To the Editor:Thymoma-associated multiorgan autoimmunity(TAMA)is a rare paraneoplastic syndrome described in patients with thymoma and characterized by multiorgan failure and graft-versus-host dis-ease(GVHD)like patho...To the Editor:Thymoma-associated multiorgan autoimmunity(TAMA)is a rare paraneoplastic syndrome described in patients with thymoma and characterized by multiorgan failure and graft-versus-host dis-ease(GVHD)like pathology affecting the skin,the gastrointestinal tract,and the liver.To date,only 21 cases are reported in liter-ature[1],with some patients presenting gastrointestinal and hep-atic manifestations,mainly colitis,diarrhea,and abnormal liver en-zymes,but the hepatic involvement has not been histologically characterized yet.展开更多
Checkpoint inhibitors,particularly programmed cell death-1/programmed death-ligand 1(PD-1/PDL1)inhibitors,have significantly advanced the treatment of Hodgkin lymphoma(HL),especially in relapsed or refractory cases.Ho...Checkpoint inhibitors,particularly programmed cell death-1/programmed death-ligand 1(PD-1/PDL1)inhibitors,have significantly advanced the treatment of Hodgkin lymphoma(HL),especially in relapsed or refractory cases.However,challenges such as resistance,immune-related adverse events(irAEs),and the need for effective patient selection remain.This review aims to explore the mechanisms of resistance to checkpoint inhibitors,including alterations in the tumor microenvironment,loss of antigen presentation,and T-cell exhaustion.Overcoming resistance may involve combination therapies,such as pairing PD-1 inhibitors with other immune checkpoint inhibitors or targeted therapies like Brentuximab vedotin.Additionally,next-generation inhibitors targeting molecules like lymphocyte-activation gene 3(LAG-3)and T-cell immunoglobulin and mucin-domain containing-3(TIM-3)show promise in addressing resistance mechanisms not overcome by PD-1 inhibitors.Identifying reliable biomarkers to predict response to checkpoint inhibitors is critical for optimizing treatment,with ongoing research focusing on tumor mutational burden(TMB),inflammatory markers,and genetic profiling.Future clinical trials will aim to refine treatment regimens,optimize therapeutic combinations,and minimize adverse effects to maximize patient benefit.展开更多
AIM: To assess the diagnostic concordance between endoscopic and histological atrophy in the United Kingdom and Japan.METHODS: Using published data,a total of 252 patients,126 in the United Kingdom and 126 in Japan,ag...AIM: To assess the diagnostic concordance between endoscopic and histological atrophy in the United Kingdom and Japan.METHODS: Using published data,a total of 252 patients,126 in the United Kingdom and 126 in Japan,aged 20 to 80 years,were evaluated. The extent of endoscopic atrophy was classified into five subgroups according to a modified Kimura-Takemoto classification system and was compared with histological findings of atrophy at five biopsy sites according to the updated Sydney system.RESULTS: The strength of agreement of the extent of atrophy between histology and visual endoscopic inspection showed good reproducibili ty,wi th a weighted kappa value of 0.76(P < 0.001). Multivariate analysis showed that three factors were associated with decreased concordance: Japanese ethnicity [odds ratio(OR) 0.22,95% confidence interval(CI) 0.11-0.43],older age(OR = 0.32,95%CI: 0.16-0.66) and endoscopic atrophy(OR = 0.10,95%CI: 0.03-0.36). The strength of agreement between endoscopic and histological atrophy,assessed by cancer risk-oriented grading,was reproducible,with a kappa value of 0.81(95%CI: 0.75-0.87). Only nine patients(3.6%) were endoscopically underdiagnosed with antral predominant rather than extensive atrophy and were considered false negatives.CONCLUSION: Endoscopic grading can predict histological atrophy with few false negatives,indicating that precancerous conditions can be identified during screening endoscopy,particularly in patients in western countries.展开更多
The treatment for hepatocellular carcinoma(HCC)relies on liver resection,which is,however,burdened by a high rate of recurrence after surgery,up to 60%at 5 years.No pre-operative tools are currently available to asses...The treatment for hepatocellular carcinoma(HCC)relies on liver resection,which is,however,burdened by a high rate of recurrence after surgery,up to 60%at 5 years.No pre-operative tools are currently available to assess the recurrence risk tailored to every single patient.Recently liquid biopsy has shown interesting results in diagnosis,prognosis and treatment allocation strategies in other types of cancers,since its ability to identify circulating tumor cells(CTCs)derived from the primary tumor.Those cells were advocated to be responsible for the majority of cases of recurrence and cancer-related deaths for HCC.In fact,after being modified by the epithelial-mesenchymal transition,CTCs circulate as“seeds”in peripheral blood,then reach the target organ as dormant cells which could be subsequently“awakened”and activated,and then initiate metastasis.Their presence may justify the disagreement registered in terms of efficacy of anatomic vs non-anatomic resections,particularly in the case of microvascular invasion,which has been recently pointed as a histological sign of the spread of those cells.Thus,their presence,also in the early stages,may justify the recurrence event also in the contest of liver transplant.Understanding the mechanism behind the tumor progression may allow improving the treatment selection according to the biological patient-based characteristics.Moreover,it may drive the development of novel biological tailored tests which could address a specific patient to neoadjuvant or adjuvant strategies,and in perspective,it could also become a new method to allocate organs for transplantation,according to the risk of relapse after liver transplant.The present paper will describe the most recent evidence on the role of CTCs in determining the relapse of HCC,highlighting their potential clinical implication as novel tumor behavior biomarkers able to influence the surgical choice.展开更多
