降钙素原联合胸部影像学检查在特发性肺纤维化急性加重中的诊断意义

目的 观察降钙素原(procalcitonin,PCT)联合胸部影像学检查在特发性肺纤维化急性加重(acute exacerbation of idiopathic pulmonary fibrosis,AE-IPF)与特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)合并肺部感染鉴别诊断中的意义.方法 22例AE-IPF患者和19例IPF合并肺部感染患者均于入院当天检测血清PCT等炎症指标,并记录影像学资料及临床症状.结果 2组性别、年龄差异无统计学意义.AE-IPF组与IPF合并肺部感染组入院时PCT水平分别为(0.28±0.17) μg/L、(1.40±0.68) μg/L,2组比较差异有显著统计学意义(t=7.40,P＜0.01).以PCT＞0.51 μg/L为标准时,敏感度为94.7％,特异度为90.9％.治疗前,2组白细胞计数、中性粒细胞计数、C反应蛋白及ESR差异无统计学意义(t值分别为1.69、1.09、1.90、1.14,P值均＞0.05).治疗10d后复查AE-IPF组及IPF合并肺部感染组PCT水平分别为(0.24±0.15) μg/L、(0.31±0.11) μg/L,2组比较差异无统计学意义(t=1.55,P=0.127).AE-IPF组治疗前、后PCT水平差异无统计学意义(t =0.80,P=0.42).IPF合并肺部感染组治疗前、后PCT水平差异有显著统计学意义(t =3.45,P＜0.01).AF-IPF患者HRCT多表现为两侧中下肺野、胸膜下新增的磨玻璃影.IPF合并肺部感染患者HRCT多有斑片状、条片状密度增高影.结论 血清PCT检测可作为鉴别IPF合并肺部感染与AE-IPF的重要指标,以PCT＞0.51 μg/L为标准时,鉴别诊断价值最高,结合患者胸部影像学检查能更好地鉴别二者.     

Acute exacerbation of idiopathic pulmonary fibrosis

BACKGROUND: The clinical course of patients with idiopathic pulmonary fibrosis (IPF) is generally marked by a decline in pulmonary function over time. Increasingly, patients have been recognized as having an acute, and often fatal, clinical deterioration, termed an acute exacerbation of IPF (AE-IPF). METHODS: Review of the current literature pertaining to AE-IPF. RESULTS: Acute exacerbations are defined by an acute onset of dyspnea (<1 month) with worsening hypoxia and progressive infiltrates seen in the absence of heart failure or infection. New ground-glass infiltrates are seen on chest CT scans with diffuse alveolar damage superimposed on a background of usual interstitial pneumonia that is evident on histopathology. The incidence is unknown and is impeded by difficulties in eliminating infection as a cause, as well as by reporting biases contained in reported series introduced by including only biopsied patients or only deaths, or by excluding patients with advanced disease. Prognosis is poor but may be influenced by diagnostic inaccuracy. Treatment with antiinflammatory therapies, such as corticosteroids, or with anticoagulation are unproven and have not as yet been fully studied. CONCLUSIONS: AE of IPF is a complication that demands additional careful study to clarify its relationship to the clinical course of patients with IPF.     

Long-term survival of more than 3 years among patients with advanced non-small cell lung cancer treated with chemotherapy

AIM: To evaluate the prognostic factors of long-term survival of more than 3 years in patients with advanced non-small cell lung cancer (NSCLC). METHODS: We retrospectively analyzed the records of 474 patients with advanced IIIB/IV NSCLC who received chemotherapy as initial treatment between September 2002 and March 2007. RESULTS: The median survival time (MST) was 12.5 mo and the 3 year and 5 year survival rates were 14.6% and 5.3%, respectively. Long-term survival of more than 3 and 5 years was observed in 65 and 16 patients, respectively. The MST for the 65 patients was 61.5 mo (range, 60.1-81.0 mo). In the 474 patients, a good performance status (PS), female sex, non-smoking status and adenocarcinoma histology were significantly associated with a favorable outcome. Furthermore, female sex, a good PS, non-smoking status and adenocarcinoma histology were significantly correlated with long-term survival of more than 3 years and most of these patients (89.2%, 58/65) received epidermal growth factor receptor-tyrosine kinase inhibitors as any line treatment. Survival analysis of long-term survivors showed that a PS of 0 was an independent prognostic factor for predicting favorable outcomes. CONCLUSION: Our results suggest that a good PS and adenocarcinoma histology play an important role in long-term survival of more than 3 years. A PS of 0 was an independent prognostic factor for predicting favorable outcomes in patients with advanced NSCLC who survived for more than 3 years.     

