The effect and safety assessment of monitoring ethanol concentration in exhaled breath combined with intelligent control of renal pelvic pressure on the absorption of perfusion fluid during flexible ureteroscopic lithotripsy.

PURPOSE: Previously, we designed a ureteral access sheath with the capability of renal pelvic pressure (RPP) measurement and a medical perfusion and aspiration platform, allowing for the intelligent control of RPP. However, the effect of different RPP levels on perfusion fluid absorption remains unclear. This randomized controlled trial aimed to investigate the effects of exhaled ethanol concentration monitoring and intelligent pressure control on perfusion fluid absorption during flexible ureteroscopic lithotripsy. METHODS: Eighty patients scheduled for flexible ureteroscopic lithotripsy were randomly divided into four groups. In groups A, B, and C, the RPPs were set at 0, - 5, and - 10 mmHg, respectively. Group D was regarded as the controls with unfixed RPP. Isotonic saline containing 1% ethanol was used as the irrigation fluid, with an average irrigation flow rate of 100 mL/min. The primary outcome of this study was the absorption of perfusion fluid that was calculated based on the exhaled ethanol concentration. The secondary outcomes included duration of operation and amounts of perfusion fluid used. Postoperative complications, pre- and postoperative renal function, infection markers, and blood gas analysis were also recorded for safety assessment. RESULTS: In all, 76 patients were involved in this study, whose demographic characteristics and preoperative conditions were comparable among groups. Under the same perfusion flow rate, the groups with fixed RPP exhibited reduced absorption of perfusion fluid, duration of operation, and perfusion volume. In particular, the lowest values were observed in group C (RPP = - 10 mmHg). In contrast to the unfixed RPP group, no considerable difference were observed in levels of BUN, Scr, WBC, CRP, and blood gas values among the fixed RPP groups. Moreover, postoperative complications showed no significant difference among groups. CONCLUSION: In flexible ureteroscopic lithotripsy, the groups with fixed RPP had less absorption of perfusion fluid and perfusion volume, shorter duration of surgery, and higher safety than the unfixed group.

How to Choose a Survival Period? The Impact of Antibiotic Use on OS or PFS in NSCLC Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

BACKGROUND: The development of immunotherapy has dramatically changed the treatment of non-small-cell lung cancer. The negative association of antibiotics on the clinical activity of immune checkpoint inhibitors in patients with NSCLC is well known. METHODS: PubMed, Embase, and Medline databases were searched until January 11, 2020. We included retrospective studies of ICIs (e.g., PD-1, PD-L1, and CTLA-4). The clinical outcomes were progression-free survival (PFS) and overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated, and subgroup and sensitivity analyses were performed. RESULTS: Our results indicated that the use of antibiotics reduced the survival of NSCLC patients treated with ICIs. The pooled HRs of PFS and OS were HR = 1.41 (95% CI = 1.23-1.61; P < 0.001) and HR = 2.16 (95% CI = 1.79-2.60; P < 0.001). We divided the studies into 5 subgroups according to antibiotic exposure time. Subgroup analysis showed that the patients that were administered antibiotics [-60 days; 0 days] or [-30 days; 0 days] before the initiation of ICIs treatment had a poorer OS rate, whereas those patients that were administered antibiotics [0 days; 30 days] after the initiation of ICIs treatment had a poorer PFS rate. In summary, ATB treatment in patients [-60 days; +30 days] near the initiation of ICIs treatment significantly reduced the survival in NSCLC patients. CONCLUSION: Our results indicated that ATB use is negatively associated with survival in NSCLC patients treated with ICIs immunotherapy. Similar studies involving a larger sample of cases are still being published. This meta-analysis identified that the timing of ATB treatment in NSCLC patients receiving ICIs immunotherapy has different effects on the OS and PFS of these patients. ATB treatment prior to the initiation of ICIs treatment affects OS, whereas ATB treatment after the initiation of ICIs treatment affects PFS.

Familial association of lung cancer with liver cancer in first-degree relatives.

