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Heparin resistance (HR) is defined as increasing requirements of heparin to maintain a therapeutic activated partial thromboplastin time (aPTT). It is commonly associated with antithrombin deficiency, increased heparin clearance and elevations in heparin binding proteins. Elevated factor VIII levels can cause decrease the aPTT levels (anticoagulant effect) without disturbing heparin activity measured by anti-Xa assay (antithrombotic effect) leading to an apparent heparin resistant state rather than a true heparin resistance. We highlight the importance of increasing awareness of apparent HR and early distinction from true resistance to avoid major life threatening hemorrhagic complications. We hereby report an unusual case of heparin resistance due to increased factor VIII levels in an elderly male with infective endocarditis.

Pancreatic tumors are resistant to conventional chemotherapies. The present study was aimed at evaluating the potential of a novel plant-derived product as a therapeutic agent for pancreatic cancer (PC). The effects of an extract from the tropical tree Annona Muricata, commonly known as Graviola, was evaluated for cytotoxicity, cell metabolism, cancer-associated protein/gene expression, tumorigenicity, and metastatic properties of PC cells. Our experiments revealed that Graviola induced necrosis of PC cells by inhibiting cellular metabolism. The expression of molecules related to hypoxia and glycolysis in PC cells (i.e. HIF-1α, NF-κB, GLUT1, GLUT4, HKII, and LDHA) were downregulated in the presence of the extract. In vitro functional assays further confirmed the inhibition of tumorigenic properties of PC cells. Overall, the compounds that are naturally present in a Graviola extract inhibited multiple signaling pathways that regulate metabolism, cell cycle, survival, and metastatic properties in PC cells. Collectively, alterations in these parameters led to a decrease in tumorigenicity and metastasis of orthotopically implanted pancreatic tumors, indicating promising characteristics of the natural product against this lethal disease.

malignant pleural mesothelioma is a relatively uncommon disease associated with asbestos exposure. its incidence increased markedly following the widespread mining and use of asbestos in many industries. the legal aspects regarding compensation cases for those who have developed this disease has raised its profile in the media, but also compounds the stress of diagnosis for patients. it has an insidious onset and may clinically and pathologically mimic other benign or malignant processes, complicating diagnosis. radical surgery may be used for a highly selected population of malignant pleural mesothelioma patients in the context of multimodality treatment in an experienced thoracic surgical centre, but there is no randomised evidence to support its benefit. in most cases surgery is used to treat symptoms or obtain tissue for diagnosis. Combination of a platinum agent and pemetrexed is now widely used and shown to prolong life. other treatments including radiotherapy, analgesics and supportive interventions are an integral part of the treatment of this disease. Further research is being undertaken on promising novel therapies for use in this disease, which will be discussed in this review. malignant pleural mesothelioma (mpm) is a neoplasm originating from mesothelial cells, which form the membranes surrounding the lung cavities. it is currently a disease mainly of the industrialised world, closely linked to asbestos exposure.1 seldom diagnosed prior to the advent of widespread asbestos mining in the early to mid twentieth century, it has risen in incidence over the last five decades.2, 3 according to the most recent australian institute of health and Welfare data, in 2009 there were 666 cases of malignant mesothelioma diagnosed in australia.4 this review will provide a brief overview of the diagnosis, current treatment modalities and some novel systemic treatment strategies that have been explored in mpm. Asbestos and malignant mesothelioma mpm is a disease with particular relevance to australia. Asbestos was first mined in Australia in the 1880s near Jones Creek, a town in nsW.5 it was not until the late 1940s when the insulating properties of asbestos rendered it a useful product in the building industry during the post war building boom, and subsequent demand for asbestos saw mining production rise exponentially in mines in nsW, tasmania, south australia and Western australia.5 there has also been widespread exposure within the building and transport industries in which asbestos was broadly utilised.6 Asbestos mining ended in Australia in 1983, and it is expected that malignant mesothelioma related to occupational exposure will plateau in the coming decade. in a Western Australian study, however, a significant increase was noted in the number of people being diagnosed with malignant meosthelioma whose only exposure to asbestos must have occurred in a non-occupational setting (most likely during home maintenance and renovation). Between 2005 and 2008, 8% of males and 5% of females diagnosed with malignant mesothelioma in this series reported non-occupational exposure as their only exposure to asbestos.6 these observations ask for confirmation in a case-controlled epidemiological study.

Thyroid disorder is a well-recognized side effect of amiodarone therapy. Thyrotoxicosis is less common than hypothyroidism. Hypokalemic periodic paralysis is one manifestation of thyrotoxicosis, and is more often seen in Oriental and Latin American men than in other demographic groups. This phenomenon, however, has not been previously described in thyrotoxicosis due to amiodarone usage. We describe a case of amiodarone-induced thyrotoxicosis in a 34-year-old man who presented with sudden lower extremity weakness, heat intolerance, and weight loss. Physical examination demonstrated fine tremors. Serum potassium level was 2.2 mEq/L on admission. Gastrointestinal and renal causes of potassium loss were excluded by history and physical examination. Further biochemical testing demonstrated abnormal thyroid function. The urinary potassium and serum bicarbonate, magnesium, and calcium levels were within normal limits. Lower extremity weakness resolved immediately after potassium replacement therapy. Methimazole therapy was initiated, and the patient was clinically euthyroid on discharge.

