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Myron Schwartz

Publications and source records attributed to Myron Schwartz.

At least 19 recordsLinked to original sources
PubMed2006

Downregulation of KLF6 is an early event in hepatocarcinogenesis, and stimulates proliferation while reducing differentiation.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) has the most rapidly rising cancer incidence in the US and Europe. The KLF6 tumor suppressor is frequently inactivated in HCC by loss-of-heterozygosity (LOH) and/or mutation. METHODS: Here we have analyzed 33 HBV- and 40 HCV-related HCCs for mRNA expression of wildtype KLF6 (wtKLF6) as well as the KLF6 variant 1 (SV1), a truncated, growth-promoting variant that antagonizes wtKLF6 function. The HCV-related tumors analyzed represented the full histologic spectrum from cirrhosis and dysplasia to metastatic cancer. RESULTS: Expression of KLF6 mRNA is decreased in 73% of HBV-associated HCCs compared to matched surrounding tissue (ST), with reductions of approximately 80% in one-third of the patients. KLF6 mRNA expression is also reduced in dysplastic nodules from patients with HCV compared to cirrhotic livers (p<0.005), with an additional, marked decrease in the very advanced, metastatic stage (p<0.05). An increased ratio of KLF6SV1/wt KLF6 is present in a subset (6/33, 18%) of the HBV-related HCCs compared to matched ST. Reconstituting KLF6 in HepG2 cells by retroviral infection decreased proliferation and related markers including cyclin D1 and beta-catenin, increased cellular differentiation based on induction of albumin, E-cadherin, and decreased alpha fetoprotein. CONCLUSIONS: We conclude that reduced KLF6 expression is common in both HBV- and HCV-related HCCs and occurs at critical stages during cancer progression. Effects of KLF6 are attributable to regulation of genes controlling hepatocyte growth and differentiation.

Biomarkers↗
PubMed2006

A molecular signature to discriminate dysplastic nodules from early hepatocellular carcinoma in HCV cirrhosis.

BACKGROUND & AIMS: Small liver nodules approximately 2 cm are difficult to characterize by radiologic or pathologic examination. Our aim was to identify a molecular signature to diagnose early hepatocellular carcinoma (HCC). METHODS: The transcriptional profiles of 55 candidate genes were assessed by quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) in 17 dysplastic nodules (diameter, 10 mm) and 20 early HCC (diameter, 18 mm) from HCV cirrhotic patients undergoing resection/transplantation and 10 nontumoral cirrhotic tissues and 10 normal liver tissues. Candidate genes were confirmed by quantitative RT-PCR in 20 advanced HCCs and by immunohistochemistry in 75 samples and validated in an independent set of 29 samples (dysplastic nodules [10] and small HCC [19; diameter, 20 mm]). RESULTS: Twelve genes were significantly, differentially expressed in early HCCs compared with dysplastic nodules (>2-fold change; area under the receiver operating characteristic curve > or =0.8): this included TERT, GPC3, gankyrin, survivin, TOP2A, LYVE1, E-cadherin, IGFBP3, PDGFRA, TGFA, cyclin D1, and HGF. Logistic regression analysis identified a 3-gene set including GPC3 (18-fold increase in HCC, P = .01), LYVE1 (12-fold decrease in HCC, P = .0001), and survivin (2.2-fold increase in HCC, P = .02), which had a discriminative accuracy of 94%. The validity of the gene signature was confirmed in a prospective testing set. GPC3 immunostaining was positive in all HCCs and negative in dysplastic nodules (22/22 vs 0/14, respectively, P < .001). Nuclear staining for survivin was positive in 12 of 13 advanced HCC cases and in 1 of 9 early tumors. CONCLUSIONS: Molecular data based on gene transcriptional profiles of a 3-gene set allow a reliable diagnosis of early HCC. Immunostaining of GPC3 confirms the diagnosis of HCC.

Biomarkers, Tumor↗
PubMed2006

Expanded criteria for hepatocellular carcinoma through down-staging prior to liver transplantation: not yet there.

The accepted treatment strategy for hepatocellular carcinoma (HCC) is supported by randomized controlled trials (RCTs), meta-analysis, and large cohort studies. For instance, the Milan criteria applied for indicating liver transplantation have been validated by several cohort studies including more than 1000 patients. Regarding medical treatments, approximately 80 RCTs have been published so far in HCC. These studies provide the evidence to support chemoembolization as the treatment for patients at intermediate stage (meta-analysis of 6 RCTs) and show the lack of benefit of tamoxifen assessed in 12 RCTs including more than 1500 patients. In this scenario, what is the evidence to advocate for the expansion of HCC criteria through down-staging prior to liver transplantation? Such an approach has never been tested through RCTs or even well-designed cohort studies including enough patients and adequate follow-up. Only a few small studies with heterogeneous target populations and treatments applied are available. The results of these studies are inconsistent and do not provide compelling evidence to accept down-staging as a standard of care.