Purpose: Besides the smoking and occupational exposures, heritable factors have been proven to be a risk factor for lung cancer by several population-based studies, which would misestimate the risk of lung cancer. Patients and methods: To quantify the magnitude of the high risk of lung cancer with family history, we performed a case-based study with 1373 enrolled individuals, which may be more accurate than a population-based study. Results: Risk of lung cancer was higher in people with lung cancer family history than in the control group (OR 2.50, p<0.001). Individuals with family history of liver cancer also had a higher risk of lung cancer than the control group (OR 1.78, p=0.038) while there was no significant difference within the individuals with family history of colorectal cancer, esophageal cancer, nasopharyngeal cancer or breast cancer. Furthermore, the risk of lung cancer in the subjects with early-onset cancers (age <50 years) was higher than the later-onset cancers (age ≥50 years), especially in individuals with family history of liver cancer (OR 9.24 vs 1.39). Risk of lung cancer in females with family history of lung cancer or liver cancer was higher than in males. Conclusion: The results of this study proved that the familial aggregation of lung cancer and liver cancer manifests higher risks of lung cancer, supporting the hypothesis that lung cancer and liver cancer are attributable to common familial predisposition.

Toxicological effects benzotriazole to the marine scallop Chlamys nobilis: a 2-month exposure study.

Benzotriazole and its associated derivatives (BTs) are widely used as ultraviolet stabilizers and corrosion inhibitors. They have been extensively found in marine environments and are bioaccumulative through the food chain. However, the toxicities of BTs to marine organisms are seldom identified and no assessment has been conducted for filter-feeding bivalves. In this study, a marine scallop Chlamys nobilis was exposed to 0, 0.01, 0.1, and 1.0 mg/L of BT for 60 days. Effects of BT on endocrine system, cytochrome P450 activity, antioxidant activity, and neural activity of C. nobilis were examined. The results showed that BT exerted significant estrogenic effects on both male and female scallops and inhibited EROD activities of C. nobilis even at 0.01 mg/L level. BT at ≥ 0.01 mg/L levels also caused significant oxidative stress on C. nobilis. Moreover, most of the adverse effects of BT to C. nobilis were found from day 35 and 0.01 mg/L was the lowest concentration with observed effects, showing the long-term toxic effects of BT to C. nobilis. Thus, the adverse effects of BT and its derivatives to marine benthic communities deserve more attention in future research.

A family history of cancer and lung cancer risk in never-smokers: A clinic-based case-control study.

OBJECTIVE: Some population-based studies involving lung cancer patients have reported that inherited susceptibility is responsible for the familial aggregation observed in non-smoking lung cancer patients; however, it has been found that the false-negative rates in clinic-ascertained probands are significantly lower than population-ascertained probands. In this clinic-based study, we sought to determine the relationship between a family history of cancer and lung cancer risk in Chinese never-smokers. METHODS: In this clinic-based case-control study, all 318 probands and 509 controls were Chinese. The data on demographic characteristics, age, gender, race, lung disease history, living environment, occupational exposure, and smoking history were collected from a structured questionnaire. Multiple conditional logistic regression was used to estimate adjusted odds ratios (aOR) and 95% CIs after adjusting for possible confounders. RESULTS: The risk of lung cancer was increased in individuals with a family history of lung (aOR, 3.21; p<0.001) or any other cancer (aOR, 1.79; p<0.001). Analyses were carried out using stratified relative gender; first-degree female relatives tended to have a higher risk than first-degree male relatives. Similarly, the aOR for a female developing a malignant tumor was two times greater than controls. CONCLUSIONS: Our analysis provides further evidence of the importance of genetic factors underlying lung cancer in patients who are never-smokers, especially in patients with a maternal history of cancer.

Sorafenib reverses resistance of gastric cancer to treatment by cisplatin through down-regulating MDR1 expression.

