Dear Editor,We aimed to describe the management of the intraoperative injury of the right external iliac artery that occurred during robot-assisted right nephroureterectomy with bladder cuff excision.Surgery was sched...Dear Editor,We aimed to describe the management of the intraoperative injury of the right external iliac artery that occurred during robot-assisted right nephroureterectomy with bladder cuff excision.Surgery was scheduled for suspected urothelial carcinoma of the distal ureter in a 60-year-old woman.The patient involved in the present research signed a dedicated form to consent to the publication of images and/or information about her.Past medical history included Brugada syndrome diagnosed in 2015,and hypercholesterolemia.Past surgical history included one cesarean section only.Family history included ovarian cancer(sister),colorectal cancer(mother),and kidney cancer(father).展开更多
Background:The efficacy of balloon angioplasty for treating peripheral artery disease is influenced by various factors,some of them not yet totally understood.This study aimed to evaluate the role of elastin content i...Background:The efficacy of balloon angioplasty for treating peripheral artery disease is influenced by various factors,some of them not yet totally understood.This study aimed to evaluate the role of elastin content in vascular responses 28 days postangioplasty using uncoated and paclitaxel-coated balloons with the same platform in femoral arteries of a healthy porcine model.Methods:Eight animals underwent balloon angioplasty on the external and internal branches of femoral arteries.Histopathologic evaluation was conducted at follow-up to assess the elastin content,vascular damage,morphological features,and neointimal formation.Results:The elastin content was significantly higher in the external than in the internal femoral artery(p=0.0014).After balloon angioplasty,it was inversely correlated with vascular injury score(ρ=−0.4510,p=0.0096),neointimal inflammation(ρ=−0.3352,p=0.0607),transmural(ρ=−0.4474,p=0.0103)and circumferential(ρ=−0.4591,p=0.0082)smooth muscle cell loss,presence of proteoglycans(ρ=−0.5172,p=0.0024),fibrin deposition(ρ=−0.3496,p=0.0499),and adventitial fibrosis(ρ=−0.6229,p=0.0002).Neointimal formation inhibition with paclitaxel was evident only in arteries with disruption of the internal elastic lamina,with a significant smaller neointimal area in arteries treated with paclitaxel-coated balloons compared to uncoated balloons(median[Q1–Q3]:10.25[7.49–15.64]vs.24.44[18.96–30.52],p=0.0434).Conclusions:Elastin content varies between branches of the femoral artery and significantly influences the integrity of the internal elastic lamina,the vessel's adaptive response,and paclitaxel efficacy after balloon angioplasty.展开更多
To analyze the importance of para-aortic node status in a series of patients who underwent pancreaticoduodenectomy (PD) in a single Institution. METHODSBetween January 2000 and December 2012, 151 patients underwent PD...To analyze the importance of para-aortic node status in a series of patients who underwent pancreaticoduodenectomy (PD) in a single Institution. METHODSBetween January 2000 and December 2012, 151 patients underwent PD with para-aortic node dissection for pancreatic adenocarcinoma in our Institution. Patients were divided into two groups: patients with negative PALNs (PALNs-), and patients with metastatic PALNs (PALNs+). Pathologic factors, including stage, nodal status, number of positive nodes and lymph node ratio, invasion of para-aortic nodes, tumor’s grading, and radicality of resection were studied by univariate and multivariate analysis. Survival curves were constructed with Kaplan-Meier method and compared with Log-rank test: significance was considered as P < 0.05. RESULTSA total of 107 patients (74%) had nodal metastases. Median number of pathologically assessed lymph nodes was 26 (range 14-63). Twenty-five patients (16.5%) had para-aortic lymph node involvement. Thirty-three patients (23%) underwent R1 pancreatic resection. One-hundred forty-one patients recurred and died for tumor recurrence, one is alive with recurrence, and 9 are alive and free of disease. Overall survival was significantly influenced by grading (P = 0.0001), radicality of resection (P = 0.001), stage (P = 0.03), lymph node status (P = 0.04), para-aortic nodes metastases (P = 0.02). Multivariate analysis showed that grading was an independent prognostic factor for overall survival (P = 0.0001), while grading (P = 0.0001) and radicality of resection (P = 0.01) were prognostic parameters for disease-free survival. Number of metastatic nodes, node ratio, and para-aortic nodes involvement were not independent predictors of disease-free and overall survival. CONCLUSIONIn this experience, lymph node status and para-aortic node metastases were associated with poor survival at univariate analysis, but they were not independent prognostic factors.展开更多
Autosomal dominant polycystic kidney disease （ADPKD） is the most common inherited monogenic kidney disease. Characterized by the development and growth of cysts that cause progressive kidney enlargement, it ultimate...Autosomal dominant polycystic kidney disease （ADPKD） is the most common inherited monogenic kidney disease. Characterized by the development and growth of cysts that cause progressive kidney enlargement, it ultimately leads to end-stage renal disease. Approximately 85% of ADPKD cases are caused by mutations in the PKD1 gene, while mutations in the PKD2 gene account for the remaining 15% of cases. The PKD1 gene encodes for polycystin-1 （PC1）, a large multi-functional memb-rane receptor protein able to regulate ion channel complexes, whereas polycystin-2 （PC2）, encoded by the PKD2 gene, is an integral membrane protein that functions as a calcium-permeable cation channel, located mainly in the endoplasmic reticulum （ER）. In the primary cilia of the epithelial cells, PC1 interacts with PC2 to form a polycystin complex that acts as a mechanosensor, regulating signaling pathways involved in the differentiation of kidney tubular epithelial cells. Despite progress in understanding the function of these proteins, the molecular mechanisms associated with the pathogenesis of ADPKD remain unclear. In this review we discuss how an imbalance between functional PC1 and PC2 proteins may disrupt calcium channel activities in the cilium, plasma membrane and ER, thereby altering intracellular calcium signaling and leading to the aberrant cell proliferation and apoptosis associated with the development and growth of renal cysts. Research in this feld could lead to the discovery of new molecules able to rebalance intracellular calcium, thereby normalizing cell proliferation and reducing kidney cyst progression.展开更多
A crucial aspect of prostate cancer grading, especially in low- and intermediate-risk cancer, is the accurate identification of Gleason pattern 4 glands, which includes ill-formed or fused glands. However, there is no...A crucial aspect of prostate cancer grading, especially in low- and intermediate-risk cancer, is the accurate identification of Gleason pattern 4 glands, which includes ill-formed or fused glands. However, there is notable inconsistency among pathologists in recognizing these glands, especially when mixed with pattern 3 glands. This inconsistency has significant implications for patient management and treatment decisions. Conversely, the recognition of glomeruloid and cribriform architecture has shown higher reproducibility. Cribriform architecture, in particular, has been linked to the worst prognosis among pattern 4 subtypes. Intraductal carcinoma of the prostate (IDC-P) is also associated with high-grade cancer and poor prognosis. Accurate identification, classification, and tumor size evaluation by pathologists are vital for determining patient treatment. This review emphasizes the importance of prostate cancer grading, highlighting challenges like distinguishing between pattern 3 and pattern 4 and the prognostic implications of cribriform architecture and intraductal proliferations. It also addresses the inherent grading limitations due to interobserver variability and explores the potential of computational pathology to enhance pathologist accuracy and consistency.展开更多
