Non-smoking Female Patients Research Articles

LYN expression predicts the response to dasatinib in a subpopulation of lung adenocarcinoma patients.

Therapies targeting SRC family kinases (SFKs) have shown efficacy in treating non-small cell lung cancer (NSCLC). However, recent clinical trials have found that the SFK inhibitor dasatinib is ineffective in some patient cohorts. Regardless, dasatinib treatment may benefit some NSCLC patient subgroups. Here, we investigated whether expression of LYN, a member of the SFK family, is associated with patient survival, the efficacy of dasatinib, and/or NSCLC cell viability. LYN expression was associated with poor overall survival in a multivariate analysis, and this association was strongest in non-smoker female patients with adenocarcinoma (ADC). In lung ADC cells, LYN expression enhanced cell proliferation, migration, and invasion. Dasatinib inhibited LYN activity and decreased cell viability in LYN-positive ADC cell lines and xenografts. Additionally, we identified the SFKs SRC and YES as candidate dasatinib targets in LYN-negative ADC cell lines. Our findings suggest that LYN is a useful prognostic marker and a selective target of dasatinib therapy in the lung ADC subpopulation especially in female non-smokers with lung ADC.

Patient-controlled Analgesia With Propacetamol-Fentanyl Mixture for Prevention of Postoperative Nausea and Vomiting in High-risk Patients Undergoing Spine Surgery: A Randomized Controlled Trial.

This randomized trial evaluated the effect of intravenous patient-controlled analgesia (IV-PCA) based on fentanyl mixed with either propacetamol or an equivalent volume of normal saline on postoperative nausea and vomiting (PONV) in highly susceptible patients undergoing spinal surgery. One hundred eight nonsmoking female patients were randomly and evenly allocated to receive IV-PCA with either propacetamol (4 g) or normal saline mixed to fentanyl (20 μg/kg). Primary study outcome was PONV incidence at 24 hours postsurgery. Secondary outcomes were nausea severity, pain intensity (100-mm visual analog scale), use of rescue antiemetics and analgesics, patient satisfaction, and adverse events at 6, 12, and 24 hours postsurgery. Postsurgery, the propacetamol versus normal saline group had lower PONV incidence at 24 hours (41% vs. 66%, P=0.011); pain intensity at rest and rescue analgesic requirements at 6 to 12 hours (30±15 vs. 41±19, P=0.008; and 25% vs. 49%, P=0.036, respectively) and at 12 to 24 hours (25±15 vs. 35±17, P=0.008; and 19% vs. 42%, P=0.044, respectively); and higher patient satisfaction score (6.4±1.4 vs. 5.7±1.8, P=0.028). In patients undergoing spinal surgery and at risk of developing PONV, continuous IV-PCA based on propacetamol mixed to fentanyl, relative to fentanyl alone, effectively reduced the incidence of PONV, pain intensity at rest, and additional use of rescue analgesics with higher patient satisfaction.

Association of CHEK2 polymorphisms with the efficacy of platinum-based chemotherapy for advanced non-small-cell lung cancer in Chinese never-smoking women.

Cell cycle checkpoint kinase 2 (CHEK2) plays an essential role in the repair of DNA damage. Single nucleotide polymorphisms (SNPs) in DNA repair genes are thought to influence treatment effects and survival of cancer patients. This study aimed to investigate the relationship between polymorphisms in the CHEK2 gene and efficacy of platinum-based doublet chemotherapy in never-smoking Chinese female patients with advanced non-small-cell lung cancer (NSCLC). Using DNA from blood samples of 272 Chinese advanced NSCLC non-smoking female patients treated with first-line platinum-based chemotherapy, we have analyzed the relationships between four SNPs in the CHEK2 gene and clinical outcomes. We found that overall survival (OS) was significantly associated with CHEK2 rs4035540 (Log-Rank P=0.020), as well as the CHEK2 rs4035540 dominant model (Log-Rank P=0.026), especially in the lung adenocarcinoma group. After multivariate analysis, patients with rs4035540 A/G genotype had a significantly better OS than those with the G/G genotype (HR =0.67, 95% CI, 0.48-0.93; P=0.016). In the toxicity analysis, it was observed that patients with the CHEK2 rs4035540 A/A genotype had a higher risk of gastrointestinal toxicity than the G/G genotype group (P=0.009). However, there are no significant associations between chemotherapy treatments and genetic variations. Our findings indicate that SNPs in CHEK2 are related to Chinese advanced NSCLC never-smoking female patients receiving platinum-based doublet chemotherapy in China. Patients with rs4035540 A/G genotype have a better OS. And patients with rs4035540 A/A genotype have a higher risk of gastrointestinal toxicity. These results point to a direction for predicting the prognosis for Chinese never-smoking NSCLC female patients. However, there are no significant associations between chemotherapy treatments and SNPs in CHEK2, which need more samples to the further study.

