The management of esophageal cancer has been evolving over the past 30 years. In the United States, multimodality treatment combining chemotherapy and radiotherapy (RT) prior to surgical resection has come to be accep...The management of esophageal cancer has been evolving over the past 30 years. In the United States, multimodality treatment combining chemotherapy and radiotherapy (RT) prior to surgical resection has come to be accepted by many as the standard of care, although debate about its overall effect on survival still exists, and rightfully so. Despite recent improvements in detection and treatment, the overall survival of patients with esophageal cancer remains lower than most solid tumors, which highlights why further advances are so desperately needed. The aim of this article is to provide a complete review of the history of esophageal cancer treatment with the addition of chemotherapy, RT, and more recently, targeted agents to the surgical management of resectable disease.展开更多
The possibility of treating degenerative diseases by stem cell-based approaches is a promising therapeutical option.Among major concerns for the clinical application of stem cells,some derive from the possibility that...The possibility of treating degenerative diseases by stem cell-based approaches is a promising therapeutical option.Among major concerns for the clinical application of stem cells,some derive from the possibility that stem cells may be rejected by the immune system as a consequence of histoincompatibility and that stem cells themselves may interfere with the normal functions of host immune response.Therefore,the immunogenicity and the immunomodulatory properties of stem cells must be carefully addressed.Although these properties are common features of different stem cell types,some peculiarities can be recognized and characterized for their proper clinical use.展开更多
Biliary stenting is clinically effective in relieving both malignant and non-malignant obstructions. However, there are high failure rates associated with tumor ingrowth and epithelial overgrowth as well as internally...Biliary stenting is clinically effective in relieving both malignant and non-malignant obstructions. However, there are high failure rates associated with tumor ingrowth and epithelial overgrowth as well as internally from biofilm development and subsequent clogging. Within the last decade, the use of prophylactic drug eluting stents as a means to reduce stent failure has been investigated. In this review we provide an overview of the current research on drug eluting biliary stents. While there is limited human trial data regarding the clinical benefit of drug eluting biliary stents in preventing stent obstruction, recent research suggests promise regarding their safety and potential efficacy.展开更多
After more than a decade of controversy on the role of stromal cells in the tumor microenvironment,the emerging data shed light on pro-tumorigenic and potential anti-cancer factors,as well as on the roots of the discr...After more than a decade of controversy on the role of stromal cells in the tumor microenvironment,the emerging data shed light on pro-tumorigenic and potential anti-cancer factors,as well as on the roots of the discrepancies.We discuss the pro-tumorigenic effects of stromal cells,considering the effects of tumor drivers like hypoxia and tumor stiffness on these cells,as well as stromal cell-mediated adiposity and immunosuppression in the tumor microenvironment,and cancer initiating cells'cellular senescence and adaptive metabolism.We summarize the emerging data supporting stromal cell therapeutic potential in cancer,discuss the possibility to reprogram stromal cells of the tumor microenvironment for anti-cancer effects,and explore some causes of discrepancies on the roles of stromal cells in cancer in the available literature.展开更多
AIM To compare features of hepatocellular carcinoma(HCC) in Hispanics to those of African Americans and Whites.METHODS Patients treated for HCC at an urban tertiary medical center from 2005 to 2011 were identified fro...AIM To compare features of hepatocellular carcinoma(HCC) in Hispanics to those of African Americans and Whites.METHODS Patients treated for HCC at an urban tertiary medical center from 2005 to 2011 were identified from a tumor registry. Data were collected retrospectively, including demographics, comorbidities, liver disease characteristics, tumor parameters, treatment, and survival(OS) outcomes. OS analyses were performed using Kaplan-Meier method.RESULTS One hundred and ninety-five patients with HCC were identified: 80.5% were male, and 22% were age 65 or older. Mean age at HCC diagnosis was 59.7 ± 9.8 years. Sixty-one point five percent of patients had Medicare or Medicaid; 4.1% were uninsured. Compared to African American(31.2%) and White(46.2%) patients, Hispanic patients(22.6%) were more likely to have diabetes(P = 0.0019), hyperlipidemia(P = 0.0001), nonalcoholic steatohepatitis(NASH)(P = 0.0021), end stage renal disease(P = 0.0057), and less likely to have hepatitis C virus(P < 0.0001) or a smoking history(P < 0.0001). Compared to African Americans, Hispanics were more likely to meet criteria for metabolic syndrome(P = 0.0491), had higher median MELD scores(P = 0.0159), ascites(P = 0.008), and encephalopathy(P = 0.0087). Hispanic patients with HCC had shorter OS than the other racial groups(P = 0.020), despite similarities in HCC parameters and treatment. CONCLUSION In conclusion, Hispanic patients with HCC have higher incidence of modifiable metabolic risk factors including NASH, and shorter OS than African American and White patients.展开更多
