Massive upper gastrointestinal hemorrhage due to invasive hepatocellular carcinoma and hepato-gastric fistula

A 36-year-old male Asian immigrant with a history of hepatitis B and hepatitis C related unresectable hepatocellular carcinoma in the left lobe of the liver presented with hematemesis and severe anemia.He was diagnosed with a liver mass that was resected 8 years ago described as a benign tumor in his home country.He had received trans-arterial chemoembolization(TACE)four months ago after subsequent diagnosis of unresectable hepatoma,and currently was receiving chemotherapy with Sorafenib.After resuscitation,a contrast enhanced computerized tomography was performed which showed fistulization of hepatocellular carcinoma into adjacent stomach.This finding was confirmed during endoscopy with direct visualization of the fistulous opening.Hepatocellular carcinoma(HCC)invading the gastrointestinal(GI)tract is rare.We present a case and literature review of HCC with local invasion of the stomach causing massive upper GI bleeding after receiving TACE.

Coexistence of gastrointestinal stromal tumor, esophageal and gastric cardia carcinomas

Gastric gastrointestinal stromal tumor (GIST), esophageal squamous cell carcinoma and gastric cardia adenocarcinoma are distinct neoplasms originating from different cell layers; therefore, simultaneous development of such carcinomas is relatively rare. Auxiliary examinations revealed coexistence of esophageal and gastric cardia carcinoma with lymph node metastasis in a 77-year-old man. Intraoperatively, an extraluminal tumor (about 6.0 cm × 5.0 cm × 6.0 cm) at the posterior wall of the gastric body, a tumor (about 2.5 cm × 2.0 cm) in the lower esophagus, and an infiltrative and stenosing tumor (about 1.0 cm × 2.0 cm) in the gastric cardia were detected. Wedge resection for extraluminal gastric tumor, radical esophagectomy for lower esophageal tumor, and cardiac resection with gastroesophageal (supra-aortic arch anastomoses) were performed. Postoperative histological examination showed synchronous occurrence of gastric GIST, esophageal squamous cell carcinoma, and gastric cardia adenocarcinoma. Furthermore, immunohistochemistry indicated strong staining for c-Kit/CD117, Dog-1, Ki-67 and smooth muscle, while expression of S-100 and CD34 was negative.

Benchmark for establishment of organoids from gastrointestinal epithelium and cancer based on available consumables and reagents

Gastrointestinal cancers are a public health problem that threatens the lives of human being. A good experimental model is a powerful tool to promote the uncovering pathogenesis and establish novel treatment methods. High-quality biomedical research requires experimental models to recapitulate the physiological and pathological states of their parental tissues as much as possible. Organoids are such experimental models. Organoids refer to small organlike cellular clusters formed by the expansion and passaging of living tissues in 3D culture medium in vitro.Organoids are highly similar to the original tissues in terms of cellular composition, cell functions, and genomic profiling. Organoids have many advantages, such as short preparation cycles, long-term storage based on cryopreservation, and reusability. In recent years, researchers carried out the establishment of organoids from gastrointestinal mucosa and cancer tissues, and accumulated valuable experiences. In order to promote effective usage and further development of organoid-related technologies in the research of gastrointestinal diseases, this study proposes a benchmark based on utilization of available experimental consumables and reagents, which are involved in the key steps such as collection and pretreatment of biospecimen, organoid construction, organoid cryopreservation and recovery, growth status evaluation, and organoid quality control. We believe that the standard for the construction and preservation of organoids derived from human gastrointestinal epithelium and cancer tissues can provide an important reference for the majority of scientific researchers.

X-ray diagnosis of synchronous multiple primary carcinoma in the upper gastrointestinal tract

