Icotinib, an EGFR tyrosine kinase inhibitor, as adjuvant therapy for patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma: a multicenter, open-label, single-arm, phase II study (ICAPE).

The survival benefit of icotinib (an oral epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor) in patients with advanced lung cancer has been confirmed in several studies. This study (ICAPE) evaluated the efficacy of icotinib as adjuvant therapy for patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma. Patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma were enrolled in the multicenter, open-label, single-arm, phase II study. Eligible patients received oral icotinib 125 mg thrice daily for 1.5 years after complete surgical resection. The primary endpoint was disease-free survival (DFS). Between March 2014 and January 2018, 79 patients were enrolled. The median follow-up time was 39.7 months with a median DFS and overall survival (OS) of 41.4 months (95% CI: 33.6-51.8) and 67.0 months (95% CI: 21.2-not reached [NR]), respectively. The 1-year, 3-year, and 5-year OS rates were 100%, 83.3%, and 61.7%, respectively. No significant difference was found in the median DFS between patients with Bcl-2 interacting mediator of cell death (BIM) mutant-type and wild-type (NR vs. 41.7 months; p = 0.75). No significant difference was found in the median DFS according to EGFR mutation types. Icotinib as adjuvant therapy demonstrated a favorable survival benefit in patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma, indicating that icotinib might be a promising treatment option for this patient population. The optimal adjuvant duration of icotinib is still not clear and needs more incoming data to answer.

Incidence of venous thromboembolism after surgery for adenocarcinoma in situ and the validity of the modified Caprini score: A propensity score-matched study.

Background: Recently, the new World Health Organization (WHO) tumor classification removed adenocarcinoma in situ (AIS) from the diagnosis of lung cancer. However, it remains unclear whether the "malignancy" item should be assessed when the modified Caprini Risk Assessment Model (RAM) is used to assess venous thromboembolism (VTE) risk in AIS. The purpose of our study is to assess differences between AIS and stage IA adenocarcinoma (AD) from a VTE perspective. Methods: A retrospective study was performed on AIS and IA adenocarcinoma in our hospital from January 2018 to December 2021, and divided into AIS group and AD group. Propensity score matching (PSM) was used to compare the incidence of VTE and coagulation function, and to analyze whether the RAM is more effective when the "malignancy" item is not evaluated in AIS. Results: 491 patients were included after screening, including 104 patients in the AIS group and 387 patients in the AD group. After PSM, 83 patients were matched. The incidence of VTE and D-dimer in the AIS group was significantly lower than that in the AD group (P<0.05).When using the RAM to score AIS, compared with retaining the "malignancy" item, the incidence of VTE in the intermediate-high-risk group was significantly higher after removing the item (7.9% vs. 36.4%, P=0.018), which significantly improved the stratification effect of the model. Conclusions: The incidence of postoperative VTE in AIS was significantly lower than that in stage IA adenocarcinoma. The stratification effect was more favorable when the "malignancy" item was not evaluated in AIS using the RAM.

Role of interleukin-17A in early graft rejection after orthotopic lung transplantation in mice.

BACKGROUND: The cellular and molecular mechanisms underlying lung allograft rejection remain poorly understood. We investigated the potential role of interleukin (IL)-17A in lung transplant rejection in a mouse model, because previous studies in clinical and rodent models have implicated IL-17A in both acute and chronic rejection. METHODS: To generate an orthotopic lung transplantation model, lungs from C57BL/6 or BALB/c mice were transplanted into C57BL/6 mice (isograft and allograft models, respectively). The effects of anti-IL-17A treatment in allograft recipients were investigated. The histological features and rejection status of isografts and allografts were assessed at 3, 7, and 28 days after transplantation, and differences in graft infiltrating cells and mRNA expression of relevant cytokines were quantified at 3 and 7 days after transplantation. RESULTS: As expected, isografts showed no obvious signs of rejection, whereas allografts exhibited minimal-to-mild rejection (grade A1-A2) by day 3 and moderate-to-severe rejection (grade A3-A4) by day 7, without evidence of obliterative bronchiolitis (OB). However, by 28 days, evidence of OB was observed in 67% (2/3) of allografts and severe rejection (grade A4) was observed in all. IL-17 mRNA expression in allografts was increased with rejection, and interferon (IFN)-γ and IL-6 mRNA expression levels followed a similar pattern. In contrast, IL-22 expression in allografts was only slightly increased. Antibody (Ab) neutralization of IL-17A diminished the signs of acute rejection at 7 days after transplantation in allografts, and this early protection was accompanied by a decrease in cellular stress according to histological evaluation, suggesting the involvement of IL-17A in the development of early post-transplantation lesions. CONCLUSIONS: Our data indicate that IL-17A is important in the pathophysiology of allograft rejection, and neutralization of IL-17A is a potential therapeutic strategy to preventing lung transplant rejection.

