Differential efficacy of tyrosine kinase inhibitors according to the types of EGFR mutations and agents in non-small cell lung cancer: a real-world study.

BACKGROUND: Both first and second-generation EGFR-TKIs are recommended in advanced NSCLC with common EGFR mutations. However, there are few data on the difference in efficacy of EGFR-TKIs based on the type of EGFR mutation and agents. METHODS: This retrospective real-world study evaluated the outcomes and clinicopathologic characteristics, including the type of EGFR mutations, of 237 advanced NSCLC patients treated with first- or second-generation (afatinib) EGFR-TKIs as first-line therapy. RESULTS: The median progression-free survival (PFS) and overall survival (OS) of all patients were 11 months (M) and 25M, respectively. In the univariate analysis, patients with exon 19 deletion (del) (n=130) had significantly longer median OS compared to those with other mutations (L858R: 84, others: 23) (30 vs. 22 M, p=0.047), without a difference in PFS (p=0.138). Patients treated with afatinib (n=60) showed significantly longer median OS compared to those treated with first-generation TKIs (gefitinib: 159, erlotinib: 18) (30 vs. 23 M, p=0.037), without a difference in PFS (p=0.179). In patients with exon 19 del, there was no significant difference in median PFS (p=0.868) or OS (p=0.361) between patients treated with afatinib and those treated with first-generation TKIs, while significantly better PFS (p=0.042) and trend in OS (p=0.069) were observed in patients receiving afatinib in other mutations. Exon 19 del was independently associated with favorable OS (p=0.028), while age >70 years (p=0.017), ECOG performance status ≥2 (p=0.001), primary metastatic disease (p=0.007), and synchronous brain metastasis (p=0.026) were independent prognostic factors of poor OS. CONCLUSIONS: The EGFR exon 19 del was associated with favorable OS in advanced NSCLC patients receiving first-line EGFR-TKIs. Moreover, in patients with exon 19 del, first-generation TKIs seem to be a reasonable treatment option if osimertinib is unavailable.

Thromboembolic events in patients who received adjuvant chemotherapy for gastric cancer: a single-center retrospective study.

BACKGROUND: Thromboembolic events (TEEs) are significant adverse events that can cause serious morbidities and mortality in cancer patients receiving chemotherapy. Patients with gastric cancer (GC) treated with palliative chemotherapy have been reported to experience a TEE incidence of 5-27%. However, very few reports have addressed TEEs in adjuvant chemotherapy (AC) for GC. METHODS: This study retrospectively analyzed 611 GC patients (stage II: 309, III: 302) who started AC with capecitabine/oxaliplatin (167 patients) or S-1 (444 patients) after undergoing curative resection between January 2013 and June 2020 at a single center. The incidence of TEEs during AC or within 1 year after AC completion was investigated, while analyzing the factors that influenced the TEEs' occurrence. RESULTS: TEEs were confirmed in 20 patients (3.3%), and TEEs occurred in almost all patients in the S-1 group (19 patients). The most common TEE types were cerebral infarction and pulmonary thromboembolism (five patients each). Although old age (≥ 70 years, p < 0.0001), S-1 treatment (p = 0.021), and hypertension (p = 0.017) were identified as significant risk factors for TEEs in univariate analysis, only old age showed a statistically significant correlation with TEEs' occurrence in multivariate analysis (odds ratio: 3.07; 95% confidence interval 1.11-8.48; p = 0.031). CONCLUSIONS: TEEs occurred in fewer patients with GC who had been treated with AC than patients who had received palliative chemotherapy in previous reports. However, elderly GC patients who are undergoing AC require more careful surveillance for possible TEEs, considering relatively higher incidence of them.

Analysis of thromboembolic events in patients with non-small cell lung cancer who received adjuvant chemotherapy: single-center real-world data.