Comparative study between transdermal nicotine and melatonin patches on postoperative pain relief after laparoscopic cholecystectomy, a double-blind, placebo-controlled trial

BackgroundThis study evaluated the efficacy of transdermal nicotine (TDN) delivery system (15 mg/16 h) or transdermal melatonin (TDM) delivery system (7 mg) 2 h preoperatively for acute postoperative pain after laparoscopic cholecystectomy compared to placebo group (C).MethodsSixty female non-smoker patients, aged 18–50 years and ASA I and II undergoing elective laparoscopic cholecystectomy under general anesthesia were included in this randomized controlled double-blind study. Patients were randomly divided into 3 groups 20 each, and C group patients received transdermal placebo patch, TDN group (15 mg/16 h) and TDM group (7 mg/8 h). Assessment of postoperative pain, sedation, hemodynamic variables such as HR and MAP, postoperative monitoring of arterial SpO2 and side effects (e.g. nausea, vomiting, pruritus, respiratory depression and hemodynamic instability) were done 30 min, 1, 2, 6 and 12 h postoperatively. Postoperative Patient’s and Surgeons’ satisfaction, Intraoperative bleeding and plasma cortisol (μg/dl) 2 h postoperatively were also assessed.ResultsThere was a significant reduction in the VAS score, total pethidine requirements (mg) and significantly higher patient’s satisfaction in TDN and TDM groups when compared with the C group postoperatively. The sedation score and surgeons’ satisfaction were significantly higher associated with a significant decrease in MAP and Intraoperative bleeding in TDM group compared to C and TDN groups postoperatively. Significant nausea and vomiting in TDN group and significant sedation in TDM group were recorded.ConclusionThe use of preoperative TDN (15 mg/16 h) or TDM (7 mg/8 h) was an effective and a safe adjuvant for acute pain after surgery.

Correlation of clinicopathologic features and driver gene mutation in non-small cell lung cancer

To study the relationship between mutations of well-known driver genes and clinicopathologic characteristics of non-small cell lung cancers (NSCLC). Scorpions amplification refractory mutation system (scorpions ARMS) fluorescence quantitative PCR was performed to investigate 205 driver gene mutation status in NSCLC in correlation with clinicopathological characteristics of the patients. Driver gene mutations were detected in 146 of 205 (71.2%) patients with NSCLC, including 81.7%(138/169) adenocarcinomas, in which mutations of nine genes were found: EGFR (63.3%, 107/169), KRAS (5.9%, 10/169), PIK3CA (4.1%, 7/169), ALK (4.1%, 7/169), ROS1 (3.0%, 5/169), RET (3.6%, 6/169), HER2 (1.8%, 3/169), NRAS (0.6%, 1/169) and BRAF (0.6%, 1/169). The frequencies of driver gene mutations were higher in adenocarcinomas, female patients and non-smokers (P<0.01, P=0.003, P<0.01, respectively). Driver gene mutation status showed no correlation with either the age or the clinical stage (P=0.281, P=0.490, respectively). However, EGFR mutations tended to occur in adenocarcinoma, female, non-smokers, and patients of ≥62 years of age (P<0.01, P<0.01, P=0.002, P=0.012, respectively). The frequency of EGFR mutation was positively correlated with the tumor histology of lepidic, acinar, papillary and micropapillary predominant growth patterns. There was no relationship between EGFR mutation and the clinical stage (P=0.237). The frequency of KRAS mutation was higher in solid predominant and invasive mucinous adenocarcinomas (P=0.015); that of PIK3CA mutation was higher in patients of ≥62 years of age, invasive mucinous adenocarcinoma and fetal adenocarcinoma (P=0.015, P=0.006, respectively). ALK, ROS1 or RET mutation positive NSCLC tended to occur in nonsmokers and have solid predominant tumors and invasive mucinous adenocarcinoma (P=0.012, P=0.017 respectively). The frequency of EML4-ALK mutation was higher in the early stage patients with solid predominant tumors and invasive mucinous adenocarcinomas (P=0.025, P=0.014, respectively); that of ROS1 rearrangement was higher in invasive mucinous adenocarcinomas (P=0.049). NRAS, BRAF and HER2 gene mutations were infrequent and their clinical significance remained to be elucidated. The relationship between mutations of well-known driver genes and clinicopathological characteristics in patients with NSCLC has diversity, the rate of mutations is higher in non-smoking female patients with adenocarcinoma.