The aetiology of OAL is undefined, although much attention has been recently focused on determining whether OAL is caused by an autoimmune disorder, chronic antigenic stimulation or both. It is becoming evident that i...The aetiology of OAL is undefined, although much attention has been recently focused on determining whether OAL is caused by an autoimmune disorder, chronic antigenic stimulation or both. It is becoming evident that infectious agents underlying chronic eye infection, as Chlamydia, may play a role in ocular lymphomagenesis. The high prevalence of Chlamydophila psittaci in patients with OAL has suggested a potential oncogenic role for its tendency to cause chronic and persistent infections, although it has been documented an evident geographical variability and response to antibiotic treatment. For C. pneumoniae, the findings so far obtained are very limited not only for identification in OAL but also for the specific treatment with antibiotics. The recent molecular and cultural evidence of C. trachomatis in patients with OAL, seems to suggest that also this pathogen may contribute to pathogenesis of such lymphoma. The potential application of bacteria-eradicating therapy at local and systemic level may ultimately result in safer and more efficient therapeutic option for patients affected by these malignancies. Moreover, a close collaboration between experts in ophthalmology, infectious diseases and hematology will help, in the future, to effectively manage this disease. This review attempts to weigh the currently available evidence regarding the role that Chlamydia play in development of OAL and focuses on patients with OAL observed at our Institution.展开更多
Acute Myeloid Leukemia (AML) is a group of genetically diverse hematopoietic malignancies arising from cell progenitors developing in the myeloid pathway or from primitive stem cells. Genetic susceptibility of AML may...Acute Myeloid Leukemia (AML) is a group of genetically diverse hematopoietic malignancies arising from cell progenitors developing in the myeloid pathway or from primitive stem cells. Genetic susceptibility of AML may account for an increased risk of AML due to partial metabolism of or biocativation of carcinogens. Chemical compounds are metabolized by a two-tiered phase detoxifying system. Polymorphisms in these pathways may lead to DNA damage and development of AML. We determined the frequencies of carcinogen metabolism gene polymorphisms (CYP1A1, del{GSTM1} and del{GSTT1}) in a case control-study based on polymorphism analysis. Fifty-eight consecutively AML patients (median age 62 years) and 174 sex and age-matched control group were assessed by a PCR-RFLP assay. There were 51 de novo and 7 secondary AML. CYP1A1*2A and CYP1A1*2C polymorphisms were more frequent in CG than AML p 0.001 and in contrast, CYP1A1*3 and CYP1A1*4 were more frequent in AML than CG p 0.001. There were no differences in del{GSTM1} neither del{GSTT1} between AML and CG (p = 0.999 and p = 0.539). Odds ratio for AML in patients harboring CYP1A1*3 was 2.36 (95% CI 1.2 - 4.5), 2.38 for CYP1A1*4 (95% CI 0.8 - 6.8). Adjusted OR was 2.63 for CYP1A1*3 (95% CI 1.4 - 5.1) and 2.66 for CYP1A1*4 (95% CI 0.9 - 7.8). In the multivariate analysis CYP1A1*3 polymorphism was a risk factor for AML with an OR for 3.99 (95%CI 1.9 - 8.6). To the best of our knowledge this is the first study to show that CYP1A1*3 heterozygous genotypes increase the risk of AML. Our data support that inherited absence of this carcinogen detoxification pathway may be an important determinant of AML.展开更多
Granulocytic or myeloid sarcoma (MS) is a rare neoplastic condition consisting of a tumor mass of myeloid blasts with or without maturation occurring at an anatomical site other than the bone marrow the association be...Granulocytic or myeloid sarcoma (MS) is a rare neoplastic condition consisting of a tumor mass of myeloid blasts with or without maturation occurring at an anatomical site other than the bone marrow the association between tuberculosis and MS is extremely rare. A 21-year-old female patient presented cough, sore throat and a suppurative swollen gum for 10 days prior to hospital admission. Physical examination revealed moderate pallor and swollen inferior gum. CBC revealed Hb6.5 g/dL, hematocrit 18.4% MCV 97 fL MCH 34 pg, WBC 18.5 ′ 109/μL (1 My/3 Bt/69 Sg/1 Eo/0 Ba/20 Ly/6 Mo), Platelets 43 ′ 109/μL. The peripheral blood smear presented with 3% blast cells (type 1) and granulocytic dysplasia. Bone marrow biopsy showed 100% cellularity. 50% of cells were from granulocytic precursors, diagnosis of granulocytic sarcoma. The diagnosis of AML was established: granulocytic sarcoma with massive gum infiltration (immature granulocytic cells) and 10% of blasts in bone marrow. The patient received induction chemotherapy (3 + 7 daunorubicin 90 mg/m2), and gum tissue culture was positive for Mycobacterium tuberculosis. Simultaneously, a qRT- PCR test confirmed the same bacteria in the gum tissue. Patient treated with isoniazid, rifampicin, pyrazinamide and ethambutol ciprofloxacin and amikacin). Remission was achieved and the patient was submitted for consolidation/ intensification (HiDAC x3) schema and referred to allogeneic HSCT. After induction and full hematological recovery there was no further evidence or recurrence of fever and lytic lesions. Currently patient is under CR and ling follow up (48 months) did not show recurrence of either AML or tuberculosis.展开更多
Only 1% - 12% of patients with lung cancer develop cutaneous metastases. While adenocarcinoma is incredibly common, it is rare for a cutaneous manifestation of the disease to be the initial presenting complaint. Skin ...Only 1% - 12% of patients with lung cancer develop cutaneous metastases. While adenocarcinoma is incredibly common, it is rare for a cutaneous manifestation of the disease to be the initial presenting complaint. Skin manifestations can be difficult to identify and can appear to be deceptively benign, leading to delays in diagnosis and treatment. ALK+ lung cancer specifically has an increased frequency of distant lymph node involvement and lymphangitic carcinomatosis relative to typical EGFR+ lung cancer. Herein we report a case of ALK-rearranged lung adenocarcinoma that initially presented as cutaneous skin metastases to the neck. Such skin lesions should be identified early, and considered as a potential manifestation of an internal malignancy. Given the poor prognosis associated with cutaneous metastases, further diagnostic tests, such as imaging or biopsy, should be done with urgency.展开更多