Cisplatin (DDP) has been successfully used in the treatment of gastric cancer; however, resistance of gastric tumors to cisplatin has also resulted in frequent treatment failure. To investigate the effect of sorafenib in reversing the resistance of human gastric cancer cell line SGC7901/DDP to treatment by cisplatin, and to examine possible underlying mechanisms. A SGC7901/DDP cell line was treated with different concentrations of sorafenib, with and without cisplatin. The reversing ability of sorafenib on cisplatin treatment was examined using MTT, FACS, and xenograft models. Western blotting and immunofluorescence were used to determine expressions of MDR1, p-Akt, and p-ERK. Sorafenib inhibited proliferation of human gastric cancer cell line SGC7901/DDP, both when used alone and in combination with cisplatin. Expression levels of MDR1, p-Akt, and p-ERK were significantly decreased after sorafenib treatment. Sorafenib may reverse resistance of human gastric cancer cell line SGC7901/DDP to cisplatin through down-regulating MDR1 expression.

Reduced chemotherapy sensitivity in EGFR-mutant lung cancer patient with frontline EGFR tyrosine kinase inhibitor.

OBJECTIVES: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a standard first-line treatment for EGFR-mutant patients with non-small cell lung cancer (NSCLC). However, it remains unclear whether frontline EGFR TKIs affect subsequent chemo-sensitivity in EGFR-mutant patients. This study compared chemo-sensitivity in patients treated with post-TKI chemotherapy and first-line chemotherapy controls. MATERIALS AND METHODS: This study included 203 EGFR-mutant patients. The study group contained 68 patients treated with chemotherapy after first-line EGFR-TKI and the control group contained 135 patients who received first-line chemotherapy. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were assessed. RESULTS: In study group, the RR of chemotherapy was 13.2% compared with 34.1% in the control group (P=0.002). The median PFS of chemotherapy in the control group was significantly longer than in the study group (6.9 vs. 3.9 months, P<0.001), while the RR (76.5% vs. 68.9%, P=0.259) and PFS (11.0 vs. 10.2 months) of EGFR-TKI were similar between first- and second-line treatment. Cox regression analyses indicated that prior EGFR-TKI treatment had a higher risk for disease progression during chemotherapy treatment [hazard ratio (HR)=3.06; 95% CI=2.12-4.42, P<0.001]. Median overall survival was 31.7 months in the control group and 23.5 months in the study group (P<0.001). The adjusted HR for death in the study group was 1.91 (95% CI=1.33-2.76; P<0.001). CONCLUSION: In EGFR-mutant patients, frontline EGFR-TKI significantly reduced the sensitivity of subsequent chemotherapy compared with that of TKI-naïve frontline chemotherapy. These findings need to be validated in further randomized trials.

Lung cancers with concomitant EGFR mutations and ALK rearrangements: diverse responses to EGFR-TKI and crizotinib in relation to diverse receptors phosphorylation.

PURPOSE: We investigated the incidence of concomitant epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements in Chinese patients with non-small cell lung cancer (NSCLC), and assessed responses to EGFR tyrosine kinase inhibitors (EGFR-TKIs) and crizotinib in such tumors. EXPERIMENTAL DESIGN: We screened 977 consecutive patients with NSCLC for the presence of concomitant EGFR mutations and ALK rearrangements by rapid amplification of cDNA ends-coupled PCR sequencing and FISH. Immunohistochemistry (IHC) and Western blotting were used to correlate the activation of EGFR, ALK, and downstream proteins with responses to EGFR-TKIs and crizotinib. RESULTS: The overall frequency of concomitant EGFR mutations and ALK rearrangements was 1.3% (13/977). EGFR/ALK co-alterations were found in 3.9% (13/336) EGFR-mutant and 18.6% (13/70) ALK-rearranged patients. Ten tumors were treated with first-line EGFR-TKIs, with a response rate of 80% (8/10). Two tumors with high phospho-ALK levels and low phospho-EGFR levels achieved stable and progressive disease, respectively. Median progression-free survival was 11.2 months. Coexpression of mutant EGFR and ALK fusion proteins in the same tumor cell populations was detected by IHC. Two cases with high phospho-ALK levels treated with crizotinib achieved partial responses; two cases with low phospho-ALK levels had progressive or stable disease. CONCLUSION: ALK rearrangements and EGFR mutations could coexist in a small subgroup of NSCLC. Advanced pulmonary adenocarcinomas with such co-alterations could have diverse responses to EGFR-TKIs and crizotinib. Relative phospho-ALK and phospho-EGFR levels could predict the efficacy of EGFR-TKI and crizotinib.