AIM:To analyze the radiological features of multiple primary carcinoma (MPC) in the upper gastrointestinal (GI) tract,study its biological characteristics and evaluate X-ray examination in its diagnosis. METHODS:Hypotonic double-contrast GI radiography was performed in 59 multiple primary carcinoma cases,pathologically proved by surgery or endoscopy biopsy. Radiological findings were analyzed. RESULTS:Of the 59 cases,esophageal MPC (EMPC) was seen in 24,esophageal and gastric MPC (EGMPC) in 27 and gastric MPC (GMPC) in 8. Of the 49 lesions found in 24 EMPC,hyperplastic type was seen in 23,medullary type in 9. The lesions were located at the upper (n = 17),middle (n = 19) or lower (n = 13) segment of the esophagus. In 27 EGMPC,the esophageal lesions were located at the middle (n = 16) or lower (n = 11) segment of the esophagus,while the gastric le-sions were located at the gastric cardia (n = 16),fundus (n = 1),body (n = 3) and antrum (n = 7). The esophageal lesions were mainly of the hyperplastic type (n = 12) or medullary type (n = 7),while the gastric lesions were mainly of the hyperplastic type (n = 18). A total of 119 lesions in the 59 patients with synchronous multiple carcinoma were proved by surgery or endoscopy biopsy,and preoperative upper radiographic examination detected 100 of them (84.03% sensitivity). Eighteen (52.94%) of the T1 lesions were found during preoperative diagnosis by radiographic examination. Moreover,only 3 (3.53%) of the T2-4 lesions were misdiagnosed. CONCLUSION:Hypotonic double-contrast upper gastrointestinal examination,providing accurate information about lesion morphology,location and size,can serve as a sensitive technique for the preoperative diagnosis of MPC.

Gastrointestinal tract injuries after thermal ablative therapies for hepatocellular carcinoma:A case report and review of the literature

BACKGROUND Radiofrequency ablation(RFA)and microwave ablation(MWA)represent the standard of care for patients with early hepatocellular carcinoma(HCC)who are unfit for surgery.The incidence of reported adverse events is low,ranging from 2.4%to 13.1%for RFA and from 2.6%to 7.5%for MWA.Gastrointestinal tract(GIT)injury is even more infrequent(0.11%),but usually requires surgery with an unfavourable prognosis.Due to its low incidence and the retrospective nature of the studies,the literature reporting this feared complication is heterogeneous and in many cases lacks information on tumour characteristics,comorbidities and treatment approaches.CASE SUMMARY A 77-year-old man who had undergone extended right hepatectomy for HCC was diagnosed with early disease recurrence with a small nodule compatible with HCC in the Sg4b segment of the liver with a subcapsular location.He was treated with percutaneous RFA and a few week later he was urgently admitted to the Surgery ward for abdominal pain and fever.A subcutaneous abscess was diagnosed and treated by percutaneous drainage.A fistulous tract was then documented by the passage of contrast material from the gastric antrum to the abdominal wall.The oesophagogastroduodenoscopy confirmed a circular wall defect at the lesser curvature of gastric antrum, leading directly to the purulentabdominal collection. An over-the-scope clip (OTSC) was used to successfullyclose the defectCONCLUSIONThis is the first reported case of RFA-related GIT injury to have been successfullytreated with an OTSC, which highlights the role of this endoscopic treatment forthe management of this complication.

Effects of 7.5% hypertonic saline on fluid balance after radical surgery for gastrointestinal carcinoma

AIM: To investigate the effects of 7.5% hypertonic saline on positive fluid balance and negative fluid balance, after radical surgery for gastrointestinal carcinoma.METHOIDS: Fifty-two patients with gastrointestinal carcinoma undergoing radical surgery were studied. The patients were assigned to receive either Ringer lactate solution following 4 mL/kg of 7.5% hypertonic saline (the experimental group, n = 26) or Ringer lactate solution (the control group, n = 26) during the early postoperative period in SICU. Fluid infusion volumes, urine outputs, fluid balance, body weight change, PaO2/FiO2 ratio, anal exhaust time as well as the incidence of complication and mortality were compared between the two groups.RESULTS: Urine outputs on the operative day and the first postoperative day in experimental group were significantly more than in control group (P＜0.000001,P= 0.000114). Fluid infusion volumes on the operative day and the first postoperative day were significantly less in experimental group than in control group (P = 0.000042,P= 0.000415). The volumes of the positive fluid balance on the operative day and during the first 48 h after surgery, in experimental group, were significantly less than in control group (P＜0.000001). Body weight gain post-surgery was significantly lower in experimental group than in control group (P＜0.000001). The body weight fall in experimental group occurred earlier than in control group (P＜0.000001). PaO2/FiO2 ratio after surgery was higher in experimental group than in control group (P = 0.000111). The postoperative anal exhaust time in experimental group was earlier than in control group (P = 0.000006). The overall incidence of complications and the incidence of pulmonary infection were lower in experimental group than in control group (P = 0.0175, P = 0.0374).CONCLUSION: 7.5% hypertonic saline has an intense diuretic effect and causes mobilization of the retained fluid, which could reduce fluid infusion volumes and positive fluid balance after radical surgery for gastrointestinal carcinoma, as well as, accelerate the early appearance of negative fluid balance after the surgery, improve the oxygen diffusing capacity of the patients' alveoli, and lower the overall incidence of complications and pulmonary infection after the surgery.