Epithelioid hemangioendothelioma (EHE) is a rare vascular-derived malignancy. Within the thorax, EHE originating in the pleura is less often reported than EHE originating in the lung. Pulmonary EHE has been referred to as a borderline or low-grade malignancy that exhibits an unpredictable course. It often is associated with a long life expectancy and occasional spontaneous remission. Because the natural history of pleural EHE is less well understood, a literature review was conducted to investigate the characteristics of the disease. Twenty-two cases of pleural EHE were identified. The disease occurred more often in men than women, appeared in the right thorax more often than the left, exhibited a virulent course, was usually refractory to systemic therapy, and was often associated with a short survival. These characteristics differ substantially from those of pulmonary EHE and suggest that the clinician should approach pleural EHE anticipating an especially aggressive malignancy which likely will not respond to current therapeutic measures.

Severe hemodynamic collapse after knee surgery from bilateral adrenal hemorrhages is rare. Even rarer is it occurring from adrenal hemorrhage as a complication of heparin induced thrombocytopenia. Due to lack of awareness of this rare complication and associated complex scenario in critically ill patients, diagnosis is often made post mortem. A diagnosis of bilateral adrenal hemorrhage should be considered in any patient presenting with non-specific symptoms of fever, abdominal pain, confusion and rapid hemodynamic collapse not responding to standard therapy. This is crucial especially in the setting of heparin induced thrombocytopenia as thrombosis and not hemorrhage is often the most feared complication of this syndrome.

Pulmonary toxicity is rarely seen with most commonly used targeted therapies. The endothelial growth factor receptor (EGFR) small-molecule tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib can cause interstitial lung disease (ILD). BCR-ABL tyrosine kinase inhibitors imatinib and dasatinib can cause pleural effusions. Infusion-related bronchospasm is common with the monoclonal antibodies to EGFR cetuximab and panitumumab, and case reports of bronchiolitis and pulmonary fibrosis have been described. Up to one-sixth of patients taking mammalian target of rapamycin (mTOR) inhibitors get a reversible interstitial pneumonitis. Bevacizumab, the monoclonal antibody to vascular endothelial growth factor (VEGF), has been associated with hemoptysis and pulmonary embolism particularly in patients with squamous cell lung cancer. Infusion-related bronchospasms, acute respiratory distress syndrome (ARDS), and interstitial pneumonitis can be seen with the anti-lymphocyte monoclonal antibodies rituximab, ofatumumab, and alemtuzumab. While most pulmonary toxicities from these therapies are mild and resolve promptly with dose reduction or discontinuation, it is important for the clinician to recognize these potential toxicities when faced with treatment-related complications. Discerning these pulmonary adverse effects may help in making decisions on diagnostic testing and therapy, particularly for those with pulmonary and cardiovascular co-morbidities.

The introduction of newer therapies and approaches for management has led to a renewed excitement in the field of lung cancer. This trend has continued in 2010 with the adoption of the new staging system recommended by the International Association for the Study of Lung Cancer (IASLC). Novel targets, such as EML4-ALK, have been identified and agents targeting these abnormalities have shown promise in uncontrolled clinical trials, while other strategies, including combining targeted agents with cytotoxic chemotherapy in unselected patients, have not proven to be successful. This review summarizes important recent clinical advances that could have a significant impact on the future care of patients with lung cancer.

Despite a decreasing incidence in the United States, small-cell lung cancer (SCLC) remains a major clinical problem, with approximately 30,000 new cases each year. The diagnosis of SCLC is usually not difficult. The Veterans Administration Lung Study Group (VALSG) staging system is less accurate than the American Joint Committee of Cancer tumor-node-metastasis (TNM) system (7th edition) at predicting survival in SCLC, especially in lower stage disease. Surgery has not played a major part in the management of SCLC, but emerging data suggest that resection may have a role in earlier stage disease. While the frontline treatment of SCLC has not changed significantly in the past decade, newer agents that are currently being investigated provide hope for better treatment of relapsed/refractory disease for the future.

Targeted agents have emerged as novel drugs in the oncology field based on our understanding of the biology of individual malignancies, and have had a promising impact in several tumors. Squamous cell carcinoma of the head and neck (SCCHN) is a common disease with little progress made in survival over the past few decades. SCCHN is characterized by overexpression of the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), both of which appear to have a prognostic value. Hence these receptors and their downstream pathways make attractive therapeutic targets. This review discusses targeted therapies currently being evaluated for their role in squamous cell carcinoma of the head and neck.

Laboratory data suggest an association between statins and risk of brain metastasis (BM) in patients diagnosed with lung cancer. Our retrospective cohort included 252 patients diagnosed with lung cancer and 55 (22%) patients subsequently developed BM. The risk of BM was significantly higher in younger patients (p < .0007). The multivariable Cox model did not show a significant association between statin use and BM from lung cancer (Hazard-Ratio (HR) = 1.20, 95% confidence interval (CI): 0.68–2.13). Future studies should focus on late stage NSCLC and examine the incidence of BM among statin users at the time of death.

While basal cell carcinoma (BCC) is the most common human malignancy, distant metastases from this are rare. Current therapy for disseminated BCC is based on anecdotal reports in the absence of clinical trials to guide management. For many years, platinum based cytotoxic chemotherapy was the mainstay of treatment. Advances in the understanding of the biology of BCC have led to the development of targeted therapies (e.g. inhibitors of the hedgehog and the epidermal growth factor receptor pathways) that are currently being investigated in this disease. This review summarizes the available data on the epidemiology and management of disseminated BCC.

The incidence of lung cancer in females is increasing, in contrast to that seen in males. In addition, the proportion of lung cancer cases in women attributable to smoking is approximately half of that seen in males. Female sex hormones, especially estrogen, may play a key role in this. Estrogen receptors ERalpha and ERbeta have been detected on lung cancer cells and there is new evidence suggesting that hormone-replacement therapy may increase both the incidence of, and mortality from, lung cancer in women. Laboratory evidence lends credence to the carcinogenic effects of estrogens in lung cancer. This article summarizes the current evidence on their role in lung cancer.