Clinical modes of EGFR tyrosine kinase inhibitor failure and subsequent management in advanced non-small cell lung cancer.

BACKGROUND: There is no published overview of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) failure modes in advanced non-small-cell lung cancer (NSCLC). This study aimed to classify the diversity of EGFR-TKI failure, and to investigate the usefulness of clinical modes in subsequent management and prognosis. METHODS: One-hundred and twenty consecutive clinical trial patients with EGFR-TKI failure were enrolled as the training set to establish a clinical model based on clinical factors. Another 107 routine patients were enrolled as the validating set according to a Bayes discriminant analysis. EGFR mutations and c-MET amplification were analyzed. Kaplan-Meier survival analysis was used to test the differences among three clinical modes and subsequent management. RESULTS: The duration of disease control, evolution of tumor burden, and clinical symptom were verified as feasible grouping variables. A correct grouping rate achieved 87.9%. The cohort was classified into three groups, as follows: 130 patients with dramatic progression, 42 with gradual progression, and 55 with local progression. Progression-free survivals (PFSs) for the dramatic progression, gradual progression, and local progression groups were 9.3, 12.9, and 9.2 months, respectively (P = 0.007). Overall survivals for the groups (OSs) were 17.1, 39.4, and 23.1 months, respectively (P < 0.001). TKI continuation was superior to switching chemotherapy in a subsequent setting for gradual progression (39.4 months vs. 17.8 months; P = 0.02). The difference of EGFR or c-MET among the three groups was not significant. CONCLUSIONS: Clinical modes of EGFR-TKI failure could favor strategies for subsequent treatment and predicting a survival benefit in advanced NSCLC.

Nedaplatin/Gemcitabine Versus Carboplatin/Gemcitabine in Treatment of Advanced Non-small Cell Lung Cancer: A Randomized Clinical Trial.

OBJECTIVE: To evaluate the efficacy and safety of nedaplatin/gemcitabine (NG) and carboplatin/gemcitabine (CG) in the management of untreated advanced non-small cell lung cancer (NSCLC). METHODS: Sixty-two patients with previously untreated advanced NSCLC were recruited between June 2006 and November 2007. Subjects were randomly assigned to the NG arm (n=30) and the CG arm (n=32). Only patients (24 and 25 in the NG and CG arms, respectively) who completed ≥2 chemotherapy cycles were included in the data analysis. The primary outcome measure was the objective response rate (ORR). The secondary outcome measures included progression-free survival (PFS), overall survival (OS) and adverse events. RESULTS: There were no statistically significant differences in the efficacy measures (ORR, P=0.305; median PFS, P=0.198; median OS, P=0.961) or in the major adverse events (grade 3/4 neutropenia, P=0.666; grade 3/4 anemia, P=0.263; grade 3/4 thrombocytopenia, P=0.212) between the two treatment arms. However, there was a trend towards higher ORR (37.5% vs. 24.0%), longer PFS (6.0 vs. 5.0 months), and less adverse events in the NG arm. CONCLUSION: NG regimen seems to be superior over CG regimen for advance NSCLS, but further investigation is needed to validate this superiority.

Posttreatment plasma VEGF levels may be associated with the overall survival of patients with advanced non-small cell lung cancer treated with bevacizumab plus chemotherapy.

