Rapidly progressive interstitial lung disease combined with pneumocystis jiroveci pneumonia in a patient with single anti-TIF-1γ antibody positive dermatomyositis in the context of an underlying tumor.

BACKGROUND: Interstitial lung disease (ILD) is a frequently observed comorbidity in autoimmune diseases such as dermatomyositis/polymyositis (DM/PM), and it is significantly associated with specific autoantibody types. One unique antibody type is the anti-transcription intermediate factor-1γ antibody (anti-TIF-1γ Ab), which has a positive rate of only 7%. It is often found in combination with malignancy and rarely with ILD, particularly rapidly progressive ILD (RPILD). In some cases, the presence of ILD in individuals with DM may indicate a paraneoplastic syndrome. Pneumocystis jiroveci pneumonia (PJP) typically occurs due to intensive immunosuppressive therapy, human immunodeficiency virus (HIV) infection, or malignancy, and rarely as an isolated condition. CASE PRESENTATION: A 52-year-old man with a history of rapid weight loss but non-HIV infected and not immunosuppressed who presented with fever, cough, dyspnea, weakness of the extremities, characteristic rash and mechanic's hand. Pathogenic tests suggested PJP, laboratory tests suggested a single anti-TIF-1γ Ab positive DM, imaging suggested ILD, and pathology revealed no malignancy. RPILD and acute respiratory distress syndrome (ARDS) developed after anti-infection and steroid hormone therapy. After mechanical support therapy such as Extracorporeal Membrane Oxygenation (ECMO), the patient developed late-onset cytomegalovirus pneumonia (CMVP), complicated bacterial infection, and ultimately death. Additionally, we discuss the potential causes of rapid weight loss, the mechanisms by which anti-TIF-1γ Ab may lead to ILD, and the possible connection between anti-TIF-1γ Ab positivity, rapid weight loss, immune abnormalities, and opportunistic infections. CONCLUSIONS: This case emphasizes the importance of early recognition of malignant tumors and pulmonary lesions, assessment of the body's immune status, prompt initiation of immunosuppressive treatment, and prevention of opportunistic infections in individuals with single anti-TIF-1γ Ab positive DM presenting with rapid weight loss.

Correlations of IFN-γ genetic polymorphisms with susceptibility to breast cancer: a meta-analysis.

The meta-analysis was conducted to evaluate the correlations between common genetic polymorphisms in the IFN-γ gene and susceptibility to breast cancer. The following electronic databases were searched without language restrictions: MEDLINE (1966 ~ 2013), the Cochrane Library Database (issue 12, 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), Web of Science (1945 ~ 2013), and the Chinese Biomedical Database (CBM) (1982 ~ 2013). Meta-analysis was performed with the use of the STATA statistical software. Odds ratios (OR) with their 95 % confidence intervals (95 % CIs) were calculated. Nine clinical case-control studies met all the inclusion criteria and were included in this meta-analysis. A total of 1,182 breast cancer patients and 1,525 healthy controls were involved in this meta-analysis. Three functional polymorphisms were assessed, including rs2069705 C>T, rs2430561 T>A, and CA repeats 2/X. Our meta-analysis results indicated that IFN-γ genetic polymorphisms might be significantly associated with an increased risk of breast cancer (allele model: OR = 1.37, 95 % CI = 1.03 ~ 1.83, P = 0.031; dominant model: OR = 1.55, 95 % CI = 1.01 ~ 2.37, P = 0.046; homozygous model: OR = 2.23, 95 % CI = 1.30 ~ 3.82, P = 0.004; respectively), especially the rs2430561 T>A polymorphism. Subgroup analysis based on ethnicity suggested that genetic polymorphisms in the IFN-γ gene were closely correlated with increased breast cancer risk among Asians (allele model: OR = 1.21, 95 % CI = 1.02 ~ 1.58, P = 0.017; dominant model: OR = 3.44, 95 % CI = 2.07 ~ 5.71, P < 0.001; recessive model: OR = 1.58, 95 % CI = 1.06 ~ 2.37, P = 0.025; homozygous model: OR = 1.83, 95 % CI = 1.19 ~ 2.80, P = 0.006; respectively), but not among Caucasians (all P > 0.05). Our meta-analysis supported the hypothesis that IFN-γ genetic polymorphisms may contribute to an increased risk of breast cancer, especially the rs2430561 T>A polymorphism among Asians.