In this editorial,a comment on the article by Díaz-López et al published in the recent issue of the 2024 is provided.We focus on the practical implications critical for providing a correct and complete diagn...In this editorial,a comment on the article by Díaz-López et al published in the recent issue of the 2024 is provided.We focus on the practical implications critical for providing a correct and complete diagnosis of mixed neuroendocrine-nonneuroendocrine neoplasm(MiNEN)in the gastrointestinal system.The diagnosis of MiNEN begins with the recognition of neuroendocrine features in one component of a biphasic tumor.The non-neuroendocrine counterpart can be virtually represented by any neoplastic type,even though the most frequent histologies are glandular and squamous.However,qualification of the neuroendocrine component requires histological and immunohistochemical confirmation.Neuroendocrine tumors are characterized by a peculiar architectural organization and bland nuclei with granular“salt and pepper”chromatin.Although neuroendocrine carcinomas have multiple and variable presentations,they typically show a solid or organoid architecture.The histological aspect needs to be confirmed by immunohistochemistry,and a diagnosis is confirmed whenever the expression of keratin and neuroendocrine markers is observed.Once both histopathological and immunohistochemical features of neuroendocrine neoplasms are identified,it is important to consider the three major pitfalls of MiNEN diagnostics:(1)Entrapment of neuroendocrine non-neoplastic cells within the tumor mass;(2)Differential diagnosis with amphicrine neoplasms;and(3)Differential diagnosis of tumors that partially express neuroendocrine markers.According to the current guidelines for diagnosing digestive MiNEN,each component must represent at least 30%of the entire neoplastic mass.Although the high-grade histopathological subtype frequently determines disease prognosis,both components can significantly affect prognosis.Thus,if one of the components,either neuroendocrine or non-neuroendocrine,does not fulfill the volumetric criteria,the guidelines still encourage reporting it.These strict criteria are essential for correctly recognizing and characterizing digestive MiNENs.This task is essential because it has prognostic relevance and substantial potential value for guiding further studies in this field.In the future,systematic analyses should be performed to validate or reconsider the current 30%cutoff value.展开更多
Microphallus/Micropenis is a rare condition with significant physical and psychological implications for affected individuals.This article comprehensively reviews micropenis,its etiology,epidemiology,and various treat...Microphallus/Micropenis is a rare condition with significant physical and psychological implications for affected individuals.This article comprehensively reviews micropenis,its etiology,epidemiology,and various treatment options.We conducted a thorough literature review to collect relevant information on micropenis and microphallus,as well as related disorders.Our primary databases were PubMed,Medline,and Google Scholar.We searched for articles published in English between 2000 and 2023.Our analysis included 67 review articles,56 research studies,11 case reports,one guideline,and one editorial.Our search terms included"microphallus","micropenis","congenital hypogonadotropic hypogonadism","androgen insensitivity syndrome","pediatric management of micropenis","testosterone therapy",and"psychosocial implications of micropenis".We focused on diagnosing micropenis and related conditions,including hormonal assessments,medical and surgical treatment options,psychosocial and psychological well-being,sexual development of adolescents,and sociocultural influences on men's perceptions of penile size.Additionally,we explored parenting and family dynamics in cases of micropenis and disorders of sex development,implications of hormonal treatment in neonates,and studies related to penile augmentation procedures and their effectiveness.The article highlights the importance of early diagnosis and intervention in addressing the physical and psychological well-being of individuals with micropenis.Surgical procedures,such as penile lengthening and girth enhancement,and non-surgical approaches like hormonal therapy are explored.The significance of psychological support,education,and lifestyle modifications is emphasized.Early management and comprehensive care are crucial for individuals with micropenis,from infancy to adolescence and beyond.A multidisciplinary approach involving urologists,endocrinologists,and mental health professionals is recommended.Regular assessment of treatment effectiveness and the need for updated guidelines are essential to provide the best possible care.Healthcare professionals should prioritize early diagnosis,and neonatologists should measure stretched penile length in neonates.A collaborative effort is needed among professionals,parents,and affected individuals to create a supportive environment that recognizes worth beyond physical differences.Continuous research and evidencebased updates are crucial for improving care standards.展开更多
Lymphoepitelioma is a particular form of undifferentiat-ed carcinoma, characterized by a prominent lymphoid stroma, originally described in the nasopharynx. Lym-phoid stroma-rich carcinomas arising in other organs hav...Lymphoepitelioma is a particular form of undifferentiat-ed carcinoma, characterized by a prominent lymphoid stroma, originally described in the nasopharynx. Lym-phoid stroma-rich carcinomas arising in other organs have been termed lymphoepithelioma-like carcinoma (LELC). In the liver, primary LELCs are very rare, and the majority has been identified as cholangiocarcino-mas. Here a rare case of lymphoepithelioma-like hepa-tocellular carcinoma (HCC) is described. A 47-year old woman presented with abdominal pain. Ultrasonogra-phy revealed a liver nodule, 2.2 cm in diameter, local-ized in the right lobe, adjacent to the gallbladder. Viral markers for hepatic B virus (HBV), hepatic C virus (HCV) and Epstein-Barr virus (EBV) were negative. The nod-ule was hypoechogenic. The patient underwent sur-gery, with resection of the nodule. Histology showed hepatocellular carcinoma, characterized by a promi-nent lymphoid infiltrate. At immunocytochemistry, tumor cells were reactive for Hep Par1 and glypican 3. Immunophenotyping of tumor infiltrating lymphocytes evidenced the predominance of CD8+ cytotoxic sup-pressor T cells. The postoperative clinical outcome was favorable and the patient was recurrence-free 15 mo after resection. This case, to the best of our knowl-edge, is the first reported non EBV and non cirrhosis-associated lymphoepithelioma-like hepatocellular carci-noma. The association between the lack of EBV infec-tion, the absence of cirrhosis, a "cytotoxic profile" of the inflammatory infiltrate and a good prognosis could identify a variant of lymphoepithelioma-like HCC with a favorable clinical outcome.展开更多