Hepatocellular carcinoma:An analysis of the expression status of stress granules and their prognostic value

BACKGROUND Hepatocellular carcinoma(HCC)is a global popular malignant tumor,which is difficult to cure,and the current treatment is limited.AIM To analyze the impacts of stress granule(SG)genes on overall survival(OS),survival time,and prognosis in HCC.METHODS The combined The Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC),GSE25097,and GSE36376 datasets were utilized to obtain genetic and clinical information.Optimal hub gene numbers and corresponding coefficients were determined using the Least absolute shrinkage and selection operator model approach,and genes for constructing risk scores and corresponding correlation coefficients were calculated according to multivariate Cox regression,respectively.The prognostic model’s receiver operating characteristic(ROC)curve was produced and plotted utilizing the time ROC software package.Nomogram models were constructed to predict the outcomes at 1,3,and 5-year OS prognostications with good prediction accuracy.RESULTS We identified seven SG genes(DDX1,DKC1,BICC1,HNRNPUL1,CNOT6,DYRK3,CCDC124)having a prognostic significance and developed a risk score model.The findings of Kaplan-Meier analysis indicated that the group with a high risk exhibited significantly reduced OS in comparison with those of the low-risk group(P<0.001).The nomogram model’s findings indicate a significant enhancement in the accuracy of OS prediction for individuals with HCC in the TCGA-HCC cohort.Gene Ontology and Gene Set Enrichment Analysis suggested that these SGs might be involved in the cell cycle,RNA editing,and other biological processes.CONCLUSION Based on the impact of SG genes on HCC prognosis,in the future,it will be used as a biomarker as well as a unique therapeutic target for the identification and treatment of HCC.

New trends in diagnosis and management of gallbladder carcinoma

Gallbladder(GB)carcinoma,although relatively rare,is the most common biliary tree cholangiocarcinoma with aggressiveness and poor prognosis.It is closely associated with cholelithiasis and long-standing large(>3 cm)gallstones in up to 90%of cases.The other main predisposing factors for GB carcinoma include molecular factors such as mutated genes,GB wall calcification(porcelain)or mainly mucosal microcalcifications,and GB polyps≥1 cm in size.Diagnosis is made by ultrasound,computed tomography(CT),and,more precisely,magnetic resonance imaging(MRI).Preoperative staging is of great importance in decisionmaking regarding therapeutic management.Preoperative staging is based on MRI findings,the leading technique for liver metastasis imaging,enhanced three-phase CT angiography,or magnetic resonance angiography for major vessel assessment.It is also necessary to use positron emission tomography(PET)-CT or ^(18)F-FDG PET-MRI to more accurately detect metastases and any other occult deposits with active metabolic uptake.Staging laparoscopy may detect dissemination not otherwise found in 20%-28.6%of cases.Multimodality treatment is needed,including surgical resection,targeted therapy by biological agents according to molecular testing gene mapping,chemotherapy,radiation therapy,and immunotherapy.It is of great importance to understand the updated guidelines and current treatment options.The extent of surgical intervention depends on the disease stage,ranging from simple cholecystectomy(T1a)to extended resections and including extended cholecystectomy(T1b),with wide lymph node resection in every case or IV-V segmentectomy(T2),hepatic trisegmentectomy or major hepatectomy accompanied by hepaticojejunostomy Roux-Y,and adjacent organ resection if necessary(T3).Laparoscopic or robotic surgery shows fewer postoperative complications and equivalent oncological outcomes when compared to open surgery,but much attention must be paid to avoiding injuries.In addition to surgery,novel targeted treatment along with immunotherapy and recent improvements in radiotherapy and chemotherapy(neoadjuvant-adjuvant capecitabine,cisplatin,gemcitabine)have yielded promising results even in inoperable cases calling for palliation(T4).Thus,individualized treatment must be applied.