Thromboembolic events (TEEs) are common in cancer patients, with increased risk of TEE by chemotherapy in patients with lung cancer. However, TEEs in patients with non-small cell lung cancer (NSCLC) who received adjuvant chemotherapy have rarely been reported. This study retrospectively analyzed real-world data of 275 patients with NSCLC treated with adjuvant chemotherapy after surgery from October, 2005 to June, 2020, in a single institution. The incidence of TEEs during or within one year of completion of adjuvant chemotherapy was investigated, and factors related to TEEs were analyzed. TEEs were confirmed in nine patients (3.3%), without fatal event related to TEEs. None of the factors, including Khorana score, was significantly associated with the occurrence of TEEs. All patients with TEEs had pathologic stage IIB or higher and a history of smoking, except for one patient. In conclusion, TEEs occurred in a smaller proportion of patients with NSCLC treated with adjuvant chemotherapy in the real world compared with those treated with palliative chemotherapy in previous reports. Furthermore, prophylactic anticoagulation in patients with NSCLC receiving adjuvant chemotherapy may not be needed except for high-risk patients, although those patients should be informed about the possible risk of TEEs.

Analysis of thromboembolic events in head and neck cancer patients who underwent concurrent chemoradiotherapy with cisplatin.

BACKGROUND/AIMS: The study investigated the incidence of thromboembolic events (TEE) in head and neck (H&N) cancer patients who received concurrent chemoradiotherapy (CCRT) with cisplatin, and analyzed the factors affecting TEE occurrence. METHODS: Two hundred and fifty-seven patients who started CCRT with cisplatin for H&N cancer from January 2005 to December 2019 were analyzed. RESULTS: TEE occurred in five patients, an incidence rate of 1.9%. The 2-, 4-, and 6-month cumulative incidences of TEE were 0.8%, 1.6%, and 1.9%, respectively. Khorana score was the only factor associated with TEE occurrence (p = 0.010). CONCLUSION: The incidence of TEE in H&N cancer patients who underwent CCRT with cisplatin was relatively low when compared to other types of cancer. However, patients with a high Khorana score require more careful surveillance for possible TEE occurrence.

The efficacy of EGFR-tyrosine kinase inhibitor in non-small cell lung cancer patients with synchronous brain metastasis: a real-world study.

BACKGROUND/AIMS: The optimal treatment (Tx) for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) remains to be determined. METHODS: A retrospective review was conducted on 77 NSCLC patients with synchronous BM who underwent first-line EGFR-tyrosine kinase inhibitor (TKI) Tx. The outcomes of patients were analyzed according to the clinicopathological characteristics including local Tx modalities. RESULTS: Fifty-nine patients underwent local Tx for BM (gamma knife surgery [GKS], 37; whole brain radiotherapy [WBRT], 18; others, four) concurrently or sequentially with EGFR-TKI. Patients treated with TKI alone showed significantly lower incidence of central nervous system (CNS) symptoms. The median progression-free survival (PFS) and overall survival (OS) after the initiation of EGFR-TKI for all patients were 9 and 19 months, respectively. In 60 patients with follow-up brain imaging, the median time to CNS progression was 15 months. Patients with EGFR exon 19 deletion had a significantly longer median OS than those with other mutations including L858R (23 months vs. 17 months). Other clinical characteristics, including CNS symptoms, number of BM, and the use of local Tx were not associated with OS, as well as PFS. In terms of the local optimal Tx modality, no difference was found between GKS and WBRT in the OS and PFS. CONCLUSION: This study suggests that EGFR-TKI may result in a favorable outcome in NSCLC patients with synchronous BM, especially in deletion 19 mutant, regardless of the extent of BM lesions or local Tx modalities. Patients with asymptomatic BM can be treated with EGFR-TKI and careful surveillance.

Peer support for smoking cessation: a protocol of systematic review and meta-analysis.