Phase Ⅱ trial of carboplatin/docetaxel in patients with resected NSCLC

AIM: To investigate the development of a safer chemotherapeutic regimen with better compliance, a total of 67 patients were enrolled as a single arm in a twostage multi-center phase Ⅱ study.METHODS: The patients received chemotherapy with carboplatin(CBDCA) with an area under the curve(AUC) of 5, and docetaxel(DTX) at 60 mg/m2 tri-weekly for three cycles after surgery. The primary endpoint of this study was compliance, while the secondary endpoints were the adverse events(AE) and recurrencefree survival(RFS).RESULTS: Sixty-one patients were treated in this study arm. The patients were 43 males and 18 females, with a median age of 64.6 years. Fifty-one patients(83.6%)completed all three cycles of therapy. The presence of Grade 3 and 4 neutropenia was noted in 25% and 66%of the patients, respectively. The non-hematological AE were less frequently reported, and no treatmentrelated death was registered. The two-year RFS and OS rates of the 61 patients were 69.8% and 88.3%,respectively.CONCLUSION: A tri-weekly schedule of CBDCA and DTX as adjuvant chemotherapy showed a favorable feasibility.     

Predictors of acute exacerbation in biopsy-proven idiopathic pulmonary fibrosis

BackgroundAcute exacerbation (AE) is a major cause of death in patients with idiopathic pulmonary fibrosis (IPF). Current evidence on AE-IPF has been largely based on clinical, rather than pathological, analyses.MethodsWe investigated AE incidence and its predictors using clinical, radiological, and pathological data of patients diagnosed with IPF by multi-disciplinary discussion.This study, a secondary analysis of previous research, included 155 patients with IPF who underwent surgical lung biopsy (SLB). Cumulative AE incidence was evaluated by the Kaplan–Meier method. Predictors of AE-IPF were analyzed with a Fine-Gray sub-distribution hazard model. Sub-analysis was performed using propensity score-matching analysis.ResultsIn this cohort, the median age of the patients was 66 years and the median percent-predicted forced vital capacity was 82.8%. The cumulative AE incidence rates at 30 days and one year post SLB were 1.9% and 7.6%, respectively. On multivariable analysis, a lower percent-predicted diffusing capacity of the lung for carbon monoxide (%DL_CO) (hazard ratio 0.98 per 1% increase, P = 0.02) and fibroblastic foci (FF)-present (vs. absent; hazard ratio 3.01, P = 0.04) were independently associated with a higher incidence of AE. The propensity score-matching analysis with adjustment for age, gender, and %DL_CO revealed that the cumulative AE incidence rate was significantly higher in the FF-present subgroup than in the FF-absent subgroup (1-year incidence rate, 10.5% vs. 0%, respectively; P = 0.04 by Gray's test).ConclusionsFF and %DL_CO were independent predictors of AE in patients with biopsy-proven IPF. FF may be associated with the pathogenesis of AE-IPF.     

Clinical benefit of radiation therapy and metallic stenting for unresectable hilar cholangiocarcinoma

