Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. To date, most patients with HCC are diagnosed at an advanced tumor stage, excluding them from potentially curative therapies (i.e., re...Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. To date, most patients with HCC are diagnosed at an advanced tumor stage, excluding them from potentially curative therapies (i.e., resection, liver transplantation, percutaneous ablation). Treatments with palliative intent include chemoembolization and systemic therapy. Among systemic treatments, the small-molecule multikinase inhibitor sorafenib has been the only systemic treatment available for advanced HCC over 10 years. More recently, other smallmolecule multikinase inhibitors (e.g., regorafenib, lenvatinib, cabozantinib) have been approved for HCC treatment. The promising immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab) are still under investigation in Europe while in the US nivolumab has already been approved by FDA in sorafenib refractory or resistant patients. Other molecules, such as the selective CDK4/6inhibitors (e.g., palbociclib, ribociclib), are in earlier stages of clinical development, and the c- MET inhibitor tivantinib did not show positive results in a phase III study. However, even if the introduction of targeted agents has led to great advances in patient response and survival with an acceptable toxicity profile, a remarkable inter-individual heterogeneity in therapy outcome persists and constitutes a significant problem in disease management. Thus, the identification of biomarkers that predict which patients will benefit from a specific intervention could significantly affect decision-making and therapy planning. Germ-line variants have been suggested to play an important role in determining outcomes of HCC systemic therapy in terms of both toxicity and treatment efficacy. Particularly, a number of studies have focused on the role of genetic polymorphisms impacting the drug metabolic pathway and membrane translocation as well as the drug mechanism of action as predictive/prognostic markers of HCC treatment. The aim of this review is to summarize and critically discuss the pharmacogenetic literature evidences, with particular attention to sorafenib and regorafenib, which have been used longer than the others in HCC treatment.展开更多
The human intestine is a natural environment ecosystem of a complex of diversified and dynamic microorganisms,determined through a process of competition and natural selection during life.Those intestinal microorganis...The human intestine is a natural environment ecosystem of a complex of diversified and dynamic microorganisms,determined through a process of competition and natural selection during life.Those intestinal microorganisms called microbiota and are involved in a variety of mechanisms of the organism,they interact with the host and therefore are in contact with the organs of the various systems.However,they play a crucial role in maintaining host homeostasis,also influencing its behaviour.Thus,microorganisms perform a series of biological functions important for human well-being.The host provides the microorganisms with the environment and nutrients,simultaneously drawing many benefits such as their contribution to metabolic,trophic,immunological,and other functions.For these reasons it has been reported that its quantitative and qualitative composition can play a protective or harmful role on the host health.Therefore,a dysbiosis can lead to an association of unfavourable factors which lead to a dysregulation of the physiological processes of homeostasis.Thus,it has previously noted that the gut microbiota can participate in the pathogenesis of autoimmune diseases,chronic intestinal inflammation,diabetes mellitus,obesity and atherosclerosis,neurological disorders(e.g.,neurological diseases,autism,etc.)colorectal cancer,and more.展开更多
Pancreatic cancer(PDAC)is an aggressive and chemoresistant disease,representing the fourth cause of cancer related deaths in western countries.Majority of patients have unresectable,locally advanced or metastatic dise...Pancreatic cancer(PDAC)is an aggressive and chemoresistant disease,representing the fourth cause of cancer related deaths in western countries.Majority of patients have unresectable,locally advanced or metastatic disease at time of diagnosis and the 5-year survival rate in these conditions is extremely low.For more than a decade gemcitabine has been the cornerstone of metastatic PDAC treatment,although survival benefit was very poor.PDAC cells are surrounded by an intense desmoplastic reaction that may create a barrier to the drugs penetration within the tumor.Recently PDAC stroma has been addressed as a potential therapeutic target.Nano albumin bound(Nab)-paclitaxel is an innovative molecule depleting tumor stroma,through interaction between albumin and secreted protein acidic and rich in cysteine.Addition of nab-paclitaxel to gemcitabine has showed activity and efficacy in metastatic PDAC first-line treatment improving survival and overall response rate vs gemcitabine alone in the MPACT phaseⅢstudy.This combination represents one of the standards of care in advanced PDAC therapy and is suitable to a broader spectrum of patients compared to other schedules.Nab-paclitaxel is under investigation as a backbone of chemotherapy in novel combinations with target agents or immunotherapy in locally advanced or metastatic PDAC.In this article,we provide an updated and critical overview about the role of nab-paclitaxel in PDAC treatment based on the latest advances in preclinical and clinical research.Furthermore,we focus on the use of nab-paclitaxel within the context of metastatic PDAC treatment landscape and we discuss about future implications in the light of current clinical ongoing trials.展开更多
