Neoadjuvant treatment of esophageal cancer

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.

Drug eluting biliary stents to decrease stent failure rates:Areview of the literature

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.

Features of hepatocellular carcinoma in Hispanics differ from African Americans and non-Hispanic Whites

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.

WJSC 6^(th) Anniversary Special Issues(1):Hematopoietic stem cell transplantation Allogeneic hematopoietic cell transplant for acute myeloid leukemia:Current state in 2013 and future directions

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.

Hepatic failure caused by plasma cell infiltration in multiple myeloma

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.

Androgen receptor in bladder cancer:A promising therapeutic target

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.

Intravascular large B-cell lymphoma presenting with altered mental status: A case report

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.

Treatments of disease relapse after allogeneic stem cell transplantation focusing on donor lymphocyte infusion

Hematopoietic stem cell transplantation (SCT) is a potentially curative treatment for patients with hematologic malignancies,such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).There has been tremendous progress in the past several decades in allogeneic SCT with better outcomes through improvements in supportive care,expansion of stem cell donor options (HLA-matched unrelated donors (MUD),haploidentical related donors,and cord blood units (CBUs)etc.),and introduction of better tolerated reduced intensity conditioning (RIC) regimens.

Metastatic well-differentiated pancreatic neuroendocrine tumors to the liver: a narrative review of systemic and surgical management

Pancreatic neuroendocrine tumors(PNETs)are a rare group of neoplasms originating from the endocrine pancreas.PNETs are classified as functional or non-functional tumors.PNETs are more often diagnosed at a higher stage with distant metastases or advanced locoregional disease.The majority of individuals with hepatic metastases will ultimately die of liver failure;therefore,the treatment of liver tumor burden is critical to providing a survival impact.While surgical resection remains the only chance of cure for disease confined to the pancreas or for locoregional disease,the treatment of advanced or metastatic PNETs is more complex and often requires a multimodal approach.This review focuses on treatment options for well and moderately differentiated PNETs with metastatic disease to the liver.These include surgery,liver-directed therapies including ablative and intra-arterial therapies,and systemic therapies such as somatostatin analogues,targeted therapies,chemotherapy,and peptide receptor radionuclide therapy.Developing an individualized treatment strategy requires careful assessment of liver tumor burden and predicted biological behavior.Aggressive surgical resection of hepatic metastases secondary to PNET primary tumors is associated with improved survival in multiple retrospective studies.General goals of treatment for metastatic disease include prolonging overall survival and progression free survival,improving quality of life,and control of symptoms.

Impact of previous anti-angiogenesis treatment in nivolumab-treated advanced non-small cell lung cancer

Aim:To in vestigate how previous systemic therapy such as an ti-a ngioge nesis can in flue nee can cer imm uno therapy for non-small cell l ung can cer(NSCLC).Methods:A total of 134 patie nts with adva need NSCLC who were treated with ni volumab were retrospectively reviewed.Correlation between status of prior anti-angiogenesis treatment and clinical characteristics were determined.Impact of prior an ti-a ngioge nesis on therapeutic outcome of ni volumab was in vestigated for tumor efficacy such as progressi on-free survival(PFS).Results:Sixtee n patie nts were treated with at least one an ti-a ngioge nesis age nt prior to ni volumab.The prior use of an tian gioge nesis age nt was associated with stage IV disease,non-squamous histology,and two or more lines of systemic therapy.Media n PFS was sig nifica ntly shorter in the prior an ti-a ngioge nesis group tha n in no prior an ti-a ngioge nesis group(8.3 vs.11.3 weeks,log-rank P 0.006).Multivariate analyses demonstrated that only prior anti-angiogenesis status was associated with worse PFS.There is also a slight trend for worse disease control rate(P 0.101,Fisher's exact test)and overall survival(P 0.200,log-ra nk)in prior an ti-a ngioge nesis group.Conclusion:This retrospective study suggests that prior anti-angiogenesis treatment negatively impacts the therapeutic outcome of immunotherapy in advanced NSCLC.

MicroRNAs in cancer biology and therapy:Current status and perspectives

The study of a class of small non-coding RNA molecules,named microRNAs(miRNAs),has advanced our understanding of many of the fundamental processes of cancer biology and the molecular mechanisms underlying tumor initiation and progression.MiRNA research has become more and more attractive as evidence is emerging that miRNAs likely play important regulatory roles virtually in all essential bioprocesses.Looking at this field over the past decade it becomes evident that our understanding of miRNAs remains rather incomplete.As research continues to reveal the mechanisms underlying cancer therapy efficacy,it is clear that miRNAs contribute to responses to drug therapy and are themselves modified by drug therapy.One important area for miRNA research is to understand the functions of miRNAs and the relevant signaling pathways in the initiation,progression and drug-resistance of tumors to be able to design novel,effective targeted therapeutics that directly target pathologically essential miRNAs and/or their target genes.Another area of increasing importance is the use of miRNA signatures in the diagnosis and prognosis of various types of cancers.As the study of noncoding RNAs is increasingly more popular and important,it is without doubt that the next several years of miRNA research will provide more fascinating results.

The peripheral T-cell lymphoma:can we pivot from the chemotherapy-predicated paradigm?

Peripheral T-cell lymphomas(PTCL)are uncommon and aggressive diseases that are difficult to study.Combination chemotherapy such as cyclophosphamide,doxorubicin,vincristine,and prednisone has been the mainstay of treatment for almost 30 years,but outcomes remain poor.The development of new targeted therapies is changing the landscape of how we treat patients with these difficult diseases.For instance,the addition of brentuximab vedotin to combination chemotherapy enhanced the outcomes in patients with CD30-positive anaplastic large cell lymphomas,but there is still a need for better therapies in the other numerous subtypes.Here we discuss the data for the existing treatment paradigm of PTCL as well as the merits of shifting toward a chemotherapy-free approach.

R-2-HG in AML . . . friend or foe?

Cytosolic isocitrate dehydrogenase 1(IDH1)and its mitochondrial counterpart,IDH2,are critical TCA cycle enzymes that catalyze the oxidative decarboxylation of isocitrate to produce alpha-ketoglutarate(a-KG).Mutations in IDH1/2 occur in∼80%of grade II-III gliomas and secondary glioblastomas,^(1–3) and in 10%to 20%of acute myeloid leukemia(AML).^(4–6) To date,all identified mutations in IDH1/2 are heterozygous,missense mutations,leading to the substitution of arginine 132 in IDH1 and arginine 172 or 140 in IDH2.