To clarify which factors may influence pathological tumor response and affect clinical outcomes in patients with locally advanced rectal carcinoma treated with neo-adjuvant chemoradiotherapy and surgery.METHODSTumor r...To clarify which factors may influence pathological tumor response and affect clinical outcomes in patients with locally advanced rectal carcinoma treated with neo-adjuvant chemoradiotherapy and surgery.METHODSTumor regression grade (TRG) according to the Dworak system and yTNM stage were assessed and correlated with pre-treatment clinico-pathological variables in 215 clinically locally advanced (cTNM stage II and III) rectal carcinomas. Prognostic value of all pathological and clinical factors on disease free survival (DFS) and cancer specific survival (CSS) was analyzed by Kaplan Meier and Cox-regression analyses.RESULTScN+ status, mucinous histotype or poor differentiation in the pre-treatment biopsy were significantly associated with lower pathological response (low Dworak grade and TNM remaining unchanged/upstaging). Cases showing acellular mucin pools in surgical specimens all had unremarkable clinical courses with no deaths or recurrences during follow-up. Dworak grade had prognostic significance for DFS and CSS. However, compared to the 5-tiered system, a simplified two-tiered grading system, in which grades 0, 1 and 2 were grouped as absent/partial regression and grades 3 and 4 were grouped as total/subtotal regression, was more reproducible and prognostically informative. The two-tiered Dworak system, yN stage, craniocaudal extension of the tumor and radial margin status were significant independent prognostic variables.CONCLUSIONOur data suggest that caution should be applied in using a conservative approach in rectal carcinomas with cN+ status, extensive/lower involvement of the rectum and mucinous histotype or poor differentiation. Although Dworak TRG is prognostically significant, a simplified two-tiered system could be preferable. Finally, cases with acellular mucin pools should be carefully evaluated to definitely exclude residual mucinous carcinoma.展开更多
Ampulla of Vater is a peculiar anatomical structure, characterized by the crossroad of three distinct epithelia: Intestinal, ductal pancreatic and biliary. Adenocarcinomas arising in this area represent an opportunity...Ampulla of Vater is a peculiar anatomical structure, characterized by the crossroad of three distinct epithelia: Intestinal, ductal pancreatic and biliary. Adenocarcinomas arising in this area represent an opportunity to understand the comparative biology of all periampullary malignancies. These neoplasms can exhibit intestinal, pancreaticobiliary or mixed features, whereas the subclassification based on morphology and immunohistochemical features failed in demonstrating a robust prognostic reliability. In the last few years, the molecular landscape of this tumor entity has been uncovered, identifying alterations that may serve as prognostic and predictive biomarkers. In this review, the histological and genetic characteristics of ampullary carcinomas are discussed, taking into account the main clinical and therapeutic implications related to this tumor type as well.展开更多
AIM To evaluate mucosal baseline m RNA expression of tissue transglutaminase 2(t TG2), interferon gamma(IFNγ), toll-like receptor 2(TLR2) and Myeloid Differentiation factor 88(MyD 88) in patients with microscopic ent...AIM To evaluate mucosal baseline m RNA expression of tissue transglutaminase 2(t TG2), interferon gamma(IFNγ), toll-like receptor 2(TLR2) and Myeloid Differentiation factor 88(MyD 88) in patients with microscopic enteritis(ME).METHODS We retrospectively enrolled 89 patients with ME of different etiology, which was defined within a 2-year mean period of follow-up. Baseline histological examination was performed on Hematoxylin-Eosin stained sections and CD3 lymphocyte immunohistochemistry was used for intraepithelial lymphocyte count(IELs). ME was defined according to the criteria of Bucharest Consensus Conference. For each patient, formalin embedded biopsy samples of the duodenum referred to the period of ME diagnosis were retrieved. Real-time polymerase chain reaction(RT-PCR) was used to detect the amount of mR NA coding for tT G2, IFNγ, TLR2 and My D88, and the quantity was expressed as fold change compared to controls. Control group was represented by duodenal normal specimens from 15 healthy subjects undergoing endoscopy for functional symptoms. Comparisons among continuous variables were performed by One way analysis of variance(ANOVA) and Bonferroni’s test. The χ~2 test was used for categorical variables. Pearson’s test was used to evaluate correlations. Receiver operating curves were drawn for all four markers to estimate sensitivity and specificity in discriminating the development of CD and GS.RESULTS After a period of follow up of 21.7 ± 11.7 mo, the following diagnoses were achieved: gluten related disorders in 48 subjects(31 CD; 17 GS) and non-gluten related ones in 41(29 Irritable Bowel Syndrome- IBS; 12 Others). CD patients had the highest tT G2 levels(8.3 ± 4.5). The ANOVA plus Bonferroni analysis showed that CD > Other ME > GS = IBS > negative controls. A cut off value of 2.258 was able to discriminate between CD and GS with a sensitivity of 52.94% and a specificity of 87.1%. Additionally, CD patients had the highest IFNγ levels(8.5 ± 4.1). ANOVA plus Bonferroni demonstrated CD > Other ME > GS = IBS > negative controls. A cut off of 1.853 was able to differentiate CD and GS with a sensitivity of 47.06% and a specificity of 96.77%. Patients with non gluten-related causes of ME exhibited the highest TLR2 levels(6.1 ± 1.9) as follows: Other ME > CD = GS = IBS > negative controls. TLR2 was unable to discriminate CD from GS. Patients with CD overexpressed MyD 88 levels similarly to non gluten-related causes of DL(7.8 ± 4.9 and 6.7 ± 2.9), thus CD = Other ME > GS = IBS > negative controls. A cut off of 3.722 was able to differentiate CD from GS with a sensitivity of 52.94% and a specificity of 74.19%. IELs count(15-25 and more than 25/100 enterocytes) strongly correlated with mR NA levels of all tested molecules(P < 0.0001).CONCLUSION Our results confirm that a single marker is unable to predict a discrimination among ME underlying conditions as well as between CD and GS. Mucosal high levels of t TG and IFNγ m RNA may predict the development of CD more than GS with high specificity, despite an expected low sensitivity. TLR2 does not discriminate the development of CD from GS. My D88 levels indicate that intestinal permeability is more increased when a severe intestinal damage underlies ME in both gluten related and unrelated conditions. Therefore, the results of the present paper do not seem to show a clear translational value.展开更多
AIM： To describe the trend in duodenal biopsy performance during routine upper gastrointestinal endoscopy in an adult Spanish population, and to analyze its value for the diagnosis of celiac disease in clinical pract...AIM： To describe the trend in duodenal biopsy performance during routine upper gastrointestinal endoscopy in an adult Spanish population, and to analyze its value for the diagnosis of celiac disease in clinical practice. METHODS： A 15 year-trend （1990 to 2004） in duodenal biopsy performed when undertaking upper gastrointestinal endoscopy was studied. We analysed the prevalence of celiac disease in the overall group, and in the subgroups with anaemia and/or chronic diarrhoea. RESULTS： Duodenal biopsy was performed in 1033 of 13 678 upper gastrointestinal endoscopies （7.6%）; an increase in the use of such was observed over the study period （1.9% in 1990-1994, 5% in 1995-1999 and 12.8% in 2000-2004）. Celiac disease was diagnosed in 22 patients （2.2%）, this being more frequent in women than in men （3% and 1% respectively）. Fourteen out of 514 （2.7%） patients with anaemia, 12 out of 141 （8.5%） with chronic diarrhoea and 8 out of 42 （19%） with anaemia plus chronic diarrhoea had celiac disease. A classical clinical presentation was observed in 55% of the cases, 23% of the patients had associated dermatitis herpetiformis and 64% presented anaemia; 9% were diagnosed by familial screening and 5% by cryptogenetic hypertransaminasaemia. CONCLUSION： Duodenal biopsy undertaken during routine upper gastrointestinal endoscopy in adults, has been gradually incorporated into clinical practice, and is a useful tool for the diagnosis of celiac disease in high risk groups such as those with anaemia and/or chronic diarrhoea.展开更多