AIM: To review a single institutional experience in clinical management of gastrointestinal stromal tumors (GIST) and analyze for factors determining treatment outcome. METHODS: Clinicopathological data of patients wi...AIM: To review a single institutional experience in clinical management of gastrointestinal stromal tumors (GIST) and analyze for factors determining treatment outcome. METHODS: Clinicopathological data of patients with a diagnosis of GIST who were treated at our institute during November 2004 to September 2009 were retrospectively reviewed. RESULTS: Ninety-nine cases were included in the analysis. Primary tumor sites were at the stomach in and small bowel in 44% and 33%, respectively. Thirty-one cases already had metastasis at presentation and the most common metastatic site was the liver. Sixty-four cases (65%) were in the high-risk category. Surgical treatment was performed in 77 cases (78%), 3 of whom received upfront targeted therapy. Complete resection was achieved in 56 cases (73% of operative cases) and of whom 27 developed local recurrence or distant metastasis at a median duration of 2 years. Imatinib was given as a primary therapy in unresectable cases (25 cases) and as an adjuvant in cases with residual tumor (21 cases). Targeted therapy gave partial response in 7 cases (15%), stable disease in 27 cases (57%) and progressive disease in 13 cases (28%). Four-year overall survival was 74% (95% CI: 61%-83%). Univariate survival analysis found that low-risk tumor, gastric site, complete resection and response to imatinib were associated with better survival. CONCLUSION: The overall outcomes of GIST can be predicted by risk-categorization. Surgery alone may not be a curative treatment for GIST. Response to targeted therapy is a crucial survival determinant in these patients.展开更多
We comment here on the article by Stefanolo et al entitled“Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet”,published in the World Journal of Gastroen...We comment here on the article by Stefanolo et al entitled“Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet”,published in the World Journal of Gastroenterology.Celiac disease is a well-recognized systemic autoimmune disorder.In genetically susceptible people,the most evident damage is located in the small intestine,and is caused and worsened by the ingestion of gluten.For that reason,celiac patients adopt a gluten-free diet(GFD),but it has some limitations,and it does not prevent re-exposure to gluten.Research aims to develop adjuvant therapies,and one of the most studied alternatives is supplementation with Aspergillus niger prolyl endopeptidase protease(AN-PEP),which is able to degrade gluten in the stomach,reducing its concentration in the small intestine.The study found a high adherence to the GFD,but did not address AN-PEP as a gluten immunogenic peptide reducer,as it was only tested in patients following a GFD and not in gluten-exposing conditions.This study opens up new research perspectives in this area and shows that further study is needed to clarify the points that are still in doubt.展开更多
Helicobacter pylori(H.pylori)infections may cause chronic gastritis,peptic ulcer disease,gastric cancers,and other conditions outside of the gastrointestinal tract.Hence,it is important to diagnose and treat it early....Helicobacter pylori(H.pylori)infections may cause chronic gastritis,peptic ulcer disease,gastric cancers,and other conditions outside of the gastrointestinal tract.Hence,it is important to diagnose and treat it early.H.pylori is resistant to certain drugs in traditional eradication therapy,so alternative therapy protocols are needed,such as high-dose amoxicillin dual therapy(HDADT).This article aims to comment on a recent paper by Costigan et al in the World Journal of Clinical Cases.In this study,the authors recruited 139 patients diagnosed with H.pylori,all treated with HDADT.Of these,93 were treatment-naïve and 46 had received at least one alternative treatment in the past.Four weeks after the end of the treatment,the urea breath test was administered to estimate the eradication rate.The total eradication rate was 56%(78/139),62%for the treatment-naïve arm and 43%for the previous treatment arm,thus indicating a lower success rate for the arm that had previously received a different treatment regimen.In conclusion,a therapeutic approach with first-line HDADT may potentially be a better treat-ment,but the results are not sufficient to recommend the use of this regimen in a country with high levels of dual resistance.展开更多