Gastrointestinal metastasis secondary to invasive lobular carcinoma of the breast:A case report

BACKGROUND Gastrointestinal metastasis of breast cancer is rare,and clinicians may not have previously encountered this disease in clinical practice.CASE SUMMARY We report a patient with invasive lobular carcinoma of the breast who developed gastrointestinal metastasis two years after modified radical surgery.Mild elevation of carbohydrate antigen 15-3 was observed in the patient at an early stage;however,diagnosis and treatment were delayed due to non-specific clinical manifestations and no identifiable metastasis observed on imaging.CONCLUSION Clinicians should pay attention to gastrointestinal metastasis of breast cancer,especially invasive lobular carcinoma of the breast.

Esthesioneuroblastoma, Thyroid Gland Carcinoma and Gastrointestinal Stromal Carcinoma

Olfactory neuroblastoma (esthesioneuroblastoma, ЕNB) is a rare tumor arising from the olfactory neuroepithelium. We report a case of ЕNB located in inferior nasal concha, combined with thyroid gland carcinoma and gastrointestinal stromal carcinoma in a 77-year-old man. The tumor was resected endonasally. When the final diagnosis of olfactory neuroblastoma was confirmed by histopathologic examination and immunohistochemical staining, the PET/CT examination was performed. The imaging revealed a small focus of a moderately increased cancer activity in the thyroid region. A gastrointestinal stromal carcinoma was detected one year after the resection of the thyroid gland. We discuss the clinical appearance of ENB, staging systems, diagnosis and management. During the endonasal surgery, ENB was removed entirely. Seven days after operation, in order to monitor the postoperative result, PET/CT was performed and a papillary thyroid cancer was detected. One year after the thyroid surgery, gastroendoscopy showed a neoplastic formation in the stomach. In conclusion, we state that when identified as aggressive tumors such as ENB, it is necessary to provide regular examinations in order to detect distant ENB metastases or other neoplastic localisations.

Role of ion channels in gastrointestinal cancer

In their seminal papers Hanahan and Weinberg described oncogenic processes a normal cell undergoes to be transformed into a cancer cell.The functions of ion channels in the gastrointestinal(GI)tract influence a variety of cellular processes,many of which overlap with these hallmarks of cancer.In this review we focus on the roles of the calcium(Ca^2+),sodium(Na^+),potassium(K^+),chloride(Cl^-)and zinc(Zn^2+)transporters in GI cancer,with a special emphasis on the roles of the KCNQ1 K+channel and CFTR Cl-channel in colorectal cancer(CRC).Ca^2+is a ubiquitous second messenger,serving as a signaling molecule for a variety of cellular processes such as control of the cell cycle,apoptosis,and migration.Various members of the TRP superfamily,including TRPM8,TRPM7,TRPM6 and TRPM2,have been implicated in GI cancers,especially through overexpression in pancreatic adenocarcinomas and down-regulation in colon cancer.Voltage-gated sodium channels(VGSCs)are classically associated with the initiation and conduction of action potentials in electrically excitable cells such as neurons and muscle cells.The VGSC NaV1.5 is abundantly expressed in human colorectal CRC cell lines as well as being highly expressed in primary CRC samples.Studies have demonstrated that conductance through NaV1.5 contributes significantly to CRC cell invasiveness and cancer progression.Zn2+transporters of the ZIP/SLC39A and ZnT/SLC30A families are dysregulated in all major GI organ cancers,in particular,ZIP4 up-regulation in pancreatic cancer(PC).More than 70 K+channel genes,clustered in four families,are found expressed in the GI tract,where they regulate a range of cellular processes,including gastrin secretion in the stomach and anion secretion and fluid balance in the intestinal tract.Several distinct types of K+channels are found dysregulated in the GI tract.Notable are hERG1 upregulation in PC,gastric cancer(GC)and CRC,leading to enhanced cancer angiogenesis and invasion,and KCNQ1 down-regulation in CRC,where KCNQ1 expression is associated with enhanced disease-free survival in stage II,III,and IV disease.Cl-channels are critical for a range of cellular and tissue processes in the GI tract,especially fluid balance in the colon.Most notable is CFTR,whose deficiency leads to mucus blockage,microbial dysbiosis and inflammation in the intestinal tract.CFTR is a tumor suppressor in several GI cancers.Cystic fibrosis patients are at a significant risk for CRC and low levels of CFTR expression are associated with poor overall disease-free survival in sporadic CRC.Two other classes of chloride channels that are dysregulated in GI cancers are the chloride intracellular channels(CLIC1,3&4)and the chloride channel accessory proteins(CLCA1,2,4).CLIC1&4 are upregulated in PC,GC,gallbladder cancer,and CRC,while the CLCA proteins have been reported to be down-regulated in CRC.In summary,it is clear,from the diverse influences of ion channels,that their aberrant expression and/or activity can contribute to malignant transformation and tumor progression.Further,because ion channels are often localized to the plasma membrane and subject to multiple layers of regulation,they represent promising clinical targets for therapeutic intervention including the repurposing of current drugs.