Acute myeloid leukemia(AML)represents a heterogeneous group of high-grade myeloid neoplasms of the elderly with variable outcomes.Though remissioninduction is an important first step in the management of AML,additiona...Acute myeloid leukemia(AML)represents a heterogeneous group of high-grade myeloid neoplasms of the elderly with variable outcomes.Though remissioninduction is an important first step in the management of AML,additional treatment strategies are essential to ensure long-term disease-free survival.Recent pivotal advances in understanding the genetics and molecular biology of AML have allowed for a risk-adapted approach in its management based on relapse-risk.Allogeneic hematopoietic cell transplantation(allo-HCT)represents an effective therapeutic strategy in AML providing the possibility of cure with potent graft-versus-leukemia reactions,with a demonstrable survival advantage in younger patients with intermediate-or poor-risk cytogenetics.Herein we review the published data regarding the role of allo-HCT in adults with AML.We searched MEDLINE/PubMed and EMBASE/Ovid.In addition,we searched reference lists of relevant articles,conference proceedings and ongoing trial databases.We discuss the role of allo-HCT in AML patients stratified by cytogenetic-and molecular-risk in first complete remission,as well as allo-HCT as an option in relapsed/refractory AML.Besides the conventional sibling and unrelated donor allografts,we review the available data and recent advances for alternative donor sources such as haploidentical grafts and umbilical cord blood.We also discuss conditioning regimens,including reduced intensity conditioning which has broadened the applicability of allo-HCT.Finally we explore recent advances and future possibilities and directions of allo-HCT in AML.Practical therapeutic recommendations have been made where possible based on available data and expert opinion.展开更多
Cancer stem cells(CSC) are thought to be malignant cells that have the capacity to initiate and maintain tumor growth and survival. Studies have described CSC in various gastrointestinal neoplasms such as colon, pancr...Cancer stem cells(CSC) are thought to be malignant cells that have the capacity to initiate and maintain tumor growth and survival. Studies have described CSC in various gastrointestinal neoplasms such as colon, pancreas and liver and gastroesophageal tumors. The mechanism by which CSC develop remains unclear. Several studies have explored the role of dysregulation of the Wnt/β-catenin, transformation growth factor-beta and hedhog pathways in generation of CSC. In this review, we discuss the various molecular abnormalities that may be related to formation of CSC in gastrointestinal malignancies, strategies to identify CSC and therapeutic strategies that are based on these concepts. Identification and targeting CSC is an intriguing area and may provide a new therapeutic option for patients with cancer including gastrointestinal malignancies. Although great progress has been made, many issues need to be addressed. Precise targeting of CSC will require precise isolation and characterization of those cells. This field is also evolving but further research is needed to identify markers that are specific for CSC.Although the application of this field has not entered the clinic yet, there continues to be significant optimism about its potential utility in overcoming cancer resistance and curing patients with cancer.展开更多
The existence of cancer stem cells has been wellestablished in acute myeloid leukemia. Initial proof of the existence of leukemia stem cells(LSCs) was accomplished by functional studies in xenograft models making use ...The existence of cancer stem cells has been wellestablished in acute myeloid leukemia. Initial proof of the existence of leukemia stem cells(LSCs) was accomplished by functional studies in xenograft models making use of the key features shared with normal hematopoietic stem cells(HSCs) such as the capacity of self-renewal and the ability to initiate and sustain growth of progenitors in vivo. Significant progress has also been made in identifying the phenotype and signaling pathways specific for LSCs. Therapeutically, a multitude of drugs targeting LSCs are in different phases of preclinical and clinical development. This review focuses on recent discoveries which have advanced our understanding of LSC biology and provided rational targets for development of novel therapeutic agents. One of the major challenges is how to target the selfrenewal pathways of LSCs without affecting normal HSCs significantly therefore providing an acceptable therapeutic window. Important issues pertinent to the successful design and conduct of clinical trials evaluating drugs targeting LSCs will be discussed as well.展开更多
Although plasma cell infiltration is not rare in autopsy of patients with multiple myeloma (MM), it is very rarely detected in living patients. This is because MM rarely causes significant liver dysfunction that requi...Although plasma cell infiltration is not rare in autopsy of patients with multiple myeloma (MM), it is very rarely detected in living patients. This is because MM rarely causes significant liver dysfunction that requires further evaluation. A 49-year-old man presented with acute renal failure and was diagnosed with kappa light chain MM stage B.Thalidomide and dexamethasone were initiated.The patient developed a continuous increase in bilirubin that led to severe cholestasis.A liver biopsy revealed plasma cell infiltration.He then rapidly progressed to liver failure and died.Treatment options are limited in MM with significant liver dysfunction.espite new drug therapies in MM,those patients with rapidly progressive liver failure appear to have a dismal outcome.展开更多