Multiple cavernous hemangiomas of the lung.

We present a rare case of multiple cavernous hemangiomas. A 19-year-old girl was seen with dyspnea and fatigue. Thoracic computed tomography showed multiple nodule shadows scattered in the lung. Lung biopsy was carried out. Postoperative histopathologic study identified the nodules as pulmonary cavernous hemangiomas.

[Early removal of the chest tube after lobectomies: a prospective randomized control study].

OBJECTIVE: To evaluate the feasibility and safety of early chest tube removal after lobectomies for lung diseases. METHODS: A prospective randomized control study was performed with data collected from lobectomies between March 2012 and September 2012. Eligible patients (n = 70) were randomized into two groups; early removal group (removal of chest tube when drainage less than 300 ml/24 h, n = 41) and traditional management group (removal of chest tube when drainage less than 100 ml/24 h, n = 29). Criteria for early removal were established and met before chest tube removal. The volume and character of drainage, time of extracting drainage tube and postoperative hospital stay were measured. All patients received standard care during hospital admission and a follow-up visit was performed after 7 days of discharge from hospital. RESULTS: There were no differences between two groups with respect to age, sex, comorbidities, or pathologic evaluation of resection specimens. The median volume of drainage within 24 h after surgery was 300 ml and within 48 h was 250 ml, there was significantly different between two groups (Z = -2.059, P = 0.039). Patients undergoing early removal management had a shorter Chest tube duration (44 hours vs. 67 hours, Z = -2.914, P = 0.004) and a shorter postoperative hospital stay (5.0 days vs. 6.0 days, Z = -3.882, P = 0.000). Analysis of data showed no statistically significant differences between the rate of pleural effusions developed, thoracentesis and complications, one week after discharge from hospital. CONCLUSIONS: Compared to the traditional management group (drainage ≤ 100 ml/24 h), early removal of chest tube after lobectomy (drainage ≤ 300 ml/24 h) is feasible and safe. It could result in a shorter hospital stay, and most importantly, reduces morbidity without the added risk of complications.

Pneumonia relevant to lung transplantation and pathogen distribution.

BACKGROUND: Pneumonia is the most common cause of morbidity and mortality in lung transplant (LT) recipients. The aim of the present study was to evaluate the incidence, etiology, risk factors and prognosis of pneumonia in LT recipients. METHODS: The LT cohort consisted of 28 recipients receiving LT in Beijing Chao-Yang Hospital from August 2005 to April 2011. Data collected included demographic data, underlying disorders, time and type of transplant, follow-up information, date of last follow-up, and patient status. A retrospective analysis was made of observational data that were prospectively collected. RESULTS: Twenty-two patients of 28 LT recipients had 47 episodes of pneumonia throughout the study period. Thirtyeight episodes of pneumonia in 19 recipients occurred post-LT with a median follow-up of 257.5 days (1-2104 days), the incidence of pneumonia was 192.4 episodes per 100 LT/year and its median time of onset was 100.5 days (0-946 days) post-transplantation. Bacteria, virus and fungi accounted for 62%, 16% and 15% of the microbial pathogens, respectively. The most frequent were Pseudomonas aeruginosa (20%), cytomegalovirus (CMV) (15%), and Aspergillus fumigatus (10%). A total of 29% (11/38) of pneumonias occurred in the first month post-LT, and then the incidence decreased gradually. The incidence of CMV pneumonia was 25% (7/28) with a median time of 97 days (10-971 days). More than one bacterial infection and CMV infection were independent risk factors for aspergillus infection. The incidence of pulmonary tuberculosis (TB) was 18% (5/28), and the history of TB was a risk factor for TB relapse. There were 58% (7/12) of recipients who died of infection, and 71% (5/7) of these died in the first year after LT. CONCLUSIONS: Pneumonia is still a major cause of morbidity and mortality in LT recipients. The most frequent microorganisms were Pseudomonas aeruginosa, CMV, and Aspergillus fumigates. The incidence of CMV pneumonia decreases with a delayed median time of onset. More than one incidence of bacterial infection and CMV infection are independent risk factors for aspergillus infection. LT recipients are at high risk for TB, and the history of TB is a risk factor for TB relapse.