Carcinoma, Hepatocellular↗
PubMed2005

Cancer history and other personal factors affect quality of life in patients with hepatitis C.

BACKGROUND: Although patients with chronic hepatitis C (CHC) have been found to have reduced quality of life, little is known about how other characteristics affect their quality of life. The purpose of this study was to investigate the effect of other characteristics, including history of cancer, on quality of life in patients with CHC. METHODS: One hundred forty patients from clinics at three hospitals in New York City completed a detailed epidemiologic interview about demographic and lifestyle characteristics and the SF-36 measuring health-related quality of life. We compared results from our patients to normative data using t-tests of differences between means. We used multivariate analyses to determine other personal and health-related factors associated with quality of life outcomes. RESULTS: Compared to normative data, these patients had reduced quality of life, particularly on physical functioning. The summary Physical Component Score (PCS) was 45.4 +/- 10.6 and the Mental Component Score (MCS) was 48.2 +/- 11.1, vs norms of 50 +/- 10.0; p-values were < 0.0001 and < 0.05, respectively. In multivariate analyses, the PCS was significantly lower among those with cancer history, > or = 2 other chronic conditions, less education, low physical activity, and higher alanine aminotransferase (ALT) levels. Cancer was more important for men, while other chronic conditions were more important for women. On the MCS, history of depression, low physical activity, alcohol use, and female gender were independently associated with poorer scores. CONCLUSION: Several health and lifestyle factors independently influence quality of life in CHC patients. Different factors are important for men and women.

Adult↗
PubMed2005

Resection and liver transplantation for hepatocellular carcinoma.

Surveillance programs in cirrhotic patients enable the detection of hepatocellular carcinoma (HCC) at early stages, when the tumor is amenable to curative treatments (60% of cases in Japan; 25 to 40% in Europe and the United States). Resection is the mainstay of treatment in noncirrhotic patients and in cirrhotics with well-preserved liver function. In modern series, a perioperative mortality < or = 3% and 5-year survival rates above 50% are expected. Tumor recurrence complicates half of the cases at 3 years, but there is no unquestionable preventive treatment. Liver transplantation provides excellent outcomes applying the Milan criteria (single nodule < or = 5 cm or two or three nodules < or = 3 cm), with 5-year survival rates of 70% and low recurrence rates. Although expansion of selection criteria is appealing, it should be assessed in the setting of prospective well-designed studies. Intention-to-treat analysis has shown that wide extended indications lead to 25% 5-year survival rates. Living donor liver transplantation is having a minor impact in HCC management. Molecular markers are needed to better select the candidates for surgery.

Carcinoma, Hepatocellular↗
PubMed2005

Survey of health needs and concerns of rural Pennsylvanians.

INTRODUCTION: This survey was undertaken to determine the most important health and safety needs of farmers and rural citizens of Pennsylvania. METHODS: In June of 2004, a one-page questionnaire was distributed by mail to 32,700 members of the Pennsylvania Farm Bureau as an attachment to their monthly newsletter. RESULTS: The lack of affordable health care insurance was overwhelmingly cited as the most important unmet health care need (73%). No other issue was chosen by more than 10 percent of respondents. This lack of affordable health insurance was also cited as the most important health or safety problem to be addressed in the respondent's communities (71%). When asked the most important health or safety problem affecting them as individuals or their community, the respondents chose "no major problem or need" as the most frequent response (46%). The issue of affordable health insurance was not an option for this question. The predominant concern regarding the lack of affordable health insurance was consistent across all regions of the Commonwealth and for farmers as well as residents of all community sizes sampled. DISCUSSION: This study would indicate that the lack of affordable health insurance is the preeminent health and safety issue for many Pennsylvania farmers and rural citizens.

Health Services Accessibility↗
PubMed2005

The financial impact of interim and prospective payment systems on home health providers in rural communities.