AIM: To determine the efficacy of external beam radiotherapy (EBRT), with or without intraluminal brachytherapy (ILBT), in patients with non-resected locally advanced hilar cholangiocarcinoma.METHODS: We analyzed 64 patients with locally advanced hilar cholangiocarcinoma, including 25 who underwent resection (17 curative and 8 non-curative), 28 treated with radiotherapy, and 11 who received best supportive care (BSC). The radiotherapy group received EBRT (50 Gy, 30 fractions), with 11 receiving an additional 24 Gy (4 fractions) ILBT by iridium-192 with remote after loading. ILBT was performed using percutaneous transhepatic biliary drainage (PTBD) route. Uncovered metallic stents (UMS) were inserted into non-resected patients with obstructive jaundice, with the exception of four patients who received percutaneous transhepatic biliary drainage only. UMS were placed endoscopically or percutaneously, depending on the initial drainage procedure. The primary endpoints were patient death or stent occlusion. Survival time of patients in the radiotherapy group was compared with that of patients in the resection and BSC groups. Stent patency was compared in the radiotherapy and BSC groups.RESULTS: No statistically significant differences in patient characteristics were found among the resection, radiotherapy, and BSC groups. Three patients in the radiotherapy group and one in the BSC group did not receive UMS insertion but received PTBD alone; cholangitis occurred after endoscopic stenting, and patients were treated with PTBD. A total of 16 patients were administered additional systemic chemotherapy (5-fluorouracil-based regimen in 9, S-1 in 6, and gemcitabine in 1). Overall survival varied significantly among groups, with median survival times of 48.7 mo in the surgery group, 22.1 mo in the radiotherapy group, and 5.7 mo in the BSC group. Patients who underwent curative resection survived significantly longer than those who were not candidates for surgery (P = 0.0076). Cumulative survival in the radiotherapy group was significantly longer than in the BSC group (P = 0.0031), but did not differ significantly from those in the non-resection group. Furthermore, the median survival time of patients in the radiotherapy group who were considered for possible resection (excluding the seven patients who were not candidates for surgery due to comorbid disease or age) was 25.9 mo. Stent patency was evaluated only in the 24 patients who received a metallic stent. Stent patency was significantly longer in the radiotherapy than in the BSC group (P = 0.0165). Biliary drainage was not eliminated in any patient. To determine the efficacy of ILBT, we compared survival time and stent patency in the EBRT alone and EBRT plus ILBT groups. However, we found no significant difference in survival time between groups or for stent patencies. Hemorrhagic gastroduodenal ulcers were observed in 5 patients (17.9%), three in the EBRT plus ILBT group and two in the EBRT alone group. Ulcers occurred 5 mo, 7 mo, 8 mo, 16 mo, and 29 mo following radiotherapy. All patients required hospitalization, but blood transfusions were unnecessary. All 5 patients recovered following the administration of anti-ulcer medication.CONCLUSION: Radiotherapy improved patient prognosis and the patency of uncovered metallic stents in patients with locally advanced hilar cholangiocarcinoma, but ILBT provided no additional benefits.     

Updated survival analysis in patients with stage IIIB or IV non-small-cell lung cancer receiving BLP25 liposome vaccine (L-BLP25): phase IIB randomized, multicenter, open-label trial

Purpose

To present an updated survival analysis of an open-label, parallel-group, phase IIB trial of BLP25 liposome vaccine (L-BLP25) in patients with stage IIIB or IV non-small-cell lung cancer (NSCLC).

Methods

Patients were randomized to either L-BLP25 plus best supportive care (BSC) or BSC alone. Patients in the L-BLP25 arm received subcutaneous vaccinations of L-BLP25 930???g weekly for 8?weeks, followed by maintenance vaccinations at 6-week intervals.

Results

Median survival time was 4.2?months longer in patients receiving L-BLP25 plus BSC (n?=?88) than in those receiving BSC alone (n?=?83; 17.2?months vs. 13.0?months, respectively; hazard ratio [HR] 0.745, 95% confidence interval [CI] 0.533?C1.042). The 3-year survival rate was 31% in patients receiving L-BLP25 plus BSC and 17% in those receiving BSC (P?=?0.035). In the stratified subset of patients with stage IIIB loco-regional (LR) disease, median survival time was 17.3?months longer in patients receiving L-BLP25 plus BSC (n?=?35) than in those receiving BSC (n?=?30; 30.6?months vs. 13.3?months, respectively; HR 0.548, 95% CI 0.301?C0.999). In this subgroup, 3-year survival was 49% in patients receiving L-BLP25 plus BSC and 27% in those receiving BSC (P?=?0.070).

Conclusions

Confirming the initial results, further follow-up continues to show that survival time for patients with stage IIIB/IV NSCLC was longer with L-BLP25 plus BSC compared with BSC alone, with the greatest difference seen in patients with stage IIIB LR disease.     