Combined laparoscopic and thoracoscopic Ivor Lewis esophagectomy for esophageal cancer: initial experience from China.

BACKGROUND: Minimally invasive Ivor Lewis esophagectomy was usually performed with either hand-sewn or circular stapler anastomosis through a small thoracotomy or using a side-to-side stapler anastomotic technique. This study aimed to present our initial results of Ivor Lewis esophagectomy using a circular-stapled anastomosis with transoral anvil technique. METHODS: Six patients with esophageal cancer underwent minimally invasive Ivor Lewis esophagectomy with an intrathoracic circular-stapled end-to-end anastomosis. The abdominal portion was operated on laparoscopically, and the thoracic portion was done using thoracoscopic techniques. A 25 mm anvil connected to a 90 cm long delivery tube was introduced transorally to the esophageal stump in a tilted position, the anvil head was then connected to circular stapler. The anastomosis was completed under direct thoracoscopic view. RESULTS: A total of six patients in this report successfully underwent total laparoscopic and thoracoscopic Ivor Lewis esophagectomy with a circular-stapled anastomosis using a transoral anvil. They were five male and one female patients, and had a mean age of 55 years (range, 38-69 years). The thoracic and abdominal operations were successfully performed without any intraoperative complications or conversion to laparotomy or thoracotomy. The passage of the anvil head was technically easy and successful in all six cases. The mean overall operative time was (260 ± 42) minutes (range, 220-300 minutes), and the mean estimated blood loss was (520 ± 160) ml (range, 130-800 ml). Patients resumed a liquid oral diet on postoperative day seven. The median length of hospital stay was 17 days (range, 9-25 days). The postoperative pathological diagnosis was esophageal squamous cell carcinoma in five patients and esophageal small cell carcinoma in one patient. Tumors were staged as T(2)N(0)M(0) in three cases, T(2)N(1)M(0) in one case, and T(3)N(0)M(0) in two cases. During the mean follow-up of 2.5 months (range, 2-4 months), there were no intraoperative technical failure of the anastomosis or major postoperative complications such as leak or stricture. CONCLUSIONS: The initial results of this small series suggest that minimally invasive Ivor Lewis esophagectomy for malignant esophageal tumor is technically feasible. However, further multi-center prospective studies and thorough evaluation are needed to evaluate the long-term results.

Elevated circulating levels of osteopontin are associated with metastasis in advanced non-small cell lung cancer.

OBJECTIVE: To investigate the relationship between postoperative metastasis and circulating levels of osteopontin in non-small cell lung cancer (NSCLC). METHODS: The expression of osteopontin mRNA were detected with RT-PCR technique. The circulating levels of osteopontin were measured through ELASA in 46 NSCLC cases that had not been received any anti-cancer treatment at the time of sampling. The tissues from fifteen patients with benign pulmonary diseases were studied as control group. RESULTS: The overall median mRNA expression level of osteopontin was approximately 70-fold higher in tumor tissues than in matched normal lung tissues (P<0.001). Over-expression of osteopontin mRNA was significantly associated with clinical stage (P=0.009). Advanced disease states had higher circulating level of osteopontin (stage I+II versus stage III+VI). In multivariate analysis, stage was the only independent factor influencing circulating levels of osteopontin. All patients were followed up for 12 months, 2 of the 46 patients with both osteopontin mRNA expression and elevated plasma osteopontin levels had local recurrence and 10 had distant metastasis. There was a significant difference in the osteopontin levels between metastasis group and non-metastasis group. CONCLUSION: Preoperative plasma levels of osteopontin are significantly associated with post-operative metastasis in advanced NSCLC.