Despite accounting for more than half of the patients diagnosed with non-small cell lung cancer (NSCLC), only 20% of elderly patients receive chemotherapy. One reason for withholding systemic therapy is the concern for an increased incidence of side-effects, especially cytopenia from bone marrow toxicity. Limited data exist regarding specific factors that affect blood count nadirs following chemotherapy.A retrospective chart review was conducted of chemotherapy-naïve patients who had received standard doses of carboplatin and paclitaxel for NSCLC. Hemoglobin levels, total white blood cell counts (WBC) and platelet counts before each chemotherapy cycle and nadir counts following each cycle were obtained. Wilcoxon test and Chi-square test were used for univariate comparisons of patient characteristics and unpaired t-test for hematological parameters. Multivariate analyses of change over time in the hematological parameters by age groups were performed using mixed models while adjusting for other clinical factors.Of the 91 consecutive patients identified from the medical records between 1992 and 2007, 37 (41%) were60 years old at diagnosis. Pre-chemotherapy and nadir values for hemoglobin, WBC and platelet counts did not vary by age over time. The nadir values correlated with the corresponding pre-chemotherapy values. Both the pre-chemotherapy and nadir values showed a decreasing trend with increasing numbers of chemotherapy cycles administered.Age does not affect the nadir counts of hemoglobin, WBC and platelets following administration of carboplatin and paclitaxel for NSCLC. Pre-chemotherapy blood counts are more important determinants of hematologic toxicity following administration of carboplatin and paclitaxel for advanced NSCLC.

Cyclins and cyclin-dependent kinases (CDK) form a key part of the regulatory proteins that govern the cell cycle. Aberrancy in their function can lead to uncontrolled growth and proliferation of the cells which forms the basis of many human diseases, especially cancers. Seliciclib (CYC202, R-roscovitine) is a second-generation CDK inhibitor that competes for ATP binding sites on these kinases, reducing tumor growth and inducing cell death. It is a direct inhibitor of cyclin E/CDK2 and also has inhibitory effects on cyclin H/CDK7 and cyclin T/CDK9. Seliciclib leads to growth arrest and apoptosis of cell lines through activation of the p53 gene, inhibition of RNA processing and blockage of the RNA polymerase II-dependent transcription, and reduction of anti-apoptotic proteins. Seliciclib has good oral bioavailability, although its absorption is slowed by food. It is distributed rapidly to the body tissues and metabolized rapidly to a carboxylated derivative that is excreted by the kidneys. The major adverse effects of seliciclib are electrolyte disturbances (hypokalemia, hyponatremia), gastrointestinal side effects (nausea, emesis, anorexia), fatigue, transient hyperglycemia, elevation of liver enzymes and reversible elevation of serum creatinine. At present, it is in Phase II trials for non-small cell lung cancer and nasopharyngeal carcinoma.

Cancer is a disease of the elderly with the majority of new diagnoses and deaths from cancer occurring in persons greater than 65 years of age. A major goal of cancer therapy, in the elderly is the preservation of functional independence and quality of life. The advent of targeted therapies has raised the hope that older patients with cancer could be treated as effectively as younger patients and without added toxicities. However, caution must be exercised while addressing the use of these therapies in the elderly population and only after taking into consideration the risks, benefits and prognosis of patients on an individual basis. This article reviews the current literature on the efficacy, cost-effectiveness and toxicity of the currently approved targeted agents in the elderly population.

Background. Concurrent chemoradiotherapy with cisplatin is the standard therapy for patients with unresectable locally advanced head and neck squamous cell carcinoma. However, cisplatin administration in patients on hemodialysis is complicated by the need to perform hemodialysis immediately after the infusion. Concurrent chemoradiation with cetuximab has been approved in definitive treatment of locally advanced head and neck cancer. Although cetuximab is not excreted via the kidneys, its use in patients on hemodialysis has not been reported. Methods and Results. We present the case of a 65-year-old man undergoing hemodialysis, with stage IVA squamous cell carcinoma of the hypopharynx. Given the logistics of performing hemodialysis immediately postcisplatin, he received concurrent chemoradiotherapy with cetuximab. He tolerated treatment well with minor side effects. Conclusion. Cetuximab can be safely used in patients with renal impairment. This is the first reported case of the use of cetuximab in a patient undergoing hemodialysis. © 2009 Wiley Periodicals, Inc. Head Neck, 2009

Elderly patients with advanced non-small cell lung cancer (NSCLC) are at higher risk for adverse events related to treatment of their disease. Chemotherapeutic agents used alone or together may increase survival, while leading to increased treatment related morbidity. New targeted agents used to treat NSCLC have yet to show sufficient improvement in disease outcomes. This review will discuss the current management of elderly patients with advanced non-small cell lung cancer.

Previous meta-analysis on three drugs combination for treatment of advanced non-small cell lung cancer (NSCLC) did not demonstrate an improvement in survival, however many of the trials included in this meta-analysis used older and less effective cytotoxic drugs. We conducted this analysis to compare the relative efficacy of third generation triplet therapy with that of standard double therapy in the treatment of advanced NSCLC.A MEDLINE search was performed using the search terms "lung cancer" and "randomized trials". Trials not utilizing a third generation cytotoxic chemotherapeutic agent (paclitaxel, docetaxel, vinorelbine, gemcitabine) were excluded. Pooled odds ratios (OR) for the objective response and toxicity rates were calculated using the Mantel-Haenszel estimate. Pooled median ratios for median survival were calculated using the weighted sum of the log-ratio of median ratios of individual study.We analyzed six randomized comparative trials involving 1932 patients. Patients receiving triplet therapy had a significantly higher response rate (OR: 1.33; 95% CI, 1.50-2.23; P0.001). Incidence of grade III/IV hematological toxicity was higher with triplet therapy. Non-hematological toxicities, with the exception of neuropathy, were similar. Median survival of triplet therapy was not significantly different from doublet (MR: 1.10; 95% CI: 0.91-1.35; P=0.059).Triplet therapy with third generation cytotoxic drugs is associated with higher tumor response rate at the expense of increased toxicity. Although triplet therapy had a better overall survival compared to doublet therapy, this did not reach statistical significance.