There has been a significant progress in the treatment of metastatic urothelial carcinoma in the last few years with the advent of immunotherapy after a long gap of no drug approvals for over 4 decades.While immunothe...There has been a significant progress in the treatment of metastatic urothelial carcinoma in the last few years with the advent of immunotherapy after a long gap of no drug approvals for over 4 decades.While immunotherapy with checkpoint inhibitors has revolutionized the treatment of urothelial carcinoma,unfortunately,only a minority of patients respond to immunotherapy.Treatment options for patients who do not respond and/or progress on immunotherapy are very limited and overall prognosis remains dismal in metastatic urothelial carcinoma.The first targeted therapy targeting the fibroblast growth factor receptor(FGFR)was recently approved for bladder cancer,but it is effective only in select patients harboring the FGFR2 and FGFR 3 mutations.Antibody drug conjugates like enfortumab vedotin have shown promising activity in clinical trials.Development of novel targeted therapies remains an area of investigation and an unmet need in bladder cancer.Exploitation of androgen receptor(AR)is a potential strategy for targeted drug development in bladder cancer.A significant proportion of urothelial carcinoma patients express AR irrespective of gender.AR signaling in urothelial carcinoma has been linked to progression through multiple mechanisms,including activation of human epidermal growth factor receptor-2(EGFR or HER-2)signaling and epithelial to mesenchymal transition(EMT).Furthermore,AR is enriched in the luminal papillary mRNA subtype of urothelial carcinoma and also mediates resistance to cisplatin-based chemotherapy.Preclinical evidence suggests that AR inhibition can successfully inhibit urothelial carcinoma growth as monotherapy and is synergistic with cisplatin-based chemotherapy.We review the preclinical and clinical evidence supporting the putative role of AR signaling in urothelial carcinoma pathogenesis,progression and its role as a novel therapeutic target and future directions.展开更多
Hereditary hemorrhagic telangiectasia(HHT) is arelatively common inherited vascular disorder that was first described in 1864, and is notable for epistaxis, telangiectasia, and arterial venous malformations. While gen...Hereditary hemorrhagic telangiectasia(HHT) is arelatively common inherited vascular disorder that was first described in 1864, and is notable for epistaxis, telangiectasia, and arterial venous malformations. While genetic tests are available, the diagnosis remains clinical, and is based on the Curacao criteria. Patients with HHT are at increased risk for both bleeding and clotting events. Because of these competing complications, hematologists are often faced with difficult clinical decisions. While the majority of management decisions revolve around bleeding complications, it is not infrequent for these patients to require anticoagulation for thrombosis. Any anticoagulation recommendations must take into account the bleeding risks associated with HHT. Recent reviews have found that HHT patients can be safely anticoagulated, with the most frequent complication being worsened epistaxis. Large clinical trials have shown that factor Ⅱa and Ⅹa inhibitors have less intracranial bleeding than warfarin, and basic coagulation research has provided a possible mechanism. This article describes the anticoagulation dilemma posed when a 62-year-old female patient with a history of bleeding events associated with HHT was diagnosed with a pulmonary embolism. The subsequent discussion focuses on the approach to anticoagulation in the HHT patient, and addresses the role of the new oral anticoagulants.展开更多
BACKGROUND Intravascular large B-cell lymphoma(IVLBCL)is a rare and aggressive subtype of non-Hodgkin lymphoma with a varied presentation and no pathognomonic findings.Early diagnosis is critical to altering the disea...BACKGROUND Intravascular large B-cell lymphoma(IVLBCL)is a rare and aggressive subtype of non-Hodgkin lymphoma with a varied presentation and no pathognomonic findings.Early diagnosis is critical to altering the disease course as early treatment with chemoimmunotherapy is required to prevent a rapidly fatal outcome.Strategies including improved awareness of this clinical entity through publication of cases with unique presentations are essential to prompt consideration of IVLBCL early in the disease workup.Here,we present a case of IVLBCL presenting with altered mental status and systemic organ dysfunction.CASE SUMMARY A 61-year-old male patient presented with flu-like symptoms and a high fever.He experienced rapid clinical deterioration with liver,kidney failure,and shock despite rapid antibiotic administration and supportive care.A broad infectious workup was negative.Intracranial imaging revealed nonspecific changes to the corpus callosum suspicious for vasculitis.Renal biopsy was non-diagnostic.After further progression of his symptoms,the family elected to withdraw care and the patient died shortly thereafter.Post-mortem analysis revealed clear multi-organ involvement by IVLBCL,prompting re-examination of the ante-mortem renal biopsy that also identified IVLBCL involvement.CONCLUSION IVLBCL is a rare disease.Communication with specialties and early biopsy is critical to establishing the diagnosis and initiating therapy.展开更多
Breast cancer is the most frequent female malignancy worldwide. Current strategies in breast cancer therapy,including classical chemotherapy, hormone therapy, and targeted therapies, are usually associated with chemor...Breast cancer is the most frequent female malignancy worldwide. Current strategies in breast cancer therapy,including classical chemotherapy, hormone therapy, and targeted therapies, are usually associated with chemoresistance and serious adverse effects. Advances in our understanding of changes affecting the interactome in advanced and chemoresistant breast tumors have provided novel therapeutic targets, including, cyclin dependent kinases, mammalian target of rapamycin,Notch, Wnt and Shh. Inhibitors of these molecules recently entered clinical trials in mono- and combination therapy in metastatic and chemo-resistant breast cancers. Anticancer epigenetic drugs, mainly histone deacetylase inhibitors and DNA methyltransferase inhibitors, also entered clinical trials. Because of the complexity and heterogeneity of breast cancer, the future in therapy lies in the application of individualized tailored regimens. Emerging therapeutic targets and the implications for personalized-based therapy development in breast cancer are herein discussed.展开更多