Extranodal NK/T-cell lymphoma, nasal type (ENKL), is an uncommon subtype of EBV associated lymphoma usually characterized by aggressive clinical course. We report an atypical sinonasal ENKL case with long-lasting indo...Extranodal NK/T-cell lymphoma, nasal type (ENKL), is an uncommon subtype of EBV associated lymphoma usually characterized by aggressive clinical course. We report an atypical sinonasal ENKL case with long-lasting indolent behaviour, developed in the setting of a polymorphic EBV-associated lymphoproliferative disorder (LPD). A 52-year-old woman had suffered from chronic sinusitis and nasal obstruction since 2000, moderately worsened during the last years (marked enlargement of the sino-nasal mucosa at MRI in 2011) with elevated anti-VCA IgG and IgM titers. Three subsequent biopsies revealed slightly increasing morphophenotypic atypia, ranging from a polymorphic B- and T-cell EBV positive proliferation (diagnosed in 2011, but not fulfilling CAEBV diagnostic criteria) to an overt monomorphic mildly atypical T LPD without necrosis and angiocentricty diagnosed as ENKL in 2013 upon immunophenotype and TCR-γ gene clonal rearrangement. Clinically indolent ENKL with low-grade morphology is extremely rare and diagnostically challenging;while the few reports in the literature describe long-survival in ENKL treated patients comparing histologically neoplastic lesions at onset and recurrences, no reports are published on the slow progression from a polymorphic EBV-related T/NK proliferation to a histologically overt clinically indolent ENKL in an untreated patient who only received occasional steroid administration.展开更多
Despite improvements achieved in terms of early detection and therapeutic approach,metastatic breast cancer remains one of the principal worldwide causes of death.In recent years,due to the heterogeneous response of e...Despite improvements achieved in terms of early detection and therapeutic approach,metastatic breast cancer remains one of the principal worldwide causes of death.In recent years,due to the heterogeneous response of each patient to chemotherapy,clinical research highlights the need of a personalized approach.Circulating tumor cells(CTCs)represents a promising tool for this purpose.Unfortunately,even if their correlation with sever-ity,outcome and metastatic nature of the tumor has been established,several issues,mainly concerning their characterization and isolation,need to be solved.In this review,latest knowledge on CTCs and metastatic pro-cess in breast cancer were analyzed,aiming to understand their clinical utility and validity for a prospective ther-apeutic scenario.展开更多
基金the European Union’s Horizon 2020 Research and Innovation Programme,No.668353
文摘Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. To date, most patients with HCC are diagnosed at an advanced tumor stage, excluding them from potentially curative therapies (i.e., resection, liver transplantation, percutaneous ablation). Treatments with palliative intent include chemoembolization and systemic therapy. Among systemic treatments, the small-molecule multikinase inhibitor sorafenib has been the only systemic treatment available for advanced HCC over 10 years. More recently, other smallmolecule multikinase inhibitors (e.g., regorafenib, lenvatinib, cabozantinib) have been approved for HCC treatment. The promising immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab) are still under investigation in Europe while in the US nivolumab has already been approved by FDA in sorafenib refractory or resistant patients. Other molecules, such as the selective CDK4/6inhibitors (e.g., palbociclib, ribociclib), are in earlier stages of clinical development, and the c- MET inhibitor tivantinib did not show positive results in a phase III study. However, even if the introduction of targeted agents has led to great advances in patient response and survival with an acceptable toxicity profile, a remarkable inter-individual heterogeneity in therapy outcome persists and constitutes a significant problem in disease management. Thus, the identification of biomarkers that predict which patients will benefit from a specific intervention could significantly affect decision-making and therapy planning. Germ-line variants have been suggested to play an important role in determining outcomes of HCC systemic therapy in terms of both toxicity and treatment efficacy. Particularly, a number of studies have focused on the role of genetic polymorphisms impacting the drug metabolic pathway and membrane translocation as well as the drug mechanism of action as predictive/prognostic markers of HCC treatment. The aim of this review is to summarize and critically discuss the pharmacogenetic literature evidences, with particular attention to sorafenib and regorafenib, which have been used longer than the others in HCC treatment.