Summary Background Risk factors for development of lung cancer include a family history of the disease. The effect of family history on lung cancer outcomes is unknown. A study was conducted to investigate this. Methods The medical records of all patients with lung cancer seen in an academic medical oncology lung cancer clinic between 1999 and 2006 were reviewed for outcomes and family history of lung cancer. χ2-test and Wilcoxon test were used for univariate comparisons, while Cox Proportional Hazards regression analysis was used to evaluate the adjusted risk of death. Univariate probability of survival was computed using Kaplan–Meier estimate and compared using the log-rank test. Results Of the 560 patients evaluated, 289 (51%) were male and 519 (93%) had a smoking history. Of the 148 patients (26%) with a family history of lung cancer, 115 had an affected first-degree relative. No association between family history and histology or stage at diagnosis was detected. Median survival in patients with a family history of lung cancer was 53 months compared to 58 months in patients without such a history (p = 0.06). Patients with a positive family history had an adjusted relative risk of death of 1.65 (95% CI: 1.07–2.56; p = 0.02) compared to those without a family history. This risk was especially increased in those with an affected first-degree relative (RR: 1.72; 95% CI: 1.08–2.75, p = 0.02). Conclusions Lung cancer patients with a first-degree relative with lung cancer have a poorer outcome than those without such a history.

PURPOSE To compare the resource utilization and clinical outcomes of medical care delivered on general internal medicine inpatient services at teaching and nonteaching services at an academic hospital. METHODS From February to October 2002, 2189 patients admitted to a 450-bed university-affiliated community hospital were assigned either to a resident-staffed teaching service (n = 1637) or to a hospitalist- or clinic-based internist nonteaching service (n = 552). We compared total hospital costs per patient, length of hospital stay (LOS), hospital readmission within 30 days, in-hospital mortality, and costs for pharmacy, laboratory, radiology, and others between teaching and nonteaching services. RESULTS Care on a teaching service was not associated with increased overall patient care costs ($5572 vs. $5576; P = .99), LOS (4.92 days vs. 5.10 days; P = .43), readmission rate (12.3% vs. 10.3%; P = .21), or in-hospital mortality (3.7% vs. 4.5%; P = .40). Mean laboratory and radiology costs were higher on the teaching service, but costs for the pharmacy and for speech therapy, occupational therapy, physical therapy, respiratory therapy, pulmonary function testing, and GI endoscopy procedures were not statistically different between the 2 services, and residents did not order more tests or procedures. Case mix and illness severity, as reflected by the distribution of the most frequent DRGs and mean number of secondary diagnoses per patient and DRG-specific LOS, were similar on the 2 services. CONCLUSIONS At our academic hospital, admission to a general internal medicine teaching service resulted in patient care costs and clinical outcomes comparable to those admitted to a nonteaching service. Journal of Hospital Medicine 2007;2:150–157. © 2007 Society of Hospital Medicine.

Almost 40% of patients with newly diagnosed small-cell lung cancer (SCLC) have disease confined to the ipsilateral hemithorax and within a single radiation port, i.e., limited-stage disease. The median survival for this group of patients after treatment is approximately 15 months, with one in every four patients surviving 2 years. Current optimal treatment consists of chemotherapy with platinum/etoposide, given concurrently with thoracic radiation. Surgery may represent an option for very early-stage disease, but its added value is uncertain. Prophylactic cranial irradiation (PCI) is used for patients with limited-stage SCLC who have achieved a complete response following initial therapy, as it decreases the risk of brain metastases and provides an overall survival benefit. Newer targeted agents are currently being evaluated in this disease and hold the promise of improving current outcomes seen in patients with early-stage disease.

e17590 Background: Race and insurance status are socio-demographic characteristics that influence extensive stage (Stage IV) lung cancer incidence (Halpern MT, et al. (2008) Association of insuranc...

7577 Background: Conditional survival (CS) has emerged as a clinically useful measure of prognosis for cancer patients with poor prognosis. We examined the efficacy of prophylactic cranial irradiat...

7550 Background: Conditional survival (CS) is a more accurate measure of survival probability among cancers associated with a poor prognosis. We calculated lung cancer-specific CS estimates to help clinicians and patients with informed decision making. Methods: Lung cancer patients with at least 3 years of follow-up were identified from the Surveillance Epidemiology and End Results registry (2004-2008). American Joint Commission on Cancer, sixth edition was used for staging non-small cell lung cancer (NSCLC). Stages 1 to 3 SCLC were classified as limited stage (LS), and stage 4 was classified was extensive stage (ES). Multivariate Cox regression models were built separately by stage to calculate the adjusted 1-6 year cancer-specific survival and overall survival. The multiplicative law of probability was then used to compute the X-year conditional survival where the (x+y) year survival is divided by y years of patients who have survived. The following were adjusted: age, sex, ethnicity, marital status, SE...

6558 Background: Demographic characteristics, especially race and insurance status, affect the incidence of lung cancer diagnosed at Stage IV1. This is the largest epidemiological study to determin...