紫杉醇联合顺铂治疗晚期非小细胞肺癌的临床观察

目的观察紫杉醇(PTX)加顺铂(CDDP)联合化疗治疗晚期非小细胞肺癌的近期疗效及毒副反应。方法PTX135~175mg/m2静脉滴注,第1天;CDDP75mg/m2,分三次用完。每21天为1个周期,连用2或3周期。结果可评价疗效者37例,其中PR16例,总有效率为43.2%。毒副反应主要是骨髓抑制和恶心呕吐。结论PTX DDP治疗晚期非小细胞肺癌可获得较高疗效,毒副反应轻,是一个较好的联合化疗方案。     

Association of the RAGE/RAGE-ligand axis with interstitial lung disease and its acute exacerbation

The receptor for advanced glycation end product (RAGE) is a transmembrane receptor highly expressed in type 1 pneumocytes of healthy lungs. RAGE is considered to play a homeostatic role in the lung, as RAGE knockout mice develop lung fibrosis as they age. In contrast, RAGE can bind numerous ligands, including high-mobility group box 1 (HMGB1). These interactions initiate pro-inflammatory signaling associated with the pathogenesis of lung injury and interstitial lung disease (ILD), including idiopathic pulmonary fibrosis (IPF).ILD is a broad category of diffuse parenchymal lung disease characterized by various extents of lung fibrosis and inflammation, and IPF is a common and progressive ILD of unknown cause. The prognosis of patients with IPF is poor, and acute exacerbation of IPF (AE-IPF) is one of the main causes of death. Recent reports indicate that acute exacerbations can occur in other ILDs (AE-ILD). Notably, ILD is frequently observed in patients with lung cancer, and AE-ILD after surgical procedures or the initiation of chemotherapy for concomitant lung cancer are clinically important due to their association with increased mortality.In this review, we summarize the associations of RAGE/soluble RAGE (sRAGE)/RAGE ligands with the pathogenesis and clinical course of ILD, including IPF and AE-IPF. Additionally, the potential use of sRAGE and RAGE ligands as predictive markers of AE-IPF and cancer treatment-triggered AE-ILD is also discussed.     

Dramatic Response to Carboplatin Plus Paclitaxel in Pancreatic Mucinous Cystadenocarcinoma with Liver Metastasis

Mucinous cystic neoplasm (MCN) of the pancreas is a rare cystic tumor occurring in the pancreatic body and tail in young to middle-aged women that is pathologically characterized by an ovarian-like stroma. Chemotherapy for recurrent/advanced pancreatic MCN has been based on chemotherapy regimens for pancreatic ductal adenocarcinoma, but the prognosis is poor. We herein report a 37-year-old woman with pancreatic mucinous cystadenocarcinoma with liver metastasis that responded dramatically to carboplatin plus paclitaxel therapy (CBDCA+PTX). CBDCA+PTX may be a treatment option for recurrent/advanced pancreatic MCN with an ovarian-like stroma.     

Outcome of treated advanced non-small cell lung cancer with and without central airway obstruction

OBJECTIVE: In patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy, we compared survival in patients with treated central airway obstruction to those who did not have central airway obstruction. METHODS: One hundred forty-four patients with advanced and inoperable NSCLC were included. These consisted of 52 consecutive patients treated with therapeutic bronchoscopy plus chemotherapy with or without radiotherapy (group A) and 92 consecutive patients who did not have central airway obstruction treated with chemotherapy alone (group B). Chemotherapy consisted of cisplatin or carboplatin, and one third-generation chemotherapy agent. RESULTS: There was no significant difference in the survival of patients with and without central airway obstruction (p = 0.395). There was no influence of the histologic subtype on survival in both groups combined and also in each group separately. Median survival in patients belonging to group A was 8.4 months and those in group B was 8.2 months; 3-, 6-, and 12-month survival rates in patients in group A were 90%, 71%, and 40%, respectively, and those in group B were 82%, 63%, and 34%. CONCLUSION: Patients having advanced NSCLC with locally treated malignant central airway obstruction in combination with chemotherapy do not have a worse survival compared to those with advanced NSCLC without central airway obstruction. Therapeutic bronchoscopy should be offered to patients with NSCLC and central airway obstruction.     

特发性肺纤维化急性加重

特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)是最常见的一种特发性间质性肺炎,目前病因不明,组织病理表现为普通型问质性肺炎.既往认为IPF是一个逐渐进展的疾病,后来认识到部分IPF患者在病程中可以无明显原因出现症状的急剧恶化,这种现象被称为 IPF急性加重(acute exacerbations of IPF,AE-IPF).最近,AE-IPF得到了广泛的重视和研究.本文将对AE-IPF的发病率和病死率、病因、临床特点、病理改变、诊断和治疗进展等方面作一综述.     

Progranulin and Activin A Concentrations are Elevated in Serum from Patients with Acute Exacerbations of Idiopathic Pulmonary Fibrosis

Purpose

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease of unknown cause with a variable course. Acute exacerbations of IPF (AE-IPF) is sudden accelerations of the disease or a superimposed idiopathic acute injury significantly reducing lung function. To examine the serum concentrations of Progranulin (PGRN) and activin A in patients with AE-IPF in a pilot study.