The objective of the study was to examine the financial impact of the interim payment system and prospective payment system (PPS) on home health agencies (HHAs) in rural communities. Data sources used included a survey of administrators in all rural HHAs in Pennsylvania and financial and utilization data provided by 10 rural HHAs in Northwest Pennsylvania. The results of survey showed that, under the PPS, 40% of the HHAs reported financial vulnerability and 24% expressed concern that the fiscal uncertainties arising from the PPS threatened their continued operation. Two prospective analyses were conducted to examine how HHAs would be further affected by payment rate changes implemented in October 2002 and April 2003. The Medicare margin in rural Pennsylvania was 23.3% during the period from October 2000 to June 2002. This margin was slightly higher than the free-standing home health Medicare margin (21.6%) reported in analyses conducted by the Medicare Payment Advisory Commission (MedPac). However, this Medicare margin did not include hospital-based HHAs. The payment rate changes implemented in 2002 and 2003 would increase the proportion of care episodes that incur financial losses, assuming service provision remains constant. As of April 2003, the proportion of all episodes with loss would rise to 46.9%, the proportion of low-utilization payment adjustment (LUPA) episodes with loss would rise to 91.1%, and the proportion of non-LUPA episodes with loss would rise to 40.2%. New payment mechanisms are profoundly affecting the finances of rural HHAs and the use of home health services by Medicare beneficiaries.

Home Care Agencies↗
PubMed2005

Thalidomide in advanced hepatocellular carcinoma with optional low-dose interferon-alpha2a upon progression.

PURPOSE: To evaluate thalidomide in advanced hepatocellular carcinoma (HCC) and to evaluate combined thalidomide and low-dose interferon-alpha2a (IFN-alpha2a) after tumor progression on thalidomide. Systemic therapy is minimally effective in HCC and tumor angiogenesis is a potential therapeutic target. PATIENTS AND METHODS: Patients with unresectable HCC were eligible if they had preserved hepatic and renal function. The initial thalidomide dosage was 200 mg daily and was adjusted for toxicity. Upon progression, patients could continue thalidomide with additional low-dosage (one million units twice daily) IFN-alpha2a. RESULTS: Thirty-eight enrolled patients were predominantly hepatitis C virus infected (53%), Child-Pugh class A (79%), and Eastern Cooperative Oncology Group performance status 0-1 (92%); 60% had extrahepatic metastasis. Confirmed disease control was seen in seven patients (18%) and included one complete and one partial response (5% response rate). The median progression-free survival was 2.1 months, and median overall survival was 5.5 months. Tumor invasion of the portal vein or vena cava, large (>10 cm) tumor, and younger age were associated with shorter overall survival. Toxicity included fatigue in 74% of patients. Six patients stopped therapy because of side effects, including two patients (5%) with grade 4 arteriothrombotic events. Five patients continued thalidomide upon progression with the addition of IFN-alpha2a; there was no disease control and 80% had grade 3 toxicity. CONCLUSIONS: Thalidomide is not well tolerated and confers limited disease control in advanced HCC. Combination thalidomide and low-dose IFN-alpha2a is neither safe nor efficacious in this population.

Adult↗
PubMed2004

Comparison of a new fibrin sealant with standard topical hemostatic agents.

BACKGROUND: Bleeding following liver resection continues to be a significant morbidity of the procedure. Fibrin sealants represent an improvement over conventional topical hemostatic agents, because they contain components that actively form clot. However, most available agents contain nonhuman protein, which represents an immunologic risk. HYPOTHESIS: An investigational surgical fibrin sealant (Crosseal; American Red Cross, Washington, DC) composed of human clottable proteins and human thrombin is more effective than standard topical hemostatic agents in reducing the time required to achieve hemostasis after liver resection. DESIGN: Prospective, randomized, controlled trial. SETTING: Fifteen major referral centers in the United States and the United Kingdom. METHODS: After liver resection using standard surgical techniques, 121 patients seen between May 1999 and May 2000 were randomized to treatment with a 2-component fibrin sealant (n=58) or to standard topical hemostatic agents, used singly or in combination (n=63). Up to 10 mL of Crosseal was administered by a spray applicator, as recommended by the manufacturer, whereas agents used in the control group were applied according to their instructions for use. MAIN OUTCOME MEASURES: The primary outcome measured was time to hemostasis. Secondary outcomes measured included blood loss between application of the hemostatic agent and closure of the abdomen, duration of postoperative biliary drainage, and the occurrence of complications, defined a priori as reoperation for any reason, development of abdominal fluid collections, or bilious appearance of drained fluid for at least 1 day postoperatively. RESULTS: The mean time to hemostasis was 282 seconds with Crosseal, compared with 468 seconds with standard agents (2-sided; P =.06), for the 116 efficacy-evaluable patients. Hemostasis was achieved within 10 minutes in 53 patients (91.4%) treated with the study fibrin sealant and in 44 control patients (69.8%) (2-sided; P =.003). Intraoperative blood loss was similar in the 2 groups. In the Crosseal group, the percentage of patients developing postoperative complications was 17.2%, compared with 36.5% in the control group (2-sided; P =.02). CONCLUSIONS: Compared with the use of standard topical hemostatic agents, Crosseal fibrin sealant significantly reduced the time to achieve hemostasis following liver resection. Patients treated with the new fibrin sealant also experienced significantly fewer postoperative complications.