Drug-induced autoimmune hepatitis(DIAIH)is a specific phenotype of druginduced liver injury that may lead to the devastating outcome of acute liver failure requiring liver transplantation.Drugs implicated in DIAIH inc...Drug-induced autoimmune hepatitis(DIAIH)is a specific phenotype of druginduced liver injury that may lead to the devastating outcome of acute liver failure requiring liver transplantation.Drugs implicated in DIAIH include antimicrobials such as nitrofurantoin and minocycline,non-steroidal anti-inflammatory drugs,statins as well as anti-tumor necrosis agents.The clinical features of druginduced liver injury are indistinguishable from idiopathic autoimmune hepatitis(AIH)as both may have positive AIH-related autoantibodies,elevated immunoglobulin G,as well as similar histopathological findings.In patients who show no clinical improvement,or there is progressive liver injury despite cessation of the suspected drug,a liver biopsy should be considered,whereby the presence of advance fibrosis on histology favors the diagnosis of idiopathic AIH.Empirical treatment with corticosteroids may be required in patients with non-resolving liver injury.A typical clinical scenario supportive of DIAIH includes a history of drug exposure with spontaneous resolution of liver injury after drug withdrawal and the absence of relapse after rapid steroid taper.In this article we report two cases of DIAIH secondary to Sorafenib and Atorvastatin along with a review of currently available literature.Early identification and treatment often lead to a favorable outcome in DIAIH.展开更多
BACKGROUND： Endoscopic ultrasound-guided fine-needle aspiration cytology was demonstrated to be a useful tool for the diagnosis and staging of pancreaticobiliary neoplastic le- sions. Nonetheless, the diagnostic valu...BACKGROUND： Endoscopic ultrasound-guided fine-needle aspiration cytology was demonstrated to be a useful tool for the diagnosis and staging of pancreaticobiliary neoplastic le- sions. Nonetheless, the diagnostic value of this procedure may be limited by low cellularity of the specimen, contamination of intestinal cells and unfeasibility of ancillary immunocy- tochemical procedures. The present study was to evaluate its usefulness in the diagnosis of neoplastic lesions.展开更多
AIM:To study the biological function of transforming growth factor a1(TGF-a 1),vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF) during the process of osteoblasts allografts to accelerate f...AIM:To study the biological function of transforming growth factor a1(TGF-a 1),vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF) during the process of osteoblasts allografts to accelerate fracture healing of osteoporosis rats.METHODS: Set up the fracture models of osteoporosis rats and do osteoblasts grafts; during different periods in the process of fracture heal ing by using immunnohistochemistry to detect the expression of TGF-a1,VEGF,bFG F and in situ hybridization to study the expression of bFGFmRNA,VEGFmRNA,TGF-a 1 mRNA,also using image analysis to deal with it.RESULTS:In experimental group, Osteoblasts can survive, even proliferate in fracture areas;VEGF,bFGF could be s een positive after 7 days of after osteoblast grafts,and there have the highest quantities about 14 days of post-transplantation.TGF-a1 could be seen positiv e after 3 days of post-transplantation,and there have the highest quantities ab out 7-10 days of post-transplantation.However there are not obviously high qua ntities in control.CONCLUSION:Osteoblasts grafts enhance bone fracture healing of osteoporosis rats.TGF-a1, VEGF and bFGF play very important roles in accel erating fracture healing of osteoporosis rats.展开更多
Fatty acids are energy substrates and cell components which participate in regulating signal transduction,transcription factor activity and secretion of bioactive lipid mediators.The acyl-CoA synthetases(ACSs)family c...Fatty acids are energy substrates and cell components which participate in regulating signal transduction,transcription factor activity and secretion of bioactive lipid mediators.The acyl-CoA synthetases(ACSs)family containing 26 family members exhibits tissue-specific distribution,distinct fatty acid substrate preferences and diverse biological functions.Increasing evidence indicates that dysregulation of fatty acid metabolism in the liver-gut axis,designated as the bidirectional relationship between the gut,microbiome and liver,is closely associated with a range of human diseases including metabolic disorders,inflammatory disease and carcinoma in the gastrointestinal tract and liver.In this review,we depict the role of ACSs in fatty acid metabolism,possible molecular mechanisms through which they exert functions,and their involvement in hepatocellular and colorectal carcinoma,with particular attention paid to long-chain fatty acids and small-chain fatty acids.Additionally,the liver-gut communication and the liver and gut intersection with the microbiome as well as diseases related to microbiota imbalance in the liver-gut axis are addressed.Moreover,the development of potentially therapeutic small molecules,proteins and compounds targeting ACSs in cancer treatment is summarized.展开更多
Recently,the use of confocal laser endomicroscopy(CLE) in the diagnosis of chronic ulcerative colitis(CUC) was reported.In this brief report we aimed to assess the application of probe-based CLE to characterize coloni...Recently,the use of confocal laser endomicroscopy(CLE) in the diagnosis of chronic ulcerative colitis(CUC) was reported.In this brief report we aimed to assess the application of probe-based CLE to characterize colonic mucosa and dysplasia in CUC.The study involved a patient presenting long-standing CUC.Confocal imaging of both the inflamed mucosa,a circumscribed lesion(dysplasiaassociated lesional mass),and adjacent colonic mucosa are demonstrated and the correlation between the CLE and histological images.Inflamed mucosa and dysplasia showed specific alteration of crypt architecture,cellular infiltration,and vessel architecture with an excellent correlation between CLE and standard histological examination.展开更多
Adult stem cells are necessary for self-renewal tissues and regeneration after damage.Especially in the intestine,which self-renews every few days,they play a key role in tissue homeostasis.Therefore,complex regulator...Adult stem cells are necessary for self-renewal tissues and regeneration after damage.Especially in the intestine,which self-renews every few days,they play a key role in tissue homeostasis.Therefore,complex regulatory mechanisms are needed to prevent hyperproliferation,which can lead in the worst case to carcinogenesis or under-activation of stem cells,which can result in dysfunctional epithelial.One main regulatory signaling pathway is the Wnt/β-catenin signaling pathway.It is a highly conserved pathway,withβ-catenin,a transcription factor,as target protein.Translocation ofβ-catenin from cytoplasm to nucleus activates the transcription of numerous genes involved in regulating stem cell pluripotency,proliferation,cell differentiation and regulation of cell death.This review presents a brief overview of the Wnt/β-catenin signaling pathway,the regulatory mechanism of this pathway and its role in intestinal homeostasis.Additionally,this review highlights the molecular mechanisms and the histomorphological features of Wnt hyperactivation.Furthermore,the central role of the Wnt signaling pathway in intestinal carcinogenesis as well as its clinical relevance in colorectal carcinoma are discussed.展开更多