The aim of the present study was to assess the efficacy of vincristine-laden platelet transfusion for patients with refractory thrombocytopenia.Twenty evaluable patients who received vincristine-laden platelets for refractory thrombocytopenia were included in this retrospective study. Vincristine (1 mg) was added to the platelets and incubated for one hour prior to transfusion. Serial platelet counts following vincristine-laden platelet transfusion and units of platelets transfused in the week prior to and the week after transfusion of vincristine-laden platelets were evaluated.The underlying diseases of the patients were lung cancer (n =4), breast cancer following autologous hematopoietic stem cell transplantation and acute myeloid leukemia (n=3 each), myelodysplastic syndrome (n=2), acute lymphoid leukemia, chronic lymphoid leukemia, chronic myeloid leukemia, multiple myeloma, ovarian cancer, aspergillosis, cytomegalovirus infection and systemic lupus erythematosus (n = 1 each). The median rate of change of platelet count after transfusion of vincristine-laden platelets was 550/microL/day (range, -1,000 to 12,8001/microL/day; p=0.003). The median change in the number of units of platelets transfused in the week following vincristine-laden platelet transfusion was -1.5 as compared to the week prior to the transfusion (p=0.031). Patients with a primary marrow disorder exhibited no difference in either the rate of change in platelet count or in the difference in the units of platelets transfused compared to those without a primary bone marrow disorder.Vincristine-laden platelet transfusion was associated with significantly increased platelet counts and a subsequent decrease in platelet transfusion.

Background The aim of the study was to determine the outcome and clinical features predictive of survival in patients with follicular lymphoma (FL) treated aggressively and to determine the rate of disease-specific mortality in patients with grade 3 FL (FL3). Materials and methods Four hundred and twenty-one patients with FL who were treated with various anthracycline-based chemotherapy regimens were included in this retrospective study. Results Patients with FL3 and a diffuse component of >50% had the worst outcome, with a hazard ratio of dying of 2.2 (95% CI 1.4–3.4) compared with patients with FL1 or FL2, and a ratio of 1.6 (95% CI 1.02–2.5) compared with FL3 with a diffuse component of ≤50% by multivariate analysis (P = 0.0026). Patients with FL3a had an outcome similar to those with FL3b. In patients with FL3 and a diffuse component of ≤50%, the overall and event-free survival curves showed a plateau for patients younger than 60 years of age. However, there were no differences in the cumulative incidence of relapse/progression or lymphoma-specific/treatment-related mortality between the two age groups. Conclusions Less than half of the patients with FL3 and a diffuse component of ≤50% treated with anthracycline-based combination chemotherapy will relapse and relapses are uncommon after 6 years. Older patients should be offered the same aggressive chemotherapy as younger patients.

BACKGROUND: With improvements in the treatment of Hodgkin lymphoma (HL) over time, we hypothesized a reduction in disease progression, and an increase in progression-free (PFS) and overall survival (OS) over the past 3 decades. METHODS: This is a retrospective study that included previously untreated HL patients reported to the Nebraska Lymphoma Study Group between 1983 and 2012. To analyze trends in outcomes, we divided the cohort into 3 time periods of 10 years each (1983-1992, 1993-2002, 2003-2012) to represent early (E), middle (M) and late (L) time periods. Patient, disease, and treatment-related factors as well as clinical outcomes (cumulative incidence of progression, PFS and OS) were compared according to time period. Multivariate analyses (MVA) were performed using Cox regression to adjust for significant covariates. RESULTS: In this retrospective review, 528 patients were identified during the study period: E (n=120), M (n=208), L (n=200). Patients in the more recent cohort (L) were more likely to be younger (p=0.008), have better performance score (p CONCLUSIONS: Changes in upfront treatment regimens for HL over the last 3 decades have resulted in significant improvement in PFS and OS, and modest improvement in the risk for progression. Disclosures No relevant conflicts of interest to declare.

The aim of this study was to determine the survival of untreated stage I and II in non-small cell lung cancer (NSCLC) patients.A retrospective analysis of medical charts of all patients diagnosed with early stage NSCLC, between January 1990 and December 2001, was conducted and patients who were not treated were identified. Data on patient's age, gender, stage of the disease, pathology, reason for non-treatment and cause of death were reviewed.Thirty-nine patients with untreated stage I and II NSCLC were identified. The median age at diagnosis was 77 years; 66.7% were men and 33.3% were women. All patients were Caucasian and 66.7% had stage I disease, 46.2% had squamous cell carcinoma, while adenocarcinoma was found in 28.2%. The major reason for non treatment was chronic obstructive pulmonary disease (64.1%) and the main cause of death was metastatic disease (48.7%). The overall mean survival was 11.9 months. The mean survival at stage I was not statistically different from the mean survival at stage II (13.7 months vs. 8.4 months) (p0.12).Patients with untreated early stages NSCLC have a very poor prognosis. Alternative therapies that are better tolerated should be investigated in these patients with early stage NSCLC who cannot be offered standard treatment.

BACKGROUND Patients with mantle cell lymphoma (MCL) have in general, lower response rates and overall survival (OS) than those with other B-cell non-Hodgkin's lymphomas. The role of hematopoietic stem cell transplantation (HSCT) in MCL is unclear. Hence we decided to study the clinical course of patients who received autologous and allogeneic HSCT for MCL. METHODS Ninety-seven patients, (80 patients-autologous; 17 patients-allogeneic) who received a HSCT for mantle cell lymphoma were included in the study. RESULTS The complete response rates at day 100 between the two groups were similar (73% vs. 62%). Day-100 mortality was higher in the allogeneic HSCT group (19% vs. 0%) (P < 0.01). The estimated 5-year relapse rates, 5-year event-free survival (EFS) and 5-year OS among the allogeneic HSCT patients were 21%, 44% and 49%, respectively, similar to 56%, 39% and 47% in the autologous group. Ten patients received HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone + high-dose methotrexate and cytarabine) +/- rituximab prior to transplant. There have been no relapses or deaths amongst these patients at a median follow-up of 16 months. CONCLUSIONS Patients treated with allogeneic HSCT had a lower relapse rate, but similar EFS and OS to autologous HSCT. Treatment of MCL with HyperCVAD +/- rituximab followed by HSCT seems promising.