BACKGROUND Wilson's disease(WD)is a rare inherited disorder of copper metabolism.Treatment consists of chelating agents,but side effects are common.We describe a patient who developed colitis during trientine trea...BACKGROUND Wilson's disease(WD)is a rare inherited disorder of copper metabolism.Treatment consists of chelating agents,but side effects are common.We describe a patient who developed colitis during trientine treatment leading to decompensation of liver cirrhosis.CASE SUMMARY A healthy 51-year-old woman was diagnosed with liver cirrhosis due to decompensation with ascites.Etiologic evaluation raised suspicion of hereditary hemochromatosis because of compound heterozygosity HFE p.C282Y/p.H63D,and phlebotomy was started.Re-evaluation showed low ceruloplasmin,increased urinary copper excretion and the presence of Kayser-Fleischer rings.WD was confirmed by genetic analysis.Because of decompensated cirrhosis,she was referred for liver transplant evaluation.Simultaneously,treatment with trientine was initiated.Liver function initially stabilized,and the patient was not accepted for a liver transplant.Shortly after this,she developed severe hemorrhagic colitis,most probably a side effect of trientine.During that episode,she decompensated with hepatic encephalopathy.Because of a second decompensating event,she was accepted for liver transplantation,and an uneventful transplantation was carried out after clinical improvement of colitis.CONCLUSION Despite WD being a rare disorder,it is important to consider because it can present with a plethora of symptoms from childhood to an elderly age.Colitis should be recognized as a serious adverse drug reaction to trientine treatment that can result in decompensated liver disease.展开更多
文摘The management of esophageal cancer has been evolving over the past 30 years. In the United States, multimodality treatment combining chemotherapy and radiotherapy (RT) prior to surgical resection has come to be accepted by many as the standard of care, although debate about its overall effect on survival still exists, and rightfully so. Despite recent improvements in detection and treatment, the overall survival of patients with esophageal cancer remains lower than most solid tumors, which highlights why further advances are so desperately needed. The aim of this article is to provide a complete review of the history of esophageal cancer treatment with the addition of chemotherapy, RT, and more recently, targeted agents to the surgical management of resectable disease.
文摘The possibility of treating degenerative diseases by stem cell-based approaches is a promising therapeutical option.Among major concerns for the clinical application of stem cells,some derive from the possibility that stem cells may be rejected by the immune system as a consequence of histoincompatibility and that stem cells themselves may interfere with the normal functions of host immune response.Therefore,the immunogenicity and the immunomodulatory properties of stem cells must be carefully addressed.Although these properties are common features of different stem cell types,some peculiarities can be recognized and characterized for their proper clinical use.
文摘Biliary stenting is clinically effective in relieving both malignant and non-malignant obstructions. However, there are high failure rates associated with tumor ingrowth and epithelial overgrowth as well as internally from biofilm development and subsequent clogging. Within the last decade, the use of prophylactic drug eluting stents as a means to reduce stent failure has been investigated. In this review we provide an overview of the current research on drug eluting biliary stents. While there is limited human trial data regarding the clinical benefit of drug eluting biliary stents in preventing stent obstruction, recent research suggests promise regarding their safety and potential efficacy.
文摘After more than a decade of controversy on the role of stromal cells in the tumor microenvironment,the emerging data shed light on pro-tumorigenic and potential anti-cancer factors,as well as on the roots of the discrepancies.We discuss the pro-tumorigenic effects of stromal cells,considering the effects of tumor drivers like hypoxia and tumor stiffness on these cells,as well as stromal cell-mediated adiposity and immunosuppression in the tumor microenvironment,and cancer initiating cells'cellular senescence and adaptive metabolism.We summarize the emerging data supporting stromal cell therapeutic potential in cancer,discuss the possibility to reprogram stromal cells of the tumor microenvironment for anti-cancer effects,and explore some causes of discrepancies on the roles of stromal cells in cancer in the available literature.
文摘AIM To compare features of hepatocellular carcinoma(HCC) in Hispanics to those of African Americans and Whites.METHODS Patients treated for HCC at an urban tertiary medical center from 2005 to 2011 were identified from a tumor registry. Data were collected retrospectively, including demographics, comorbidities, liver disease characteristics, tumor parameters, treatment, and survival(OS) outcomes. OS analyses were performed using Kaplan-Meier method.RESULTS One hundred and ninety-five patients with HCC were identified: 80.5% were male, and 22% were age 65 or older. Mean age at HCC diagnosis was 59.7 ± 9.8 years. Sixty-one point five percent of patients had Medicare or Medicaid; 4.1% were uninsured. Compared to African American(31.2%) and White(46.2%) patients, Hispanic patients(22.6%) were more likely to have diabetes(P = 0.0019), hyperlipidemia(P = 0.0001), nonalcoholic steatohepatitis(NASH)(P = 0.0021), end stage renal disease(P = 0.0057), and less likely to have hepatitis C virus(P < 0.0001) or a smoking history(P < 0.0001). Compared to African Americans, Hispanics were more likely to meet criteria for metabolic syndrome(P = 0.0491), had higher median MELD scores(P = 0.0159), ascites(P = 0.008), and encephalopathy(P = 0.0087). Hispanic patients with HCC had shorter OS than the other racial groups(P = 0.020), despite similarities in HCC parameters and treatment. CONCLUSION In conclusion, Hispanic patients with HCC have higher incidence of modifiable metabolic risk factors including NASH, and shorter OS than African American and White patients.