To the Editor:The risk of de novo cancer increases by 2 to 7-fold after liver transplantation[1].The most common de novo cancers are both solid(non-melanoma skin cancers,colorectal carcinoma,genito-urinary and head-ne...To the Editor:The risk of de novo cancer increases by 2 to 7-fold after liver transplantation[1].The most common de novo cancers are both solid(non-melanoma skin cancers,colorectal carcinoma,genito-urinary and head-neck cancer)[2,3]as well as hematologic malignancies,in particular the so-called post-transplant lymphoproliferative disorder[4].展开更多
Pancreatic cancer is a lethal malignancy,whose precursor lesions are pancreatic intraepithelial neoplasm,intraductal papillary mucinous neoplasm,intraductal tubulopapillary neoplasm,and mucinous cystic neoplasm.To bet...Pancreatic cancer is a lethal malignancy,whose precursor lesions are pancreatic intraepithelial neoplasm,intraductal papillary mucinous neoplasm,intraductal tubulopapillary neoplasm,and mucinous cystic neoplasm.To better understand the biology of pancreatic cancer,it is fundamental to know its precursors and to study the mechanisms of carcinogenesis.Each of these precursors displays peculiar histological features,as well as specific molecular alterations.Starting from such pre-invasive lesions,this review aims at summarizing the most important aspects of carcinogenesis of pancreatic cancer,with a specific focus on the recent advances and the future perspectives of the research on this lethal tumor type.展开更多
文摘Dear Editor,We aimed to describe the management of the intraoperative injury of the right external iliac artery that occurred during robot-assisted right nephroureterectomy with bladder cuff excision.Surgery was scheduled for suspected urothelial carcinoma of the distal ureter in a 60-year-old woman.The patient involved in the present research signed a dedicated form to consent to the publication of images and/or information about her.Past medical history included Brugada syndrome diagnosed in 2015,and hypercholesterolemia.Past surgical history included one cesarean section only.Family history included ovarian cancer(sister),colorectal cancer(mother),and kidney cancer(father).
基金iVascular,S.L.U.,Camíde Can Ubach,11–Nave 3,08620 Sant Vicençdels Horts,Barcelona,Spain。
文摘Background:The efficacy of balloon angioplasty for treating peripheral artery disease is influenced by various factors,some of them not yet totally understood.This study aimed to evaluate the role of elastin content in vascular responses 28 days postangioplasty using uncoated and paclitaxel-coated balloons with the same platform in femoral arteries of a healthy porcine model.Methods:Eight animals underwent balloon angioplasty on the external and internal branches of femoral arteries.Histopathologic evaluation was conducted at follow-up to assess the elastin content,vascular damage,morphological features,and neointimal formation.Results:The elastin content was significantly higher in the external than in the internal femoral artery(p=0.0014).After balloon angioplasty,it was inversely correlated with vascular injury score(ρ=−0.4510,p=0.0096),neointimal inflammation(ρ=−0.3352,p=0.0607),transmural(ρ=−0.4474,p=0.0103)and circumferential(ρ=−0.4591,p=0.0082)smooth muscle cell loss,presence of proteoglycans(ρ=−0.5172,p=0.0024),fibrin deposition(ρ=−0.3496,p=0.0499),and adventitial fibrosis(ρ=−0.6229,p=0.0002).Neointimal formation inhibition with paclitaxel was evident only in arteries with disruption of the internal elastic lamina,with a significant smaller neointimal area in arteries treated with paclitaxel-coated balloons compared to uncoated balloons(median[Q1–Q3]:10.25[7.49–15.64]vs.24.44[18.96–30.52],p=0.0434).Conclusions:Elastin content varies between branches of the femoral artery and significantly influences the integrity of the internal elastic lamina,the vessel's adaptive response,and paclitaxel efficacy after balloon angioplasty.
文摘To analyze the importance of para-aortic node status in a series of patients who underwent pancreaticoduodenectomy (PD) in a single Institution. METHODSBetween January 2000 and December 2012, 151 patients underwent PD with para-aortic node dissection for pancreatic adenocarcinoma in our Institution. Patients were divided into two groups: patients with negative PALNs (PALNs-), and patients with metastatic PALNs (PALNs+). Pathologic factors, including stage, nodal status, number of positive nodes and lymph node ratio, invasion of para-aortic nodes, tumor’s grading, and radicality of resection were studied by univariate and multivariate analysis. Survival curves were constructed with Kaplan-Meier method and compared with Log-rank test: significance was considered as P < 0.05. RESULTSA total of 107 patients (74%) had nodal metastases. Median number of pathologically assessed lymph nodes was 26 (range 14-63). Twenty-five patients (16.5%) had para-aortic lymph node involvement. Thirty-three patients (23%) underwent R1 pancreatic resection. One-hundred forty-one patients recurred and died for tumor recurrence, one is alive with recurrence, and 9 are alive and free of disease. Overall survival was significantly influenced by grading (P = 0.0001), radicality of resection (P = 0.001), stage (P = 0.03), lymph node status (P = 0.04), para-aortic nodes metastases (P = 0.02). Multivariate analysis showed that grading was an independent prognostic factor for overall survival (P = 0.0001), while grading (P = 0.0001) and radicality of resection (P = 0.01) were prognostic parameters for disease-free survival. Number of metastatic nodes, node ratio, and para-aortic nodes involvement were not independent predictors of disease-free and overall survival. CONCLUSIONIn this experience, lymph node status and para-aortic node metastases were associated with poor survival at univariate analysis, but they were not independent prognostic factors.
基金Supported by University of Ferrara local funds:FAR 2012,2013,2014 and Regione Emilia Romagna grant(Ricerca Regione-Università)2007-2009
文摘Autosomal dominant polycystic kidney disease （ADPKD） is the most common inherited monogenic kidney disease. Characterized by the development and growth of cysts that cause progressive kidney enlargement, it ultimately leads to end-stage renal disease. Approximately 85% of ADPKD cases are caused by mutations in the PKD1 gene, while mutations in the PKD2 gene account for the remaining 15% of cases. The PKD1 gene encodes for polycystin-1 （PC1）, a large multi-functional memb-rane receptor protein able to regulate ion channel complexes, whereas polycystin-2 （PC2）, encoded by the PKD2 gene, is an integral membrane protein that functions as a calcium-permeable cation channel, located mainly in the endoplasmic reticulum （ER）. In the primary cilia of the epithelial cells, PC1 interacts with PC2 to form a polycystin complex that acts as a mechanosensor, regulating signaling pathways involved in the differentiation of kidney tubular epithelial cells. Despite progress in understanding the function of these proteins, the molecular mechanisms associated with the pathogenesis of ADPKD remain unclear. In this review we discuss how an imbalance between functional PC1 and PC2 proteins may disrupt calcium channel activities in the cilium, plasma membrane and ER, thereby altering intracellular calcium signaling and leading to the aberrant cell proliferation and apoptosis associated with the development and growth of renal cysts. Research in this feld could lead to the discovery of new molecules able to rebalance intracellular calcium, thereby normalizing cell proliferation and reducing kidney cyst progression.