We sought to find blood-based biomarkers that can be used to predict efficacy in advanced non-small cell lung cancer patients treated with bevacizumab plus chemotherapy. Blood was collected before treatment and after 6 weeks of therapy from patients who were participating in a phase 4 trial. Plasma vascular endothelial growth factor (VEGF) levels were evaluated by ELISA. A total of eight single nucleotide polymorphisms in four candidate genes were analyzed by PCR and sequencing. A total of 45 patients enrolled in a clinical trial at Guangdong General Hospital between August 2007 and March 2008 were used as subjects. The median survival times of OS was 25.6 and 13.4 months in the low and high groups, respectively, when the median posttreatment plasma VEGF level (46.63 pg/ml) was used as the cut-off point (P = 0.0284). Patients carrying the AA genotype at the -6C > A polymorphism in laminin 5 (LN5) were more likely to exhibit reduced hemoglobin compared with patients carrying the CA/CC genotype (OR = 8.364, χ(2) = 5.34, P = 0.021). Similar associations were found at the -89A > G and -260C > A polymorphisms in LN5. Patients with the CC genotype at the -6C > A polymorphism in LN5 had an increased risk of neutropenia than those with the CA/AA genotype (OR = 4.444, χ(2) = 5.116, P = 0.030). Our results show improved survival in patients with lower posttreatment plasma VEGF levels treated with bevacizumab plus chemotherapy; thus, the posttreatment plasma VEGF level may be a promising biomarker to predict clinical benefit early in the course of therapy. Polymorphisms in LN5 were associated with a reduced level of hemoglobin and neutropenia.

[Clinical observation of lumbar spinal stenosis treated with deep puncture at Jiaji (EX-B 2)].

OBJECTIVE: To explore the clinical efficacy on lumbar spinal stenosis treated with deep puncture at Jiaji (EX-B 2) with round-sharp needle. METHODS: One hundred and fifty cases of lumbar spinal stenosis were divided randomly into a deep puncture at Jiaji (EX-B 2) group (deep puncture group) and a conventional needling group, 75 cases in each one. In deep puncture group, the round-sharp needle was used to puncture Jiaji (EX-B 2) deeply to the nerve root in vertebral canal. Additionally, the conventional acupuncture with filiform needle was applied at the acupoints selected according to the symptoms, such as Shenshu (BL 23), Weizhong (BL 40), Zusanli (ST 36) and Zhibian (BL 54), etc. In conventional needling group, acupuncture with filiform needle was adopted at the acupoints as those in deep puncture group. The clinical symptom scores and efficacies of the patients in two groups were observed after 4 weeks treatment and 3 months of follow-up visit separately. RESULTS: After treatment and in follow-up visit, the clinical symptom scores all increased apparently for the patients in two groups (all P < 0.01). The result in deep puncture group was superior to that in conventional needling group (both P < 0.01). In deep puncture group, the total effective rates were 100.0% (75/75) and 96.0 (72/75) after treatment and in follow-up visit respectively, which were all superior to 92.0% (69/75) and 84.0% (63/75) in conventional needling group (both P < 0.05). CONCLUSION: The deep puncture at Jiaji (EX-B 2) with round-sharp needle achieves superior efficacy as compared with the conventional needling therapy in treatment of lumbar spinal stenosis. The prognosis of it is better and the disease is hardly recurred.

Impact of smoking status and pathologic type on epidermal growth factor receptor mutations in lung cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations in lung carcinomas can make the disease more responsive to the treatment with tyrosine kinase inhibitors. We aimed to evaluate the prevalence of EGFR mutations in a large series of lung carcinomas. METHODS: We examined 1195 consecutive lung cancer patients for EGFR mutations in exons 18, 19, and 21 using direct sequencing of polymerase chain reaction products. A detailed smoking history was obtained. Patients were categorized as never smokers (< 100 lifetime cigarettes), former smokers (quit > 1 year ago), or current smokers (quit < 1 year ago). RESULTS: There were EGFR mutations in 9 (4.5%) of 201 squamous carcinomas, in 1 (2%) of 50 large cell carcinomas, and in 1 (2.3%) of 44 small cell carcinomas that were investigated. Three hundred and twenty-seven mutations were found in the series of 858 adenocarcinomas (38.1%). Among 858 lung adenocarcinomas, we detected EGFR mutations in 250 (48.6%) of 514 never smokers, 39 (33.9%) of 115 former smokers, and 38 (16.6%) of 229 current smokers. Significantly fewer EGFR mutations were found in people who smoked for more than 15 pack-years (P = 0.0002) or stopped smoking less than 15 years ago (P = 0.033) compared with individuals who never smoked. CONCLUSIONS: Adenocarcinoma is the most frequent EGFR mutation pathologic type in lung cancer. The likelihood of EGFR mutations in exons 18, 19 and 21 decreases as the number of pack-years increases. Mutations were less common in people who smoked for more than 15 pack-years or who stopped smoking cigarettes less than 15 years ago. These data can assist clinicians in assessing the likelihood of exons 18, 19, or 21 EGFR mutations in Chinese patients with lung cancer when mutational analysis is not feasible.

