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Afatinib is an irreversible tyrosine kinase inhibitor (TKI) targeting the epidermal growth factor receptor (EGFR), which is utilized for the treatment of patients with advanced lung cancer that harbors EGFR mutations. No studies have evaluated the clinical efficacy of LCT in patients treated with first-line afatinib. In this study, we retrospectively enrolled patients with advanced lung adenocarcinomas harboring susceptible EGFR mutations who were diagnosed and treated with first-line afatinib in three hospitals. A total of 254 patients were enrolled, including 30 (12%) patients who received LCT (15 patients received definitive radiotherapy for the primary lung mass and 15 patients received curative surgery). Patients who received LCT had a significantly longer PFS than those who did not (median PFS: 32.8 vs. 14.5 months, p = 0.0008). Patients who received LCT had significantly longer OS than those who did not (median OS: 67.1 vs. 34.5 months, p = 0.0011). Multivariable analysis showed LCT was an independent prognostic factor for improved PFS (adjusted hazard ratio [aHR] [95% confidence interval (CI)]: 0.44 [0.26–0.73], p = 0.0016) and OS (aHR [95% CI]: 0.26 [0.12–0.54], p = 0.0004). The analyses using propensity score-weighting showed consistent results. We conclude that LCT may improve clinical outcomes, in terms of PFS and OS, in patients with advanced EGFR-mutant lung adenocarcinomas who are treated with first-line afatinib.

Simple Summary Lung cancer treatment has always been challenging as its metastasis rate is higher than other cancers. Cancer stemness promotes cancer metastasis, and it is important to understand the mechanism behind the cancer-stemness-mediated metastasis. CD44 is a well-known cancer stem cell marker and plays a role in tumor metastasis in different cancer types. In this study, we investigated the role of CD44 in lung cancer metastasis by using clinical studies as well as in vitro and in vivo studies. We found that CD44 promotes the migration and invasion abilities of lung cancer cells through ERK–ZEB1 signaling. This study provided evidence that CD44 may be a possible therapeutic target to decrease lung cancer metastasis. Abstract Lung cancer is a malignancy with high mortality worldwide, and metastasis occurs at a high frequency even when cancer spread is not detectable at primary operation. Cancer stemness plays an important role in malignant cancer behavior, treatment resistance, and cancer metastasis. Therefore, understanding the molecular pathogenesis behind cancer-stemness-mediated metastasis and developing effective approaches to prevent metastasis are key issues for improving cancer treatment. In this study, we investigated the role of CD44 stemness marker in lung cancer using in vitro and clinical studies. Immunohistochemical staining of lung cancer tissue specimens revealed that primary tumors with higher CD44 expression showed increased metastasis to regional lymph nodes. Flow cytometry analysis suggested that CD44 positive cells were enriched in the metastatic lymph nodes compared to the primary tumors. CD44 overexpression significantly increased migration and invasion abilities of lung cancer cells through CD44-induced ERK phosphorylation, ZEB1 upregulation, and Claudin-1 downregulation. Furthermore, ERK inhibition suppressed the migration and invasion abilities of CD44-overexpressing lung cancer cells. In summary, our in vitro and clinical results indicate that CD44 may be a potential prognostic and therapeutic marker for lung cancer patients.