The aim of this work is to emphasize the importance of a differential diagnosis of von Brunn’s nests in cats from other urothelial neoplastic disorders, as transitional cell carcinoma, for a subsequent optimal care. ...The aim of this work is to emphasize the importance of a differential diagnosis of von Brunn’s nests in cats from other urothelial neoplastic disorders, as transitional cell carcinoma, for a subsequent optimal care. Von Brunn’s nests and cysts are submucosal benign urothelial processes, related to irritative stimuli (calculi and urinary infections), characterized by an invagination with buds and clusters of normal urothelium in the lamina propria. They are common findings in the urinary bladder of human beings, but few cases have been described in dogs and cats. We report macroscopic, histopathological and, in one case, immunohistochemical features of these rare forms in the left ureters of two cats. Macroscopic evidence during surgery of ureteral nodules in two cats was accompanied by histopathological diagnosis and, in one case, by immunohistochemical assessment. Histopathology was coherent with a rare condition characterized by nests and islands of normal urothelium in the lamina propria and submucosa, with formation of cysts and moderate focal subacute inflammation. In one case epithelial cells of the nests showed well differentiated urothelial cells with an intense immunoreactivity to pan-cytokeratin (CK AE1/AE3), CK19 in the first outer layers, a slight immunoreactivity to CK20 and a low proliferative activity using MIB-1 (Ki67).展开更多
OBJECTIVE To evaluate the anticancer activity of andrographolide(AGP)and its semisynthetic analogues(SRJ09and SRJ23)in pancreatic adenocarcinoma(PDAC)cell lines harbouring therapeutically highly relevant oncogenic K-r...OBJECTIVE To evaluate the anticancer activity of andrographolide(AGP)and its semisynthetic analogues(SRJ09and SRJ23)in pancreatic adenocarcinoma(PDAC)cell lines harbouring therapeutically highly relevant oncogenic K-ras glycine-12(KRAS-G12)mutant proteins.In a landmark publication,we revealed that AGP and its derivatives bind KRAS protein to inhibit RAS signaling PNAS,110:10201-06).This discovery prompted the initiation of this investigation.METHODS The cell growth inhibitory effect of the compounds on PDAC cell lines〔PANC-1(KRAS-G12D),Capan-2(KRAS-G12V),and MIA PaCa-2(KRASG12C)〕,was assessed by MTT assay.RESULTS In comparison with AGP and SRJ09,SRJ23 showed the greatest growth inhibition in all PDAC cell lines with mutant KRAS proteins.The inhibitory effect of SRJ23 on the cell growth was similar for all PDAC cell lines.AGP exerted selective growth inhibition against PANC-1(KRAS-G12D)cells,while the growth inhibition of SRJ09 was selective towards Capan-2(KRAS-G12V)cells.CONCLUSION AGP and SRJ09 showed selectivity for PDAC cell lines with specific KRAS mutations.This suggests the mutational status of KRAS protein and the structural features of these two compounds orchestrally determined the magnitude of cell growth inhibition in PDAC cell lines.The higher potency of SRJ23 implies it could be developed into an anticancer agent for the treatment of mutant KRAS-driven malignancies.To this end,efforts are in progress to derive new molecules from this compound for further improvement of potency.展开更多
The term fibromatosis describes fibrotic tumor-like lesions of the skin which are seen in all age groups. They may be congenital or acquired and occur as single or multiple lesions. Classification of fibromatosis incl...The term fibromatosis describes fibrotic tumor-like lesions of the skin which are seen in all age groups. They may be congenital or acquired and occur as single or multiple lesions. Classification of fibromatosis includes several clinical and pathologic variants. Progressive nodular fibrosis of the skin is a rare condition which has been scarcely reported in the literature and never in pediatric age. The clinical presentation is not specific showing asymptomatic, reddish-brown nodules. Histology shows abundance of spindle-shaped dermal fibroblasts. Here we describe an unusual pediatric case and discuss the diagnosis, which is possible only with histopathology, and the importance of differential diagnosis.展开更多
Introduction: Kaposi sarcoma disease is a proliferative and multifocal disorder with dual components, vascular and fibroblastic cellular, cutaneous and visceral expression. Kaposi Sarcoma can affect the ocular surface...Introduction: Kaposi sarcoma disease is a proliferative and multifocal disorder with dual components, vascular and fibroblastic cellular, cutaneous and visceral expression. Kaposi Sarcoma can affect the ocular surface and adnexa and can masquerade as other entities, delaying prompt diagnosis can lead to diagnostic wandering delaying treatment. Our aim is to describe a case of KS of the eyelid in an HIV seronegative patient. Case Presentation: A seventy-year-old man developed a bilateral growing tumoral reddish purple vascular mass on both the lower and upper eyelid involving rapidly for 6 months. Both feet and the two shanks show the presence of a brown-violet tumor-shaped formation. The patient was negative for HIV. Histology examination showed a nodular tumor-like mass with a fibro hemangioma-epitheliomatous. Polymerase chain reaction was positive for human herpes virus 8. Initial chemotherapy followed by surgery was proposed to the patient. Unfortunately, the patient rejected treatment and was lost to follow-up. Conclusion: This case reports the difficulty of managing KS in developing countries.展开更多