Role of hepatocyte nuclear factor 4-alpha in gastrointestinal and liver diseases

Hepatocyte nuclear factor 4-alpha(HNF4α)is a highly conserved member of nuclear receptor superfamily of ligand-dependent transcription factors that is expressed in liver and gastrointestinal organs(pancreas,stomach,and intestine).In liver,HNF4αis best known for its role as a master regulator of liver-specific gene expression and essential for adult and fetal liver function.Dysregulation of HNF4αexpression has been associated with many human diseases such as ulcerative colitis,colon cancer,maturity-onset diabetes of the young,liver cirrhosis,and hepatocellular carcinoma.However,the precise role of HNF4αin the etiology of these human pathogenesis is not well understood.Limited information is known about the role of HNF4αisoforms in liver and gastrointestinal disease progression.There is,therefore,a critical need to know how disruption of the expression of these isoforms may impact on disease progression and phenotypes.In this review,we will update our current understanding on the role of HNF4αin human liver and gastrointestinal diseases.We further provide additional information on possible use of HNF4αas a target for potential therapeutic approaches.

Unusual complication in patient with Gardner's syndrome: Coexistence of triple gastrointestinal perforation and lower gastrointestinal bleeding: A case report and review of literature

Gardner's syndrome(GS) is a rare syndrome with autosomal dominant inheritance, which is characterized by multiple intestinal polyps, dental anomalies, desmoid tumors, and soft tissue tumors. All gastrointestinal symptoms seen in GS are associated with the underlying familial adenomatosis polyposis and abdominal desmoid tumors, with the most common symptoms being anemia, lower gastrointestinal bleeding, abdominal pain, diarrhea, obstruction, and mucous defecation. To our best knowledge, no case of GS that has presented with gastrointestinal perforation and bleeding has ever been reported in the English language medical literature. A 37-year-old male who had been diagnosed with GS five years earlier was referred to our clinic for lower gastrointestinal bleeding. Despite the absence of a bleeding focus on conventional angiography, the patient was operated on with laparotomy, due to the persistence of both signs and symptoms of mild peritonitis. On the laparotomy, the patient was noted to have areas of perforation in the duodenum, splenic flexura, and midrectum. The third and fourth part of the duodenum, the proximal 15 cm segment of the jejunum, a 10 cm segment of the terminal ileum, the whole colon, and the upper and middle rectum were resected, and duodenojejunal side-to-side anastomosis and terminal ileostomy were performed. The histopathological analysis of the large mass measuring 30 cm × 20 cm was reported as a desmoid tumor. The pathological examination of the tumor foci detected in the colonic specimen revealed poorly differentiated adenosquamous carcinoma.

Molecular regulatory mechanism of ferroptosis and its role in gastrointestinal oncology:Progress and updates

Gastrointestinal(GI)tumors,including liver,pancreatic,gastric,and colorectal cancers,have a high incidence rate and low survival rate due to the lack of effective therapeutic methods and frequent relapses.Surgery and postoperative chemoradiotherapy have largely reduced the fatality rates for most GI tumors,but these therapeutic approaches result in poor prognoses due to severe adverse reactions and the development of drug resistance.Recent studies have shown that ferroptosis plays an important role in the onset and progression of GI tumors.Ferroptosis is a new non-apoptotic form of cell death,which is iron-dependent,non-apoptotic cell death characterized by the accumulation of lipid reactive oxygen species(ROS).The activation of ferroptosis can lead to tumor cell death.Thus,regulating ferroptosis in tumor cells may become a new therapeutic approach for tumors,making it become a research hotspot.Current studies suggest that ferroptosis is mainly triggered by the accumulation of lipid ROS.Furthermore,several studies have indicated that ferroptosis may be a new approach for the treatment of GI tumors.Here,we review current research progress on the mechanism of ferroptosis,current inducers and inhibitors of ferroptosis,and the role of ferroptosis in GI tumors to propose new methods for the treatment of such tumors.