Lung adenocarcinoma is one of the leading causes of cancer-related death worldwide. We showed transcriptomic profiles in three pairs of tumors and adjacent non-tumor lung tissues using next-generation sequencing (NGS) to screen protein-coding RNAs and microRNAs. Combined with meta-analysis from the Oncomine and Gene Expression Omnibus (GEO) databases, we identified a representative genetic expression signature in lung adenocarcinoma. There were 9 upregulated genes, and 8 downregulated genes in lung adenocarcinoma. The analysis of the effects from each gene expression on survival outcome indicated that 6 genes (AGR2, SPDEF, CDKN2A, CLDN3, SFN, and PHLDA2) play oncogenic roles, and 7 genes (PDK4, FMO2, CPED1, GNG11, IL33, BTNL9, and FABP4) act as tumor suppressors in lung adenocarcinoma. In addition, we also identified putative genetic interactions, in which there were 5 upregulated microRNAs with specific targets - hsa-miR-183-5p-BTNL9, hsa-miR-33b-5p-CPED1, hsa-miR-429-CPED1, hsa-miR-182-5p-FMO2, and hsa-miR-130b-5p-IL33. These 5 microRNAs have been shown to be associated with tumorigenesis in lung cancer. Our findings suggest that these genetic interactions play important roles in the progression of lung adenocarcinoma. We propose that this molecular change of genetic expression may represent a novel signature in lung adenocarcinoma, which may be developed for diagnostic and therapeutic strategies in the future.

Surgery for esophageal cancer is invasive and challenging, and always to be followed with arduous post-operative care and recovery. This study, maybe one of the first in Asian populations, is to determine whether a reinvented protocol for perioperative management for esophageal cancer surgery which is being implemented in our department, will lead to a faster convalescence and also significantly decrease financial burdens garnered by patients during hospitalization.Operated on by the same surgeon and team in the same hospital, consecutive patients who had received esophagectomy and reconstruction for esophageal squamous cell carcinoma were retrospectively reviewed. On the basis of two different treatment periods, patients were divided into two groups: A and B. Group A was patients who had received the new reinvented protocol between 2012 and 2016, while group B patients were those having received the previous protocol between 2008 and 2011. Their demographics, post-operative outcome, and hospital charges were collected and compared.There were 64 patients in group A, and 69 in group B. Ventilator days (P0.001), ICU stay (P0.001), and post-operative stay (P0.001) were significantly shorter in group A patients. Complication rates were similar between the two groups. No hospital mortality was noted in either group. Hospital charges in group A were found to be perceptively lower, although not statistically significant (P value =0.078).The current protocol of perioperative care effectively ameliorated convalescence after esophagectomy and reconstruction for esophageal squamous cell carcinoma without increasing complication rate or mortality. It is also potentially more practical in future health care policies during this era of financial shortage.

Purpose Lung cancer with malignant peritoneal carcinomatosis and malignant ascites is rare, often indicates the terminal stage, and is refractory to treatment. The median survival time of lung cancer patients with malignant ascites has been reported to be as short as 15 days to 2 months in retrospective studies. Methods We reviewed all lung cancer patients who had cytologically or pathologically proven malignant ascites and received aggressive therapy including chemotherapy, anti-angiogenesis agents and target therapy at a Taiwan hospital from January 2015 to December 2017. In addition, we searched PubMed using the terms "lung cancer," "peritoneal carcinomatosis" and "malignant ascites" to find other studies reporting experience of such treatment. Results Three consecutive lung cancer patients with malignant ascites (3/265, 1.13%) were included in this case series study, all of whom received bevacizumab with three other drugs (erlotinib, afatinib and gemcitabine). All of the patients showed a good response to treatment with a marked decrease in ascites. Two of the patients had a long progression-free survival time of more than 5 months. In the literature review, several cases reports and case series documented the treatment efficacy, however no prospective or retrospective studies reported treatment strategies. Conclusions Aggressive treatment for lung cancer with malignant ascites is encouraged when possible. Bevacizumab-based treatment may serve as one effective treatment strategy for non-squamous cell lung carcinoma with malignant ascites. Further prospective trials are urgently needed.