Low-grade intestinal inflammation plays a key role in the pathophysiology of irritable bowel syndrome(IBS), and this role is likely to be multifactorial. The aim of this review was to summarize the evidence on the spe...Low-grade intestinal inflammation plays a key role in the pathophysiology of irritable bowel syndrome(IBS), and this role is likely to be multifactorial. The aim of this review was to summarize the evidence on the spectrum of mucosal inflammation in IBS, highlighting the relationship of this inflammation to the pathophysiology of IBS and its connection to clinical practice. We carried out a bibliographic search in Medline and the Cochrane Library for the period of January 1966 to December 2014, focusing on publications describing an interaction between inflammation and IBS. Several evidences demonstrate microscopic and molecular abnormalities in IBS patients. Understanding the mechanisms underlying low-grade inflammation in IBS may help to design clinical trials to test the efficacy and safety of drugs that target this pathophysiologic mechanism.展开更多
AIM： TO establish the prevalence of He/icobacterpy/on （H. pylori） infection in patients with a bleeding peptic ulcer after consumption of non-steroidal antiinflammatory drugs （NSAIDs）.METHODS： A very early upper...AIM： TO establish the prevalence of He/icobacterpy/on （H. pylori） infection in patients with a bleeding peptic ulcer after consumption of non-steroidal antiinflammatory drugs （NSAIDs）.METHODS： A very early upper endoscopy was performed to find the source of upper gastrointestinal bleeding and to take biopsy specimens for analysis of H. pylori infection by the rapid urease （CLO） test, his- tological examination, and bacterial culture. TgG anti- CagA were also sought. The gold standard for identifying H. pylori infection was positive culture of biopsy specimens or contemporary positivity of the CLO test and the presence of H. pylori on tissue sections.RESULTS： Eighty patients, 61 males （76.3%）, mean age 61.2 ~ 15.9 years, were consecutively enrolled. Forty-seven （58.8%） patients occasionally consumed NSAIDs, while 33 （41.3%） were on chronic treatment with low-dose aspirin （LD ASA）. Forty-four （55.0%） patients were considered infected by H. pylori. The infection rate was not different between patients who occasionally or chronically consumed NSAIDs. The culture of biopsy specimens had a sensitivity of 86.4% and a specificity of 100%; corresponding figures for histological analysis were 65.9% and 77.8%, for the CLO test were 68.2% and 75%, for the combined use of histology and the CLO test were 56.8% and 100%, and for IgG anti-CagA were 90% and 98%. The high- est accuracy （92.5%） was obtained with the culture of biopsy specimens.CONCLUSION： Patients with a bleeding peptic ulcer after NSAID/LD ASA consumption frequently have H. pylori infection. Biopsy specimen culture after an early upper gastrointestinal tract endoscopy seems the most efficient test to detect this infection.展开更多
To study dermatological manifestation of T-lymphoblastic lymphoma and to help clinicians in the diagnosis, we report here the case of a 75-year-old patient who presented with violaceous nodules acquired during the las...To study dermatological manifestation of T-lymphoblastic lymphoma and to help clinicians in the diagnosis, we report here the case of a 75-year-old patient who presented with violaceous nodules acquired during the last 4 wk and affecting the scalp and right arm. The diagnosis of systemic lymphoma was suggested upon the appearance of cutaneous tumors, palpable lymph nodes and general symptoms including asthenia and weight-loss. The pathology features: positive immunostaining for CD3 and terminal deoxynucleotidyl transferase(Td T) and staging, led us to the final diagnosis of T-lymphoblastic lymphoma(T-LBL) with cutaneous involvement. He received a CHOP regimen as first-line treatment. Unfortunately, the patient relapsed and died 8 mo after the treatment initiation. T-LBL may be diagnosed by skin lesions. Additional immunostaining including Td T and experienced histopathologists are needed to correctly classify this aggressive disease and discuss the correct management including bone-marrow transplantation where appropriate.展开更多
AIM: To evaluate the prevalence of John Cunningham virus(JC virus) in a small cohort of patients with colon cancer and to assess its presence in hepatic metastasis.METHODS: Nineteen consecutive patients with histologi...AIM: To evaluate the prevalence of John Cunningham virus(JC virus) in a small cohort of patients with colon cancer and to assess its presence in hepatic metastasis.METHODS: Nineteen consecutive patients with histologically diagnosed colon cancer were included in our study, together with ten subjects affected by histologically and serologically diagnosed hepatitis C virus infection. In the patients included in the colon cancer group, JC virus was searched for in the surgical specimen; in the control group, JC virus was searched for in the hepatic biopsy. The difference in the prevalence of JC virus in the hepatic biopsy between the two groups was assessed through the χ2 test.RESULTS: Four out of 19 patients with colon cancer had a positive polymerase chain reaction(PCR) test for JC virus, and four had liver metastasis. Among the patients with liver metastasis, three out of four had a positive PCR test for JC virus in the surgical specimen and in the liver biopsy; the only patient with liver metastasis with a negative test for JC virus also presented a negative test for JC virus in the surgical specimen. In the control group of patients with hepatitis C infection, none of the ten patients presented JC virus infection in the hepatic biopsy. The difference between the two groups regarding JC virus infection was statistically significant(χ2 = 9.55, P = 0.002).CONCLUSION: JC virus may play a broader role than previously thought, and may be mechanistically involved in the late stages of these tumors.展开更多