EGFR-tyrosine kinase inhibitor treatment in a patient with advanced non-small cell lung cancer and concurrent exon 19 and 21 EGFR mutations: A case report and review of the literature.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are considered to be effective treatments for advanced non-small cell lung cancer (NSCLC) patients with sensitizing EGFR mutations, including exon 19 deletion and exon 21 L858R mutations. However, with the development of EGFR mutation detection assays, patients with complex EGFR mutations are emerging, and their response to EGFR-TKIs remains unclear. The present study reports a case of a 62-year-old, non-smoking female patient with advanced NSCLC, presenting with concurrent EGFR 19+21 sensitizing mutations, who had a poor response to the first-line EGFR-TKI erlotinib and succumbed 5 months subsequent to diagnosis. Furthermore, the present study performed a literature review, and 18 patients with complex EGFR 19+21 mutations that had received EGFR-TKIs were identified. The majority of these patients responded well to EGFR-TKIs. To the best of our knowledge, the present case is the first to report a patient with lung adenocarcinoma with complex EGFR 19+21 sensitizing mutations that had a poor clinical response to a first-line EGFR-TKI. Despite the 70% response rate of sensitizing EGFR-mutant NSCLCs to EGFR-TKIs, there is still a proportion of patients that experience de novo resistance, and heterogeneity is likely to be important in this resistance mechanism. Therefore, comprehensive genomic detection assays and multi-targeted therapies for patients with NSCLC with complex EGFR mutations require additional investigation.

Polymorphism of rs9387478 correlates with overall survival in female nonsmoking patients with lung cancer.

Our previous study identified rs9387478 as a new susceptibility locus associated with lung cancer in never-smoking women in Asia; however, the clinical and prognostic significance of this finding is not known. We analyzed the relationship between the rs9387478 single nucleotide polymorphism and i) clinical parameters and ii) overall survival time in 505 female nonsmoking lung cancer patients, using the chi-square test and Kaplan-Meier analysis with the log-rank test, respectively. We further established the epidermal growth factor receptor (EGFR) mutation status and assessed its association with rs9387478 genotypes as well as the efficacy of EGFR tyrosine kinase inhibitors. The frequency of the AA genotype was significantly higher in the EGFR-mutation-negative group than in the EGFR-mutation-positive group (32% vs. 16%, χ2 = 13.025, p = 0.011). Patients with the CC genotype had a better overall survival time than patients with the AA/AC genotype (median survival time: 54.2 vs. 32.9 months, χ2 = 4.593, p = 0.032). The distribution of rs9387478 genotypes differed according to the clinical disease stage. This study indicates that the rs9387478 genotype was associated with overall survival in nonsmoking female patients with lung cancer, although it was not significant after adjusting for multiple testing. The identification of the location of the rs9387478 single nucleotide polymorphism in the genomic interval containing the DCBLD1 and ROS1 genes, together with the finding that the rs9387478 polymorphism correlates with EGFR mutation status, may have important implications for therapeutic approaches targeting EGFR or ROS1 in patients with lung cancer.

Histological and micro-computed tomographic observations after maxillary sinus augmentation with porous hydroxyapatite alloplasts: a clinical case series.

