Evaluation of correlation of serum lipid profile in patients with oral cancer and precancer and its association with tobacco abuse

J Oral Pathol Med (2010) 39 141–148 Background: Cholesterol at either higher/lower level can be troublesome. Health issues related to higher than normal levels have received much public attention because of their relationship to incidence of heart disease, whereas implications of decreased cholesterol levels remain unclear. Present study tried to evaluate and correlate the decreased cholesterol levels in Oral cancer, Oral precancer and in tobacco abuse. Methods: Total Cholesterol ( TC), High Density Lipoproteins (HDL), Very Low Density Lipoproteins (VLDL), Low Density Lipoproteins (LDL) and Triglyceride (Tri) were estimated in 210 subjects. Out of these 210 subjects, 70 subjects were histopathologically confirmed Oral Cancer, 70 subjects were histopathologically confirmed Oral precancer (OPC) and 70, age and sex matched, healthy subjects who are not having Oral Cancer, Oral precancer and who had no history of any major illness in the past. These groups were subdivided into: Subjects with No Habit of Tobacco (NHT) and Subjects With Habit of Tobacco (WHT). Results: There was significant decrease in TC, HDL, VLDL, and triglyceride in Oral Cancer group; and significant decrease in TC, and HDL in Oral precancer group as compared to Control. Mean serum lipid profile levels were not significantly different in subjects between NHT and WHT. Conclusions: There is an inverse relationship between serum lipid profile and Oral Cancer and Oral precancer. There was no overall significant correlation of serum lipid profile with tobacco abuse.     

Alcoholic liver disease and malnutrition

Malnutrition, both protein energy malnutrition (PEM) and deficiencies in individual nutrients, is a frequent complication of alcoholic liver disease (ALD). Severity of malnutrition correlates with severity of ALD. Malnutrition also occurs in patients with cirrhosis due to etiologies other than alcohol. The mechanisms for malnutrition are multifactorial, and malnutrition frequently worsens in the hospital due to fasting for procedures and metabolic complications of liver disease, such as hepatic encephalopathy. Aggressive nutritional support is indicated in inpatients with ALD, and patients often need to be fed through an enteral feeding tube to achieve protein and calorie goals. Enteral nutritional support clearly improves nutrition status and may improve clinical outcome. Moreover, late-night snacks in outpatient cirrhotics improve nutritional status and lean body mass. Thus, with no FDA-approved therapy for ALD, careful nutritional intervention should be considered as frontline therapy.     

Centered versus noncentered source for intracoronary artery radiation therapy: a model based on the Scripps Trial

Background The Scripps Trial was a randomized study of intracoronary artery radiation therapy with iridium 192 used to treat restenotic vessels. We used the intravascular ultrasound data from the Scripps Trial to investigate whether a lumen-centered gamma or beta radiation source would reduce radiation dose heterogeneity compared with the noncentered source position used. Methods Analysis included 28 patients with stent placement in 20 native vessels and 8 saphenous vein grafts enrolled in this trial. Radiation dosimetry for gamma radiation was calculated to deliver 800 cGy to the far field target, provided the maximum dose to the near field target did not exceed 3000 cGy. Prescribed dosimetry for beta radiation by use of yttrium 90 was 1600 cGy at 2 mm distance from the source. Results The calculated average minimum source to target distance by use of a lumen-centered source increased by 0.18 mm from 1.70 ± 0.25 to 1.88 ± 0.36 mm, whereas the maximum distance decreased by 0.17 mm from 3.64 ± 0.60 to 3.47 ± 0.43 mm (P < .05). On the basis of these distances, the maximum radiation dose, as well as radiation dose heterogeneity (ratio of maximum to minimum), would have been reduced in 22 of 28 patients by use of a lumen-centered gamma or beta source (P < .005). The reduction in dose heterogeneity was substantially greater with a beta source compared with a gamma source (48% vs 16% reduction). Conclusions Centering of the intracoronary artery radiation therapy delivery catheter within the vessel lumen can significantly reduce radiation dose heterogeneity when compared with a noncentered source position. This dose reduction is substantially greater for a beta compared with a gamma source. (Am Heart J 2002;143:342-8.)     