The coronavirus disease 2019(COVID-19)pandemic has caused detrimental effects on many aspects of healthcare practice.Screening programs for the commonest malignancies,namely colorectal cancer(CRC),breast cancer and ce...The coronavirus disease 2019(COVID-19)pandemic has caused detrimental effects on many aspects of healthcare practice.Screening programs for the commonest malignancies,namely colorectal cancer(CRC),breast cancer and cervical cancer have been discontinued or interrupted since the beginning of restriction measures aimed to limit transmission of the new coronavirus infection.Robust evidence exists in favour of the role of screening campaigns in reducing mortality from CRC.In fact,the majority of pre-malignant lesions of the colon and rectum can be diagnosed with colonoscopy and treated by endoscopic or surgical resection.Besides,colonoscopy screening allows the diagnosis of CRCs in their pre-clinical stage.Italy was one of the first European countries where a high level of COVID-19 infections and deaths was observed,and one of the first where lockdowns and strict measures were adopted to reduce the risk of COVID-19 diffusion among the population.A systematic review of the literature was performed,including the PubMed,Scopus,Web of Sciences,and Reference Citation Analysis databases,with the aim of critically evaluating the impact of the COVID-19 pandemic on CRC screening in Italy.We found that reduction of CRC screening activity surpassed 50%in most endoscopic units,with almost 600000 fewer CRC screening exams conducted in the first 5 mo of 2020 vs the same period of 2019.While the consequences of the discontinuation of endoscopy screening for the prognosis and mortality of CRC will be evident in the next few years,recent data confirm that CRC is currently treated at a more advanced stage than in the pre-COVID-19 era.Since delays in CRC prevention and early diagnosis may translate to increased CRC-specific mortality,world healthcare systems should adopt strategies to maintain the regularity of CRC screening during subsequent peaks of the COVID-19 pandemic,or future events that might hamper screening programs.展开更多
Technological advances have greatly improved our knowledge of myelopoiesis,for example,with the discovery of granulocyte‒monocyte‒dendritic cell(DC)progenitors(GMDPs),monocyte‒DC progenitors(MDPs),common DC progenitor...Technological advances have greatly improved our knowledge of myelopoiesis,for example,with the discovery of granulocyte‒monocyte‒dendritic cell(DC)progenitors(GMDPs),monocyte‒DC progenitors(MDPs),common DC progenitors(CDPs)and common monocyte progenitors(cMoPs)on the basis of flow cytometry approaches.Concomitantly,some progress has been made in characterizing the very early phases of human neutropoiesis with the description of novel CD66b^(+)progenitors,including eNePs,PMs w/o eNePs,ProNeus,and PreNeus.More recently,we identified four SSC^(lo)Lin^(-)CD66b^(-)CD45^(dim)CD34^(+)/CD34^(dim/-)CD64^(dim)CD115^(-)cells as the earliest precursors specifically committed to the neutrophil lineage present in human bone marrow(BM),which we called neutrophil-committed progenitors(NCPs,from NCP1s to NCP4s).In this study,we report the isolation and characterization of two new SSC^(hi)CD66b^(-)CD64^(dim)CD115^(-)NCPs that,by phenotypic,transcriptomic,maturation and immunohistochemistry properties,as well as by flow cytometric side-scattered light(SSC),stand after NCP4s but precede promyelocytes during the neutropoiesis cascade.Similar to SSC^(lo)CD45RA^(+)NCP2s/NCP3s and SSC^(lo)CD45RA^(-)NCP1s/NCP4s,these cells exhibit phenotypic differences in CD45RA expression levels and,therefore,were named SSC^(hi)CD45RA^(+)NCP5s and SSC^(hi)CD45RA^(-)NCP6s.Moreover,NCP5s were more immature than NCP6s,as determined by cell differentiation and proliferative potential,as well as by transcriptomic and phenotypical features.Finally,by examining whether NCPs and all other CD66b^(+)neutrophil precursors are altered in representative hematological malignancies,we found that,in patients with chronic-phase chronic myeloid leukemia(CP-CML),but not with systemic mastocytosis(SM),there is an increased frequency of BM NCP4s,NCP6s,and all downstream CD45RA-negative neutrophil progenitors,suggesting their expansion in CML pathogenesis.Taken together,our data advance our knowledge of human neutropoiesis.展开更多
Background The debate over the overall benefits of self-monitoring of blood glucose in type 2 diabetes patients is still continuing.We aimed to assess the difference in glycaemic control and coronary heart disease （...Background The debate over the overall benefits of self-monitoring of blood glucose in type 2 diabetes patients is still continuing.We aimed to assess the difference in glycaemic control and coronary heart disease （CHD） risk levels of experimental type 2 diabetes patients provided with facilities for self-monitoring blood glucose and their counterparts without such facilities.Methods Sixty-one patients who had no prior experience in using glucometers were studied as intervention （n=30） and control （n=31） groups.The intervention group was trained in self-monitoring of blood glucose and documentation.Baseline blood glucose and fasting blood glucose were measured and the intervention patients were provided with glucometers and advised to self-monitor their fasting and postprandial blood glucose over six months.The 10-year CHD risk levels were determined with the United Kingdom Prospective Diabetes Study-derived risk engine calculator.Results The age and diabetes duration were similar in the two groups （P 〉0.05）.The majority of the patients were unemployed or retired females with only a primary level education.After 3 months,the haemogolbin A1c （HbA1c） levels of the control patients remained unchanged （（7.8±0.3）% vs.（7.9±0.4）%,P 〉0.05） whereas the HbA1c levels of the intervention patients were significantly reduced from the baseline at three （（9.6±0.3）% vs.（7.8±0.3）%,P 〈0.001） and six （（9.2±0.4）% vs.（7.5±0.3）%,P 〈0.001） months.Interestingly,while the 10-year CHD risk level of the control group remained unchanged after three months,that of the intervention group was remarkably reduced at three and six months from the baseline level （（7.4±1.3）% vs.（4.5±0.9）%,P=0.056）.Conclusion Self-monitoring of blood glucose in type 2 diabetes patients significantly improved glycaemic control and the CHD risk profile,suggesting that type 2 diabetes patients will potentially benefit from inclusion of glucose meters and testing strips in their health-care package.展开更多