文摘The aetiology of OAL is undefined, although much attention has been recently focused on determining whether OAL is caused by an autoimmune disorder, chronic antigenic stimulation or both. It is becoming evident that infectious agents underlying chronic eye infection, as Chlamydia, may play a role in ocular lymphomagenesis. The high prevalence of Chlamydophila psittaci in patients with OAL has suggested a potential oncogenic role for its tendency to cause chronic and persistent infections, although it has been documented an evident geographical variability and response to antibiotic treatment. For C. pneumoniae, the findings so far obtained are very limited not only for identification in OAL but also for the specific treatment with antibiotics. The recent molecular and cultural evidence of C. trachomatis in patients with OAL, seems to suggest that also this pathogen may contribute to pathogenesis of such lymphoma. The potential application of bacteria-eradicating therapy at local and systemic level may ultimately result in safer and more efficient therapeutic option for patients affected by these malignancies. Moreover, a close collaboration between experts in ophthalmology, infectious diseases and hematology will help, in the future, to effectively manage this disease. This review attempts to weigh the currently available evidence regarding the role that Chlamydia play in development of OAL and focuses on patients with OAL observed at our Institution.
基金supported by the grant providedby CNPq(Conselho Nacional de Desenvolvimento Científico e Tecnológico).The fellowship grant supported by CNPq was Luís Arthur Flores Pelloso,process number 140232/2001-0,period 03/01/2001 to 02/28/2005.
文摘Acute Myeloid Leukemia (AML) is a group of genetically diverse hematopoietic malignancies arising from cell progenitors developing in the myeloid pathway or from primitive stem cells. Genetic susceptibility of AML may account for an increased risk of AML due to partial metabolism of or biocativation of carcinogens. Chemical compounds are metabolized by a two-tiered phase detoxifying system. Polymorphisms in these pathways may lead to DNA damage and development of AML. We determined the frequencies of carcinogen metabolism gene polymorphisms (CYP1A1, del{GSTM1} and del{GSTT1}) in a case control-study based on polymorphism analysis. Fifty-eight consecutively AML patients (median age 62 years) and 174 sex and age-matched control group were assessed by a PCR-RFLP assay. There were 51 de novo and 7 secondary AML. CYP1A1*2A and CYP1A1*2C polymorphisms were more frequent in CG than AML p 0.001 and in contrast, CYP1A1*3 and CYP1A1*4 were more frequent in AML than CG p 0.001. There were no differences in del{GSTM1} neither del{GSTT1} between AML and CG (p = 0.999 and p = 0.539). Odds ratio for AML in patients harboring CYP1A1*3 was 2.36 (95% CI 1.2 - 4.5), 2.38 for CYP1A1*4 (95% CI 0.8 - 6.8). Adjusted OR was 2.63 for CYP1A1*3 (95% CI 1.4 - 5.1) and 2.66 for CYP1A1*4 (95% CI 0.9 - 7.8). In the multivariate analysis CYP1A1*3 polymorphism was a risk factor for AML with an OR for 3.99 (95%CI 1.9 - 8.6). To the best of our knowledge this is the first study to show that CYP1A1*3 heterozygous genotypes increase the risk of AML. Our data support that inherited absence of this carcinogen detoxification pathway may be an important determinant of AML.
文摘Granulocytic or myeloid sarcoma (MS) is a rare neoplastic condition consisting of a tumor mass of myeloid blasts with or without maturation occurring at an anatomical site other than the bone marrow the association between tuberculosis and MS is extremely rare. A 21-year-old female patient presented cough, sore throat and a suppurative swollen gum for 10 days prior to hospital admission. Physical examination revealed moderate pallor and swollen inferior gum. CBC revealed Hb6.5 g/dL, hematocrit 18.4% MCV 97 fL MCH 34 pg, WBC 18.5 ′ 109/μL (1 My/3 Bt/69 Sg/1 Eo/0 Ba/20 Ly/6 Mo), Platelets 43 ′ 109/μL. The peripheral blood smear presented with 3% blast cells (type 1) and granulocytic dysplasia. Bone marrow biopsy showed 100% cellularity. 50% of cells were from granulocytic precursors, diagnosis of granulocytic sarcoma. The diagnosis of AML was established: granulocytic sarcoma with massive gum infiltration (immature granulocytic cells) and 10% of blasts in bone marrow. The patient received induction chemotherapy (3 + 7 daunorubicin 90 mg/m2), and gum tissue culture was positive for Mycobacterium tuberculosis. Simultaneously, a qRT- PCR test confirmed the same bacteria in the gum tissue. Patient treated with isoniazid, rifampicin, pyrazinamide and ethambutol ciprofloxacin and amikacin). Remission was achieved and the patient was submitted for consolidation/ intensification (HiDAC x3) schema and referred to allogeneic HSCT. After induction and full hematological recovery there was no further evidence or recurrence of fever and lytic lesions. Currently patient is under CR and ling follow up (48 months) did not show recurrence of either AML or tuberculosis.