Self inflicted, bilateral oleogranuloma of the breast: report of a bizarre case

A 30-year-old male was admitted with bilateral painful breast enlargement of 6 months duration. There was a past history of surgery for similar bilateral swellings, which was then diagnosed as fibrocystic disease. On examination both breasts were firm to hard, tender & adherent to deeper structures. A single axillary lymph node was palpable on each side. The clinical diagnosis was sarcoma of the breast. After initial denial, the patient confessed to having injected gear oil into both the breasts,for the purpose of augmentation. He was a homosexual.     

Coronary revascularisation in cardiac amyloidosis

We present a case of coronary artery bypass grafting in a 78-year-old man with triple vessel disease and concomitant cardiac amyloidosis. Postoperatively, he developed a profound low cardiac output state and multiorgan failure. He died 3 weeks following surgery. Bypass surgery is rarely performed in patients with cardiac amyloidosis, and there is little in the literature regarding outcomes. The few published cases present a bleak picture, and hence percutaneous coronary intervention should always be preferred.     

Clinical Benefit From Pemetrexed Before and After Crizotinib Exposure and From Crizotinib Before and After Pemetrexed Exposure in Patients With Anaplastic Lymphoma Kinase-Positive Non–Small-Cell Lung Cancer

BackgroundCrizotinib produces high response rates and prolonged PFS in ALK+ NSCLC. Retrospective analyses suggest enhanced sensitivity to pemetrexed in crizotinib naive ALK+ NSCLC. Cross-resistance between crizotinib and pemetrexed has not been previously investigated.Patients and MethodsPatients with stage IV ALK+ NSCLC treated with PEM-CRIZ, or CRIZ-PEM were identified. Overall PFS and PFS excluding central nervous system events (eCNS) were compared.ResultsObjective response rates in evaluable patients were 66% (PEM-CRIZ) and 75% (CRIZ-PEM) for pemetrexed and 84% (CRIZ-PEM) and 66% (PEM-CRIZ) for crizotinib. For PEM-CRIZ (n = 29), median PFS and eCNS PFS were both 6 months with pemetrexed, and 10 and 14.5 months, respectively, with crizotinib. For CRIZ-PEM (n = 9), median PFS and eCNS PFS were 4.5 and 3 months, respectively, with pemetrexed, and 8.5 and 7.5 months, respectively, with crizotinib. There was a statistically significant increase in the risk of an overall PFS event with pemetrexed when administered after crizotinib (P = .0277; hazard ratio [HR], 2.5898; 95% confidence interval [CI], 1.1100-6.0424), but differences in the risk of an eCNS PFS event were not significant (P = 0.4913; HR, 1.3521; 95% CI, 0.5727-3.1920). Neither overall nor eCNS PFS for patients while taking crizotinib was associated with a sequence effect relative to pemetrexed.ConclusionCrizotinib and pemetrexed are active drugs in ALK+ NSCLC. PFS benefit appeared higher with crizotinib than with pemetrexed. PFS benefit from pemetrexed was less after crizotinib compared with before crizotinib, however, this difference was only statistically significant for overall and not eCNS PFS. Pemetrexed exposure did not seem to affect crizotinib outcomes.     

Retracted: Genistein enhances the effect of epidermal growth factor receptor tyrosine kinase inhibitors and inhibits nuclear factor kappa B in nonsmall cell lung cancer cell lines

BACKGROUND:

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) have shown modest clinical benefit in patients with relapsed nonsmall cell lung cancer (NSCLC). Down‐regulation of Akt appears to correlate with the antitumor activity of EGFR‐TKIs. Akt activates nuclear factor kappa B (NF‐κB), which transcribes genes important for cell survival, invasion, and metastasis. The authors hypothesized that genistein, through the inhibition of NF‐κB, could enhance the activity of EGFR‐TKIs in NSCLCs.