文摘To the Editor:Thymoma-associated multiorgan autoimmunity(TAMA)is a rare paraneoplastic syndrome described in patients with thymoma and characterized by multiorgan failure and graft-versus-host dis-ease(GVHD)like pathology affecting the skin,the gastrointestinal tract,and the liver.To date,only 21 cases are reported in liter-ature[1],with some patients presenting gastrointestinal and hep-atic manifestations,mainly colitis,diarrhea,and abnormal liver en-zymes,but the hepatic involvement has not been histologically characterized yet.
文摘Checkpoint inhibitors,particularly programmed cell death-1/programmed death-ligand 1(PD-1/PDL1)inhibitors,have significantly advanced the treatment of Hodgkin lymphoma(HL),especially in relapsed or refractory cases.However,challenges such as resistance,immune-related adverse events(irAEs),and the need for effective patient selection remain.This review aims to explore the mechanisms of resistance to checkpoint inhibitors,including alterations in the tumor microenvironment,loss of antigen presentation,and T-cell exhaustion.Overcoming resistance may involve combination therapies,such as pairing PD-1 inhibitors with other immune checkpoint inhibitors or targeted therapies like Brentuximab vedotin.Additionally,next-generation inhibitors targeting molecules like lymphocyte-activation gene 3(LAG-3)and T-cell immunoglobulin and mucin-domain containing-3(TIM-3)show promise in addressing resistance mechanisms not overcome by PD-1 inhibitors.Identifying reliable biomarkers to predict response to checkpoint inhibitors is critical for optimizing treatment,with ongoing research focusing on tumor mutational burden(TMB),inflammatory markers,and genetic profiling.Future clinical trials will aim to refine treatment regimens,optimize therapeutic combinations,and minimize adverse effects to maximize patient benefit.
文摘AIM: To assess the diagnostic concordance between endoscopic and histological atrophy in the United Kingdom and Japan.METHODS: Using published data,a total of 252 patients,126 in the United Kingdom and 126 in Japan,aged 20 to 80 years,were evaluated. The extent of endoscopic atrophy was classified into five subgroups according to a modified Kimura-Takemoto classification system and was compared with histological findings of atrophy at five biopsy sites according to the updated Sydney system.RESULTS: The strength of agreement of the extent of atrophy between histology and visual endoscopic inspection showed good reproducibili ty,wi th a weighted kappa value of 0.76(P < 0.001). Multivariate analysis showed that three factors were associated with decreased concordance: Japanese ethnicity [odds ratio(OR) 0.22,95% confidence interval(CI) 0.11-0.43],older age(OR = 0.32,95%CI: 0.16-0.66) and endoscopic atrophy(OR = 0.10,95%CI: 0.03-0.36). The strength of agreement between endoscopic and histological atrophy,assessed by cancer risk-oriented grading,was reproducible,with a kappa value of 0.81(95%CI: 0.75-0.87). Only nine patients(3.6%) were endoscopically underdiagnosed with antral predominant rather than extensive atrophy and were considered false negatives.CONCLUSION: Endoscopic grading can predict histological atrophy with few false negatives,indicating that precancerous conditions can be identified during screening endoscopy,particularly in patients in western countries.
文摘The treatment for hepatocellular carcinoma(HCC)relies on liver resection,which is,however,burdened by a high rate of recurrence after surgery,up to 60%at 5 years.No pre-operative tools are currently available to assess the recurrence risk tailored to every single patient.Recently liquid biopsy has shown interesting results in diagnosis,prognosis and treatment allocation strategies in other types of cancers,since its ability to identify circulating tumor cells(CTCs)derived from the primary tumor.Those cells were advocated to be responsible for the majority of cases of recurrence and cancer-related deaths for HCC.In fact,after being modified by the epithelial-mesenchymal transition,CTCs circulate as“seeds”in peripheral blood,then reach the target organ as dormant cells which could be subsequently“awakened”and activated,and then initiate metastasis.Their presence may justify the disagreement registered in terms of efficacy of anatomic vs non-anatomic resections,particularly in the case of microvascular invasion,which has been recently pointed as a histological sign of the spread of those cells.Thus,their presence,also in the early stages,may justify the recurrence event also in the contest of liver transplant.Understanding the mechanism behind the tumor progression may allow improving the treatment selection according to the biological patient-based characteristics.Moreover,it may drive the development of novel biological tailored tests which could address a specific patient to neoadjuvant or adjuvant strategies,and in perspective,it could also become a new method to allocate organs for transplantation,according to the risk of relapse after liver transplant.The present paper will describe the most recent evidence on the role of CTCs in determining the relapse of HCC,highlighting their potential clinical implication as novel tumor behavior biomarkers able to influence the surgical choice.
