall survival slightly over a year.However,the landscape of treatment is evolving,with new strategies and therapies offering a glimmer of hope.

Advancements and challenges in the treatment of esophageal cancer:A comprehensive review

Esophageal cancer(EC)is an aggressive malignancy with a poor prognosis,ranking seventh in incidence and sixth cancer-related deaths globally.EC is classified in two main types,the esophageal squamous cell carcinoma(ESCC)and esophageal adenocarcinoma(EAC),with ESCC being more common in Eastern Europe,South Asia,and Africa,while EAC is prevalent in Western Europe and North America.Molecular analysis identifies three subgroups of ESCC,each with distinct genetic mutations and treatment responses.Early-stage EC is often difficult to detect,leading to late-stage diagnoses that necessitate systemic drug therapies,including molecular-targeted therapies and immunotherapies.Immunotherapy,particularly immune checkpoint inhibitor,has shown promising results in improving survival rates for metastatic or persistent EC.It is particularly important to target to multidisciplinary combination therapies,integrating surgery,chemoradiotherapy,targeted therapy and immunotherapy.Additionally,radioimmunotherapy is being explored for its potential to enhance treatment efficacy,especially in advanced and metastatic tumors.However,the pathological complete response rate to neoadjuvant chemoradiotherapy remains suboptimal,highlighting the need for novel treatment strategies.Future research should focus on optimizing treatment combinations and identifying predictive biomarkers to improve clinical outcomes for EC patients.

Billroth II anastomosis combined with brown anastomosis reduce reflux gastritis in gastric cancer patients

BACKGROUND The surgeon performing a distal gastrectomy,has an arsenal of reconstruction techniques at his disposal,Billroth II among them.Braun anastomosis performed during a Billroth II procedure has shown evidence of superiority over typical Billroth II,in terms of survival,with no impact on postoperative morbidity and mortality.AIM To compare Billroth II vs Billroth II and Braun following distal gastrectomy,regarding their postoperative course.METHODS Patients who underwent distal gastrectomy during 2002-2021,were separated into two groups,depending on the surgical technique used(Billroth II:74 patients and Billroth II and Braun:28 patients).The daily output of the nasogastric tube(NGT),the postoperative day that NGT was removed and the day the patient started per os feeding were recorded.Postoperative complications were at the same time noted.Data were then statistically analyzed.RESULTS There was difference in the mean NGT removal day and the mean start feeding day.Mean total postoperative NGT output was lower in Braun group(399.17 mL vs 1102.78 mL)and it was statistically significant(P<0.0001).Mean daily postoperative NGT output was also statistically significantly lower in Braun group.According to the postoperative follow up 40 patient experienced bile reflux and alkaline gastritis from the Billroth II group,while 9 patients who underwent Christodoulidis G et al.Billroth II and Braun compared with Billroth II WJM https://www.wjgnet.com 2 March 20,2024 Volume 14 Issue 1 Billroth II and Braun anastomosis were presented with the same conditions(P<0.05).CONCLUSION There was evidence of superiority of Billroth II and Braun vs typical Billroth II in terms of bile reflux,alkaline gastritis and NGT output.

Pivotal role of exosomes in diagnosis and treatment of esophageal cancer in a new era of precision medicine

In this editorial we comment on the article published by Ning et al,“Role of exosomes in metastasis and therapeutic resistance in esophageal cancer”.Esophageal cancer(EC)represents a significant global health concern,being the seventh most common and sixth in terms of mortality worldwide.Despite the advances in therapeutic modalities,the management of patients with EC remains challenging,with a 5-year survival rate of only 25%and a limited eligibility for curative surgery due to its late diagnosis.Conventional screening methods are impractical for the early detection of EC,given their either invasive or insensitive nature.The advent of liquid biopsy,with a focus on circulating tumor cells,circulating tumor DNA,and exosomes,heralds a non-invasive avenue for cancer detection.Exosomes,small vesicles involved in intercellular communication,are highlighted as potential biomarkers for EC diagnosis and prognosis.Along with a diverse cargo encompassing various types of RNA,DNA molecules,proteins,and metabolites,exosomes emerge as key players in tumorigenesis,tumor development,and metastasis.Their significance extends to carrying distinctive biomarkers,including microRNAs(miRNAs),long non-coding RNAs,and circular RNAs,underscoring their potential diagnostic and prognostic value.Furthermore,exosomes may be utilized for therapeutic purposes in the context of EC treatment,serving as efficient delivery vehicles for therapeutic agents such as chemotherapeutic medicines and miRNAs.In this editorial we delve into the applications of exosomes for the early detection and treatment of EC,as well as the future perspectives.