BACKGROUND: Peer-support programs are a useful social support strategy for populations trying to quit smoking who are willing to maintain smoking abstinence. This study is a protocol for a systematic review and meta-analysis to assess the effectiveness of peer support for smoking cessation. METHODS: This protocol will be conducted in accordance with the Cochrane Handbook of Systematic Reviews of Interventions 6.2. We will conduct a comprehensive search in the Cochrane Central Register of Controlled Trials, ovidEmbase, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature, ovidMEDLINE, Google Scholar, and Open Grey, as well as the Trials Register of Promoting Health Interventions in EPPI-Centre, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, and reference lists of included papers. The review will include randomized controlled trials of peer support interventions aimed to stop smoking in any population. Two reviewers will independently screen and select relevant studies. Version 2 of the Cochrane tool that assesses risk of bias in randomized trials will be used to assess the risk of bias in the included studies. The primary outcomes will be defined as the tobacco abstinence rate and adverse events. If a quantitative synthesis is not appropriate, a synthesis without meta-analysis will be undertaken. DISCUSSION: This review will provide the best available evidence regarding the effects of peer support interventions to quit smoking. The results from this study will help to inform healthcare providers on the optimal peer support intervention modalities such as intensity, delivery methods, type of support provider, and duration of the intervention. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020196288.

Interferon-γ-Inducible Chemokines as Prognostic Markers for Lung Cancer.

Interferon (IFN)-γ-inducible chemokines in the CXCR3/ligand axis are involved in cell-mediated immunity and play a significant role in the progression of cancer. We enrolled patients with lung cancer (n = 144) and healthy volunteers as the controls (n = 140). Initial blood samples were collected and concentrations of IFN-γ and IFN-γ-inducible chemokines CXCL9, CXCL10, and CXCL11 were measured using enzyme-linked immunosorbent assay. Of patients with lung cancer, 125 had non-small cell lung cancer (NSCLC) and 19 had small cell lung cancer. The area under the curve (AUC) (95% CI) of CXCL9 was 0.83 (0.80-0.89) for differentiating lung cancer patients from controls. The levels of all the markers were significantly higher in NSCLC patients with stage IV than in those with stages I-III. A Kaplan-Meier survival analysis showed that NSCLC cancer patients with higher levels of all markers showed poorer survival than those with lower levels. In Cox multivariate analysis of patients with NSCLC, independent prognostic factors for overall survival were CXCL9 and CXCL11. CXCL9 was the only independent prognostic factor for cancer-specific survival. Serum IFN-γ-inducible chemokines may be useful as clinical markers of metastasis and prognosis in NSCLC, and CXCL9 levels showed the most significant results.

Trastuzumab-based palliative chemotherapy for HER2-positive gastric cancer: a single-center real-world data.

BACKGROUND: Since the results of the ToGA trial were published, trastuzumab-based chemotherapy has been used as the standard first-line treatment for HER2-positive recurrent or primary metastatic gastric cancer (RPMGC). However, the real-world data has been rarely reported. Therefore, we investigated the outcomes of trastuzumab-based chemotherapy in a single center. METHODS: This study analyzed the real-world data of 47 patients with HER2-positive RPMGC treated with trastuzumab-based chemotherapy in a single institution. RESULTS: With the median follow-up duration of 18.8 months in survivors, the median overall survival (OS) and progression-free survival were 12.8 and 6.9 months, respectively, and the overall response rate was 64%. Eastern Cooperative Oncology Group performance status 2 and massive amount of ascites were independent poor prognostic factors for OS, while surgical resection before or after chemotherapy was associated with favorable OS, in multivariate analysis. In addition, 5 patients who underwent conversion surgery after chemotherapy demonstrated an encouraging median OS of 30.8 months, all with R0 resection. CONCLUSIONS: Trastuzumab-based chemotherapy in patients with HER2-positive RPMGC in the real world demonstrated outcomes almost comparable to those of the ToGA trial. Moreover, conversion surgery can be actively considered in fit patients with a favorable response after trastuzumab-based chemotherapy.

Blood lead levels in relation to smoking and chronic obstructive pulmonary disease (COPD): a study from Korean National Health and Nutrition Examination Survey (KNHANES).