文摘The aim of this work is to emphasize the importance of a differential diagnosis of von Brunn’s nests in cats from other urothelial neoplastic disorders, as transitional cell carcinoma, for a subsequent optimal care. Von Brunn’s nests and cysts are submucosal benign urothelial processes, related to irritative stimuli (calculi and urinary infections), characterized by an invagination with buds and clusters of normal urothelium in the lamina propria. They are common findings in the urinary bladder of human beings, but few cases have been described in dogs and cats. We report macroscopic, histopathological and, in one case, immunohistochemical features of these rare forms in the left ureters of two cats. Macroscopic evidence during surgery of ureteral nodules in two cats was accompanied by histopathological diagnosis and, in one case, by immunohistochemical assessment. Histopathology was coherent with a rare condition characterized by nests and islands of normal urothelium in the lamina propria and submucosa, with formation of cysts and moderate focal subacute inflammation. In one case epithelial cells of the nests showed well differentiated urothelial cells with an intense immunoreactivity to pan-cytokeratin (CK AE1/AE3), CK19 in the first outer layers, a slight immunoreactivity to CK20 and a low proliferative activity using MIB-1 (Ki67).
基金The project supported by Ministry of Education,Malaysia(Research University Grant Scheme Grant 04-02-12-2017RUFundamental Research Grant Scheme Grant 04-02-13-1324FR)
文摘OBJECTIVE To evaluate the anticancer activity of andrographolide(AGP)and its semisynthetic analogues(SRJ09and SRJ23)in pancreatic adenocarcinoma(PDAC)cell lines harbouring therapeutically highly relevant oncogenic K-ras glycine-12(KRAS-G12)mutant proteins.In a landmark publication,we revealed that AGP and its derivatives bind KRAS protein to inhibit RAS signaling PNAS,110:10201-06).This discovery prompted the initiation of this investigation.METHODS The cell growth inhibitory effect of the compounds on PDAC cell lines〔PANC-1(KRAS-G12D),Capan-2(KRAS-G12V),and MIA PaCa-2(KRASG12C)〕,was assessed by MTT assay.RESULTS In comparison with AGP and SRJ09,SRJ23 showed the greatest growth inhibition in all PDAC cell lines with mutant KRAS proteins.The inhibitory effect of SRJ23 on the cell growth was similar for all PDAC cell lines.AGP exerted selective growth inhibition against PANC-1(KRAS-G12D)cells,while the growth inhibition of SRJ09 was selective towards Capan-2(KRAS-G12V)cells.CONCLUSION AGP and SRJ09 showed selectivity for PDAC cell lines with specific KRAS mutations.This suggests the mutational status of KRAS protein and the structural features of these two compounds orchestrally determined the magnitude of cell growth inhibition in PDAC cell lines.The higher potency of SRJ23 implies it could be developed into an anticancer agent for the treatment of mutant KRAS-driven malignancies.To this end,efforts are in progress to derive new molecules from this compound for further improvement of potency.
文摘The term fibromatosis describes fibrotic tumor-like lesions of the skin which are seen in all age groups. They may be congenital or acquired and occur as single or multiple lesions. Classification of fibromatosis includes several clinical and pathologic variants. Progressive nodular fibrosis of the skin is a rare condition which has been scarcely reported in the literature and never in pediatric age. The clinical presentation is not specific showing asymptomatic, reddish-brown nodules. Histology shows abundance of spindle-shaped dermal fibroblasts. Here we describe an unusual pediatric case and discuss the diagnosis, which is possible only with histopathology, and the importance of differential diagnosis.
文摘Introduction: Kaposi sarcoma disease is a proliferative and multifocal disorder with dual components, vascular and fibroblastic cellular, cutaneous and visceral expression. Kaposi Sarcoma can affect the ocular surface and adnexa and can masquerade as other entities, delaying prompt diagnosis can lead to diagnostic wandering delaying treatment. Our aim is to describe a case of KS of the eyelid in an HIV seronegative patient. Case Presentation: A seventy-year-old man developed a bilateral growing tumoral reddish purple vascular mass on both the lower and upper eyelid involving rapidly for 6 months. Both feet and the two shanks show the presence of a brown-violet tumor-shaped formation. The patient was negative for HIV. Histology examination showed a nodular tumor-like mass with a fibro hemangioma-epitheliomatous. Polymerase chain reaction was positive for human herpes virus 8. Initial chemotherapy followed by surgery was proposed to the patient. Unfortunately, the patient rejected treatment and was lost to follow-up. Conclusion: This case reports the difficulty of managing KS in developing countries.
