Fibrin sealant for esophageal anastomosis: A phase II study.

BACKGROUND: Esophagectomy is a pivotal curative modality for localized esophageal or esophagogastric junction cancer (EC or EJC). Postoperative anastomotic leakage (AL) remains problematic. The use of fibrin sealant (FS) may improve the strength of esophageal anastomosis and reduce the incidence of AL. AIM: To assess the efficacy and safety of applying FS to prevent AL in patients with EC or EJC. METHODS: In this single-arm, phase II trial (Clinicaltrial.gov identifier: NCT03529266), we recruited patients aged 18-80 years with resectable EC or EJC clinically staged as T1-4aN0-3M0. An open or minimally invasive McKeown esophagectomy was performed with a circular stapled anastomosis. After performing the anastomosis, 2.5 mL of porcine FS was applied circumferentially. The primary endpoint was the proportion of patients with AL within 3 mo. RESULTS: From June 4, 2018, to December 29, 2018, 57 patients were enrolled. At the data cutoff date (June 30, 2019), three (5.3%) of the 57 patients had developed AL, including two (3.5%) with esophagogastric AL and one (1.8%) with gastric fistula. The incidence of anastomotic stricture and other major postoperative complications was 1.8% and 17.5%, respectively. The median time needed to resume oral feeding after operation was 8 d (Interquartile range: 7.0-9.0 d). No adverse events related to FS were recorded. No deaths occurred within 90 d after surgery. CONCLUSION: Perioperative sealing with porcine FS appears safe and may prevent AL after esophagectomy in patients with resectable EC or EJC. Further phase III studies are warranted.

Specific Safety Profile of Bevacizumab in Asian Patients With Advanced NSCLC: A Meta-Analysis.

Randomized studies have obtained varying findings regarding the benefits and toxicities of bevacizumab in the treatment of nonsmall cell lung cancer (NSCLC). It is unclear whether the discrepancies among trials are due to ethnic/racial differences. We therefore performed a meta-analysis of all published, randomized, controlled clinical trials involving bevacizumab in patients with NSCLC to assess its effectiveness and safety in Asian and non-Asian populations. Results from the phase II JO19907 trial, the phase III AVAiL and ECOG 4599 trials, and the phase IV SAiL trials were used to calculate the benefits and toxicities of bevacizumab in Asian and non-Asian patients. Combined statistical estimates, including hazard ratios and odds ratios, were calculated using fixed-effects and random-effects models. A total of 4308 patients were evaluated. Combining bevacizumab with different chemotherapy regimens resulted in similar objective response rates, overall survival, and progression-free survival in Asian and non-Asian populations. Disease control rates, however, were only reported in Asian populations. The rates of severe bleeding (relative risk [RR], 2.17; P = 0.02) and thromboembolism (RR, 3.65; P < 0.0001) were significantly higher, while the rate of severe proteinuria was significantly lower (RR, 0.43; P < 0.0001), in non-Asian than in Asian populations. The rates of severe hypertension (P = 0.71) and hemoptysis (P = 0.66) were similar in Asian and non-Asian populations. Bevacizumab combined with chemotherapy for first-line NSCLC treatment showed similar benefits in Asian and non-Asian populations, but had specific safety profiles in each.

Clinicopathological features and outcome of gastric metastases from primary lung cancer: A case report and systematic review.

Primary lung cancer is the fourth most frequently diagnosed cancer, but gastric metastasis from lung cancer is extremely rare. Little is known about its clinicopathological features, prognosis and optimal treatment strategy. The present study reports a case of primary lung cancer that metastasized to the stomach and to the best of our knowledge, is the first to identify discordance in epidermal growth factor receptor (EGFR) mutation status between the primary tumor and gastric metastasis. The study also systematically searched the Medline database for similar cases to provide a literature review. Data concerning the clinicopathological features, treatment strategies and outcomes were extracted and analyzed. In total, 22 eligible cases were identified from 16 studies. The average age at presentation was 67.3 years and there was a male predominance of 90.9%. Epigastric pain (45.5%) was the most common chief complaint, followed by melena (22.7%), nausea/vomiting (13.6%) and hematemesis (9.1%). Three patients were asymptomatic. Five patients sought the initial consultation for gastrointestinal symptoms. The median time between the primary lung cancer diagnosis and the confirmation of gastric metastasis was five months. Endoscopically, gastric lesions were described as polypoid masses or volcano-like ulcers, mostly involving the gastric corpus, which were identified in 62.5% of the 16 cases in which information regarding the site of metastasis was available. Gastric metastases were reported from adenocarcinoma, squamous cell carcinoma, small cell lung cancer and pleomorphic carcinoma of the lung. The median survival following comprehensive treatment strategies was four months, and the one-year post-metastasis survival rate was 35.3%. In conclusion, although primary lung cancer metastasis to the stomach is rare, clinicians should be aware of the possibility of its occurrence. Comprehensive and personalized treatment may be beneficial to patients. EGFR tyrosine-kinase inhibitor therapy may be the treatment of choice for non-small cell lung carcinoma patients harboring an activating EGFR mutation in the metastatic lesion.