The efficacy and safety of thermal ablation for patients with lung malignancy: a meta-analysis of 12 studies in China.

BACKGROUND: Thermal ablation has been increasingly used in the treatment of lung cancer in recent years. This meta-analysis aims to investigate the therapeutic effect and safety of thermal ablation plus chemotherapy as compared with chemotherapy alone in treating patients with lung malignancy in China based on current evidence. METHODS: Databases including PubMed, Web of Science, Embase and the Cochrane Library were searched for clinical reports. Additional literature search was also performed by searching the reference list of included studies and latest reviews. Raw data including objective response rate, disease control rate, progression-free survival, overall survival and the incidence of major complication were extracted and pooled. RESULTS: A total of 12 studies in China including 1282 patients with lung malignancy were included in this meta-analysis. The number of studies that reported data of objective response rate, disease control rate, progression-free survival, overall survival and major complication was 8, 7, 7, 6 and 7, respectively. The combination therapy of thermal ablation plus chemotherapy showed a significantly better efficacy in improving objective response rate (odds ratio = 2.73; P < 0.001) and disease control rate (odds ratio = 2.43; P < 0.001) as compared with chemotherapy alone. Thermal ablation was also a significant protective factor for progression-free survival (hazard ratio = 0.43; P < 0.001) and overall survival (hazard ratio = 0.49; P < 0.001). Besides, thermal ablation did not increase the risk of major complication (odds ratio = 0.75; P = 0.252). CONCLUSION: The present meta-analysis based on these studies in China suggested that thermal ablation is a promising technique to provide better disease response and survival outcomes for patients with lung malignancy. Thermal ablation is worth further promotion in treating lung malignancy and application in clinical practice.

A retrospective study of low-dose apatinib combined with S-1 in patients with advanced non-small cell lung cancer.

BACKGROUND: The current regimens for advanced non-small cell lung cancer (NSCLC) patients are deficient due to failings in standard treatments. This retrospective study aimed to assess the efficacy and safety of low-dose apatinib in combination with S-1 therapy in a NSCLC setting. METHODS: In this retrospective study, advanced NSCLC patients who failed standard treatment in Changzhou Cancer Hospital of Soochow University were screened for eligibility. Progression-free survival (PFS) was set as the primary endpoint. Overall response rate (ORR), disease control rate (DCR), overall survival (OS), and the safety profile were considered to be the secondary endpoints. RESULTS: A total of 31 eligible patients were included. The median PFS (mPFS) was 102 days (95% CI: 57-147 days). ORR was achieved in 7 patients (22.6%; 95% CI: 11.1-38.2%) and DCR was maintained in 23 patients (74.2%; 95% CI: 58.2-86.5%). The median OS (mOS) was 422 days (95% CI: 148-696 days). Patients with a history of smoking tended to have a shorter OS without significant differences (HR =4.105, 95% CI: 0.874-19.288, P=0.074). Treatment-related grade III toxicity was observed in 5 patients (16%) and common grade I or II adverse events (AEs) were fatigue (42%), hypertension (32%), and hand-foot-skin reaction (23%). CONCLUSIONS: Combination of low-dose apatinib and S-1 could be an effective and tolerable choice for advanced NSCLC patients who are unable to benefit from standard treatment; however, further exploration in larger clinical trials is needed.

Response and acquired resistance to crizotinib in Chinese patients with lung adenocarcinomas harboring MET Exon 14 splicing alternations.