文摘Low-grade intestinal inflammation plays a key role in the pathophysiology of irritable bowel syndrome(IBS), and this role is likely to be multifactorial. The aim of this review was to summarize the evidence on the spectrum of mucosal inflammation in IBS, highlighting the relationship of this inflammation to the pathophysiology of IBS and its connection to clinical practice. We carried out a bibliographic search in Medline and the Cochrane Library for the period of January 1966 to December 2014, focusing on publications describing an interaction between inflammation and IBS. Several evidences demonstrate microscopic and molecular abnormalities in IBS patients. Understanding the mechanisms underlying low-grade inflammation in IBS may help to design clinical trials to test the efficacy and safety of drugs that target this pathophysiologic mechanism.
文摘AIM： TO establish the prevalence of He/icobacterpy/on （H. pylori） infection in patients with a bleeding peptic ulcer after consumption of non-steroidal antiinflammatory drugs （NSAIDs）.METHODS： A very early upper endoscopy was performed to find the source of upper gastrointestinal bleeding and to take biopsy specimens for analysis of H. pylori infection by the rapid urease （CLO） test, his- tological examination, and bacterial culture. TgG anti- CagA were also sought. The gold standard for identifying H. pylori infection was positive culture of biopsy specimens or contemporary positivity of the CLO test and the presence of H. pylori on tissue sections.RESULTS： Eighty patients, 61 males （76.3%）, mean age 61.2 ~ 15.9 years, were consecutively enrolled. Forty-seven （58.8%） patients occasionally consumed NSAIDs, while 33 （41.3%） were on chronic treatment with low-dose aspirin （LD ASA）. Forty-four （55.0%） patients were considered infected by H. pylori. The infection rate was not different between patients who occasionally or chronically consumed NSAIDs. The culture of biopsy specimens had a sensitivity of 86.4% and a specificity of 100%; corresponding figures for histological analysis were 65.9% and 77.8%, for the CLO test were 68.2% and 75%, for the combined use of histology and the CLO test were 56.8% and 100%, and for IgG anti-CagA were 90% and 98%. The high- est accuracy （92.5%） was obtained with the culture of biopsy specimens.CONCLUSION： Patients with a bleeding peptic ulcer after NSAID/LD ASA consumption frequently have H. pylori infection. Biopsy specimen culture after an early upper gastrointestinal tract endoscopy seems the most efficient test to detect this infection.
基金The grants from Lyon 1 University(to Thomas L),the Hospices Civils de Lyon
文摘To study dermatological manifestation of T-lymphoblastic lymphoma and to help clinicians in the diagnosis, we report here the case of a 75-year-old patient who presented with violaceous nodules acquired during the last 4 wk and affecting the scalp and right arm. The diagnosis of systemic lymphoma was suggested upon the appearance of cutaneous tumors, palpable lymph nodes and general symptoms including asthenia and weight-loss. The pathology features: positive immunostaining for CD3 and terminal deoxynucleotidyl transferase(Td T) and staging, led us to the final diagnosis of T-lymphoblastic lymphoma(T-LBL) with cutaneous involvement. He received a CHOP regimen as first-line treatment. Unfortunately, the patient relapsed and died 8 mo after the treatment initiation. T-LBL may be diagnosed by skin lesions. Additional immunostaining including Td T and experienced histopathologists are needed to correctly classify this aggressive disease and discuss the correct management including bone-marrow transplantation where appropriate.
文摘AIM: To evaluate the prevalence of John Cunningham virus(JC virus) in a small cohort of patients with colon cancer and to assess its presence in hepatic metastasis.METHODS: Nineteen consecutive patients with histologically diagnosed colon cancer were included in our study, together with ten subjects affected by histologically and serologically diagnosed hepatitis C virus infection. In the patients included in the colon cancer group, JC virus was searched for in the surgical specimen; in the control group, JC virus was searched for in the hepatic biopsy. The difference in the prevalence of JC virus in the hepatic biopsy between the two groups was assessed through the χ2 test.RESULTS: Four out of 19 patients with colon cancer had a positive polymerase chain reaction(PCR) test for JC virus, and four had liver metastasis. Among the patients with liver metastasis, three out of four had a positive PCR test for JC virus in the surgical specimen and in the liver biopsy; the only patient with liver metastasis with a negative test for JC virus also presented a negative test for JC virus in the surgical specimen. In the control group of patients with hepatitis C infection, none of the ten patients presented JC virus infection in the hepatic biopsy. The difference between the two groups regarding JC virus infection was statistically significant(χ2 = 9.55, P = 0.002).CONCLUSION: JC virus may play a broader role than previously thought, and may be mechanistically involved in the late stages of these tumors.