Methods

Twenty-one patients with AE-IPF were compared with 23 patients with stable IPF as a control group. Serum PGRN and activin A levels, arterial blood gas measurements, and lung function were determined in these two groups.

Results

Peripheral blood PGRN and activin A levels in patients with AE-IPF were 83.7 + 10.0 and 14.2 ± 1.7 ng/ml (mean + SD), respectively; higher than those in the control group 61.0 + 5.8 and 5.8 + 1.0 (p < 0.001). PGRN and activin A levels were significantly negatively correlated with carbon monoxide diffusion capacity r = − 0.857 (p < 0.001) and r = − 0.757 (p < 0.001).

Conclusion

Progranulin (PGRN) and activin A may be involved in the pathogenesis of AE-IPF. They may be possible markers of disease activity in AE-IPF.

     

Pemetrexed plus platinum or gemcitabine plus platinum for advanced non‐small cell lung cancer: final survival analysis from a multicentre randomized phase II trial in the East Asia region and a meta‐analysis

Background and Objective: Pemetrexed plus platinum has shown efficacy as a first‐line treatment for advanced non–small cell lung cancer (NSCLC), but little is known about its efficacy and safety in East Asian patients. We report the final analysis of overall survival (OS) from a multicentre, randomized, phase II trial in chemotherapy‐naive Chinese patients with advanced NSCLC. An additional meta‐analysis was performed to systematically evaluate pemetrexed/platinum as first‐line treatment for advanced NSCLC. Methods: Eligible patients received up to six cycles of pemetrexed, 500 mg/m² plus cisplatin, 75 mg/m² (day 1) or gemcitabine, 1000 mg/m² (days 1 and 8) plus cisplatin, 75 mg/m² (day 1). OS and toxicity were assessed. Results: A total of 254 patients were randomized, and 251 were eligible for inclusion in the efficacy and safety analyses. Median OS in the pemetrexed/cisplatin arm was 15.3 months, compared with 16.9 months in the gemcitabine/cisplatin arm [hazard ratio (HR) 1.09; 95% confidence interval (CI) 0.80–1.48; log‐rank P = 0.4888). There was a trend towards improved survival in both arms. Patients in the pemetrexed/cisplatin arm showed a lower incidence of drug‐related grade 3 to 4 leukopenia and thrombocytopenia. Meta‐analysis showed that pemetrexed‐platinum treatment was associated with 19% longer survival among females (HR 0.81; 95% CI 0.69–0.96) and 17% longer survival among patients with non‐squamous cell lung cancer (HR 0.83; 95% CI 0.73–0.95). Conclusions: In Chinese patients with advanced NSCLC, pemetrexed/cisplatin treatment resulted in comparable OS outcomes and was better tolerated than gemcitabine/cisplatin. Meta‐analysis supports the use of pemetrexed‐platinum as first‐line treatment for female patients and those with the non‐squamous cell subtype of advanced NSCLC.     

Serum S100A8 and S100A9 as prognostic biomarkers in acute exacerbation of idiopathic pulmonary fibrosis

BackgroundAcute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a devastating and life-threatening condition during its clinical course. Biomarkers for precisely anticipating the prognosis of AE-IPF remain to be fully established. The objective of this study was to clarify whether S100A8 and S100A9, which are calcium-binding proteins mainly produced by activated neutrophils, are significant prognostic biomarkers in AE-IPF.MethodsThirty-seven patients with AE-IPF who were diagnosed and treated at our hospital were retrospectively evaluated. The serum levels of S100A8 and S100A9 were measured using enzyme-linked immunosorbent assay, and the relationships between these levels and clinical parameters or prognosis were evaluated.ResultsThe serum levels of S100A8 (median 386.5 ng/mL) and S100A9 (median 60.2 ng/mL) in patients with AE-IPF were significantly higher than those in age-matched healthy controls and in patients at IPF diagnosis (p < 0.001 for all combinations). The serum levels of S100A8 negatively correlated with percent forced vital capacity (r = −0.356, p = 0.049) and positively correlated with peripheral white blood cell number (r = 0.509, p = 0.002). Immunohistochemical staining of autopsy lung specimens showed that neutrophils, present mainly in the alveolar septum, were positive for S100A8 and S100A9. Patients with AE-IPF with higher levels of S100A8 or S100A9 showed significantly worse 3-month survival than those with lower levels (log-rank test, both p = 0.028). Finally, in multivariate analysis, the serum levels of both S100A8 and S100A9 were significant prognostic factors (hazard ratio 4.032, p = 0.023 and hazard ratio 4.327, p = 0.012).ConclusionThe serum levels of S100A8 and S100A9 at AE were significant prognostic biomarkers in patients with AE-IPF.     