BackgroundIt is important to visualize the phenomenon which occurs in actual clinical cases to decide the timing of implant placement subsequently after sinus graft. Although several clinical cases of bone augmentation using xenograft have been evaluated, the number of those reports which have described bone remodeling by alloplasty are not sufficient.FindingsIn the present report, to investigate bone remodeling histologically after maxillary sinus augmentation with porous hydroxyapatite alloplast, bone cores from the sinus floor of three female nonsmoking patients (aged 64–73 years) were collected 6 months after sinus lift surgery, embedded in methyl methacrylate resin, and prepared by conventional methods. Bone architecture and graft residues were evaluated by micro-computed tomography of the same specimens. Hematoxylin–eosin and Villanueva–Goldner staining revealed mature osteoblasts and multinucleated osteoclasts on the grafted sinus floor and surface of residual hydroxyapatite particles. The particulate interspace was partially filled with osteoid and calcified tissue and showed active vascularization.ConclusionThe results suggested that bone regeneration and angiogenesis within and between porous hydroxyapatite particles were sufficiently found after 6 month histologically in the grafted sinus floor.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-1885-2) contains supplementary material, which is available to authorized users.

Polymorphisms in pre-miRNA genes and cooking oil fume exposure as well as their interaction on the risk of lung cancer in a Chinese nonsmoking female population

BackgroundMicroRNAs (miRNAs) are suggested to be very important in the development of lung cancer. This study assesses the association between polymorphisms in miRNA-related (miR)-26a-1, miR-605, and miR-16-1 genes and risk of lung cancer, as well as the effect of gene–environment interaction between miRNA polymorphisms and cooking fume exposure on lung cancer.MethodsA case–control study including 268 diagnosed nonsmoking female lung cancer patients and 266 nonsmoking female controls was carried out. Three miRNA polymorphisms (miR-26a-1 rs7372209, miR-605 rs2043556, and miR-16-1 rs1022960) were analyzed. Both additive and multiplicative interactions were assessed.ResultsMiR-16-1 rs1022960 may be associated with the risk of lung cancer. Carriers with TT genotype of miR-16-1 rs1022960 were observed to have a decreased risk of lung cancer compared with CC and CT genotype carriers (odds ratio =0.550, 95% confidence interval =0.308–0.983, P=0.044). MiR-26a-1 rs7372209 and miR-605 rs2043556 showed no statistically significant associations with lung cancer risk. There were no significant associations between the three single nucleotide polymorphisms and lung adenocarcinoma. People with exposure to both risk genotypes of miR-26a-1 rs7372209 and cooking oil fumes were more likely to develop lung cancer than those with only genetic risk factor or cooking oil fumes (odds ratios were 2.136, 1.255, and 1.730, respectively). The measures of biological interaction and logistic models indicate that gene–environment interactions were not statistically significant on additive scale or multiplicative scale.ConclusionMiR-16-1 rs1022960 may be associated with the risk of lung cancer in a Chinese nonsmoking female population. The interactions between miRNA polymorphisms (miR-26a-1 rs7372209, miR-605 rs2043556, and miR-16-1 rs1022960) and cooking oil fumes were not statistically significant.

Concomitance of P-gp/LRP Expression with EGFR Mutations in Exons 19 and 21 in Non-Small Cell Lung Cancers.

PurposeTraditional chemotherapy is the main adjuvant therapy for the treatment of non-small cell lung cancer (NSCLC). However, the emergence of multi-drug resistance (MDR) has greatly restricted the curative effect of chemotherapy. Therefore, it is necessary to find a method to treat MDR NSCLC clinically. It is worth investigating whether NSCLCs that are resistant to traditional chemotherapy can be effectively treated with tyrosine kinase inhibitors targeting epidermal growth factor receptor (EGFR).Materials and MethodsThe expression of P-glycoprotein (P-gp) and lung resistance-related protein (LRP) was detected by immunohistochemistry, and mutations in EGFR (exons 19 and 21) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (exon 2) were detected by high-resolution melting analysis (HRMA) of surgical NSCLC specimens from 127 patients who did not undergo traditional chemotherapy or radiotherapy. A Pearson chi-square test was performed to analyze the correlations between the expression of P-gp and LRP and mutations in EGFR and KRAS.ResultsThe expression frequencies of P-gp and LRP were significantly higher in adenocarcinomas from non-smoking patients; the expression frequency of LRP was significantly higher in cancer tissue from female patients. The frequency of EGFR mutations was significantly higher in well to moderately differentiated adenocarcinomas from non-smoking female patients. The frequency of EGFR mutations in the cancers that expressed P-gp, LRP, or both P-gp and LRP was significantly higher than that in cancers that did not express P-gp or LRP.ConclusionNSCLCs expressing P-gp/LRP bear the EGFR mutation in exon 19 or 21 easily.