Primary spontaneous pneumothorax (PSP) is a common clinical problem. However, PSP recurrence is still a major concern. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a protective role against oxidative airway diseases. The aim was to investigate the role of Nrf2 in PSP patients and its correlation with recurrence.Eighty-nine patients were enrolled and received wedge resection of lung with identifiable blebs. Nrf2 expression in resected lung tissues was determined by immunohistochemistry (IHC) and correlated with clinicopathological variables. The prognostic value of Nrf2 for incidence-of-recurrence was determined by Kaplan-Meier estimates and the significance of differences was evaluated by the log-rank test.Nrf2 staining was predominantly observed in alveolar macrophages and type II pneumocytes of PSP patients and correlated with recurrence (P0.001 and P=0.001, respectively) and PSP location (macrophages, P=0.013). High Nrf2 expression was correlated with better incidence-of-recurrence (macrophages, P=0.003; type II pneumocytes, P=0.003). Moreover, incidence-of-recurrence was better in patients with higher Nrf2 expression, especially those in the age ≤20, male, and non-smoking groups (macrophages, P=0.009, 0.006, and 0.012; type II pneumocytes, P=0.003, 0.011, and 0.010, respectively).High Nrf2 expression in alveolar macrophages and type II pneumocytes was significantly associated with the decreased recurrence risk and was the independent factor predicting a better incidence-of-recurrence in PSP. Our results suggest that Nrf2 activation in high risk patients may be a potential target for reducing PSP recurrence.

Lung adenocarcinoma is one of the leading causes of cancer-related death worldwide. We showed transcriptomic profiles in three pairs of tumors and adjacent non-tumor lung tissues using next-generation sequencing (NGS) to screen protein-coding RNAs and microRNAs. Combined with meta-analysis from the Oncomine and Gene Expression Omnibus (GEO) databases, we identified a representative genetic expression signature in lung adenocarcinoma. There were 9 upregulated genes, and 8 downregulated genes in lung adenocarcinoma. The analysis of the effects from each gene expression on survival outcome indicated that 6 genes (AGR2, SPDEF, CDKN2A, CLDN3, SFN, and PHLDA2) play oncogenic roles, and 7 genes (PDK4, FMO2, CPED1, GNG11, IL33, BTNL9, and FABP4) act as tumor suppressors in lung adenocarcinoma. In addition, we also identified putative genetic interactions, in which there were 5 upregulated microRNAs with specific targets - hsa-miR-183-5p-BTNL9, hsa-miR-33b-5p-CPED1, hsa-miR-429-CPED1, hsa-miR-182-5p-FMO2, and hsa-miR-130b-5p-IL33. These 5 microRNAs have been shown to be associated with tumorigenesis in lung cancer. Our findings suggest that these genetic interactions play important roles in the progression of lung adenocarcinoma. We propose that this molecular change of genetic expression may represent a novel signature in lung adenocarcinoma, which may be developed for diagnostic and therapeutic strategies in the future.

Minimally invasive surgery is the current trend of approach in various fields. Since May 2006, our team has started implementing needlescopic video-assisted thoracic surgery as the standard surgical treatment for primary spontaneous pneumothorax. During a seventeen-month period, 62 consecutive patients with primary spontaneous pneumothorax were operated on. The ages, sex ratio, operative times, blood loss, postoperative pain in visual analog scale (VAS), length of stay and hospital costs were recorded and compared with that of another 62 consecutive patients who received conventional video-assisted thoracic surgery between July 2004 and April 2006. Only the postoperative pain in VAS was significantly lower in the needlescopic video-assisted thoracic surgery group; the rest remained the same. Also the wounds were almost undetectable in the needlescopic video-assisted thoracic surgery patients. There were no major complications, mortality or recurrence in either group. Needlescopic video-assisted thoracic surgery is a high-tech technique which provides safety, effectiveness, economy and outcome comparable to that of conventional techniques. It is also associated with less pain and better cosmetics.