文摘A crucial aspect of prostate cancer grading, especially in low- and intermediate-risk cancer, is the accurate identification of Gleason pattern 4 glands, which includes ill-formed or fused glands. However, there is notable inconsistency among pathologists in recognizing these glands, especially when mixed with pattern 3 glands. This inconsistency has significant implications for patient management and treatment decisions. Conversely, the recognition of glomeruloid and cribriform architecture has shown higher reproducibility. Cribriform architecture, in particular, has been linked to the worst prognosis among pattern 4 subtypes. Intraductal carcinoma of the prostate (IDC-P) is also associated with high-grade cancer and poor prognosis. Accurate identification, classification, and tumor size evaluation by pathologists are vital for determining patient treatment. This review emphasizes the importance of prostate cancer grading, highlighting challenges like distinguishing between pattern 3 and pattern 4 and the prognostic implications of cribriform architecture and intraductal proliferations. It also addresses the inherent grading limitations due to interobserver variability and explores the potential of computational pathology to enhance pathologist accuracy and consistency.
文摘In this editorial,a comment on the article by Díaz-López et al published in the recent issue of the 2024 is provided.We focus on the practical implications critical for providing a correct and complete diagnosis of mixed neuroendocrine-nonneuroendocrine neoplasm(MiNEN)in the gastrointestinal system.The diagnosis of MiNEN begins with the recognition of neuroendocrine features in one component of a biphasic tumor.The non-neuroendocrine counterpart can be virtually represented by any neoplastic type,even though the most frequent histologies are glandular and squamous.However,qualification of the neuroendocrine component requires histological and immunohistochemical confirmation.Neuroendocrine tumors are characterized by a peculiar architectural organization and bland nuclei with granular“salt and pepper”chromatin.Although neuroendocrine carcinomas have multiple and variable presentations,they typically show a solid or organoid architecture.The histological aspect needs to be confirmed by immunohistochemistry,and a diagnosis is confirmed whenever the expression of keratin and neuroendocrine markers is observed.Once both histopathological and immunohistochemical features of neuroendocrine neoplasms are identified,it is important to consider the three major pitfalls of MiNEN diagnostics:(1)Entrapment of neuroendocrine non-neoplastic cells within the tumor mass;(2)Differential diagnosis with amphicrine neoplasms;and(3)Differential diagnosis of tumors that partially express neuroendocrine markers.According to the current guidelines for diagnosing digestive MiNEN,each component must represent at least 30%of the entire neoplastic mass.Although the high-grade histopathological subtype frequently determines disease prognosis,both components can significantly affect prognosis.Thus,if one of the components,either neuroendocrine or non-neuroendocrine,does not fulfill the volumetric criteria,the guidelines still encourage reporting it.These strict criteria are essential for correctly recognizing and characterizing digestive MiNENs.This task is essential because it has prognostic relevance and substantial potential value for guiding further studies in this field.In the future,systematic analyses should be performed to validate or reconsider the current 30%cutoff value.
文摘Microphallus/Micropenis is a rare condition with significant physical and psychological implications for affected individuals.This article comprehensively reviews micropenis,its etiology,epidemiology,and various treatment options.We conducted a thorough literature review to collect relevant information on micropenis and microphallus,as well as related disorders.Our primary databases were PubMed,Medline,and Google Scholar.We searched for articles published in English between 2000 and 2023.Our analysis included 67 review articles,56 research studies,11 case reports,one guideline,and one editorial.Our search terms included"microphallus","micropenis","congenital hypogonadotropic hypogonadism","androgen insensitivity syndrome","pediatric management of micropenis","testosterone therapy",and"psychosocial implications of micropenis".We focused on diagnosing micropenis and related conditions,including hormonal assessments,medical and surgical treatment options,psychosocial and psychological well-being,sexual development of adolescents,and sociocultural influences on men's perceptions of penile size.Additionally,we explored parenting and family dynamics in cases of micropenis and disorders of sex development,implications of hormonal treatment in neonates,and studies related to penile augmentation procedures and their effectiveness.The article highlights the importance of early diagnosis and intervention in addressing the physical and psychological well-being of individuals with micropenis.Surgical procedures,such as penile lengthening and girth enhancement,and non-surgical approaches like hormonal therapy are explored.The significance of psychological support,education,and lifestyle modifications is emphasized.Early management and comprehensive care are crucial for individuals with micropenis,from infancy to adolescence and beyond.A multidisciplinary approach involving urologists,endocrinologists,and mental health professionals is recommended.Regular assessment of treatment effectiveness and the need for updated guidelines are essential to provide the best possible care.Healthcare professionals should prioritize early diagnosis,and neonatologists should measure stretched penile length in neonates.A collaborative effort is needed among professionals,parents,and affected individuals to create a supportive environment that recognizes worth beyond physical differences.Continuous research and evidencebased updates are crucial for improving care standards.
文摘Lymphoepitelioma is a particular form of undifferentiat-ed carcinoma, characterized by a prominent lymphoid stroma, originally described in the nasopharynx. Lym-phoid stroma-rich carcinomas arising in other organs have been termed lymphoepithelioma-like carcinoma (LELC). In the liver, primary LELCs are very rare, and the majority has been identified as cholangiocarcino-mas. Here a rare case of lymphoepithelioma-like hepa-tocellular carcinoma (HCC) is described. A 47-year old woman presented with abdominal pain. Ultrasonogra-phy revealed a liver nodule, 2.2 cm in diameter, local-ized in the right lobe, adjacent to the gallbladder. Viral markers for hepatic B virus (HBV), hepatic C virus (HCV) and Epstein-Barr virus (EBV) were negative. The nod-ule was hypoechogenic. The patient underwent sur-gery, with resection of the nodule. Histology showed hepatocellular carcinoma, characterized by a promi-nent lymphoid infiltrate. At immunocytochemistry, tumor cells were reactive for Hep Par1 and glypican 3. Immunophenotyping of tumor infiltrating lymphocytes evidenced the predominance of CD8+ cytotoxic sup-pressor T cells. The postoperative clinical outcome was favorable and the patient was recurrence-free 15 mo after resection. This case, to the best of our knowl-edge, is the first reported non EBV and non cirrhosis-associated lymphoepithelioma-like hepatocellular carci-noma. The association between the lack of EBV infec-tion, the absence of cirrhosis, a "cytotoxic profile" of the inflammatory infiltrate and a good prognosis could identify a variant of lymphoepithelioma-like HCC with a favorable clinical outcome.