BACKGROUND: Lead exposure is a resurgent environmental issue globally. Smoking can be a source of lead exposure, although the majority of lead poisonings originate from workplace exposures. However, no study has been undertaken concerning the blood lead levels based on the chronic obstructive pulmonary disease (COPD), smoking status, and other risk factors of COPD. This cross-sectional study was conducted to investigate the blood lead levels according to COPD and clinical variables associated with COPD. METHODS: Data (total number =53,829) were collected from the Korean National Health and Nutrition Examination Survey (IV in 2008 and 2009, V in 2010-2012, and VI in 2013). Multivariable linear regression analyses were performed to determine variables associated with elevated blood lead levels. RESULTS: Univariate regression analysis showed that male sex, older age, smoking, occupation level, income level, education level, and presence of COPD were related to higher blood lead levels, whereas the other co-morbidities including diabetes, hypertension, cerebral stroke, osteoporosis, asthma, and depression were not related (P<0.05). Multivariable regression analysis demonstrated that older age, male sex, smoking, occupation, and education level were independently associated with higher blood lead levels (P<0.05). CONCLUSIONS: Smoking status, occupation, and education level along with old age and male sex were independently associated with higher blood lead levels; however, COPD was not after adjustment of all confounding factors.

Cancer development in patients with COPD: a retrospective analysis of the National Health Insurance Service-National Sample Cohort in Korea.

BACKGROUND: COPD is a well-known risk factor for lung cancer, independent of smoking behavior. By investigating the retrospective National Health Insurance Service-National Sample Cohort (NHIS-NSC) in Korea, this study attempted to prove the hypothesis that COPD is a risk factor for major cancers developing outside of the lungs. We also aimed to investigate the environmental factors associated with the development of lung cancer in COPD patients. METHODS: This study analyzed data from the NHIS-NSC over a 12-year period. Among the 514,795 subjects in the NHIS-NSC, 16,757 patients who were diagnosed with any cancer from 2002 to 2003 were excluded. This cohort enrolled six arms consisting of never-smokers without COPD (N = 313,553), former smokers without COPD (N = 41,359), smokers without COPD (N = 112,627), never-smokers with COPD (N = 7789), former smokers with COPD (N = 1085), and smokers with COPD (N = 2677). RESULTS: Incident rate of lung cancer per 100,000 person-year was higher according to smoking and COPD (216 in non-COPD and 757 in COPD among never-smokers, 271 in non-COPD and 1266 in COPD among former smokers, 394 in non-COPD and 1560 in COPD among smokers, p <  0.01). Old age, male sex, lower BMI, low exercise level, history of diabetes mellitus, smoking, and COPD were independent factors associated with the development of lung cancer (p <  0.01). Multi-variable analyses showed that COPD, regardless of smoking status, contributed to the development of lung cancer, and colorectal cancer and liver cancer among other major cancers (p <  0.01). CONCLUSION: Our data suggested that COPD was an independent risk factor for the development of lung cancer, and colorectal cancer and liver cancer among other major cancers in the Korean population, regardless of smoking status.

Residential Radon Exposure and Cigarette Smoking in Association with Lung Cancer: A Matched Case-Control Study in Korea.

Residential radon exposure and cigarette smoking are the two most important risk factors for lung cancer. The combined effects thereof were evaluated in a multi-center matched case-control study in South Korea. A total of 1038 participants were included, comprising 519 non-small cell lung cancer cases and 519 age- and sex- matched community-based controls. Residential radon levels were measured for all participants. Multivariate logistic regression was used to calculate odds ratios (OR) for lung cancer according to radon exposure (high ≥ 100 Bq/m3 vs. low < 100 Bq/m3), smoking status, and combinations of the two after adjusting for age, sex, indoor hours, and other housing information. The median age of the participants was 64 years, and 51.3% were women. The adjusted ORs (95% confidence intervals [CIs]) for high radon and cigarette smoking were 1.56 (1.03-2.37) and 2.53 (1.60-3.99), respectively. When stratified according to combinations of radon exposure and smoking status, the adjusted ORs (95% CIs) for lung cancer in high-radon non-smokers, low-radon smokers, and high-radon smokers were 1.40 (0.81-2.43), 2.42 (1.49-3.92), and 4.27 (2.14-8.52), respectively, with reference to low-radon non-smokers. Both residential radon and cigarette smoking were associated with increased odds for lung cancer, and the difference in ORs according to radon exposure was much greater in smokers than in non-smokers.

Combination versus single-agent as palliative chemotherapy for gastric cancer.