The most common indolent lymphoma, follicular lymphoma comprises 35% of adult non-Hodgkin's lymphoma (NHL) in the United States and 22% worldwide. Features associated with adverse outcome include age, male gender, disease stage, and performance status, with the International Prognostic Index being the most widely used risk classification system. Long-term disease-free survival is possible in select patient subgroups after treatment, but very late relapses suggest that quiescent lymphoma cells might be harbored for long periods of time. Radiation therapy is the mainstay of treatment for limited-stage follicular lymphoma, but there is some experience with chemotherapy and combined chemoradiation. When to initiate treatment in patients with advanced disease is controversial, but options include various combined chemotherapy regimens, monoclonal antibodies, radiolabeled antibodies, and bone marrow or stem cell transplantation. Future directions in the treatment of follicular lymphoma include vaccines, antisense therapy, and proteasome inhibitors.

The aim of this study was to determine the incidence of HER-2/neu, VEGF and CD117 overexpression in soft tissue sarcomas (STS) and to study the effect of this overexpression, if present, on survival in patients with specific histological subtypes of STS.We conducted a retrospective observational study on patients diagnosed with STS during the period of 1986-2001. HER-2/neu overexpression was measured in these patients by immunohistochemistry (IHC) using the Hercep test developed by DAKO. VEGF expression was detected by the avidin-biotin-complex method using Santa Cruz biotechnology (SC 7629). Immunohistochemical staining for c-kit was performed using a 1:250 dilution of the rabbit polyclonal antibody A4502 (IMPATH, CA) with the EnVision detection system.Two hundred and seventy three patients were diagnosed as having STS between 1986 and 2001, however of these patients, only 90 (51 females and 49 males) had enough sample available for testing. Patients who overexpressed VEGF had a significantly shorter survival (23 vs. 52 months; p=0.01). There was no effect of overexpression of either CD117 or HER-2/neu on survival. Studying the individual histological subtypes we found that, in malignant fibrous histiocytoma, overexpression of either VEGF or CD117 increased survival (41.3 vs. 19.5 months, p=0.01; and 84.5 vs. 17 months, p=0.006 respectively). In leiomyosarcoma, VEGF overexpression significantly decreased survival (7.5 vs. 76 months, p=0.03), while CD117 overexpression significantly increased survival (70.9 vs. 46.3 months, p=0.03).VEGF overexpression is associated with an adverse outcome in STS. Whether this is true of any particular histological subtype is unclear and needs further investigation. Also, site-specific agents targeting these three bio-markers (alone or with conventional therapy) may have a therapeutic role and need to be elaborated in future clinical trials.

The examination of Prussian-blue-stained bone marrow aspirates for the presence or absence of histiocytic iron granules has been considered the gold standard in evaluating iron-depeleted states. We performed this study to evaluate the predictive accuracy of absent stainable bone marrow iron for iron deficiency anemia (IDA). A retrospective study was performed on an unselected series of 53 consecutive bone marrow biopsy specimens. Only those patients who had totally depleted iron stores and who had iron studies done within 6 months of bone marrow biopsy were included in the study. Based on these criteria, 12 patients were found eligible. After complete evaluation to determine the cause of the patient's illness, the final diagnosis was IDA in only 6 patients (50%). There was no significant difference between the two groups as regards hemoglobin level, reticulocyte count, serum iron levels, total iron binding capacity, red blood cell mean corpuscular volume, ferritin and the transferrin saturation levels. The finding of absent bone marrow iron stores is not necessarily predictive of iron deficiency anemia. The finding of absent stores of iron in the bone marrow needs to be taken in conjunction with other laboratory findings and the clinical scenario while making a diagnosis of IDA, since certain other hematological diseases may co-exist.

The aim of this study was to evaluate the relationship, if any, between pesticide exposure and overexpression of the HER-2/neu oncoprotein in extensive stage small cell lung cancer (ESSCLC).The records of all patients with a diagnosis of ESSCLC from January 1991 through April 2001 were reviewed in our retrospective study. Pesticide risk (herbicide and insecticide) was assessed by telephone interviews using a predetermined questionnaire with emphasis on type of exposure, use of protective measures, and duration of exposure. An exposure index was calculated (h/day x days/year x years), and patients with an index2400 h were considered as exposed. HER-2/neu overexpression was assessed by immunohistochemistry using the Hercep test developed by Dako. Statistical analysis was performed using SPSS-10.A total of 193 patients (84 females and 109 males), with a mean age of 68.5 years (range, 42-90 years) were included in the study. Of these, 57 (29.5%) revealed HER-2/neu overexpression by immunohistochemistry. After adjusting for age, smoking, Eastern Cooperative Oncology Group score, and treatment, HER-2/neu overexpression was associated with a statistically significant diminished survival (P0.001; Mann-Whitney U test). We contacted 53 of 57 patients with overexpression and 121 of 136 patients without HER-2/neu overexpression to ascertain a history of pesticide exposure. Forty-one of 53 (77.4%) patients with HER-2/neu overexpression and 47 of the 121 patients without overexpression (38.8%) were exposed to pesticides. We found that patients with history of pesticide exposure had a higher risk of having HER-2/neu overexpression (odds ratio, 5.38; P0.01, 95% confidence interval, 2.5-11.2)HER-2/neu is overexpressed in approximately 30% patients with ESSCLC and is associated with decreased survival. Also, pesticide exposure seems to be related to HER-2/neu overexpression seen in our patient population. Future studies are needed to validate our findings and also to determine which pesticide(s)/pesticide components are actually responsible for HER-2/neu overexpression seen in ESSCLC.