Frequency of EGFR mutations in lung adenocarcinoma with malignant pleural effusion: Implication of cancer biological behaviour regulated by EGFR mutation.

OBJECTIVE: A retrospective single-centre study to compare the clinical features of patients with lung adenocarcinoma with and without epidermal growth factor receptor (EGFR) mutations. METHODS: Pretreatment medical records of patients with lung adenocarcinoma were reviewed. DNA was extracted from paraffin wax-embedded tumour tissue for analysis of EGFR mutations. Malignant pleural effusion (MPE) was diagnosed by cytopathological testing of pleural fluid. RESULTS: EGFR mutations (19-Del and L858R) were recorded in 81/283 patients (28.6%). MPE was found in 42/283 patients (14.8%). In patients with stage IV disease, the frequency of EGFR mutations was higher in those with MPE than in those without MPE. EGFR mutations were independently associated with female sex, no history of smoking and presence of MPE. CONCLUSIONS: There was a positive association between EGFR mutation and the presence of MPE. EGFR mutations may play an important role in the formation of MPE.

Caspase-3 expression in metastatic lymph nodes of esophageal squamous cell carcinoma is prognostic of survival.

AIM: To assess whether differential expression of caspase-3 in paired metastatic lymph nodes (LNs) is prognostic of survival in patients with resectable esophageal squamous cell carcinoma (ESCC). METHODS: Capases-3 expression was evaluated immunohistochemically in 122 pairs of primary ESCCs and regional metastatic LNs assembled on tissue microarrays. The impact of caspase-3 expression on survival outcomes was analyzed by the Kaplan-Meier method and Cox proportional hazards regression model. RESULTS: The level of caspase-3 expression was significantly higher in LN metastases than in primary tumors (P < 0.001). Caspase-3 expression in the primary tumors was associated with longer median survival (23 mo vs 21 mo, P = 0.033), whereas higher expression in paired metastatic LNs was associated with shorter median survival (20 mo vs 22 mo, P = 0.043). Multivariate analysis showed that both were independent prognostic factors. CONCLUSION: Caspase-3 expression in metastatic LNs may be a potential independent predictor of poorer overall survival in patients with resected ESCC and LN metastasis. Protein expression in metastatic tumors may be a biomarker prognostic of survival.

Role of the stem cell-associated intermediate filament nestin in malignant proliferation of non-small cell lung cancer.

BACKGROUND: Nestin is associated with neoplastic transformation, but the mechanisms by which nestin contributes to invasion and malignancy of lung cancer remain unknown. Considering that proliferation is necessary for malignant behavior, we investigated the mechanism of nestin action in association with the proliferative properties of non-small cell lung cancer (NSCLC). METHODS: Nestin expression was examined in NSCLC specimens and cell lines. Associations with clinicopathological features, including prognosis and proliferative markers, were evaluated. Effects of nestin knockdown on proliferation and the signaling pathways involved were further investigated. RESULTS: Nestin was expressed in most cancer specimens and all the tumor cell lines analyzed. High nestin expression in malignant tissue was associated with high Ki-67 or PCNA levels and poor patient outcomes. Conversely, knockdown of nestin expression led to significant inhibition of tumor cell proliferation, decreased colony forming ability, and cell cycle G1 arrest. Furthermore, nestin knockdown resulted in inhibition of Akt and GSK3ß activation. CONCLUSIONS: Our data demonstrate that nestin expression in NSCLC cells is associated with poor prognosis of patients and tumor cell proliferation pathway. Downregulation of nestin efficiently inhibited lung cancer cell proliferation, which might be through affecting cell cycle arrest and Akt-GSK3ß-Rb signaling pathway.

Impact of thoracic recurrent laryngeal node dissection: 508 patients with tri-incisional esophagectomy.

BACKGROUND: To evaluate the feasibility and safety of recurrent laryngeal nerve (RLN) lymph node (LN) dissection, this study compared the postoperative complications and survival between modern two-field lymphadenectomy (MTL) and modified standard two-field lymphadenectomy (MSTL) by using the propensity score matching method. METHODS: After generating propensity scores given the covariates of age, sex, tumor length, tumor location, tumor grade, and clinical stage, 254 patients with MTL were matched to 254 MSTL patients using the nearest available score matching. The LNs resected during MSTL were paraesophageal and preparatracheal LNs in the upper mediastinum, in addition to those resected during standard two-field lymphadenectomy. RESULTS: RLN LNs were those most commonly affected by nodal metastasis in our series (26 %). Metastasis in RLN LNs was found in around 35, 25, and 20 % of patients with cancer in the upper, middle, and lower thoracic esophagus, respectively. LN metastasis was confined to the RLN region in 49 patients. Even 35 % of patients with pT1 tumors had positive RLN LNs. MTL increased the mean number of resected LNs when compared to MSTL (29 vs.15; p < 0.001). Recurrence was more frequent in those assigned MSTL than those assigned MTL (p < 0.001). The 5-year overall survival (OS) and disease-free survival (DFS) rate for MTL were 50.7 and 42 % compared to 35.3 and 28.2 % for MSTL (both p < 0.001), respectively. Postoperative complications were more frequent following MTL when compared to the MSTL. However, no statistically significant difference in postoperative complications was observed between the two groups. CONCLUSIONS: Adding the removal of RLN LNs might improve OS and DFS with acceptable morbidity for patients with ESCC.