BACKGROUND: Although combination chemotherapy (CC) is generally recommended in recurrent or primary metastatic gastric cancer (RPMGC), the results of randomized trials are conflicting. METHODS: A retrospective review was conducted on 687 RPMGC patients who received palliative chemotherapy. We compared the overall survival (OS) between CC and single-agent chemotherapy (SC) among these patients, and we analyzed the clinicopathological characteristics affecting outcome including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). RESULTS: Although 521 patients (75.8%) underwent CC, SC was more frequently performed in elderly patients (57.6%) and ECOG performance status (PS) 2 or 3 (65.8%) patients (p < 0.0001, in each case). The median OS of patients who received CC was significantly longer than that of patients who received SC (11 vs. 8 months, p < 0.0001). No difference in OS between CC and SC was observed in elderly patients (p = 0.583), poor PS (p = 0.810), signet ring cell (p = 0.347), palliative surgical resection (p = 0.307), and high PLR (p = 0.120), with a significant interaction between age and type of regimen (p = 0.012). Moreover, there was no difference in OS between CC and SC after propensity score matching (p = 0.322). Multivariate analysis revealed that palliative resection and ≥ second-line chemotherapy were independently associated with favorable OS (p < 0.0001, in each case), whereas poor PS (p = 0.004), signet ring cell (p < 0.0001), peritoneal metastasis (p = 0.04), high NLR (p = 0.001), and high PLR (p = 0.033) were independent prognostic factors of poor OS. CONCLUSIONS: Although CC is the standard of care in RPMGC, SC can be considered a reasonable option in certain subgroups, such as elderly patients.

The role of surgical resection before palliative chemotherapy in advanced gastric cancer.

The role of palliative surgical resection in recurrent or metastatic gastric cancer is still controversial. A retrospective review was conducted on 689 patients who received palliative chemotherapy for recurrent (n = 307) or primary metastatic (n = 382) gastric cancer. Among 131 patients (89 primary metastatic and 42 recurrent) with surgical resection before chemotherpay, 75 underwent gastrectomy, 42 metastasectomy, and 14 gastrectomy with metastasectomy. The median overall survival (OS) of patients who underwent surgical resection was significantly longer than that of patients who received chemotherapy alone (18 vs. 9 months, p < 0.0001). The OS benefit of surgical resection was consistent across subgroups. In multivariate analysis, surgical resection was independently associated with favorable OS (hazard ratio = 0.42, p < 0.0001). Moreover, patients with surgical resection showed favorable OS both in univariate (p < 0.0001) and multivariate (p < 0.0001) analysis even after propensity score matching. In addition, the median OS of patients who underwent gross complete resection (n = 54) was significantly longer than that of patients who underwent incomplete resection (n = 77) (30 vs. 15 months, p = 0.002). The present study suggests that judicious use of surgical resection before chemotherapy in recurrent or metastatic gastric cancer patients may result in a favorable outcome, especially when complete resection is achievable.

The role of third-line chemotherapy in recurrent or metastatic gastric cancer: A cohort study with propensity score matching analysis.

In recurrent or metastatic gastric cancer, second-line chemotherapy is generally recommended in current guidelines. Although third-line therapy is often performed in daily practice in some countries, there are only a few reports about its benefits.A retrospective review was conducted on 682 patients who underwent at least first-line chemotherapy for recurrent (n = 297) or primary metastatic (n = 385) disease. Clinicopathological characteristics and overall survival (OS) were analyzed according to lines of chemotherapy.One hundred sixty-seven patients (24.5%) underwent third- or further-line therapy. Third- or further-line therapy was frequently performed in patients with young age (<70) (P < .0001), Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 (P < .0001), surgical resection before first-line therapy (P = .007), and first-line combination regimen (P = .001). The median OS for all patients after the initiation of first-line therapy was 10 months. The median OS of patients who received third- or further-line therapy was significantly longer than that of patients who received second- or lesser-line therapy (18 vs 8 months, P < .0001). The multivariate analysis revealed that third- or further-line therapy was independently associated with favorable OS (hazard ratio = 0.58, P < .0001). Moreover, patients who received third- or further-line therapy demonstrated better OS both in univariate (P = .002) and multivariate (P < .0001) analysis even after propensity score matching using baseline characteristics. The median OS after the start of third-line chemotherapy was 6 months. In addition, ECOG PS 0 or 1 at the initiation of third-line therapy (P < .0001) and surgical resection (P = .009) were independently associated with longer OS after third-line therapy.The current study suggests that third-line therapy could be recommended for recurrent or metastatic gastric cancer patients with good PS after progression from second-line chemotherapy in clinical practice.