Role of radiomics in the diagnosis and treatment of gastrointestinal cancer

Gastrointestinal cancer(GIC)has high morbidity and mortality as one of the main causes of cancer death.Preoperative risk stratification is critical to guide patient management,but traditional imaging studies have difficulty predicting its biological behavior.The emerging field of radiomics allows the conversion of potential pathophysiological information in existing medical images that cannot be visually recognized into high-dimensional quantitative image features.Tumor lesion characterization,therapeutic response evaluation,and survival prediction can be achieved by analyzing the relationships between these features and clinical and genetic data.In recent years,the clinical application of radiomics to GIC has increased dramatically.In this editorial,we describe the latest progress in the application of radiomics to GIC and discuss the value of its potential clinical applications,as well as its limitations and future directions.

Application of Big Data analysis in gastrointestinal research

Big Data,which are characterized by certain unique traits like volume,velocity and value,have revolutionized the research of multiple fields including medicine.Big Data in health care are defined as large datasets that are collected routinely or automatically,and stored electronically.With the rapidly expanding volume of health data collection,it is envisioned that the Big Data approach can improve not only individual health,but also the performance of health care systems.The application of Big Data analysis in the field of gastroenterology and hepatology research has also opened new research approaches.While it retains most of the advantages and avoids some of the disadvantages of traditional observational studies(case-control and prospective cohort studies),it allows for phenomapping of disease heterogeneity,enhancement of drug safety,as well as development of precision medicine,prediction models and personalized treatment.Unlike randomized controlled trials,it reflects the real-world situation and studies patients who are often under-represented in randomized controlled trials.However,residual and/or unmeasured confounding remains a major concern,which requires meticulous study design and various statistical adjustment methods.Other potential drawbacks include data validity,missing data,incomplete data capture due to the unavailability of diagnosis codes for certain clinical situations,and individual privacy.With continuous technological advances,some of the current limitations with Big Data may be further minimized.This review will illustrate the use of Big Data research on gastrointestinal and liver diseases using recently published examples.

Mixed neuroendocrine–nonneuroendocrine neoplasms of the gastrointestinal system:An update

Mixed neuroendocrine-nonneuroendocrine neoplasms(Mi NENs)of the digestive tract are a rare heterogeneous group of tumors that present many challenges in terms of diagnosis and treatment.Over the years,the diagnostic criteria,classification,and clinical behavior of these tumors have been the subjects of ongoing debate,and the various changes in their nomenclature have strengthened the challenges associated with Mi NENs.This review is performed to provide an understanding of the key factors involved in the evolution of the designation of these tumors as Mi NEN,highlight the current diagnostic criteria,summarize the latest data on pathogenesis and provide information on available treatments.Moreover,this work seeks to increase the awareness about these rare neoplasms by presenting the clinicopathological features and prognostic factors that play important roles in their behavior and discussing their different regions of origin in the gastrointestinal system(GIS).Currently,the Mi NEN category also includes tumors in the GIS with a nonneuroendocrine component and epithelial tumors other than adenocarcinoma,depending on the organ of origin.Diagnosis is based on the presence of both morphological components in more than 30%of the tumor.However,this value needs to be reconfirmed with further studies and may be a limiting factor in the diagnosis of Mi NEN by biopsy.Furthermore,available clinicopathological data suggest that the inclusion of amphicrine tumors in the definition of Mi NEN is not supportive and warrants further investigation.The diagnosis of these tumors is not solely based on immunohistochemical findings.They are not hybrid tumors and both components can act independently;thus,careful grading of each component separately is required.In addition to parameters such as the metastatic state of the tumor at the time of diagnosis and the feasibility of surgical resection,the aggressive potential of both components has paramount importance in the choice of treatment.Regardless of the organ of origin within the GIS,almost Mi NENs are tumors with poor prognosis and are frequently encountered in the elderly and men.They are most frequently reported in the colorectum,where data from molecular studies indicate a monoclonal origin;however,further studies are required to provide additional support for this origin.

