Notes

Therapy-induced Genetic make-up methylation inactivates MCT1 as well as provides growth cellular material prone to MCT4 inhibition.
Finally also the link between the mesangial and the podocyte injury and the tubulointerstitial scarring, as well as the mechanisms involved need to be better clarified.In the past few decades pediatric urolithiasis has become more frequent. The reason for this increase is not completely clear but has been attributed to changes in climate, nutritional habits and possibly other environmental factors. Although less frequent than adult stone disease, urolithiasis in the pediatric age group is also related to significant morbidity, particularly since stones tend to recur, and, thus, should not be underestimated. Most children with idiopathic stone disease have an underlying metabolic abnormality substantiating the importance of metabolic evaluation already following initial diagnosis of urolithiasis. Identification of the metabolic abnormality allows for more specific prescription of non pharmacological and pharmacological interventions aimed at preventing recurrent stone formation. A better understanding of the causes of kidney stone disease will provide better strategies for stone prevention in children.
The incidence of grade 3/4 adverse effects due to S-1 therapy and the efficacy of S-1-based therapy vs. S-1 monotherapy have not been well described. We conducted an updated meta-analysis to evaluate this problem.

We searched the electronic databases, including PubMed, Embase, and Cochrane database to investigate the effects of phase 2 and 3 prospective clinical trials on first-line S-1 therapy in cancer patients. Data from included studies were pooled using Stata version 12.0.

Twenty eight studies were included. First-line S-1 monotherapy showed low incidence of grade 3/4 adverse effects. And the highest rate grade 3/4 hematological event was neutropenia [7%, 95% confidence interval (CI) 5-8%]; the highest rate grade 3/4 non-hematological event was anorexia (7%, 95% CI 6-9%). Longer overall survival (OS) time and progression-free survival (PFS) time was exhibited in S-1-based therapy, compared with S-1 monotherapy [hazard ratio (HR) 0.836, 95% CI 0.761-0.911, P=0.000, and HR 0.650, 95% CI 0.540-0.759, P=0.000, respectively]. However, the incidence of grade 3/4 adverse effects was also higher in S-1-based therapy than S-1 monotherapy in cancer patients, with relative risk (RR) of neutropenia and anorexia were respectively 4.62 (95% CI 2.92-7.30) and 1.46 (95% CI 0.84-2.55).

S-1 monotherapy was demonstrated with low incidence of high grade adverse effects, therefore it is well tolerated for majority cancer patients; S-1-based therapy significantly improved OS and PFS compared with S-1 monotherapy, with an increased risk of high grade adverse effects.
S-1 monotherapy was demonstrated with low incidence of high grade adverse effects, therefore it is well tolerated for majority cancer patients; S-1-based therapy significantly improved OS and PFS compared with S-1 monotherapy, with an increased risk of high grade adverse effects.
The clinical benefit of erlotinib in treating epidermal growth factor receptor (EGFR) wildtype non-small cell lung cancer (NSCLC) has been questioned. We examined the impact of erlotinib in confirmed EGFR wildtype patients in two placebo-controlled phase III trials the National Cancer Institute of Canada Clinical Trials Group BR.21 (BR.21) and Sequential Tarceva in Unresectable Non-Small Cell Lung Cancer (SATURN) trials.

Combined re-analysis of progression-free survival (PFS) and overall survival (OS) in patients with known wildtype EGFR, estimated by Kaplan-Meier curves and compared by two-sided log-rank test. Cox proportional hazards model was used to estimate hazard ratios (HR) adjusted for potential confounders. Additional analyses assessed comparability of patients with known and unknown EGFR mutation status to determine generalizability of the two study populations.

Mutation status was known in 25% (n=184 of 731) of the BR.21, and 49% (n=437 of 889) of the SATURN populations, of which 82% (n=150) and 89% (n=388) respectively had wildtype EGFR. HR for PFS was 0.71 (95% CI, 0.59-0.85; P<0.01) and for OS was 0.72 (95% CI, 0.59-0.88; P<0.01). Baseline characteristics and outcome (PFS and OS) distributions were similar for patients with known and unknown EGFR status, suggesting generalizability of the EGFR wildtype data. Erlotinib benefit was sustained in all clinical subsets.

Erlotinib provided a consistent and significant improvement in survival for patients with EGFR wildtype NSCLC in both studies, individually and in combination. The benefit of erlotinib does not appear to be limited to patients with activating mutations of EGFR.
Erlotinib provided a consistent and significant improvement in survival for patients with EGFR wildtype NSCLC in both studies, individually and in combination. The benefit of erlotinib does not appear to be limited to patients with activating mutations of EGFR.
Multidisciplinary care is rarely practiced in community healthcare settings where the majority of patients receive lung cancer care in the US. We sought direct input from patients and their informal caregivers on their experience of lung cancer care delivery.