METHODS:

Three NSCLC cell lines with various EGFR mutation status and sensitivities to EGFR‐TKIs were selected: H3255 (L858R), H1650 (del E746‐A750), and H1781 (wild‐type EGFR). Cells were treated with erlotinib, gefitinib, genistein, or the combination of each of the EGFR‐TKIs with genistein. Cell survival and apoptosis were assessed, and expression levels of EGFR, pAkt, cyclooxygenase‐2 (COX‐2), E‐cadherin, prostaglandin E₂ (PGE₂), and NF‐κB were measured.

RESULTS:

Both EGFR‐TKIs demonstrated growth inhibition and apoptosis in each of the cell lines, but H1650 and H1781 were much less sensitive. Genistein demonstrated some antitumor activity in all cell lines, but enhanced growth inhibition and apoptosis when combined with the EGFR‐TKIs in each of the cell lines. Both combinations down‐regulated NF‐κB significantly more than either agent alone in H3255. In addition, the combinations reduced the expression of EGFR, pAkt, COX‐2, and PGE_2, consistent with inactivation of NF‐κB.

CONCLUSIONS:

The authors concluded that genistein enhances the antitumor effects of EGFR‐TKIs in 3 separate NSCLC cell lines. This enhanced activity is in part because of greater reduction in the DNA‐binding activity of NF‐κB when EGFR‐TKIs were combined with genistein. Cancer 2009. © 2009 American Cancer Society.     

Updated Efficacy and Safety Data and Impact of the EML4-ALK Fusion Variant on the Efficacy of Alectinib in Untreated ALK-Positive Advanced Non–Small Cell Lung Cancer in the Global Phase III ALEX Study

IntroductionAt the prior data cutoff (February 9, 2017) the ALEX trial showed superior investigator-assessed progression-free survival (PFS) for alectinib versus crizotinib in untreated, anaplastic lymphoma kinase (ALK)-positive, advanced NSCLC (hazard ratio = 0.47, 95% confidence interval: 0.34–0.65, p < 0.001). The median PFS in the alectinib arm was not reached versus 11.1 months with crizotinib. Retrospective analyses suggest that the echinoderm microtubule-associated protein-like 4 gene-ALK variant (EML4-ALK) may influence ALK-inhibitor treatment benefit. We present updated analyses, including exploratory subgroup analysis by EML4-ALK variant, after an additional 10 months’ follow-up (cutoff December 1, 2017).MethodsPatients were randomized to receive twice-daily alectinib, 600 mg, or crizotinib, 250 mg, until disease progression, toxicity, death, or withdrawal. PFS was determined by the investigators. Baseline plasma and tissue biomarker samples were analyzed by using hybrid-capture, next-generation sequencing to determine EML4-ALK variant.ResultsBaseline characteristics were balanced. Investigator-assessed PFS was prolonged with alectinib (stratified hazard ratio = 0.43, 95% confidence interval: 0.32–0.58). The median PFS times were 34.8 months with alectinib and 10.9 months with crizotinib. EML4-ALK fusions were detectable in 129 patient plasma samples and 124 tissue samples; variants 1, 2, and 3/ab did not affect PFS, objective response rate, or duration of response. Investigator-assessed PFS was longer for alectinib than for crizotinib across EML4-ALK variants 1, 2, and 3a/b in plasma and tissue. Despite longer treatment duration (27.0 months in the case of alectinib versus 10.8 months in the case of crizotinib), the safety of alectinib compared favorably with that of crizotinib.ConclusionAlectinib continues to demonstrate superior investigator-assessed PFS versus crizotinib in untreated ALK-positive NSCLC, irrespective of EML4-ALK variant.     

Pembrolizumab in Combination With Erlotinib or Gefitinib as First-Line Therapy for Advanced NSCLC With Sensitizing EGFR Mutation

Introduction

Anti-EGFR agents are standard treatments for patients with EGFR-mutant advanced NSCLC. The feasibility of combining erlotinib or gefitinib with the anti–programmed death 1 immunotherapy pembrolizumab was evaluated in the phase 1/2 KEYNOTE-021 study (NCT02039674).