Medical thoracoscopy and gastroscopy for the treatment of intrathoracic anastomotic leakage following esophagectomy.

Intrathoracic anastomotic leakage following esophagectomy is extremely difficult to manage appropriately. The outcomes of conservative management strategies are often disappointing, particularly in patients who develop adhesions of the pleural cavity and multiloculated empyema. This study describes a novel approach using combined thoracoscopy and gastroscopy in two cases. Thoracoscopy under local anesthesia was used to dissect the septations within the multiloculated empyema and remove the infected focus by direct visualization, and gastroscopy was subsequently performed to place a nasogastric or sump tube around the leak. The outcomes of both procedures were satisfactory: the empyemas almost completely resolved, the anastomotic leak closed quickly and there was adequate lung re-expansion. Accordingly, the combination of thoracoscopy and gastroscopy for the treatment of intrathoracic anastomotic leak post-esophagectomy may be an effective, safe, minimally-invasive, simple and inexpensive procedure.

[A new retrievable nitinol alloy stents for treatment of refractory benign esophageal strictures].

OBJECTIVE: To explore long-term effect of the treatment of refractory benign esophageal strictures with a novel retrievable fully covered stent made of nitinol alloy. METHODS: From November 2009 to May 2011, the stents were placed in 8 patients with refractory benign esophageal strictures in the Department of Thoracic Surgery at the Cancer Center of Sun Yat-sen University. Esophago-gastro-duodenoscopy and barium swallow examinations were performed respectively on the 1st, 7th, 30th, 60th day after implantations of the stents and 1,2,3,6 months or even longer after removal of the stents in order to assess the long-term effect on the improvement of dysphagia and the development of complications. RESULTS: The stents were successful deployed in all the patients. The dysphagia scores were improved instantly and significantly as compared to the preoperative scores(P<0.05). Seven patients had long-term improvement of dysphagia. The dwelling time of all the stents ranged from 4 to 60 weeks, with a median of 16.8 weeks. Six patients had their stent removed after a dwelling time of 4 to 18 weeks(median 9.7 weeks). The follow-up period was 1.5-9 months (median 6.1 months). The improvement of dysphagia was also significant during follow-up after removal of the stents(P<0.05). At the most recent follow up, two patients still had the stent in place. The first one has already been followed up for 15 months and was still on regular diet. The other one experienced improvement of dysphagia score up to two months after placement, but downgraded to 3 by the third month. Relapse of stenosis occurred in 1 patient, migration in 2 patients, and tissue hyperplasia in 3 patients, of whom 2 developed inward growth of granulation tissue due to the rupture of the covering membrane. CONCLUSIONS: The new retrievable fully covered stent made of nitinol alloy significantly improves the swallowing function of patients with intractable benign esophageal strictures after implantation and after removal of the stents, with low incidence of long-term restenosis. However, the high rate of migrations and the poor quality of the covering membrane further implies that the design of the new stent still needs to be improved.

Serum protein profiles in myasthenia gravis.

BACKGROUND: The diagnosis of myasthenia gravis (MG) remains challenging. We performed a proteome-wide search for potential serum protein diagnostic markers for MG using surface-enhanced laser desorption/ionization (SELDI) time-of-flight mass spectrometry (TOFMS). METHODS: Proteomic spectra from 80 MG patients and 80 healthy individuals were generated by SELDI. Samples from 56 MG patients and 56 healthy individuals in the training set were analyzed to set up the decision tree. Samples from 24 MG patients and 24 healthy individuals were used for cross-validation testing. RESULTS: The SELDI TOFMS analysis generated 101 peaks, representing differentially expressed proteins between 1000 and 20000 Da. Among them, 9 peaks were down-regulated and 30 others were up-regulated in the MG sera compared with the controls. The decision tree used the peak at M4168.94 Da and M1122.57 Da as splitters in the classification process. In the training set, 112 samples were classified as MG or control group, with a sensitivity of 100% and specificity of 89.3%; the 10-fold cross-validated analysis identified the optimal decision tree with the lowest relative cross-validated cost of 0.080. In the test set, the decision tree generated was able to identify 20 of 24 MG patients and 21 of 24 healthy individuals with a sensitivity of 83.3% and a specificity of 87.5%. CONCLUSIONS: SELDI TOFMS is a useful tool for the detection and identification of potential serum biomarkers that can diagnose MG with high sensitivity and specificity.