Acute exacerbation of idiopathic pulmonary fibrosis—a review of current and novel pharmacotherapies

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive form of lung disease of unknown etiology for which a paucity of therapies suggest benefit, and for which none have demonstrated improved survival. Acute exacerbation of IPF (AE-IPF) is defined as a sudden acceleration of the disease or an idiopathic acute injury superimposed on diseased lung that leads to a significant decline in lung function. An AE-IPF is associated with a mortality rate as high as 85% with mean survival periods of between 3 to 13 days. Under these circumstances, mechanical ventilation (MV) is controversial, unless used a as a bridge to lung transplantation. Judicious fluid management may be helpful. Pharmaceutical treatment regimens for AE-IPF include the use of high dose corticosteroids with or without immunosuppressive agents such as cyclosporine A (CsA), and broad spectrum antibiotics, despite the lack of convincing evidence demonstrating benefit. Newer research focuses on abnormal wound healing as a cause of fibrosis and preventing fibrosis itself through blocking growth factors and their downstream intra-cellular signaling pathways. Several novel pharmaceutical approaches are discussed.     

紫杉醇单药及联合顺铂治疗老年晚期非小细胞肺癌的临床观察

目的观察紫杉醇（TAX）单药与TAX＋顺铂（DDP）治疗老年晚期NSCLC的疗效和不良反应。方法经病理学或细胞学证实的58例晚期非小细胞肺癌随机分为两组，A组：应用TAX单药化疗，B组：TAX＋DDP联合化疗，21天为一个周期，均治疗2周期以上。观察经两方案治疗后的缓解率（RR）、临床获益率（CR＋PR＋SD）、1年生存率和不良反应。结果A组及B组的有效率分别为31．0％和37．9％（P=0．22）；临床获益率（CR＋PR＋SD）分别为72．4％和79．3％（P=0．73）；1年生存率分别为43．3％和46．4％（P=0．52）；单药组的消化道毒性、骨髓毒性及肾脏损伤均显著低于联合组（P〈0．05）。结论紫杉醇单药或联合顺铂均是治疗老年晚期NSCLC的较好方案，二者疗效相似，单药紫杉醇毒副反应更少见，较易为老年患者接受。     

Impact of biliary stent-related events in patients diagnosed with advanced pancreatobiliary tumours receiving palliative chemotherapy

AIM: To determine the impact(morbidity/mortality) of biliary stent-related events(SRE)(cholangitis or stent obstruction) in chemotherapy-treated pancreaticobiliary patients.METHODS: All consecutive patients with advanced pancreatobiliary cancer and a biliary stent in-situ prior to starting palliative chemotherapy were identified retrospectively from local electronic case-note records(Jan 13 to Jan 15). The primary end-point was SRE rate and the time-to-SRE(defined as time from first stenting before chemotherapy to date of SRE). Progressionfree survival and overall survival were measured from the time of starting chemotherapy. Kaplan-Meier, Cox and Fine-Gray regression(univariate and multivariable) analyses were employed, as appropriate. For the analysis of time-to-SRE, death was considered as a competing event.RESULTS: Ninety-six out of 693 screened patients were eligible; 89% had a metal stent(the remainder were plastic). The median time of follow-up was 9.6 mo(range 2.2 to 26.4). Forty-one patients(43%)developed a SRE during follow-up [cholangitis(39%), stent obstruction(29%), both(32%)]. There were no significant differences in baseline characteristics between the SRE group and no-SRE groups. Recorded SRE-consequences were: none(37%), chemotherapy delay(24%), discontinuation(17%) and death(22%). The median time-to-SRE was 4.4 mo(95%CI: 3.6-5.5). Patients with severe comorbidities(P 0.001) and patients with ≥ 2 baseline stents/biliary procedures [HR = 2.3(95%CI: 1.2-4.44), P = 0.010] had a shorter time-to-SRE on multivariable analysis. Stage was an independent prognostic factor for overall survival(P = 0.029) in the multivariable analysis adjusted for primary tumour site, performance status and development of SRE(SRE group vs no-SRE group).CONCLUSION: SREs are common and impact on patient's morbidity. Our results highlight the need for prospective studies exploring the role of prophylactic strategies to prevent/delay SREs.     