Relationship between mutations of epidermal growth factor receptor gene and clinicopathologic features of non-small cell lung cancers

To explore the relationship between the mutations of epidermal growth factor receptor (EGFR) gene and clinicopathological characteristics in patients with non-small cell lung cancers (NSCLC). Paraffin-embedded tissue specimens were obtained from 1444 patients with NSCLC. The genomic DNA was extracted. Mutations of EGFR gene (exons 19 and 21) were detected by real-time PCR. DNA was available in 1410 cases. Somatic mutations of the EGFR gene were identified in 401 cases (27.8%). Among patients with EGFR mutations, 41.4% (n=166) had del E746-A750 of exon19, 6.7% (n=27) had del L747-P753insS of exon 19, 50.3% (n=201) had L858R of exon 21, and 1.5% (n=6) had L861Q of exon 21. Woman, non-smoker and adenocarcinoma showed a higher percentage of EGFR mutation (43.2%, 37.6%, and 33.5%, respectively). However, there was no association among age, grades, lymph node metastasis, and TNM stages (P>0.05). The mutation rate of BAC subtype (61.3%, 19/31) and adenocarcinoma with BAC features (48.0%, 12/25) was significantly higher than that of conventional adenocarcinoma (32.4%, 336/1038). A further assess of the smoking status found a trend that the more increased smoking exposure, the lower the incidence of EGFR mutations. A multivariable analysis revealed that adenocarcinoma, never smoking, and female were independently associated with EGFR mutations (odds rations=3.381, 2.393, and 1.727, respectively). The detection rate of EGFR mutation is higher in Chinese patients, especially in non-smoking female patients with adenocarcinoma. Real-time PCR is a sensitive and accurate method to detect the mutations of EGFR gene and can therefore provide useful information for clinical treatment.

Cigarette Smoke and Estrogen Signaling in Human Airway Smooth Muscle

Aims: Cigarette smoke (CS) in active smokers and second-hand smoke exposure exacerbate respiratory disorders such as asthma and chronic bronchitis. While women are known to experience a more asthmatic response to CS than emphysema in men, there is limited information on the mechanisms of CS-induced airway dysfunction. We hypothesize that CS interferes with a normal (protective) bronchodilatory role of estrogens, thus worsening airway contractility. Methods: We tested effects of cigarette smoke extract (CSE) on 17β-estradiol (E₂) signaling in enzymatically-dissociated bronchial airway smooth muscle (ASM) obtained from lung samples of non-smoking female patients undergoing thoracic surgery. Results: In fura-2 loaded ASM cells, CSE increased intracellular calcium ([Ca²⁺]_i) responses to 10µM histamine. Acute exposure to physiological concentrations of E₂ decreased [Ca²⁺]_i responses. However, in 24h exposed CSE cells, although expression of estrogen receptors was increased, the effect of E₂ on [Ca²⁺]_i was blunted. Acute E₂ exposure also decreased store-operated Ca²⁺ entry and inhibited stromal interaction molecule 1 (STIM1) phosphorylation: effects blunted by CSE. Acute exposure to E₂ increased cAMP, but less so in 24h CSE-exposed cells. 24h CSE exposure increased S-nitrosylation of ERα. Furthermore, 24h CSE-exposed bronchial rings showed increased bronchoconstrictor agonist responses that were not reduced as effectively by E₂ compared to non-CSE controls. Conclusion: These data suggest that CS induces dysregulation of estrogen signaling in ASM, which could contribute to increased airway contractility in women exposed to CS.