文摘The human intestine is a natural environment ecosystem of a complex of diversified and dynamic microorganisms,determined through a process of competition and natural selection during life.Those intestinal microorganisms called microbiota and are involved in a variety of mechanisms of the organism,they interact with the host and therefore are in contact with the organs of the various systems.However,they play a crucial role in maintaining host homeostasis,also influencing its behaviour.Thus,microorganisms perform a series of biological functions important for human well-being.The host provides the microorganisms with the environment and nutrients,simultaneously drawing many benefits such as their contribution to metabolic,trophic,immunological,and other functions.For these reasons it has been reported that its quantitative and qualitative composition can play a protective or harmful role on the host health.Therefore,a dysbiosis can lead to an association of unfavourable factors which lead to a dysregulation of the physiological processes of homeostasis.Thus,it has previously noted that the gut microbiota can participate in the pathogenesis of autoimmune diseases,chronic intestinal inflammation,diabetes mellitus,obesity and atherosclerosis,neurological disorders(e.g.,neurological diseases,autism,etc.)colorectal cancer,and more.
文摘Pancreatic cancer(PDAC)is an aggressive and chemoresistant disease,representing the fourth cause of cancer related deaths in western countries.Majority of patients have unresectable,locally advanced or metastatic disease at time of diagnosis and the 5-year survival rate in these conditions is extremely low.For more than a decade gemcitabine has been the cornerstone of metastatic PDAC treatment,although survival benefit was very poor.PDAC cells are surrounded by an intense desmoplastic reaction that may create a barrier to the drugs penetration within the tumor.Recently PDAC stroma has been addressed as a potential therapeutic target.Nano albumin bound(Nab)-paclitaxel is an innovative molecule depleting tumor stroma,through interaction between albumin and secreted protein acidic and rich in cysteine.Addition of nab-paclitaxel to gemcitabine has showed activity and efficacy in metastatic PDAC first-line treatment improving survival and overall response rate vs gemcitabine alone in the MPACT phaseⅢstudy.This combination represents one of the standards of care in advanced PDAC therapy and is suitable to a broader spectrum of patients compared to other schedules.Nab-paclitaxel is under investigation as a backbone of chemotherapy in novel combinations with target agents or immunotherapy in locally advanced or metastatic PDAC.In this article,we provide an updated and critical overview about the role of nab-paclitaxel in PDAC treatment based on the latest advances in preclinical and clinical research.Furthermore,we focus on the use of nab-paclitaxel within the context of metastatic PDAC treatment landscape and we discuss about future implications in the light of current clinical ongoing trials.
文摘AIM: To review a single institutional experience in clinical management of gastrointestinal stromal tumors (GIST) and analyze for factors determining treatment outcome. METHODS: Clinicopathological data of patients with a diagnosis of GIST who were treated at our institute during November 2004 to September 2009 were retrospectively reviewed. RESULTS: Ninety-nine cases were included in the analysis. Primary tumor sites were at the stomach in and small bowel in 44% and 33%, respectively. Thirty-one cases already had metastasis at presentation and the most common metastatic site was the liver. Sixty-four cases (65%) were in the high-risk category. Surgical treatment was performed in 77 cases (78%), 3 of whom received upfront targeted therapy. Complete resection was achieved in 56 cases (73% of operative cases) and of whom 27 developed local recurrence or distant metastasis at a median duration of 2 years. Imatinib was given as a primary therapy in unresectable cases (25 cases) and as an adjuvant in cases with residual tumor (21 cases). Targeted therapy gave partial response in 7 cases (15%), stable disease in 27 cases (57%) and progressive disease in 13 cases (28%). Four-year overall survival was 74% (95% CI: 61%-83%). Univariate survival analysis found that low-risk tumor, gastric site, complete resection and response to imatinib were associated with better survival. CONCLUSION: The overall outcomes of GIST can be predicted by risk-categorization. Surgery alone may not be a curative treatment for GIST. Response to targeted therapy is a crucial survival determinant in these patients.