Adult↗
PubMed2004

Frequent inactivation of the tumor suppressor Kruppel-like factor 6 (KLF6) in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, reflecting incomplete characterization of underlying mechanisms and lack of early detection. Kruppel-like factor 6 (KLF6) is a ubiquitously expressed zinc finger transcription factor that is deregulated in multiple cancers through loss of heterozygosity (LOH) and/or inactivating somatic mutation. We analyzed the potential role of the KLF6 tumor suppressor gene in 41 patients who had HCC associated with hepatitis C virus (16 patients), hepatitis B virus (12 patients, one of whom was coinfected with hepatitis C virus), and other etiologies (14 patients) by determining the presence of LOH and mutations. Overall, LOH and/or mutations were present in 20 (49%) of 41 tumors. LOH of the KLF6 gene locus was present in 39% of primary HCCs, and the mutational frequency was 15%. LOH and/or mutations were distributed across all etiologies of HCC evaluated, including patients who did not have cirrhosis. Functionally, wild-type KLF6 decreased cellular proliferation of HepG2 cells, while patient-derived mutants did not. In conclusion, we propose that KLF6 is deregulated by loss and/or mutation in HCC, and its inactivation may contribute to pathogenesis in a significant number of these tumors.

Base Sequence↗
PubMed2004

Liver transplantation in patients with hepatocellular carcinoma.

The preferred therapy for hepatocellular carcinoma (HCC) apparently confined to the liver is surgical removal of the tumor. If the location of the tumor and the functional status of the liver are such that resection with an adequate margin can be achieved with low likelihood of subsequent hepatic failure, liver resection is the preferred approach. When HCC apparently localized to the liver is diagnosed in a patient who, by virtue of tumor characteristics or diminished hepatic reserve, is not a candidate for liver resection, liver transplantation becomes a consideration. This work outlines the approach at The Mount Sinai Hospital to the diagnosis, evaluation, preoperative management, transplantation, and posttransplant follow-up in patients with unresectable HCC. The allocation of livers to patients with HCC is reviewed, and predictors of tumor recurrence and results of liver transplantation for HCC are discussed. Finally, the impact of viral hepatitis and of immunosuppression on transplant outcome are discussed.

Carcinoma, Hepatocellular↗
PubMed2004

Fulminant and fatal gas gangrene of the stomach in a healthy live liver donor.

A 57-year-old male with a history of hypercholesterolemia and anxiety but otherwise in good health volunteered to donate the right lobe of his liver to his brother. The operation was performed uneventfully, without transfusion. Postoperatively he did well, until he developed tachycardia, profound hypotension, and coffee ground emesis on postoperative day 3. Despite resuscitative measures, he arrested and expired. Autopsy demonstrated gas gangrene of the stomach as the underlying cause of the hemorrhage and numerous colonies of Gram-positive bacilli were identified. Subsequent polymerase chain reaction (PCR) analysis identified these bacteria to be Clostridium perfringens (C. perfringens) type D. This patient's death was devastating, both to his family and his medical team. The impact of his death has transcended that of an individual occurrence. In conclusion, herein we present the facts and discuss this extraordinary example of florid clostridial infection and toxin-mediated shock. It was completely unexpected and probably unpreventable, and its cause was almost inconceivable.

Clostridium perfringens↗
PubMed2004

Liver transplantation for neuroendocrine tumors.

Liver transplantation for the treatment of metastatic neuroendocrine tumors (NETs) is radical. Although cure is not impossible, it is improbable. The reported experience with transplantation for NETs is limited to less than 150 cases with widely varying results and few 5-year disease-free survivors. We reviewed our experience with transplantation for patients with NETs. Fourteen symptomatic patients with unresectable NET liver metastases who had failed medical management were listed for transplantation. Two patients listed for transplantation underwent prior right lobectomies. Three patients were listed but did not undergo transplantation: one was lost to follow-up, one died 14 months after listing, and one remains waiting over 4 years. Eleven patients underwent liver transplantation, three with living donor grafts. There were four men (36.4%) and seven women (63.6%) who had a mean age of 51.2+/-6.3 years. Three patients had distal pancreatectomies and one patient had a Whipple procedure at the time of transplantation. There were six nonfunctioning tumors (54.6%), three carcinoid tumors (27.3%), and two (18.2%) Vipomas. In one patient, with fulminant hepatic failure, the NET was an incidental finding in the explant. The 1- and 5-year survival among transplanted patients is 73% and 36%, respectively, with a mean follow-up of 34+/-40 months (range 0 to 119 months). Of the three patients surviving more than 5 years, only one was disease free. In carefully selected patients with metastatic NETs, liver transplantation may be an appropriate option.

Adult↗