EGFR Exon 19 Deletion is Associated With Favorable Overall Survival After First-line Gefitinib Therapy in Advanced Non-Small Cell Lung Cancer Patients.

OBJECTIVES: Exon 19 deletion and L858R mutation in exon 21 of the epidermal growth factor receptor (EGFR) are both common mutations that predict a good response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). However, the existence of clinically significant difference in sensitivity to EGFR tyrosine kinase inhibitors among different EGFR mutation subtypes is still a matter of debate. MATERIALS AND METHODS: The outcome of 60 EGFR mutation-positive advanced NSCLC patients who received first-line gefitinib therapy (250 mg/d) was retrospectively analyzed according to EGFR mutation subtypes. RESULTS: The median progression-free survival (PFS) and overall survival (OS) after the initiation of gefitinib therapy for all patients was 11 and 26 months, respectively. Univariate analysis showed that patients with exon 19 deletion (n=28) had significantly longer median PFS (20 vs. 8 mo, P=0.004) and OS (36 vs. 22 mo, P=0.001) compared with those with L858R mutation (n=25) and uncommon or dual mutations (n=7). Multivariate analysis revealed that exon 19 deletion (P=0.007) was an independent prognostic factor of favorable PFS, with an independent association with poor PFS of male sex (P=0.049). Exon 19 deletion was also independently associated with favorable OS (P<0.0001), whereas male sex (P=0.004) and primary metastatic disease (P=0.032) were independent prognostic factors of poor OS. CONCLUSIONS: The EGFR exon 19 deletion was associated with favorable PFS and OS in patients receiving first-line gefitinib treatment. The EGFR mutation subtype should be considered when making treatment decision or designing clinical trials for chemotherapy-naive, EGFR mutation-positive advanced NSCLC patients.

Vitamin D Deficiency Is Associated with Rapid Decline in Exercise Capacity in Male Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Vitamin D is suggested to play a role in airway and systemic inflammation in chronic obstructive pulmonary disease (COPD). Low serum 25-hydroxyvitamin D (25-OHD) levels have been suggested to be associated with lower lung function and poorer exercise capacity in COPD. OBJECTIVES: The main purpose of this study was to investigate the effects of vitamin D deficiency on the change in exercise capacity in male COPD patients. METHODS: A total of 156 male subjects were selected from the Korean Obstructive Lung Disease cohort. Vitamin D deficiency was subdivided into three subgroups: mild, moderate, and severe deficiency groups. Rapid decline was defined as an annual rate of change in exercise capacity ≥17 m. Exercise capacity was assessed by 6-minute walk distance (6MWD). RESULTS: Significant differences were observed in the serum levels of 25-OHD, the number of patients with vitamin D sufficiency, and moderate-to-severe deficiency between rapid decliners (n = 40) and non-rapid decliners (n = 116). No differences were found between the groups for age, smoking status, lung function, and 6MWD. Multivariate analysis showed that vitamin D deficiency was independently related to rapid decline in exercise capacity (p = 0.028). A statistically significant difference was observed among the subgroups of vitamin D deficiency in terms of the change in exercise capacity (p < 0.001). The annual decline in exercise capacity was prominent in the severe deficiency group (23.1 m/year). CONCLUSION: This study shows that vitamin D deficiency is associated with rapid decline in exercise capacity in male patients with COPD.

High expression of Bcl-2 predicts poor outcome in diffuse large B-cell lymphoma patients with low international prognostic index receiving R-CHOP chemotherapy.

