CD166(pos) subpopulation from differentiated human ES and iPS cells support repair of acute lung injury.

Previous efforts to derive lung progenitor cells from human embryonic stem (hES) cells using embryoid body formation or stromal feeder cocultures had been limited by low efficiencies. Here, we report a step-wise differentiation method to drive both hES and induced pluripotent stem (iPS) cells toward the lung lineage. Our data demonstrated a 30% efficiency in generating lung epithelial cells (LECs) that expresses various distal lung markers. Further enrichment of lung progenitor cells using a stem cell marker, CD166 before transplantation into bleomycin-injured NOD/SCID mice resulted in enhanced survivability of mice and improved lung pulmonary functions. Immunohistochemistry of lung sections from surviving mice further confirmed the specific engraftment of transplanted cells in the damaged lung. These cells were shown to express surfactant protein C, a specific marker for distal lung progenitor in the alveoli. Our study has therefore demonstrated the proof-of-concept of using iPS cells for the repair of acute lung injury, demonstrating the potential usefulness of using patient's own iPS cells to prevent immune rejection which arise from allogenic transplantation.

Significance of coexistent granulomatous inflammation and lung cancer.

AIMS: Coexistence of lung cancer and granulomatous inflammation in the same patient confuses clinicians. We aimed to document the prevalence, clinicopathological features, treatment outcomes and prognosis in patients with coexisting granulomatous inflammation undergoing curative lung resection for lung cancer, in a tuberculosis (TB)-endemic country. METHODS: An observational cohort study of patients with lung cancer undergoing curative resection between 2012 and 2015 in a tertiary centre in Singapore. RESULTS: One hundred and twenty-seven patients underwent lung resection for cancer, out of which 19 (14.9%) had coexistent granulomatous inflammation in the resected specimen. Median age was 68 years and 58.2% were males. Overall median (range) survival was 451 (22-2452) days. Eighteen (14%) patients died at median duration of 271 days after surgery. The postsurgery median survival for those alive was 494 (29-2452) days in the whole group. Subgroup analysis did not reveal any differences in age, gender, location of cancer, radiological features, type of cancer, chemotherapy, history of TB or survival in patients with or without coexistent granulomatous inflammation. CONCLUSIONS: Incidental detection of granulomatous inflammation in patients undergoing lung resection for cancer, even in a TB-endemic country, may not require any intervention. Such findings may be due to either mycobacterial infection in the past or 'sarcoid reaction' to cancer. Although all patients should have their resected specimen sent for acid-fast bacilli culture and followed up until the culture results are reported, the initiation of the management of such patients as per existing lung cancer management guidelines does not affect their outcome adversely.

EGFR kinase inhibitors and gastric acid suppressants in EGFR-mutant NSCLC: a retrospective database analysis of potential drug interaction.

BACKGROUND: Erlotinib and gefitinib are weak base drugs whose absorption and clinical efficacy may be impaired by concomitant gastric acid suppressive (AS) therapy, yet proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2As) are widely indicated in non-small cell lung cancer (NSCLC) patients for the prevention and treatment of erlotinib-induced gastrointestinal injury and corticosteroid-associated gastric irritation. We assessed the clinical relevance of this potential drug-drug interaction (DDI) in a retrospective cohort of EGFR-mutant NSCLC patients. RESULTS: The AS usage rate was 35%. In the overall cohort, AS users did not experience poorer OS (HR: 1.47, 95% CI: 0.92 - 2.35, P = 0.10; median, 11.4 versus 17.5 months) or PFS (HR = 1.37, 95% CI: 0.89 - 2.12, P = 0.16; median, 7.6 versus 8.7 months) compared with non-users in multivariate Cox regression analysis. However, subgroup analyses indicated that AS usage was associated with significantly poorer OS and PFS in patients who had fewer or milder comorbidities (Charlson comorbidity index ≤ 2), those with Karnofsky performance status < 90, and never-smokers. MATERIALS AND METHODS: A retrospective database analysis of 157 patients given erlotinib or gefitinib for EGFR-mutant advanced NSCLC from two institutions was conducted. Patients were classified as AS-users if the periods of AS and anti-EGFR therapy overlapped by ≥ 30%. Overall survival (OS) and progression-free survival (PFS) were assessed according to AS usage. CONCLUSIONS: Concomitant AS therapy did not have an adverse impact on OS and/or PFS in the overall cohort. Our subgroup findings should be regarded exploratory and require replication in a large prospective cohort.