文摘To clarify which factors may influence pathological tumor response and affect clinical outcomes in patients with locally advanced rectal carcinoma treated with neo-adjuvant chemoradiotherapy and surgery.METHODSTumor regression grade (TRG) according to the Dworak system and yTNM stage were assessed and correlated with pre-treatment clinico-pathological variables in 215 clinically locally advanced (cTNM stage II and III) rectal carcinomas. Prognostic value of all pathological and clinical factors on disease free survival (DFS) and cancer specific survival (CSS) was analyzed by Kaplan Meier and Cox-regression analyses.RESULTScN+ status, mucinous histotype or poor differentiation in the pre-treatment biopsy were significantly associated with lower pathological response (low Dworak grade and TNM remaining unchanged/upstaging). Cases showing acellular mucin pools in surgical specimens all had unremarkable clinical courses with no deaths or recurrences during follow-up. Dworak grade had prognostic significance for DFS and CSS. However, compared to the 5-tiered system, a simplified two-tiered grading system, in which grades 0, 1 and 2 were grouped as absent/partial regression and grades 3 and 4 were grouped as total/subtotal regression, was more reproducible and prognostically informative. The two-tiered Dworak system, yN stage, craniocaudal extension of the tumor and radial margin status were significant independent prognostic variables.CONCLUSIONOur data suggest that caution should be applied in using a conservative approach in rectal carcinomas with cN+ status, extensive/lower involvement of the rectum and mucinous histotype or poor differentiation. Although Dworak TRG is prognostically significant, a simplified two-tiered system could be preferable. Finally, cases with acellular mucin pools should be carefully evaluated to definitely exclude residual mucinous carcinoma.
基金Supported by the Italian Association for Cancer Research,No.12182
文摘Ampulla of Vater is a peculiar anatomical structure, characterized by the crossroad of three distinct epithelia: Intestinal, ductal pancreatic and biliary. Adenocarcinomas arising in this area represent an opportunity to understand the comparative biology of all periampullary malignancies. These neoplasms can exhibit intestinal, pancreaticobiliary or mixed features, whereas the subclassification based on morphology and immunohistochemical features failed in demonstrating a robust prognostic reliability. In the last few years, the molecular landscape of this tumor entity has been uncovered, identifying alterations that may serve as prognostic and predictive biomarkers. In this review, the histological and genetic characteristics of ampullary carcinomas are discussed, taking into account the main clinical and therapeutic implications related to this tumor type as well.
文摘AIM To evaluate mucosal baseline m RNA expression of tissue transglutaminase 2(t TG2), interferon gamma(IFNγ), toll-like receptor 2(TLR2) and Myeloid Differentiation factor 88(MyD 88) in patients with microscopic enteritis(ME).METHODS We retrospectively enrolled 89 patients with ME of different etiology, which was defined within a 2-year mean period of follow-up. Baseline histological examination was performed on Hematoxylin-Eosin stained sections and CD3 lymphocyte immunohistochemistry was used for intraepithelial lymphocyte count(IELs). ME was defined according to the criteria of Bucharest Consensus Conference. For each patient, formalin embedded biopsy samples of the duodenum referred to the period of ME diagnosis were retrieved. Real-time polymerase chain reaction(RT-PCR) was used to detect the amount of mR NA coding for tT G2, IFNγ, TLR2 and My D88, and the quantity was expressed as fold change compared to controls. Control group was represented by duodenal normal specimens from 15 healthy subjects undergoing endoscopy for functional symptoms. Comparisons among continuous variables were performed by One way analysis of variance(ANOVA) and Bonferroni’s test. The χ~2 test was used for categorical variables. Pearson’s test was used to evaluate correlations. Receiver operating curves were drawn for all four markers to estimate sensitivity and specificity in discriminating the development of CD and GS.RESULTS After a period of follow up of 21.7 ± 11.7 mo, the following diagnoses were achieved: gluten related disorders in 48 subjects(31 CD; 17 GS) and non-gluten related ones in 41(29 Irritable Bowel Syndrome- IBS; 12 Others). CD patients had the highest tT G2 levels(8.3 ± 4.5). The ANOVA plus Bonferroni analysis showed that CD > Other ME > GS = IBS > negative controls. A cut off value of 2.258 was able to discriminate between CD and GS with a sensitivity of 52.94% and a specificity of 87.1%. Additionally, CD patients had the highest IFNγ levels(8.5 ± 4.1). ANOVA plus Bonferroni demonstrated CD > Other ME > GS = IBS > negative controls. A cut off of 1.853 was able to differentiate CD and GS with a sensitivity of 47.06% and a specificity of 96.77%. Patients with non gluten-related causes of ME exhibited the highest TLR2 levels(6.1 ± 1.9) as follows: Other ME > CD = GS = IBS > negative controls. TLR2 was unable to discriminate CD from GS. Patients with CD overexpressed MyD 88 levels similarly to non gluten-related causes of DL(7.8 ± 4.9 and 6.7 ± 2.9), thus CD = Other ME > GS = IBS > negative controls. A cut off of 3.722 was able to differentiate CD from GS with a sensitivity of 52.94% and a specificity of 74.19%. IELs count(15-25 and more than 25/100 enterocytes) strongly correlated with mR NA levels of all tested molecules(P < 0.0001).CONCLUSION Our results confirm that a single marker is unable to predict a discrimination among ME underlying conditions as well as between CD and GS. Mucosal high levels of t TG and IFNγ m RNA may predict the development of CD more than GS with high specificity, despite an expected low sensitivity. TLR2 does not discriminate the development of CD from GS. My D88 levels indicate that intestinal permeability is more increased when a severe intestinal damage underlies ME in both gluten related and unrelated conditions. Therefore, the results of the present paper do not seem to show a clear translational value.
文摘AIM： To describe the trend in duodenal biopsy performance during routine upper gastrointestinal endoscopy in an adult Spanish population, and to analyze its value for the diagnosis of celiac disease in clinical practice. METHODS： A 15 year-trend （1990 to 2004） in duodenal biopsy performed when undertaking upper gastrointestinal endoscopy was studied. We analysed the prevalence of celiac disease in the overall group, and in the subgroups with anaemia and/or chronic diarrhoea. RESULTS： Duodenal biopsy was performed in 1033 of 13 678 upper gastrointestinal endoscopies （7.6%）; an increase in the use of such was observed over the study period （1.9% in 1990-1994, 5% in 1995-1999 and 12.8% in 2000-2004）. Celiac disease was diagnosed in 22 patients （2.2%）, this being more frequent in women than in men （3% and 1% respectively）. Fourteen out of 514 （2.7%） patients with anaemia, 12 out of 141 （8.5%） with chronic diarrhoea and 8 out of 42 （19%） with anaemia plus chronic diarrhoea had celiac disease. A classical clinical presentation was observed in 55% of the cases, 23% of the patients had associated dermatitis herpetiformis and 64% presented anaemia; 9% were diagnosed by familial screening and 5% by cryptogenetic hypertransaminasaemia. CONCLUSION： Duodenal biopsy undertaken during routine upper gastrointestinal endoscopy in adults, has been gradually incorporated into clinical practice, and is a useful tool for the diagnosis of celiac disease in high risk groups such as those with anaemia and/or chronic diarrhoea.