文摘Only 1% - 12% of patients with lung cancer develop cutaneous metastases. While adenocarcinoma is incredibly common, it is rare for a cutaneous manifestation of the disease to be the initial presenting complaint. Skin manifestations can be difficult to identify and can appear to be deceptively benign, leading to delays in diagnosis and treatment. ALK+ lung cancer specifically has an increased frequency of distant lymph node involvement and lymphangitic carcinomatosis relative to typical EGFR+ lung cancer. Herein we report a case of ALK-rearranged lung adenocarcinoma that initially presented as cutaneous skin metastases to the neck. Such skin lesions should be identified early, and considered as a potential manifestation of an internal malignancy. Given the poor prognosis associated with cutaneous metastases, further diagnostic tests, such as imaging or biopsy, should be done with urgency.
文摘Acute myeloid leukemia(AML)represents a heterogeneous group of high-grade myeloid neoplasms of the elderly with variable outcomes.Though remissioninduction is an important first step in the management of AML,additional treatment strategies are essential to ensure long-term disease-free survival.Recent pivotal advances in understanding the genetics and molecular biology of AML have allowed for a risk-adapted approach in its management based on relapse-risk.Allogeneic hematopoietic cell transplantation(allo-HCT)represents an effective therapeutic strategy in AML providing the possibility of cure with potent graft-versus-leukemia reactions,with a demonstrable survival advantage in younger patients with intermediate-or poor-risk cytogenetics.Herein we review the published data regarding the role of allo-HCT in adults with AML.We searched MEDLINE/PubMed and EMBASE/Ovid.In addition,we searched reference lists of relevant articles,conference proceedings and ongoing trial databases.We discuss the role of allo-HCT in AML patients stratified by cytogenetic-and molecular-risk in first complete remission,as well as allo-HCT as an option in relapsed/refractory AML.Besides the conventional sibling and unrelated donor allografts,we review the available data and recent advances for alternative donor sources such as haploidentical grafts and umbilical cord blood.We also discuss conditioning regimens,including reduced intensity conditioning which has broadened the applicability of allo-HCT.Finally we explore recent advances and future possibilities and directions of allo-HCT in AML.Practical therapeutic recommendations have been made where possible based on available data and expert opinion.
文摘Cancer stem cells(CSC) are thought to be malignant cells that have the capacity to initiate and maintain tumor growth and survival. Studies have described CSC in various gastrointestinal neoplasms such as colon, pancreas and liver and gastroesophageal tumors. The mechanism by which CSC develop remains unclear. Several studies have explored the role of dysregulation of the Wnt/β-catenin, transformation growth factor-beta and hedhog pathways in generation of CSC. In this review, we discuss the various molecular abnormalities that may be related to formation of CSC in gastrointestinal malignancies, strategies to identify CSC and therapeutic strategies that are based on these concepts. Identification and targeting CSC is an intriguing area and may provide a new therapeutic option for patients with cancer including gastrointestinal malignancies. Although great progress has been made, many issues need to be addressed. Precise targeting of CSC will require precise isolation and characterization of those cells. This field is also evolving but further research is needed to identify markers that are specific for CSC.Although the application of this field has not entered the clinic yet, there continues to be significant optimism about its potential utility in overcoming cancer resistance and curing patients with cancer.
文摘The existence of cancer stem cells has been wellestablished in acute myeloid leukemia. Initial proof of the existence of leukemia stem cells(LSCs) was accomplished by functional studies in xenograft models making use of the key features shared with normal hematopoietic stem cells(HSCs) such as the capacity of self-renewal and the ability to initiate and sustain growth of progenitors in vivo. Significant progress has also been made in identifying the phenotype and signaling pathways specific for LSCs. Therapeutically, a multitude of drugs targeting LSCs are in different phases of preclinical and clinical development. This review focuses on recent discoveries which have advanced our understanding of LSC biology and provided rational targets for development of novel therapeutic agents. One of the major challenges is how to target the selfrenewal pathways of LSCs without affecting normal HSCs significantly therefore providing an acceptable therapeutic window. Important issues pertinent to the successful design and conduct of clinical trials evaluating drugs targeting LSCs will be discussed as well.
文摘Although plasma cell infiltration is not rare in autopsy of patients with multiple myeloma (MM), it is very rarely detected in living patients. This is because MM rarely causes significant liver dysfunction that requires further evaluation. A 49-year-old man presented with acute renal failure and was diagnosed with kappa light chain MM stage B.Thalidomide and dexamethasone were initiated.The patient developed a continuous increase in bilirubin that led to severe cholestasis.A liver biopsy revealed plasma cell infiltration.He then rapidly progressed to liver failure and died.Treatment options are limited in MM with significant liver dysfunction.espite new drug therapies in MM,those patients with rapidly progressive liver failure appear to have a dismal outcome.
文摘There has been a significant progress in the treatment of metastatic urothelial carcinoma in the last few years with the advent of immunotherapy after a long gap of no drug approvals for over 4 decades.While immunotherapy with checkpoint inhibitors has revolutionized the treatment of urothelial carcinoma,unfortunately,only a minority of patients respond to immunotherapy.Treatment options for patients who do not respond and/or progress on immunotherapy are very limited and overall prognosis remains dismal in metastatic urothelial carcinoma.The first targeted therapy targeting the fibroblast growth factor receptor(FGFR)was recently approved for bladder cancer,but it is effective only in select patients harboring the FGFR2 and FGFR 3 mutations.Antibody drug conjugates like enfortumab vedotin have shown promising activity in clinical trials.Development of novel targeted therapies remains an area of investigation and an unmet need in bladder cancer.Exploitation of androgen receptor(AR)is a potential strategy for targeted drug development in bladder cancer.A significant proportion of urothelial carcinoma patients express AR irrespective of gender.AR signaling in urothelial carcinoma has been linked to progression through multiple mechanisms,including activation of human epidermal growth factor receptor-2(EGFR or HER-2)signaling and epithelial to mesenchymal transition(EMT).Furthermore,AR is enriched in the luminal papillary mRNA subtype of urothelial carcinoma and also mediates resistance to cisplatin-based chemotherapy.Preclinical evidence suggests that AR inhibition can successfully inhibit urothelial carcinoma growth as monotherapy and is synergistic with cisplatin-based chemotherapy.We review the preclinical and clinical evidence supporting the putative role of AR signaling in urothelial carcinoma pathogenesis,progression and its role as a novel therapeutic target and future directions.