We conducted focus groups of patient and caregiver dyads. Patients had received care for lung cancer in or out of a multidisciplinary thoracic oncology clinic coordinated by a nurse navigator. Focus groups were audiotaped, transcribed, and analyzed using Creswell's 7-step process. Recurring overlapping themes were developed using constant comparative methods within the Grounded Theory framework.

A total of 46 participants were interviewed in focus groups of 5 patient-caregiver dyads. Overlapping themes were a perception that multidisciplinary care improved physician collaboration, patient-physician communication, and patient convenience, while reducing redundancy in testing. Improved coordination decreased confusion, stress, and anxiety. Negative elity care. Additional studies to compare these perspectives to those of other key stakeholders, including clinicians, hospital administrators and representatives of third party payers, will facilitate better understanding of the role of multidisciplinary care programs in lung cancer care delivery.Three models of care are described, including two models of multidisciplinary care for thoracic malignancies. check details The pros and cons of each model are discussed, the evidence supporting each is reviewed, and the need for more (and better) research into care delivery models is highlighted. Key stakeholders in thoracic oncology care delivery outcomes are identified, and the need to consider stakeholder perspectives in designing, validating and implementing multidisciplinary programs as a vehicle for quality improvement in thoracic oncology is emphasized. The importance of reconciling stakeholder perspectives, and identify meaningful stakeholder-relevant benchmarks is also emphasized. Metrics for measuring program implementation and overall success are proposed.More lung cancer patients are being diagnosed at an earlier stage due to improved diagnostic imaging techniques, a trend that is expected to accelerate with the dissemination of lung cancer screening. Surgical resection has always been considered the standard treatment for patients with early-stage non-small cell lung cancer (NSCLC). However, non-surgical treatment options for patients with early-stage NSCLC have evolved significantly over the past decade with many new and exciting alternative treatments now available. These alternative treatments include radiofrequency ablation (RFA), microwave ablation (MWA), percutaneous cryoablation therapy (PCT), photodynamic therapy (PDT) and external beam radiation therapy (EBRT), including stereotactic body radiation therapy (SBRT) and accelerated hypofractionated radiation therapy. We describe the established alternatives to surgical resection, their advantages and disadvantages, potential complications and efficacy. We then describe the optimal treatment approach for patients with early-stage NSCLC based on tumor operability, size and location. Finally, we discuss future directions and whether any alternative therapies will challenge surgical resection as the treatment of choice for patients with operable early-stage lung cancer.Accurate post-operative prognostication and management heavily depend on pathologic nodal stage. Patients with nodal metastasis benefit from post-operative adjuvant chemotherapy, those with mediastinal nodal involvement may also benefit from adjuvant radiation therapy. However, the quality of pathologic nodal staging varies significantly, with major survival implications in large populations of patients. We describe the quality gap in pathologic nodal staging, and provide evidence of its potential reversibility by targeted corrective interventions. One intervention, designed to improve the surgical lymphadenectomy, specimen labeling, and secure transfer between the operating theatre and the pathology laboratory, involves use of pre-labeled specimen collection kits. Another intervention involves application of an improved method of gross dissection of lung resection specimens, to reduce the inadvertent loss of intrapulmonary lymph nodes to histologic examination for metastasis. These corrective interventions are the subject of a regional dissemination and implementation project in diverse healthcare systems in a tri-state region of the United States with some of the highest lung cancer incidence and mortality rates. We discuss the potential of these interventions to significantly improve the accuracy of pathologic nodal staging, risk stratification, and the quality of specimens available for development of stage-independent prognostic markers in lung cancer.Surgical resection remains the most important curative treatment modality for non-small cell lung cancer, but variations in short- and long-term surgical outcomes jeopardize the benefit of surgery for certain patients, operated on by certain types of surgeons, at certain types of institutions. We discuss current understanding of surgical quality measures, and their role in promoting understanding of the causes of outcome disparities after lung cancer surgery. We also discuss the use of minimally invasive surgical resection approaches to expand the playing field for surgery in lung cancer care, and end with a discussion of the future role of surgery in a world of alternative treatment possibilities.The tumor, node and metastasis (TNM) classification of malignant tumors was proposed by Pierre Denoit in the mid-20(th) century to code the anatomic extent of tumors. Soon after, it was accepted by the Union for International Cancer Control and by the American Joint Committee on Cancer, and published in their respective staging manuals. Till 2002, the revisions of the TNM classification were based on the analyses of a database that included over 5,000 patients, and that was managed by Clifton Mountain. These patients originated from North America and almost all of them had undergone surgical treatment. To overcome these limitations, the International Association for the Study of Lung Cancer proposed the creation of an international database of lung cancer patients treated with a wider range of therapeutic modalities. The changes introduced in the 7(th) edition of the TNM classification of lung cancer, published in 2009, derived from the analysis of an international retrospective database of 81,495 patients. The revisions for the 8(th) edition, to be published in 2016, will be based on a new retrospective and prospective international database of 77,156 patients, and will mainly concern tumor size, extrathoracic metastatic disease, and stage grouping.
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