Background Implantable venous access port (IVAP)-related blood stream infections (BSIs) are one of the most common complications of implantable venous ports. The risk factors and pathogens for IVAP-related BSIs are still controversial. Methods We retrospectively reviewed all patients who received IVAPs at a Hospital in Taiwan from January 1, 2011 to June 31, 2014. Two types of venous port, BardPort® 6.6 fr (Bard port) and Autosuture Chemosite® 7.5 fr (TYCO port) were used. All patients with clinically proven venous port-related BSIs were enrolled. Results A total of 552 patients were enrolled. There were 34 episodes of IVAP-related BSIs during the study period for a total incidence of 0.177 events/1000 catheter days. Port type (TYCO vs. Bard, HR = 7.105 (95 % confidence interval (CI), 1.688–29.904), p = 0.0075), age > 65 years (HR = 2.320 (95 % CI, 1.179–4.564), p = 0.0148), and lung cancer (HR = 5.807 (95 % CI, 2.946–11.447), p 65 years, and lung cancer were all significant risk factors for IVAP-related BSIs, and no sign of infection was significantly associated with the growth of gram-negative bacilli.

Malignant smooth muscle tumors usually develop in the uterus and gastrointestinal tract due to the abundance of smooth muscle. They rarely develop in the soft tissue of the mediastinum. We report a 44-year-old male with neurofibromatosis type I who suffered from leiomyosarcoma extending between the left supraclavicle and the left-side middle mediastinum. The patient received debulking surgery to salvage the compromised airway and disabled upper limb. He then refused adjuvant therapy and expired 7 months postoperatively due to recurrence. To our knowledge, this type of case has never been reported in the literature.

Whether the outcome of primary spontaneous pneumothorax (PSP) when treated with needlescopic video-assisted thoracic surgery is positive is still under scrutiny. The present study was conducted to compare the needlescopic approach with the conventional approach. One-hundred and six patients with primary spontaneous pneumothorax who had undergone needlescopic video-assisted thoracic surgery (NVATS) between May 2006 and August 2008 were reviewed. Their age, gender, smoking status, BMI, side of attack, operative indications, operative time, intraoperative blood loss, postoperative length of stay, postoperative pain in visual analog scale (VAS), postoperative recurrence and follow-up period were recorded. These data were compared with those of 89 patients with PSP who had undergone conventional video-assisted thoracic surgery (CVATS) between June 2002 and April 2006. The operative time was shorter (NVATS: 82.36 ± 35.58 min, CVATS: 99.78 ± 35.74 min; p = 0.008) and intraoperative blood loss was less (NVATS: 16.67 ± 25.90 ml, CVATS: 24.36 ± 26.86 ml; p = 0.04) for the NVATS group. The postoperative pain in VAS was significantly less in NVATS. No major complication or mortality was found in either group. For treatment of primary spontaneous pneumothorax, NVATS is a safe and effective option. Further, it has the added benefit of less pain and improved cosmetics.

Objectives More than 50% of patients with primary spontaneous pneumothorax have contralateral blebs/bullae, and about a quarter will develop a contralateral pneumothorax. The purpose of this prospective study was to determine the need for elective treatment of asymptomatic contralateral blebs/bullae in patients presenting with primary spontaneous pneumothorax. Methods From May 2006 through June 2008, results from 35 patients with ipsilateral primary spontaneous pneumothorax without contralateral blebs receiving unilateral video-assisted thoracic surgery, 35 patients with ipsilateral primary spontaneous pneumothorax with contralateral blebs receiving unilateral video-assisted thoracic surgery, and 16 patients with ipsilateral primary spontaneous pneumothorax receiving bilateral video-assisted thoracic surgery for positive contralateral blebs were collected. Their demographic and operating data were also recorded. Results There was no significant difference in age, gender, smoking percentage, body mass index (kg/m 2 ), blood loss, and postoperative pain among groups. There was longer operative time and length of stay in group receiving bilateral surgery. Within the follow-up period of 16.68 ± 9.91 months (median, 17.50), no recurrence on either lung was found in the group operated on both sides, while contralateral occurrence was found in 17.14% of the group with ipsilateral primary spontaneous pneumothorax with contralateral blebs receiving unilateral video-assisted thoracic surgery within the period of 18.15 ± 8.07 months (median, 21). Conclusion The study showed that the preemptive video-assisted thoracic surgery for the contralateral blebs/bullae effectively prevented the contralateral occurrence.