The prognostic significance of Bcl-2, Bcl-6, p53, topoisomerase II, and ß-tubulin expression was evaluated in diffuse large B-cell lymphoma (DLBCL) patients treated with cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab. Eight-year progression-free survival (PFS, P = 0.006) and overall survival (OS, P = 0.001) of patients with high Bcl-2 expression were significantly inferior to those of patients with low expression without prognostic significance of Bcl-6, p53, topoisomerase II, and ß-tubulin expression. High expression of Bcl-2 was associated with poor PFS (P = 0.045) and OS (P = 0.004) only in patients with low international prognostic index (IPI). In multivariate analysis, high expression of Bcl-2 was a significant independent prognostic factor of poor PFS (P = 0.026) and OS (P = 0.007) along with high IPI. In conclusion, the expression of Bcl-2 may be a useful prognostic factor, especially in DLBCL patients with low IPI.

Effects of pentoxifylline on proteinuria and glucose control in patients with type 2 diabetes: a prospective randomized double-blind multicenter study.

BACKGROUND: Pentoxifylline is a methylxanthine derivative with significant anti-inflammatory, anti-fibrotic, and anti-proliferative properties. Studies have shown that pentoxifylline may have renoprotective effects in patients with diabetic nephropathy. However, most of these studies were limited by small sample sizes. Therefore, we investigated whether pentoxifylline could reduce proteinuria in patients with diabetic nephropathy and residual proteinuria who received an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB). We also studied the effects of pentoxifylline on glycemic control, insulin resistance, and inflammatory parameters. METHODS: This was a prospective, randomized double-blind, placebo-controlled, multi-center study. A total of 174 patients with type 2 diabetes and albuminuria (>30 mg/g of creatinine) who were taking the recommended dosage of ACEI or ARB for > 6 months and receiving conventional therapy for diabetes were randomly assigned to receive pentoxifylline (1200 mg, daily; n = 87) or a placebo (n = 87) for 6 months. The endpoints were the effects of pentoxifylline on proteinuria, renal function, glucose control, and inflammatory parameters. RESULTS: The percentage changes in proteinuria from baseline in the pentoxifylline and placebo groups were a decrease of 23 % and 4 %, respectively (p = 0.012). In addition, significant reductions in fasting plasma glucose, glycated hemoglobin, and insulin resistance according to the homeostasis model assessment were observed in the pentoxifylline group compared to those in the placebo group. However there was no significant difference in serum tumor necrosis factor (TNF)-α between the groups. CONCLUSIONS: Pentoxifylline therapy reduced proteinuria and improved glucose control and insulin resistance without significant change of serum TNF-α in patients with type 2 diabetic nephropathy. Therefore, pentoxifylline is a potential therapeutic alternative for treating diabetes and diabetic nephropathy. TRIAL REGISTRATION: NCT01382303.

VE1 antibody is not highly specific for the BRAF V600E mutation in thyroid cytology categories with the exception of malignant cases.

OBJECTIVES: We evaluated the utility of the VE1 antibody that can detect a mutant protein resulting from the BRAF V600E mutation as a diagnostic tool for thyroid fine-needle aspiration cytology (FNAC). METHODS: We performed VE1 immunocytochemistry on 202 FNAC specimens from surgically confirmed thyroid nodules. The results were compared with the molecular analyses of the BRAF mutation in these specimens matched with their corresponding histology. RESULTS: Diagnoses of FNAC specimens included benign (9.4%), atypia of undetermined significance/follicular lesion of undetermined significance (11.4%), follicular neoplasm/suspicious for follicular neoplasm (2.0%), suspicious for malignancy (9.4%), and malignancy (65.8%). VE1 immunostaining was positive in 71.3% of FNAC specimens. The overall sensitivity of the VE1 antibody was 88.8%, specificity was 71.2%, positive predictive value was 88.2%, negative predictive value was 72.4%, and diagnostic accuracy was 83.7%. CONCLUSIONS: VE1 immunocytochemistry in thyroid FNAC as a screening test for BRAF mutations is highly specific for malignant category cases but can be suboptimal due to its high false-positive rate for the nonmalignant cases.