Comprehensive analysis of genes, pathways, and TFs in nonsmoking Taiwan females with lung cancer

ABSTRACTPurpose: The aim of this study was to investigate the molecular mechanism of lung cancer among nonsmoking Taiwan females. Materials and methods: By using the GSE19804 microarray data accessible from Gene Expression Omnibus (GEO) database, we identified differentially expressed genes (DEGs) between nonsmoking female lung cancer patients and healthy controls (!logFC! >1.5 and p-value < 0.05). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene ontology (GO) enrichment analysis was performed using Database for Annotation, Visualization and Integrated Discovery (DAVID). The Search Tool for the Retrieval of Interacting Genes (STRING) tool was utilized to build a protein–protein interaction (PPI) network, followed by the construction of a transcriptional regulatory network based on Transcription factor (TRANSFAC) database. Results: As a result, 320 DEGs were identified between nonsmoking female patients with lung cancer and healthy controls. Pathway enrichment analysis showed significantly enriched pathways such as extracellular matrix (ECM)-receptor interaction and peroxisome proliferator-activated receptor (PPAR) signaling pathway, both of which were enriched with genes COL11A1 (encoding collagen XI alpha-1 chain protein), COL1A1, cluster of differentiation 36(CD36). GO enrichment analysis found that DEGs were significantly related to chemotaxis, vasculature development and cell adhesion GO terms. IL-6 was the node of the PPI network. Critical transcription factors (TFs) including CCAAT/enhancer-binding protein delta (CEBPD) and Rel/NF-κB were also identified. Conclusions: Our study revealed that ECM-receptor interaction, PPAR signaling pathways, and important biomolecules including COL11A1, COL1A1, CD36, IL-6, CEBPD, and Rel/NF-κB might be involved in lung cancer. This study might pave the way for the development and application of targeted therapeutics of lung cancer irrelevant to smoking.

Effect of Ketamine as an Adjunct to Intravenous Patient-Controlled Analgesia, in Patients at High Risk of Postoperative Nausea and Vomiting Undergoing Lumbar Spinal Surgery

Song, J. W.*†; Shim, J. K.*†; Song, Y.*†; Yang, S. Y.‡; Park, S. J.*; Kwak, Y. L.*†§ Author Information

Abstract 1857: Prognostic biomarker for SNP (-617C-A) in ARE-like loci of the NRF2 gene in lung adenocarcinoma

Abstract Purpose: We here report that SNP (c.-617C&amp;gt;A; rs6721961) in the ARE-like region of NRF2 gene is associated with Japanese non-smoking female patients with adenocarcinoma and their overall survival. Experimental Design: We prepared genomic DNA samples from 387 Japanese patients with primary lung cancer and detected a SNP (-617C&amp;gt;A) in NRF2 gene by the rapid genetic testing method we developed in this study. We analyzed the association between the SNP in the NRF2 gene and overall survival. Results:Patients harboring wild-type -617C/C, -617C/A, and -617A/A alleles numbered 216 (55.8%), 147 (38.0%), and 24 (6.2%), respectively. Multivariate logistic regression models revealed that SNP homozygote (-617A/A) was significantly related to gender. Its frequency was four-fold higher in female patients than in males (10.8% female vs 2.7% male) and was associated with female non-smokers with adenocarcinoma. Interestingly, lung cancer patients carrying the SNP homozygous alleles (-617A/A) and the 309T (WT) allele in the MDM2 gene exhibited remarkable survival over 1,700 days after surgical operation (log-rank p=0.021). Conclusion: SNP homozygous (-617 A/A) alleles in the NRF2 gene are associated with female non-smokers with adenocarcinoma and regarded as a prognostic biomarker for assessing overall survival of patients with lung adenocarcinoma. Citation Format: Yasuko Okano, Yasushi Ichikawa, Yohei Miyagi, Keiichi Kondo, Yutaka Natsumeda. Prognostic biomarker for SNP (-617C-A) in ARE-like loci of the NRF2 gene in lung adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1857. doi:10.1158/1538-7445.AM2014-1857

Intranasal nicotine increases postoperative nausea and is ineffective in reducing pain following laparoscopic bariatric surgery in tobacco-Naïve females: a randomized, double blind trial.