Approximately 10% of lung adenocarcinomas harbor aberrations that are targetable using the approved multitargeted TKI crizotinib. MET exon 14 skipping mutation predicts for response to crizotinib in human lung adenocarcinomas. However, a substantial part of patients still has no sufficient tissue to perform genomic analysis. As a promising noninvasive biomarker and potential surrogate for the entire tumor genome, circulating tumor DNA (ctDNA) has been applied to the detection of driver gene mutations. Here we described the MET exon 14 splicing mutations in cell-free circulating-tumor DNA by next-generation sequencing (NGS) technology. Patient firstly responded to crizotinib therapy within four months, however, three acquired mutation in the MET kinase domain, D1228N/H and Y1230H, were found at the time of disease progression. To our knowledge, this is the first clinical report of three mutations simultaneously arising in a patient with MET exon 14 splicing mutation.

Overexpression of kallikrein gene 10 is a biomarker for predicting poor prognosis in gastric cancer.

AIM: To analyze the expression of kallikrein gene 10 (KLK10) in gastric cancer and to determine whether KLK10 has independent prognostic value in gastric cancer. METHODS: We studied KLK10 expression in 80 histologically confirmed gastric cancer samples using real-time quantitative reverse transcription-PCR and hK10 expression using immunohistochemistry. Correlations with clinicopathological variables (lymph node metastasis, depth of invasion and histology) and with outcomes (disease-free survival and overall survival) during a median follow-up period of 31 mo were assessed. Gastric cancer tissues were then classified as KLK10 positive or negative. RESULTS: KLK10 was found to be highly expressed in 57/80 (70%) of gastric cancer samples, while its expression was very low in normal gastric tissues. Positive relationships between KLK10 expression and lymph node metastasis (P = 0.048), depth of invasion (P = 0.034) and histology (P = 0.015) were observed. Univariate survival analysis revealed that gastric cancer patients with positive KLK10 expression had an increased risk for relapse/metastasis and death (P = 0.005 and 0.002, respectively). Cox multivariate analysis indicated that KLK10 was an independent prognostic indicator of disease-free survival and overall survival in patients with gastric cancer. CONCLUSION: KLK10 expression is an independent biomarker of unfavorable prognosis in patients with gastric cancer.

Determination of an optimal standardized uptake value of fluorodeoxyglucose for positron emission tomography imaging to assess pathological volumes of cervical cancer: a prospective study.

PURPOSE: To determine the optimal standardized uptake value (SUV) of (18)F-fluorodeoxyglucose ((18)F-FDG) for positron emission tomography (PET) imaging, at which the PET-defined gross tumor volume (GTVPET) best matches with the pathological volume (GTVPATH) in the cervical cancer. MATERIALS AND METHODS: Ten patients with the cervical cancer who underwent surgery were enrolled in this study. The excised specimens were processed for whole-mount serial sections and H-E staining. The tumor borders were outlined in sections under a microscope, histopathological images were scanned and the GTVPATH calculated. The GTVPET was delineated automatically by using various percentages relative to the maximal SUV and absolute SUV. The optimal threshold SUV was further obtained as the value at which the GTVPET best matched with the GTVPATH. RESULTS: An average of 85 ± 10% shrinkage of tissue was observed after the formalin fixation. The GTVPATH was 13.38 ± 2.80 cm(3) on average. The optimal threshold on percentile SUV and absolute SUV were 40.50% ± 3.16% and 7.45 ± 1.10, respectively. The correlation analysis showed that the optimal percentile SUV threshold was inversely correlated with GTVPATH (p<0.05) and tumor diameter (p<0.05). The absolute SUV was also positively correlated with SUVmax (p<0.05). CONCLUSION: The pathological volume could provide the more accurate tumor volume. The optimal SUV of FDG for PET imaging by use of GTVPATH as standard for cervical cancer target volume delineation was thus determined in this study, and more cases are being evaluated to substantiate this conclusion.