文摘The coronavirus disease 2019(COVID-19)pandemic has caused detrimental effects on many aspects of healthcare practice.Screening programs for the commonest malignancies,namely colorectal cancer(CRC),breast cancer and cervical cancer have been discontinued or interrupted since the beginning of restriction measures aimed to limit transmission of the new coronavirus infection.Robust evidence exists in favour of the role of screening campaigns in reducing mortality from CRC.In fact,the majority of pre-malignant lesions of the colon and rectum can be diagnosed with colonoscopy and treated by endoscopic or surgical resection.Besides,colonoscopy screening allows the diagnosis of CRCs in their pre-clinical stage.Italy was one of the first European countries where a high level of COVID-19 infections and deaths was observed,and one of the first where lockdowns and strict measures were adopted to reduce the risk of COVID-19 diffusion among the population.A systematic review of the literature was performed,including the PubMed,Scopus,Web of Sciences,and Reference Citation Analysis databases,with the aim of critically evaluating the impact of the COVID-19 pandemic on CRC screening in Italy.We found that reduction of CRC screening activity surpassed 50%in most endoscopic units,with almost 600000 fewer CRC screening exams conducted in the first 5 mo of 2020 vs the same period of 2019.While the consequences of the discontinuation of endoscopy screening for the prognosis and mortality of CRC will be evident in the next few years,recent data confirm that CRC is currently treated at a more advanced stage than in the pre-COVID-19 era.Since delays in CRC prevention and early diagnosis may translate to increased CRC-specific mortality,world healthcare systems should adopt strategies to maintain the regularity of CRC screening during subsequent peaks of the COVID-19 pandemic,or future events that might hamper screening programs.
基金funding from Associazione Italiana per la Ricerca sul Cancro(AIRC,IG-27613 to MAC,IG-29348 and 5x1000 no.22757 to AS)Ministero dellistruzione,dellUniversita e della Ricerca(PRIN 20227YR8AW and PRIN2022W839FM to MAC and NT,respectively)+1 种基金University of Verona(RIBA2022 to PS)supported by the European Cooperation in Science and Technology(COST)Action CA20117 Mye-InfoBank(www.mye-infobank.eu).
文摘Technological advances have greatly improved our knowledge of myelopoiesis,for example,with the discovery of granulocyte‒monocyte‒dendritic cell(DC)progenitors(GMDPs),monocyte‒DC progenitors(MDPs),common DC progenitors(CDPs)and common monocyte progenitors(cMoPs)on the basis of flow cytometry approaches.Concomitantly,some progress has been made in characterizing the very early phases of human neutropoiesis with the description of novel CD66b^(+)progenitors,including eNePs,PMs w/o eNePs,ProNeus,and PreNeus.More recently,we identified four SSC^(lo)Lin^(-)CD66b^(-)CD45^(dim)CD34^(+)/CD34^(dim/-)CD64^(dim)CD115^(-)cells as the earliest precursors specifically committed to the neutrophil lineage present in human bone marrow(BM),which we called neutrophil-committed progenitors(NCPs,from NCP1s to NCP4s).In this study,we report the isolation and characterization of two new SSC^(hi)CD66b^(-)CD64^(dim)CD115^(-)NCPs that,by phenotypic,transcriptomic,maturation and immunohistochemistry properties,as well as by flow cytometric side-scattered light(SSC),stand after NCP4s but precede promyelocytes during the neutropoiesis cascade.Similar to SSC^(lo)CD45RA^(+)NCP2s/NCP3s and SSC^(lo)CD45RA^(-)NCP1s/NCP4s,these cells exhibit phenotypic differences in CD45RA expression levels and,therefore,were named SSC^(hi)CD45RA^(+)NCP5s and SSC^(hi)CD45RA^(-)NCP6s.Moreover,NCP5s were more immature than NCP6s,as determined by cell differentiation and proliferative potential,as well as by transcriptomic and phenotypical features.Finally,by examining whether NCPs and all other CD66b^(+)neutrophil precursors are altered in representative hematological malignancies,we found that,in patients with chronic-phase chronic myeloid leukemia(CP-CML),but not with systemic mastocytosis(SM),there is an increased frequency of BM NCP4s,NCP6s,and all downstream CD45RA-negative neutrophil progenitors,suggesting their expansion in CML pathogenesis.Taken together,our data advance our knowledge of human neutropoiesis.
文摘Background The debate over the overall benefits of self-monitoring of blood glucose in type 2 diabetes patients is still continuing.We aimed to assess the difference in glycaemic control and coronary heart disease （CHD） risk levels of experimental type 2 diabetes patients provided with facilities for self-monitoring blood glucose and their counterparts without such facilities.Methods Sixty-one patients who had no prior experience in using glucometers were studied as intervention （n=30） and control （n=31） groups.The intervention group was trained in self-monitoring of blood glucose and documentation.Baseline blood glucose and fasting blood glucose were measured and the intervention patients were provided with glucometers and advised to self-monitor their fasting and postprandial blood glucose over six months.The 10-year CHD risk levels were determined with the United Kingdom Prospective Diabetes Study-derived risk engine calculator.Results The age and diabetes duration were similar in the two groups （P 〉0.05）.The majority of the patients were unemployed or retired females with only a primary level education.After 3 months,the haemogolbin A1c （HbA1c） levels of the control patients remained unchanged （（7.8±0.3）% vs.（7.9±0.4）%,P 〉0.05） whereas the HbA1c levels of the intervention patients were significantly reduced from the baseline at three （（9.6±0.3）% vs.（7.8±0.3）%,P 〈0.001） and six （（9.2±0.4）% vs.（7.5±0.3）%,P 〈0.001） months.Interestingly,while the 10-year CHD risk level of the control group remained unchanged after three months,that of the intervention group was remarkably reduced at three and six months from the baseline level （（7.4±1.3）% vs.（4.5±0.9）%,P=0.056）.Conclusion Self-monitoring of blood glucose in type 2 diabetes patients significantly improved glycaemic control and the CHD risk profile,suggesting that type 2 diabetes patients will potentially benefit from inclusion of glucose meters and testing strips in their health-care package.