[Completely minimally invasive Ivor Lewis esophagectomy: the preliminary experience of circular-stapled anastomosis with the trans-oral anvil].

OBJECTIVE: to present the preliminary results of minimally invasive Ivor Lewis esophagectomy using a circular-stapled anastomosis with trans-oral anvil technique. METHODS: six patients with esophageal cancer received minimally invasive Ivor Lewis oesophagectomy from April 2010 to June 2010. There were 5 males and 1 female with mean age of 55 years (ranging 38 to 69 years). The lesion located in cardiac in 1 case, in lower third of the esophagus in 4 cases and in middle third in 1 case. The abdominal portion was operated laparoscopically. The thoracic portion was done using thoracoscopic techniques. The esophago-gastric anastomosis was created using a 25 mm anvil passed trans-orally and connected to a 90 cm long polyvinyl chloride delivery tube through an opening in the esophageal stump. The anastomosis was completed by joining the anvil to a circular stapler (end-to-end anastomosis stapler) inserted into the gastric conduit. RESULTS: six patients with esophageal squamous cell cancer (n = 5) and small-cell cancer (n = 1) underwent an Ivor Lewis esophagectomy. All the operation was successfully performed without intra-operative technical failures of the anastomosis. There was no severe postoperative complications. The mean operation time was 380 min. The mean blood loss was 300 ml. pTNM staging: T2N0M0 in 3 cases, T2N1M0 in 1 case and T3N0M0 in 2 cases. CONCLUSIONS: the circular-stapled anastomosis with the trans-oral anvil is an efficient and safe technique for esophago-gastric anastomosis.

[The expression of galectin-3 and osteopontin in occult metastasis of non-small cell lung cancer].

OBJECTIVE: To study the relationship between expression of galectin-3 (Gal-3) and osteopontin (OPN) in occult metastasis in non-small cell lung cancer. METHODS: Forty-six patients of non-small cell lung cancer (NSCLC) from January 2006 to October 2007 were selected. There were 28 males and 18 females, aged from 33 to 77 years old. The levels of lung tissues Gal-3 and OPN were detected by RT-PCR, and the levels of blood plasma's were measured by ELISA. RESULTS: There were 12 patients who had metastasized. In un-metastasis group the Gal-3 and OPN mRNA expression levels were significantly lower than that in metastasis group: mean value were 0.07 +/- 0.17 and 0.17 +/- 0.25 in un-metastasis group, while 0.73 +/- 0.23 and 0.79 +/- 0.24 in metastasis group. Blood plasma levels of Gal-3 (18.8 +/- 7.9) microg/L and OPN (153.5 +/- 63.5) microg/L in NSCLC which were detected from metastasis group were higher than un-metastasis group of (9.2 +/- 5.6) microg/L and (89.2 +/- 24.0) microg/L. CONCLUSIONS: High serum levels of Gal-3 and OPN and high expression of Gal-3 and OPN mRNA in NSCLC are closely related to the occurrence and metastasis of NSCLC. They may be indexes of evaluating the occult metastasis in NSCLC.

A method for profiling gangliosides in animal tissues using electrospray ionization-tandem mass spectrometry.

Gangliosides are critical in many functions of mammalian cells but present as a minor lipid component with many molecular species of subtle differences. Conventional strategies for profiling gangliosides suffer from poor reproducibility, low sensitivity, and low-throughput capacity. Prior separation of gangliosides by thin-layer chromatography and/or high-performance liquid chromatography not only was laborious and tedious but also could introduce uneven losses of molecular species. We developed a new strategy of using electrospray ionization-tandem mass spectrometry (ESI-MS/MS) to profile gangliosides with high-throughput potential. This strategy involves three new findings: (i) collision-induced fragmentation of gangliosides gave rise to a common ion of m/z 290, a derivative of N-acetylneuraminic acid; (ii) phospholipids exert a profound suppression of ganglioside detection in ESI-MS/MS to prevent a direct detection in total cellular lipid extracts; and (iii) enrichment of gangliosides in the aqueous phase from total cellular lipid extracts eliminates the damping effect of phospholipids and permits direct precursor scan.