Can EGFR-Tyrosine Kinase Inhibitors (TKI) Alone Without Talc Pleurodesis Prevent Recurrence of Malignant Pleural Effusion (MPE) in Lung Adenocarcinoma.

BACKGROUND AND OBJECTIVE: Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKIs) are effective against lung adenocarcinoma. However, limited data is available assessing the effectiveness of EGFR-TKI use in preventing re-accumulation of MPE. To our knowledge, there is no literature on comparison of talc pleurodesis with EGFR-TKIs alone on re-accumulation of MPE in Asian population. We investigated if EGFR-TKI therapy for advanced lung adenocarcinoma with malignant pleural effusion (MPE) is also successful in preventing pleural fluid re-accumulation following initial drainage. METHODS: An observational cohort study of patients with lung adenocarcinoma and MPE in the year 2012 was conducted. RESULTS: 70 patients presented with MPE from lung adenocarcinoma. Fifty six underwent EGFR mutation testing of which 39 (69.6%) had activating EGFR mutation and 34 (87.1%) received TKI. 20 were managed by pleural fluid drainage only whereas 14 underwent talc pleurodesis following pleural fluid drainage. Time taken for the pleural effusion to re-accumulate in those with and without pleurodesis was 9.9 vs. 11.7 months, p=0.59 respectively. More patients (n=10, 25.6%) with activating EGFR mutation presented with complete opacification (white-out) of the hemithorax compared to none without activating EGFR mutation (p=0.02). CONCLUSION: In TKI eligible patients, early talc pleurodesis may not confer additional benefit in preventing re-accumulation of pleural effusion and may be reserved for non-adenocarcinoma histology, or EGFR negative adenocarcinoma. Complete opacification of the hemithorax on presentation may serve as an early radiographic signal of positive EGFR mutation status.

Spontaneous hemopneumothorax: our experience with surgical management.

BACKGROUND: Spontaneous hemopneumothorax is rare, accounting for only 1%-12% of patients presenting with spontaneous pneumothorax. The optimal management of these patients remains controversial with no definitive guidelines on patient selection and timing of surgery. The aim of this study was to review our institution's surgical experience in the management of patients with spontaneous hemopneumothorax. METHODS: We performed a retrospective review of all patients with spontaneous hemopneumothorax who underwent surgery from January 2000 to June 2013. Patient data were obtained from our institution's primary spontaneous pneumothorax database. RESULTS: Of 510 patients who underwent surgery for spontaneous pneumothorax, 33 (6.4%) developed spontaneous hemopneumothorax. The mean age was 24.0 years (range 16-40 years). In 30 (90.9%) patients, it was their first presentation of pneumothorax. There were 25 (75.8%) patients with Vanderschueren stage III spontaneous pneumothorax. Blood loss ranged from 250 to 3000 mL (mean 1280 mL). In 28 patients, a torn adhesion band was the source of bleeding. Thoracotomy was the surgical approach in 9 (27.3%) patients, and video-assisted thoracic surgery was used in 24 (72.7%). One patient required reoperation for retained clots. There was no mortality. CONCLUSION: Our results suggest that surgical management of spontaneous hemopneumothorax can be undertaken with minimal morbidity and mortality. With the increasing use of video-assisted thoracic surgery, definitive surgical management of spontaneous hemopneumothorax can be instituted earlier.

Pleural fat-forming variant of solitary fibrous tumor.

The fat-forming variant of solitary fibrous tumor is rare. It occurs predominantly in the deep soft tissues of the retroperitoneum and thigh. We describe a case of fat-forming solitary fibrous tumor arising from the pleura, which was successfully treated using a video-assisted thoracoscopic approach. The patient remained free of recurrence 2 years after surgery and continues to be under long-term follow-up.

Mediastinal impalement with a fibreglass sheet.