Relative abundance of EGFR mutations predicts benefit from gefitinib treatment for advanced non-small-cell lung cancer.

PURPOSE: Our aim was to determine whether abundance of epidermal growth factor receptor (EGFR) mutations in tumors predicts benefit from treatment with EGFR-tyrosine kinase inhibitors (TKIs) for advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We detected EGFR mutations in 100 lung cancer samples using direct DNA sequencing and amplification refractory mutation system (ARMS). Mutation-positive tumors by both methods carried high abundance of EGFR mutations. Tumors that were mutation positive by ARMS but mutation negative by direct DNA sequencing harbored low abundance of EGFR mutations. Mutation-negative tumors by both methods carried wild-type EGFR. All patients received gefitinib treatment. The correlation between EGFR mutation abundance and clinical benefit from gefitinib treatment was analyzed. RESULTS: Of 100 samples, 51 and 18 harbored high and low abundances of EGFR mutations, respectively; 31 carried wild-type EGFR. Median progression-free survival (PFS) was 11.3 (95% CI, 7.4 to 15.2) and 6.9 months (95% CI, 5.5 to 8.4) in patients with high and low abundances of EGFR mutations, respectively (P = .014). Median PFS of patients with low abundance of EGFR mutations was significantly longer than that of those with wild-type tumors (2.1 months; 95% CI, 1.0 to 3.2; P = .010). Objective response rates (ORRs) were 62.7%, 44.4%, and 16.1%, and overall survival (OS) rates were 15.9 (95% CI, 13.4 to 18.3), 10.9 (95% CI, 2.7 to 19.1), and 8.7 months (95% CI, 4.6 to 12.7) for patients with high abundance of EGFR mutations, low abundance of EGFR mutations, and wild-type EGFR, respectively. The difference between patients with high and low abundances of EGFR mutations was not significant regarding ORR and OS. CONCLUSION: The relative EGFR mutation abundance could predict benefit from EGFR-TKI treatment for advanced NSCLC.

Manifestation of leukoencephalopathy in a patient with advanced non-small cell lung cancer following treatment with gefitinib.

The present case is a patient with advanced non-small cell lung cancer (NSCLC) who developed leukoencephalopathy following radiotherapy and gefitinib treatments. There are rarely reports of such incidences because the median survival period of advanced NSCLC is only ten months. The features of leukoencephalopathy in this case were atypical for radiation leukoencephalopathy, so it was suspected that the leukoencephalopathy was associated with gefitinib.

[Clinical observation on three-combination needling method for treatment of primary trigeminal neuralgia].

OBJECTIVE: To probe into a better therapy for primary trigeminal neuralgia. METHODS: Eighty-six cases were randomly divided into an observation group (n = 46) and a control group (n = 40). The observation group were treated with the three-combination needling method, i. e. acupuncture, acupoint-injection and fire-needle therapy, and the control group with acupuncture and acupoint-injection. After treatment of 2 courses, their therapeutic effects were assessed. RESULTS: The total effective rate of 93.5% and the cured rate of 60.9% in the observation group were better than 65.0% and 22.5% in the control group, with significant differences (both P < 0.01). CONCLUSION: The three-combination needling method has obvious clinical therapeutic effect on primary trigeminal neuralgia.