文摘Hereditary hemorrhagic telangiectasia(HHT) is arelatively common inherited vascular disorder that was first described in 1864, and is notable for epistaxis, telangiectasia, and arterial venous malformations. While genetic tests are available, the diagnosis remains clinical, and is based on the Curacao criteria. Patients with HHT are at increased risk for both bleeding and clotting events. Because of these competing complications, hematologists are often faced with difficult clinical decisions. While the majority of management decisions revolve around bleeding complications, it is not infrequent for these patients to require anticoagulation for thrombosis. Any anticoagulation recommendations must take into account the bleeding risks associated with HHT. Recent reviews have found that HHT patients can be safely anticoagulated, with the most frequent complication being worsened epistaxis. Large clinical trials have shown that factor Ⅱa and Ⅹa inhibitors have less intracranial bleeding than warfarin, and basic coagulation research has provided a possible mechanism. This article describes the anticoagulation dilemma posed when a 62-year-old female patient with a history of bleeding events associated with HHT was diagnosed with a pulmonary embolism. The subsequent discussion focuses on the approach to anticoagulation in the HHT patient, and addresses the role of the new oral anticoagulants.
文摘BACKGROUND Intravascular large B-cell lymphoma(IVLBCL)is a rare and aggressive subtype of non-Hodgkin lymphoma with a varied presentation and no pathognomonic findings.Early diagnosis is critical to altering the disease course as early treatment with chemoimmunotherapy is required to prevent a rapidly fatal outcome.Strategies including improved awareness of this clinical entity through publication of cases with unique presentations are essential to prompt consideration of IVLBCL early in the disease workup.Here,we present a case of IVLBCL presenting with altered mental status and systemic organ dysfunction.CASE SUMMARY A 61-year-old male patient presented with flu-like symptoms and a high fever.He experienced rapid clinical deterioration with liver,kidney failure,and shock despite rapid antibiotic administration and supportive care.A broad infectious workup was negative.Intracranial imaging revealed nonspecific changes to the corpus callosum suspicious for vasculitis.Renal biopsy was non-diagnostic.After further progression of his symptoms,the family elected to withdraw care and the patient died shortly thereafter.Post-mortem analysis revealed clear multi-organ involvement by IVLBCL,prompting re-examination of the ante-mortem renal biopsy that also identified IVLBCL involvement.CONCLUSION IVLBCL is a rare disease.Communication with specialties and early biopsy is critical to establishing the diagnosis and initiating therapy.
文摘Breast cancer is the most frequent female malignancy worldwide. Current strategies in breast cancer therapy,including classical chemotherapy, hormone therapy, and targeted therapies, are usually associated with chemoresistance and serious adverse effects. Advances in our understanding of changes affecting the interactome in advanced and chemoresistant breast tumors have provided novel therapeutic targets, including, cyclin dependent kinases, mammalian target of rapamycin,Notch, Wnt and Shh. Inhibitors of these molecules recently entered clinical trials in mono- and combination therapy in metastatic and chemo-resistant breast cancers. Anticancer epigenetic drugs, mainly histone deacetylase inhibitors and DNA methyltransferase inhibitors, also entered clinical trials. Because of the complexity and heterogeneity of breast cancer, the future in therapy lies in the application of individualized tailored regimens. Emerging therapeutic targets and the implications for personalized-based therapy development in breast cancer are herein discussed.
文摘BACKGROUND Wilson's disease(WD)is a rare inherited disorder of copper metabolism.Treatment consists of chelating agents,but side effects are common.We describe a patient who developed colitis during trientine treatment leading to decompensation of liver cirrhosis.CASE SUMMARY A healthy 51-year-old woman was diagnosed with liver cirrhosis due to decompensation with ascites.Etiologic evaluation raised suspicion of hereditary hemochromatosis because of compound heterozygosity HFE p.C282Y/p.H63D,and phlebotomy was started.Re-evaluation showed low ceruloplasmin,increased urinary copper excretion and the presence of Kayser-Fleischer rings.WD was confirmed by genetic analysis.Because of decompensated cirrhosis,she was referred for liver transplant evaluation.Simultaneously,treatment with trientine was initiated.Liver function initially stabilized,and the patient was not accepted for a liver transplant.Shortly after this,she developed severe hemorrhagic colitis,most probably a side effect of trientine.During that episode,she decompensated with hepatic encephalopathy.Because of a second decompensating event,she was accepted for liver transplantation,and an uneventful transplantation was carried out after clinical improvement of colitis.CONCLUSION Despite WD being a rare disorder,it is important to consider because it can present with a plethora of symptoms from childhood to an elderly age.Colitis should be recognized as a serious adverse drug reaction to trientine treatment that can result in decompensated liver disease.