Cytokine gene polymorphisms in idiopathic pulmonary fibrosis

AIM: To characterize cytokine gene polymorphisms in patients with idiopathic pulmonary fibrosis (IPF) compared to healthy controls. METHODS: Fifty-six IPF patients were involved in the study. The control population consisted of 144 healthy volunteers without history of lung disease. All of the patients were diagnosed with IPF according to the American Thoracic Society/European Respiratory Society consensus statement. Polymorphisms in the interleukin (IL)-1, IL-1, IL-1R, IL-1RA, IL-2, IL-4, IL-6, IL-10, IL-12, tumour necrosis factor, interferon, transforming growth factor, IL-1, IL-2, IL-4 and IL-4RA genes were characterized by polymerase chain reaction with sequence-specific primers. Statistical analysis was performed using the MedCalc statistical software. A Bonferroni correction of significance at an alpha of 0.05 was used for multiple analyses. A corrected P value less than 0.0023 (0.05/22) was considered significant. RESULTS: We found significant differences in the IL-4 promoter region polymorphisms between IPF patients and controls. Namely, polymorphisms of IL-4 (-590) [computed tomography (CT) in 32 of 56 patients vs 27 of 144 controls; P < 0.0001] and IL-4 (-33) (CT in 25 of 56 patients vs 27 of 144 controls; P = 0.0006) differed between both groups. With regard to haplotypes, we found differences in the frequencies for haplotype 1 of IL-4 (-1098) (-590) (-33) between IPF and controls (TCC in 23 of 56, TTC in 10 of 56, and TTT in 21 of 56 patients vs TCC in 112 of 144, TTC in 0 of 144, and TTT in 32 of 144 controls; P < 0.0001). We did not find significant differences in gene polymorphism frequencies of other cytokines in the IPF group vs the controls. CONCLUSION: We hypothesize that IL-4 promoter polymorphisms could be involved in the pathogenesis of IPF, likely via enhancement of the T_h2 cytokine milieu with exaggerated fibroproliferative healing.     

Chemotherapy and resection for gastric cancer with synchronous liver metastases

AIM: To investigate the effect of surgery and chemotherapy for gastric cancer with multiple synchronous liver metastases (GCLM). METHODS: A total of 114 patients were entered in this study, and 20 patients with multiple synchronous liver metastases were eligible. After screening with preoperative chemotherapy, 20 patients underwent curative gastrectomy and hepatectomy for GCLM; 14 underwent major hepatectomy, and the remaining six underwent minor hepatectomy. There were 94 patients without aggressive treatment, and they were in the non-operative group. Two regimens of perioperative chemotherapy were used: S-1 and cisplatin (SP) in 12 patients, and docetaxel, cisplatin and 5-fluorouracil (DCF) in eight patients. These GCLM patients were given preoperative chemotherapy consisting of two courses chemotherapy of SP or DCF regimens. After chemotherapy, gastrectomy and hepatectomy were preformed. Evaluation of patient survival was by follow-up contact using telephone and outpatient records. All patients were assessed every 3 mo during the first year and every 6 mo thereafter. RESULTS: Twenty patients underwent gastrectomy and hepatectomy and completed their perioperative chemotherapy and hepatic arterial infusion before and after surgery. Ninety-four patients had no aggressive treatment of liver metastases because of technical difficulties with resection and severe cardiopulmonary dysfunction. In the surgery group, there was no toxicity greater than grade 3 during the course of chemotherapy. The response rate was 100% according to the Response Evaluation Criteria in Solid Tumors Criteria. For all 114 patients, the overall survival rate was 8.0%, 4.0%, 4.0% and 4.0% at 1, 2, 3 and 4 years, respectively, with a median survival time (MST) of 8.5 mo (range: 0.5-48 mo). For the 20 patients in the surgery group, MST was 22.3 mo (range: 4-48 mo). In the 94 patients without aggressive treatment, MST was 5.5 mo (range: 0.5-21 mo). There was a significant difference between the surgery and unresectable patients (P = 0.000). Thr