A 58-year-old male presented with fatigue, tiredness, and pruritus after hot showers and an elevated white blood cell count (20000/mm(3)). A diagnosis of polycythemia vera (PV) was made after investigation revealed a low erythropoietin and elevated leukocyte alkaline phosphatase (LAP) score; he was treated with repeated phlebotomies. Two years later he developed elevated white counts again and investigation revealed Philadelphia chromosome positive (19/20 cells) chronic myelocytic leukemia (CML). The karyotype also revealed trisomy 9 in 1 of 20 cells. He was treated with imatinib mesylate and went into clinical, hematologic, cytogenetic, and molecular remission. Repeat chromosomal analysis revealed absence of Philadelphia chromosome and BCR/ABL translocation but presence of trisomy 9. To our knowledge, this is the first reported case of coexisting PV and CML both associated with separate chromosomal abnormalities. This also raises an interesting therapeutic consideration of using concomitant imatinib mesylate and hydroxyurea.

Of the major myeloproliferative syndromes (MPS) [polycythemia vera (PV), essential thrombocythemia (ET), chronic myeloid leukemia (CML) and myelofibrosis (MF)], PV and ET are reported to be associated with increased thrombotic complications. However, the relationship between these myeloproliferative syndromes and coronary artery disease (CAD) is unclear.We performed a retrospective chart review to evaluate the prevalence of CAD in patients with diagnosed with MPS between 1991 and 2001.One hundred and eighty-one patients (100 males, 81 females) with a mean age of 72.5 years were included. Twenty-nine patients, 19 males and 10 females (16%, 95% CI: 12.0-24.0) had CAD. These included 6/53 (11.3%, 95% CI: 1.5-20.2) patients with CML, 1/26 (3.8%, 95% CI: -4.4 to 12.8) patients with PV, 5/30 (16.7%, 95% CI: 2.5-30.8) patients with ET, 3/7 (42.9%, 95% CI: 12.3-87.7) patients with MF and 14/65 (21.5%, 95% CI: 13.1-37.8) patients with co-existent MPS. Comparing the risk of CAD with CML as a baseline, MF had an OR of 8.2 (p0.01, 95% CI: 1.7-39), PV-0.4 (p = 0.4, 95% CI: 0.04-3.2), ET-1.6 (p = 0.7, 95% CI: 0.43-6.2) and patients with co-existent MPS-2.8 (p=0.07, 95% CI: 0.91-8.6). However, after adjusting for age, sex, dyslipidemia, diabetes, hypertension and tobacco use, the difference in the prevalence of CAD between the various categories of MPS was not significant.Contrary to conventional belief, we did not find an increased prevalence of CAD in patients with either PV or ET. In fact, patients with MF had a significantly higher prevalence of CAD. However, this difference appears to be due to the increased age at diagnosis of MF. The conventional risk factors for CAD appear to be the major determinants of CAD among patients with MPS.

The prevention of skin cancer relies not only on the knowledge of the risks of ultraviolet rays, but also on the appropriate measures to minimize solar exposure. We conducted a questionnaire-based survey among a rural population to evaluate perceptions regarding (i) sun-related behaviors, (ii) measures taken to protect themselves, and (iii) self-skin assessment knowledge. Questions included data on patients’ knowledge of deleterious effects of sun exposure, their habits and perceptions about adequate protection, their knowledge of a suspicious cutaneous lesion, and if a physician had spoken to them about the risks of ultraviolet/solar exposure. One hundred and six adults (38 males and 68 females) seen in a primary care clinic were enrolled in our study. Of these, only 38.7% of our patients were concerned about their risk of cutaneous malignancies. On analysis of the sun-protection variables, we found an increased use of tanning beds among women and an increased use of hats in men. Interestingly, we also found that only 18% of respondents used sunscreen when anticipating sun exposure. With suspicious skin lesions, color of the lesion appeared to be the most concerning factor for the subjects, with increasing size being the second most likely factor of concern. Only 11.3% of respondents had a physician-performed skin assessment and only 19.8% performed self-skin assessments at least yearly. There seems to be a lack of appropriate knowledge regarding precancerous and cancerous skin lesions among rural communities. Increased patient education is urgently necessary in rural populations to decrease the growing incidence of cutaneous malignancies.

To evaluate the prevalence and role of vascular endothelial growth factor (VEGF) overexpression in soft tissue sarcoma (STS). VEGF expression was detected by the avidin-biotin-complex method using Santa Cruz biotechnology (SC 7629). The expression of VEGF was assessed according to the percentage of immunoreactive cells: more than 10% of the cells staining were graded as positive. No detectable staining or

Co-morbidity has a major impact on survival in early and late-stage lung carcinoma. Patients maintained on dialysis are potentially at increased risk of cancer. However, since very few studies have examined the clinical course of lung cancer in patients with chronic kidney disease (CKD), we felt it was important to study the course of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) in this patient population. We performed a retrospective chart review of patients diagnosed with lung cancer and co-existent CKD. 107 patients (101 males and six females), with a mean age at diagnosis of 69 years (range: 39-86 years) were included in our study. Of these, 17 (15.9%) patients had SCLC while 87 (81.3%) had NSCLC. Dyspnea, weight loss, and chest pain were the most common symptoms at presentation in our patient population occurring in 25, 20, and 15% of patients, respectively. The median survival of all the patients in the study was 10 months (range: 0-116 months). Patients with SCLC had a median survival of 7 months. Patients with NSCLC had a median survival of 10 months. We found that the clinical course and survival in patients with lung cancer and CKD appear to be comparable to that of patients with lung cancer, but without kidney dysfunction. Hence though treatment of lung cancer does need to be individualized in the setting of CKD, it should not dissuade the clinician from treating the malignancy.