Nicotine is a known analgesic. Our primary aim was to test the hypothesis that intranasal nicotine administered intraoperatively reduces the need for postoperative opioids. The secondary outcomes included evaluation of both postoperative pain and nausea and vomiting (PONV). Nonsmoking female patients undergoing laparoscopic bariatric operations were randomized to receive either 3 mg intranasal nicotine (N = 42) or placebo spray (N = 47) at the conclusion of surgery. Postoperative opioid use converted to intravenous morphine equivalents (iv MEQ) and PONV rates were recorded during both the recovery room postanesthesia care unit (PACU) stay and the first 24 postoperative hours. All patients received multimodal antiemetic prophylaxis. Total iv MEQ were not significantly reduced during the PACU stay in patients receiving nicotine (median [interquartile range (IQR)], 5.3 [0, 10.0] mg for nicotine vs. 5.2 [0, 12.7] mg for placebo, one-tailed P = 0.414) or for the first 24 h following PACU discharge (39.6 [20.0, 52.5] mg for nicotine vs. 32.7 [20.3, 51.3] mg for placebo, one-tailed P = 0.752). For the combined period (PACU + 24-h post-PACU discharge), iv MEQ were 45.8 [27.0, 58.6] mg for nicotine and 39.4 [23.5, 60.0] mg for placebo, one-tailed P = 0.801. Compared to placebo, a higher percentage of patients administered nicotine received antiemetics in the PACU (57.1 vs. 25.5 %, P = 0.002). Intraoperative intranasal nicotine did not exhibit opioid-sparing effect in nonsmoking bariatric female patients. Despite antiemetic prophylaxis, the use of nicotine was associated with the higher frequency of the use of rescue antiemetics in PACU.

Successful video-assisted thoracoscopic lobectomy in a pregnant woman with lung cancer

A 38-year-old non-smoking female patient was evaluated at our hospital for an increasing mass in the right lower lung field at 24 weeks of gestation. Computed tomography revealed an approximately 7.5-cm diameter mass in the right lower lung lobe. After assessing the benefits to the patient and risks to the fetus, we performed a lobectomy with mediastinal lymph node dissection using video-assisted thoracoscopy. Three months postoperatively, the patient delivered a healthy male baby. The patient is alive 10 months following the lobectomy, and no evidence of recurrence and distant metastasis is noted. The 6-month-old infant is also doing well postpartum.

Up-regulation of microRNA-183-3p is a potent prognostic marker for lung adenocarcinoma of female non-smokers

Lung cancer in never smokers presents predominately as adenocarcinoma and in females. MicroRNA-183 (miR-183) has various expression patterns in types of human cancers. In the present study, we evaluated the expression of miR-183-3p in female lung adenocarcinoma and adjacent noncancerous tissues and explored its relationship with clinicopathological characteristics and prognosis. In the present study, a hundred female nonsmoking patients who were newly diagnosed and histologically confirmed as lung adenocarcinoma at Tianjin Medical University Cancer Hospital were included. miR-183-3p expression of surgically removed NSCLC tissues and their corresponding normal lung tissues was measured by qRT-PCR assay. Associations of miR-183-3p expression with clinicopathological features were determined using the Student's t test. Log-rank test, and Cox proportional hazards model were used for survival analysis. At first, miR-183-3p was up-regulated in lung cancer tissues when compared with the corresponding noncancerous lung tissues. Moreover, the expression of miR-183-3p in tumor tissue was found to be associated with lymph node metastasis (P = 0.043), clinical stage (P = 0.015), and EGFR mutation (P = 0.003). At last, high miR-183-3p expression was also associated with both poor overall survival and progression-free survival of women with lung adenocarcinoma (P = 0.005 and P = 0.010, respectively). This study suggested that miR-183-3p expression might be involved in lung cancer pathogenesis and progression, and could be used as a potential prognostic biomarker of female lung adenocarcinoma.