Mediastinal impalement injuries are uncommon and often fatal. There have been very few reported cases of survival following mediastinal impalement. Patients who present with these injuries always undergo operative intervention regardless of their underlying haemodynamic status or associated injuries. We herein present a case of mediastinal impalement injury, where a sheet of fibreglass had fractured the manubrium and entered the anterior mediastinum with no associated great vessel injury. The fibreglass sheet was removed via a partial sternotomy and the patient made an uneventful postoperative recovery.

Routine endoscopy to detect anastomotic leakage after esophagectomy.

BACKGROUND: This study evaluated the safety and efficacy of endoscopy in diagnosing anastomotic leaks after esophagectomy. METHODS: One hundred consecutive postesophagectomy patients, all having reconstruction using the stomach, underwent endoscopy in the first week after operation. The anastomosis and gastric mucosa were examined for evidence of ischemia, necrosis, and leak. RESULTS: There was no evidence that the procedure caused damage to the anastomosis or gastric conduit. The results of 79 examinations were normal, 15 showed gastric ischemia, 2 showed a leak, and 4 showed ischemia plus leakage. The 15 patients with ischemia alone were monitored with a repeat endoscopy after a further week: a late leak developed in 1 patient that was diagnosed at the second examination. No further leaks developed subsequently, making endoscopy 100% accurate in the diagnosis of leaks after esophagectomy. CONCLUSIONS: Esophagoscopy within 1 week of esophagectomy is a safe and highly accurate method of diagnosing leaks and provides unique information on the condition of the stomach. We believe it allows a more targeted approach to patient care in the context of anastomotic healing and in the treatment of leaks.

Endovascular management of traumatic thoracic aortic transection.

The conventional treatment of traumatic thoracic aortic transection is open surgical repair but it is associated with high rates of morbidity and mortality, particularly in patients with multiple injuries. We reviewed our experience of endovascular repair of traumatic thoracic aortic transection. Between March 2002 and December 2007, 7 patients (male 6, female 1; mean age 40 years) with multiple injuries secondary to blunt trauma underwent endovascular stenting. One patient required adjunctive surgery to facilitate endovascular stenting. Mean intensive care unit stay was 8.6 days (range, 3-16 days). Arterial access in all patients was obtained by femoral cut-down. The mean operating time was 122 min. Technical success was achieved in all cases. There was no mortality. One patient suffered a right parietal stroke, but none developed procedure-related paralysis. The mean follow-up period was 18.6 months (range, 6-48 months). There was no evidence of endoleak, stent migration, or late pseudoaneurysm formation on follow-up computed tomography. Endovascular stents can be used to treat traumatic thoracic aortic transection, with low rates of morbidity and mortality. Although early and midterm results are promising, the long-term durability of endovascular stenting for traumatic thoracic aortic transection remains unknown.

A randomized, double-blind, placebo-controlled trial of a COX-2 inhibitor (Rofecoxib) in patients undergoing coronary artery bypass surgery.

The endothelium of patients with coronary artery disease shows increased expression of cyclooxygenase-2 (COX-2) during coronary artery bypass graft surgery (CABG) using cardiopulmonary bypass. This, together with serotonin, may lead to coronary microvessel spasm, which potentially, can contribute to myocardial ischemia and injury after surgery. We performed a randomized, double-blind, placebo-controlled trial in patients undergoing isolated CABG to determine whether short-term treatment with a selective COX-2 inhibitor, Rofecoxib (25 mg), given preoperatively and for 5 days after operation, can offer better myocardial protection in patients undergoing CABG by measuring serial cardiac troponin T (cTnT) levels. The study was powered to recruit 150 consecutive patients undergoing isolated CABG but the study was terminated prematurely by the worldwide withdrawal of rofecoxib. There were highly statistically significant (P<0.001) increases in cTnT in both groups at each time point (1, 6, 24 and 48 h after onset of cardiopulmonary bypass) compared to preoperative levels. cTnT levels were similar at all post-operative time points between the 2 groups. There is no evidence that short-term treatment with rofecoxib has a myocardial protective effect in patients undergoing CABG. There is also no evidence that its effect is deleterious to the myocardium in patients undergoing CABG.