Sarcomas currently represent 1% of adult malignancies and 15% of pediatric malignancies. To determine the prevalence of HER-2/neu overexpression by the histologic type and to identify a possible predictive role in patients with sarcoma, we performed a retrospective study on subjects with a biopsy-proven diagnosis of a soft tissue sarcoma. HER-2/neu overexpression was evaluated using immunohistochemistry (IHC) performed on paraffin-embedded specimens. An IHC score of 2+ or greater was considered positive for overexpression. Two hundred seventy-three patients with soft tissue sarcoma were identified (164 females, 109 males) with a mean age of 56 (range: 1-93). The most common tumors identified were malignant fibrous histiocytoma (MFH) (18.3%), dermatofibrosarcoma (DFS) (16. 1% ), leiomyosarcoma (13.2%) and carcinosarcomas (CS) (7.3%). Of the 273 specimens, 29(10.6%) revealed HER-2/neu overexpression. CS, MFH, and DFS specimens showed the highest incidence of HER-2/neu overexpression (40%, 26%, and 18.2%, respectively). The incidence of HER-2/neu overexpression was found to be significantly higher in patients with a survival of less than 8 months (p = 0.035). This demonstrates that HER-2/neu overexpression is preferentially seen in certain soft tissue sarcomas, and when present is associated with a poorer prognosis in patients with sarcoma. Further studies would delineate whether HER-2/neu overexpression renders sarcomas chemoresistant and thus adversely affects outcome. In addition, there may be a role for Herceptin (trastuzumab) alone, or in combination with conventional therapy, in patients with CS, MHF, and DFS.

The endothelium is a dynamic organ and responds to various physical and humoral conditions. The endothelium secretes several biologically active substances, both vasoconstrictors and vasodilators, which control these processes. Endothelial function is most commonly assessed as the vasodilatory response to stimuli. Several endothelium-dependent agonists have been identified, each of which acts through a membrane receptor. Nitric oxide which is continuously synthesized by the endothelium has a wide range of biological properties that maintain vascular homeostasis. It is a potent vasodilator and inhibitor of platelet aggregation and thus has an important protective role. Endothelial dysfunction in hypercholesterolemic patients is in large part due to a reduced bioavailability of NO. Traditional coronary risk factors, especially hypercholesterolemia, produce endothelial dysfunction even in patients with normal blood vessels. The underlying mechanisms involve a local inflammatory response, release of cytokines and growth factors, activation of oxidation-sensitive mechanisms in the arterial wall, modulation of intracellular signaling pathways, increased oxidation of low-density lipoprotein cholesterol, and quenching of nitric oxide. Clinical studies have shown a significant improvement in endothelial dysfunction following lowering of serum cholesterol levels, infusion of nitric oxide donors like L-arginine and exercise training. Clinical trials are underway examining the role of endothelin-1 receptor antagonists like bosentan in the prevention of graft atherosclerosis.

Thyroid disorder is a well-recognized side effect of amiodarone therapy. Thyrotoxicosis is less common than hypothyroidism. Hypokalemic periodic paralysis is one manifestation of thyrotoxicosis, and is more often seen in Oriental and Latin American men than in other demographic groups. This phenomenon, however, has not been previously described in thyrotoxicosis due to amiodarone usage. We describe a case of amiodarone-induced thyrotoxicosis in a 34-year-old man who presented with sudden lower extremity weakness, heat intolerance, and weight loss. Physical examination demonstrated fine tremors. Serum potassium level was 2.2 mEq/L on admission. Gastrointestinal and renal causes of potassium loss were excluded by history and physical examination. Further biochemical testing demonstrated abnormal thyroid function. The urinary potassium and serum bicarbonate, magnesium, and calcium levels were within normal limits. Lower extremity weakness resolved immediately after potassium replacement therapy. Methimazole therapy was initiated, and the patient was clinically euthyroid on discharge.

Mantle cell lymphoma (MCL) is a low-grade lymphoproliferative malignancy that is extremely refractory to chemotherapy. Commonly used treatments have yielded unfavorable response rates (30% complete remission). We evaluated the incidence of c-kit (CD117) and vascular endothelial growth factor (VEGF) overexpression in patients with MCL in an effort to identify possible targets for therapeutic intervention.Patients with a diagnosis of MCL based on CD5 positivity associated with cyclin D1 positivity and CD23 negativity on the lymph node/bone marrow specimen were included in our retrospective study. CD117 overexpression was performed using immunohistochemistry on archival specimens. VEGF expression was detected by the avidin-biotin-complex method.Between 1997 and 2001, we identified 17 patients with MCL (9 males, 8 females) with a mean age of 57 years (age range: 42-66 years). The mean overall survival was 34 months (range: 11-60 months). VEGF expression was identified in 7 out of 17 (41.18%) patients with MCL. Among the VEGF-positive patients (n = 7, 41.1%), the mean survival was 24 months (range: 11-42 months), while patients without VEGF expression (n = 10, 58.9%) had a mean survival of 44 months (range: 21-60 months). CD117 expression was identified in only 2 out of 17 (1.17%) patients in our study.Our study evaluated the role of c-kit and VEGF overexpression in MCL. Although CD117 may not be of therapeutic significance, target-directed signal transduction inhibition therapy using VEGF-inhibitors may be a distinct possibility in a select group of patients with MCL. Future larger studies are urgently needed to elaborate the role of VEGF in MCL.