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Introduction: Paclitaxel is used to treat cancer of the ovaries, breast, and lung. Common side effects include hematologic, GI, and neuropathic. To date, there are only a handful of reported cases of pulmonary interstitial pneumonitis related specifically to Paclitaxel [1]. We report a case of Paclitaxel induced severe pulmonary interstitial pneumonitis responsive to steroid treatment. Case: A 46-year-old non-smoking female patient with stage III breast cancer, treated with neo-adjuvant dose-dense Adriamycin/cyclophosphamide/Paclitaxel was hospitalized three days after receiving her first dose of Paclitaxel for increasing dyspnea over the three days. Her O2 saturation was 78% on room air and heart rate was 156beats/min. Chest CTA showed no evidence of a pulmonary embolism, but revealed densely consolidated bilateral pulmonary infiltrates. She was placed on oxygen 2l/min via nasal cannula. Within seven hours, supplemental oxygen requirements increased to 15l via 100% non re-breather mask, and one hour later to 100% FiO2 on Bipap. Thirty minutes later, continued hypoxia prompted intubation and 90% FIO2 on a ventilator. Extensive work up including cultures, viral panels, and fungal panels was unrevealing. Bronchoscopy with BAL to evaluate the infiltrates was unrevealing. BAL was negative for malignant cells, and revealed only scattered respiratory cells, mixed inflammation, and macrophages present. A possibility of Paclitaxel induced pulmonary interstitial pneumonitis was entertained. Paclitaxel was discontinued. Methylprednisolone 60mg IV every 6 hours was initiated. Within two days the infiltrates cleared with improvement in patient's FiO2 requirements to 30%. She was successfully extubated. Given negative BAL, negative infectious work up, along with resolution with discontinuation of Paclitaxel and initiation of steroids, a diagnosis of Paclitaxel induced severe pulmonary interstitial pneumonitis was made. Discussion: Severe pulmonary interstitial pneumonitis is a rare toxicity with Paclitaxel use. The presenting signs and symptoms include dyspnea and bilateral pulmonary infiltrates with a response to high dose systemic steroids. Other etiologies of sudden onset of respiratory compromise should be ruled out. There are few reported cases of this rare adverse side effect. Given the rapidity of progression and risk of fatality, heightened awareness of this process can be life saving. Conclusion: This case illustrates the importance of clinical suspicion of Paclitaxel induced severe pulmonary interstitial pneumonitis in patients with acute hypoxia. While rare and under reported, early recognition of this rapidly progressive, life-threatening, adverse effect is essential in appropriate treatment using systemic steroids leading to a rapid response.

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Introduction: INTRO: Incidence of hiatal hernias (HH) increases with age. Approximately 60% of individuals aged 50 or older have a HH. [1] A giant HH is a hernia that includes at least 30% of the stomach in the chest, although a uniform definition does not exist; most commonly, a giant HH is a type III hernia with a sliding and paraesophageal component [2]. Patients with a giant HH generally present with pain, heartburn or a history of heartburn, dysphagia, vomiting, and anemia. We present a case of giant HH presenting with hematemesis. Case: An 83-year-old non-smoking female patient, with breast cancer who underwent breast biopsy and sentinel node dissection 2 days prior, presented to her local hospital with severe lower chest discomfort, nausea and vomiting with episodes of hematemesis. Initial workup with chest x-ray revealed a giant chest abnormality (figure 1). Pulmonary was consulted to evaluate the giant chest mass. Further review of imaging revealed a giant paraesophageal hiatal hernia with most of her stomach residing in the chest. The stomach was massively dilated and appeared volvulized. She had endoscopy at an outside facility and they drained a liter of fluid from her stomach. A nasogastric tube was placed. However, the stomach remained massively dilated and did not appear to be emptying. She was transferred for further care. Upon transfer, the patient was on a 100% nonrebreather due to difficulty breathing. Her pain and nausea had improved; however, she remained dyspneic. She had mild tenderness in the epigastrium and her white count was elevated at 18,000. She was taken to the operating room by cardiothoracic surgery urgently for reduction of her giant paraesophageal hiatal hernia. On the date of discharge, she was satting 93% on room air. Pathology of the hernia sac revealed mesothelial lined fibrous tissue consistent with hernia sac. Discussion: HH is the protrusion of the upper part of the stomach into the thorax through a tear or weakness in the diaphragm. A HH is classified by type as follows: type I indicates sliding hernia; type II, paraesophageal hernia ( 5%); type III, mixed sliding and paraesophageal hernia; and type IV, herniation of additional organs (eg, colon, omentum, spleen). [3] A giant HH is a hernia that includes at least 30% of the stomach in the chest and most commonly is a type III hernia with a sliding and paraesophageal component. This case illustrates the varied presentations of giant HH and the need for early suspicion given the need for surgical intervention. Conclusion: This case illustrates the need to consider giant HH in the presence of hematemesis. Early recognition of this rare entity can lead to early surgical intervention.