文摘Drug-induced autoimmune hepatitis(DIAIH)is a specific phenotype of druginduced liver injury that may lead to the devastating outcome of acute liver failure requiring liver transplantation.Drugs implicated in DIAIH include antimicrobials such as nitrofurantoin and minocycline,non-steroidal anti-inflammatory drugs,statins as well as anti-tumor necrosis agents.The clinical features of druginduced liver injury are indistinguishable from idiopathic autoimmune hepatitis(AIH)as both may have positive AIH-related autoantibodies,elevated immunoglobulin G,as well as similar histopathological findings.In patients who show no clinical improvement,or there is progressive liver injury despite cessation of the suspected drug,a liver biopsy should be considered,whereby the presence of advance fibrosis on histology favors the diagnosis of idiopathic AIH.Empirical treatment with corticosteroids may be required in patients with non-resolving liver injury.A typical clinical scenario supportive of DIAIH includes a history of drug exposure with spontaneous resolution of liver injury after drug withdrawal and the absence of relapse after rapid steroid taper.In this article we report two cases of DIAIH secondary to Sorafenib and Atorvastatin along with a review of currently available literature.Early identification and treatment often lead to a favorable outcome in DIAIH.
文摘BACKGROUND： Endoscopic ultrasound-guided fine-needle aspiration cytology was demonstrated to be a useful tool for the diagnosis and staging of pancreaticobiliary neoplastic le- sions. Nonetheless, the diagnostic value of this procedure may be limited by low cellularity of the specimen, contamination of intestinal cells and unfeasibility of ancillary immunocy- tochemical procedures. The present study was to evaluate its usefulness in the diagnosis of neoplastic lesions.
文摘AIM:To study the biological function of transforming growth factor a1(TGF-a 1),vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF) during the process of osteoblasts allografts to accelerate fracture healing of osteoporosis rats.METHODS: Set up the fracture models of osteoporosis rats and do osteoblasts grafts; during different periods in the process of fracture heal ing by using immunnohistochemistry to detect the expression of TGF-a1,VEGF,bFG F and in situ hybridization to study the expression of bFGFmRNA,VEGFmRNA,TGF-a 1 mRNA,also using image analysis to deal with it.RESULTS:In experimental group, Osteoblasts can survive, even proliferate in fracture areas;VEGF,bFGF could be s een positive after 7 days of after osteoblast grafts,and there have the highest quantities about 14 days of post-transplantation.TGF-a1 could be seen positiv e after 3 days of post-transplantation,and there have the highest quantities ab out 7-10 days of post-transplantation.However there are not obviously high qua ntities in control.CONCLUSION:Osteoblasts grafts enhance bone fracture healing of osteoporosis rats.TGF-a1, VEGF and bFGF play very important roles in accel erating fracture healing of osteoporosis rats.
基金Supported by the Interdisziplinäres Zentrum für Klinische Forschung(IZKF-MSP-06)of University Hospital Jena.
文摘Fatty acids are energy substrates and cell components which participate in regulating signal transduction,transcription factor activity and secretion of bioactive lipid mediators.The acyl-CoA synthetases(ACSs)family containing 26 family members exhibits tissue-specific distribution,distinct fatty acid substrate preferences and diverse biological functions.Increasing evidence indicates that dysregulation of fatty acid metabolism in the liver-gut axis,designated as the bidirectional relationship between the gut,microbiome and liver,is closely associated with a range of human diseases including metabolic disorders,inflammatory disease and carcinoma in the gastrointestinal tract and liver.In this review,we depict the role of ACSs in fatty acid metabolism,possible molecular mechanisms through which they exert functions,and their involvement in hepatocellular and colorectal carcinoma,with particular attention paid to long-chain fatty acids and small-chain fatty acids.Additionally,the liver-gut communication and the liver and gut intersection with the microbiome as well as diseases related to microbiota imbalance in the liver-gut axis are addressed.Moreover,the development of potentially therapeutic small molecules,proteins and compounds targeting ACSs in cancer treatment is summarized.
文摘Recently,the use of confocal laser endomicroscopy(CLE) in the diagnosis of chronic ulcerative colitis(CUC) was reported.In this brief report we aimed to assess the application of probe-based CLE to characterize colonic mucosa and dysplasia in CUC.The study involved a patient presenting long-standing CUC.Confocal imaging of both the inflamed mucosa,a circumscribed lesion(dysplasiaassociated lesional mass),and adjacent colonic mucosa are demonstrated and the correlation between the CLE and histological images.Inflamed mucosa and dysplasia showed specific alteration of crypt architecture,cellular infiltration,and vessel architecture with an excellent correlation between CLE and standard histological examination.
文摘Adult stem cells are necessary for self-renewal tissues and regeneration after damage.Especially in the intestine,which self-renews every few days,they play a key role in tissue homeostasis.Therefore,complex regulatory mechanisms are needed to prevent hyperproliferation,which can lead in the worst case to carcinogenesis or under-activation of stem cells,which can result in dysfunctional epithelial.One main regulatory signaling pathway is the Wnt/β-catenin signaling pathway.It is a highly conserved pathway,withβ-catenin,a transcription factor,as target protein.Translocation ofβ-catenin from cytoplasm to nucleus activates the transcription of numerous genes involved in regulating stem cell pluripotency,proliferation,cell differentiation and regulation of cell death.This review presents a brief overview of the Wnt/β-catenin signaling pathway,the regulatory mechanism of this pathway and its role in intestinal homeostasis.Additionally,this review highlights the molecular mechanisms and the histomorphological features of Wnt hyperactivation.Furthermore,the central role of the Wnt signaling pathway in intestinal carcinogenesis as well as its clinical relevance in colorectal carcinoma are discussed.
文摘To the Editor:The risk of de novo cancer increases by 2 to 7-fold after liver transplantation[1].The most common de novo cancers are both solid(non-melanoma skin cancers,colorectal carcinoma,genito-urinary and head-neck cancer)[2,3]as well as hematologic malignancies,in particular the so-called post-transplant lymphoproliferative disorder[4].
基金Supported by the Associazione Italiana Ricerca sul Cancro,No.12182Cassini Project
文摘Pancreatic cancer is a lethal malignancy,whose precursor lesions are pancreatic intraepithelial neoplasm,intraductal papillary mucinous neoplasm,intraductal tubulopapillary neoplasm,and mucinous cystic neoplasm.To better understand the biology of pancreatic cancer,it is fundamental to know its precursors and to study the mechanisms of carcinogenesis.Each of these precursors displays peculiar histological features,as well as specific molecular alterations.Starting from such pre-invasive lesions,this review aims at summarizing the most important aspects of carcinogenesis of pancreatic cancer,with a specific focus on the recent advances and the future perspectives of the research on this lethal tumor type.