Role of nuclear receptor NR4A2 in gastrointestinal inflammation and cancers

NR4A2 is a transcription factor belonging to the steroid orphan nuclear receptor superfamily.It was originally considered to be essential in the generation and maintenance of dopaminergic neurons,and associated with neurological disorders such as Parkinson's disease.Recently,NR4A2 has been found to play a critical role in some inflammatory diseases and cancer.NR4A2 can be efficiently trans-activated by some proinflammatory cytokines,such as tumor necrosis factor-α,interleukin-1β,and vascular endothelial growth factor(VEGF).The nuclear factor-κB signaling pathway serves as a principal regulator of inducible NR4A expression in immune cells.NR4A2 can trans-activate Foxp3,a hallmark specifically expressed in regulatory T(Treg) cells,and plays a critical role in the differentiation,maintenance,and function of Treg cells.NR4A2 in T lymphocytes is pivotal for Treg cell induction and suppression of aberrant induction of Th1 under physiological and pathological conditions.High density of Foxp3 + Treg cells is significantly associated with gastrointestinal inflammation,tumor immune escape,and disease progression.NR4A2 is produced at high levels in CD133 + colorectal carcinoma(CRC) cells and significantly upregulated by cyclooxygenase-2-derived prostaglandin E 2 in a cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)-dependent manner in CRC cells.The cAMP/PKA signaling pathway is the common pathway of NR4A2-related inflammation and cancer.NR4A2 trans-activates osteopontin,a direct target of the Wnt/β-catenin pathway associated with CRC invasion,metastasis,and poor prognosis.Knockdown of endogenous NR4A2 expression attenuates VEGF-induced endothelial cell proliferation,migration and in vivo angiogenesis.Taken together,NR4A2 emerges as an important nuclear factor linking gastrointestinal inflammation and cancer,especially CRC,and should serve as a candidate therapeutic target for inflammation-related gastrointestinal cancer.

Metastatic breast cancer to the gastrointestinal tract:A case series and review of the literature

Metastatic breast cancer involving the hepatobiliary tract or ascites secondary to peritoneal carcinomatosis has been well described. Luminal gastrointestinal tract involvement is less common and recognition of the range of possible presentations is important for early and accurate diagnosis and treatment. We report 6 patients with a variety of presentations of metastatic breast cancer of the luminal gastrointestinal tract. These include oropharyngeal and esophageal involvement presenting as dysphagia with one case of pseudoachalasia, a linitis plastica-like picture with gastric narrowing and thickened folds, small bowel obstruction and multiple strictures mimicking Crohn’s disease, and a colonic neoplasm presenting with obstruction. Lobular carcinoma, representing only 10% of breast cancers is more likely to metastasize to the gastrointestinal tract. These patients presented with gastrointestinal manifestations after an average of 9.5 years and as long as 20 years from initial diagnosis of breast cancer. Given the increased survival of breast cancer patients with current therapeutic regimes, more unusual presentations of metastatic disease, including involvement of the gastrointestinal tract can be anticipated.

Molecular factors,diagnosis and management of gastrointestinal tract neuroendocrine tumors:An update

The prevalence of gastrointestinal neuroendocrine tumors(GI-NETs) is increasing,and despite recent advances in their therapy,it remains inadequate in patients with advanced well-differentiated neuroendocrine tumors.These tumors present many challenges concerning the molecular basis and genomic profile,pathophysiology,clinicopathological features,histopathologic classification,diagnosis and treatment.There has been an ongoing debate on diagnostic criteria and clinical behavior,and various changes have been made over the last few years.Neuroendocrine carcinoma of the gastrointestinal system is a rare but highly malignant neoplasm that is genetically distinct from gastrointestinal system neuroendocrine tumors(NETs).The diagnosis and management have changed over the past decade.Emerging novel biomarkers and metabolic players in cancer cells are useful and promising new diagnostic tools.Progress in positron emission tomography-computerized tomography and scintigraphy with new radioactive agents(^(64)Cu-DOTATATE or ^(68)Ga-DOTATATE) replacing enough octreoscan,has improved further the current diagnostic imaging.Promising results provide targeted therapies with biological agents,new drugs,chemotherapy and immunotherapy.However,the role of surgery is important,since it is the cornerstone of management.Simultaneous resection of small bowel NETs with synchronous liver metastases is a surgical challenge.Endoscopy offers novel options not only for diagnosis but also for interventional management.The therapeutic option should be individualized based on current multidisciplinary information.