文摘We comment here on the article by Stefanolo et al entitled“Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet”,published in the World Journal of Gastroenterology.Celiac disease is a well-recognized systemic autoimmune disorder.In genetically susceptible people,the most evident damage is located in the small intestine,and is caused and worsened by the ingestion of gluten.For that reason,celiac patients adopt a gluten-free diet(GFD),but it has some limitations,and it does not prevent re-exposure to gluten.Research aims to develop adjuvant therapies,and one of the most studied alternatives is supplementation with Aspergillus niger prolyl endopeptidase protease(AN-PEP),which is able to degrade gluten in the stomach,reducing its concentration in the small intestine.The study found a high adherence to the GFD,but did not address AN-PEP as a gluten immunogenic peptide reducer,as it was only tested in patients following a GFD and not in gluten-exposing conditions.This study opens up new research perspectives in this area and shows that further study is needed to clarify the points that are still in doubt.
文摘Helicobacter pylori(H.pylori)infections may cause chronic gastritis,peptic ulcer disease,gastric cancers,and other conditions outside of the gastrointestinal tract.Hence,it is important to diagnose and treat it early.H.pylori is resistant to certain drugs in traditional eradication therapy,so alternative therapy protocols are needed,such as high-dose amoxicillin dual therapy(HDADT).This article aims to comment on a recent paper by Costigan et al in the World Journal of Clinical Cases.In this study,the authors recruited 139 patients diagnosed with H.pylori,all treated with HDADT.Of these,93 were treatment-naïve and 46 had received at least one alternative treatment in the past.Four weeks after the end of the treatment,the urea breath test was administered to estimate the eradication rate.The total eradication rate was 56%(78/139),62%for the treatment-naïve arm and 43%for the previous treatment arm,thus indicating a lower success rate for the arm that had previously received a different treatment regimen.In conclusion,a therapeutic approach with first-line HDADT may potentially be a better treat-ment,but the results are not sufficient to recommend the use of this regimen in a country with high levels of dual resistance.
文摘Extranodal NK/T-cell lymphoma, nasal type (ENKL), is an uncommon subtype of EBV associated lymphoma usually characterized by aggressive clinical course. We report an atypical sinonasal ENKL case with long-lasting indolent behaviour, developed in the setting of a polymorphic EBV-associated lymphoproliferative disorder (LPD). A 52-year-old woman had suffered from chronic sinusitis and nasal obstruction since 2000, moderately worsened during the last years (marked enlargement of the sino-nasal mucosa at MRI in 2011) with elevated anti-VCA IgG and IgM titers. Three subsequent biopsies revealed slightly increasing morphophenotypic atypia, ranging from a polymorphic B- and T-cell EBV positive proliferation (diagnosed in 2011, but not fulfilling CAEBV diagnostic criteria) to an overt monomorphic mildly atypical T LPD without necrosis and angiocentricty diagnosed as ENKL in 2013 upon immunophenotype and TCR-γ gene clonal rearrangement. Clinically indolent ENKL with low-grade morphology is extremely rare and diagnostically challenging;while the few reports in the literature describe long-survival in ENKL treated patients comparing histologically neoplastic lesions at onset and recurrences, no reports are published on the slow progression from a polymorphic EBV-related T/NK proliferation to a histologically overt clinically indolent ENKL in an untreated patient who only received occasional steroid administration.
文摘Despite improvements achieved in terms of early detection and therapeutic approach,metastatic breast cancer remains one of the principal worldwide causes of death.In recent years,due to the heterogeneous response of each patient to chemotherapy,clinical research highlights the need of a personalized approach.Circulating tumor cells(CTCs)represents a promising tool for this purpose.Unfortunately,even if their correlation with sever-ity,outcome and metastatic nature of the tumor has been established,several issues,mainly concerning their characterization and isolation,need to be solved.In this review,latest knowledge on CTCs and metastatic pro-cess in breast cancer were analyzed,aiming to understand their clinical utility and validity for a prospective ther-apeutic scenario.