Heterotopic pancreas in the stomach:A case report and literature review

Ectopic pancreas is defined as pancreatic tissue found outside the usual anatomic location of the pancreas. It is often an incidental finding and can be found at different sites in the gastrointestinal tract. It may become clinically evident when complicated by pathologic changes such as inflammation, bleeding, obstruction, and malignant transformation. In this report, a 40 years old woman with epigastric pain due to ectopic pancreatic tissue in the stomach is described. The difficulty of making an ac- curate diagnosis is highlighted. The patient has remained free of symptoms since she underwent wedge resection of the lesion three years ago. Frozen sections may help in deciding the extent of resection intraoperatively. Al- though ectopic pancreas is rare, it should be considered in the differential diagnosis of a submucosal gastric tumour.

Impact of antiplatelet treatment on colorectal cancer staging characteristics

AIM: To evaluate whether antiplatelet medication leads to an earlier stage colorectal cancer (CRC) diagnosis. METHODS: From January 2002 until March 2010, patients that presented to our institution with the initial diagnosis of CRC and were submitted to an open curative CRC resection or a palliative procedure were retrospectively reviewed. Exclusion criteria were the use of antithrombotic medication, i.e., coumarins, and appendiceal malignancies. Data acquired from medical files included age, gender, past medical history, antithrombotic treatment received prior to endoscopic diagnosis, preoperative imaging staging, location of the tumor, surgical and final histopathological report. Patients that did not receive any antithrombotic medication prior to the endoscopic diagnosis comprised the control group of the study, while patients that were on antiplatelet medication comprised the antiplatelet group. Primary end point was a comparison of CRC stage in the two groups of the study. CRC presenting symptoms and the incidence of each cancer stage in the two groups were also evaluated. RESULTS: A total of 387 patients with the diagnosis of CRC were submitted to our department for further surgical treatment. Ninety-eight patients (25.32%), with a median age of 71 years (range 52-91 years), were included in the antiplatelet group, while 289 (74.67%) patients, with a median age of 67 years (range 41-90 years), were not in any thrombosis prophylaxis medication (control group). Thirty-one patients were treated with some kind of palliative procedure, either endoscopic, such as endoscopic stent placement, or surgical, such as de-compressive colostomy or deviation. Coronary disease (77.55% - 76 patients), stroke recurrence prevention (14.28% - 14 patients) and peripheral arterial disease (8.16% - 8 patients) were the indications for the administration of antiplatelet treatment (aspirin, clopidogrel, ticlopidine or dipyridamole) in the antiplatelet group. All patients on aspirin treatment received a dosage of 100 mg/d, while the minimum prophylactic dosages were also used for the rest of the antiplatelet drugs. Investigation of an iron deficiency anemia (147 patients), per rectum blood loss (84 patients), bowel obstruction and/or perforation (81 patients), bowel habits alterations (32 patients), non-specific symptoms, such as weight loss, intermittent abdominal pain and fatigue, (22 patients) or population screening (21 patients) were the indications for the endoscopic investigation in both groups. Bleeding, either chronic presenting as anemia or acute was significantly higher (P = 0.002) for the antiplatelet arm of the study (71 patients - 72.4% of the antiplatelet group vs 160 patients - 55.3% of the control group). The mean tumor, node and metastasis stage was 2.57 ± 0.96 for the control group, 2.27 ± 0.93 for the antiplatelet group (P = 0.007) and 2.19 ± 0.92 for the subgroup of patients taking aspirin (P = 0.003). The incidence of advanced disease (stage IV) was lower for the antiplatelet group of the study (P = 0.033). CONCLUSION: The adverse effect of bleeding that is justifiably attached to this drug category seems to have a favorable impact on the staging characteristics of CRC.

Giant abdominal osteosarcoma causing intestinal obstruction treated with resection and adjuvant chemotherapy

Extraskeletal osteosarcoma(ESOS)is an uncommon tumor that accounts for 1% of all soft tissue sarcomas and 4% of all osteosarcomas. Its presentation may be atypical,while pain has been described as the most common symptom. Radiological findings include a large mass in the soft-tissues with massive calcifications,but no attachment to the adjacent bone or periosteum. We present the case of a 73-year-old gentle man who presented with a palpable,tender abdominal mass and symptoms of bowel obstruction. Computer tomography images revealed a large space-occupying heterogeneous,hyper dense soft tissue mass involving the small intestine. Explorative laparotomy revealed a large mass in the upper mesenteric root of the small intestine,measuring 22 cm × 12 cm × 10 cm in close proximity with the cecum,which was the cause of the bowel obstruction. Pathology confirmed the diagnosis of an ESOS. ESOS is an uncommon malignant soft tissue tumor with poor prognosis and a 5-year survival rate of less than 37%. Regional recurrence and distant metastasis to lungs,regional lymph nodes and liver can occur within the first three years of diagnosis in a high rate(45% and 65% respectively). Wide surgical resection of the mass followed by adjuvant chemotherapy or radiotherapy has been the treatment of choice.