Neoadjuvant nivolumab with or without platinum-doublet chemotherapy based on PD-L1 expression in resectable NSCLC (CTONG1804): a multicenter open-label phase II study.

This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive (N) and nivolumab-chemotherapy (N/C) combinations based on PD-L1 expression. Eligible patients exhibited resectable clinical stage IIA-IIIB (AJCC 8th edition) NSCLC without EGFR/ALK alterations. Patients received either mono-nivolumab (N) or nivolumab + nab-paclitaxel+ carboplatin (N/C) for three cycles based on PD-L1 expression. The primary endpoint was the major pathological response (MPR). Key secondary endpoints included the pathologic complete response (pCR), objective response rate (ORR), and event-free survival (EFS). Baseline PD-L1 expression and perioperative circulating tumor DNA (ctDNA) status were correlated with pCR and EFS. Fifty-two patients were enrolled, with 46 undergoing surgeries. The MPR was 50.0% (26/52), with 25.0% (13/52) achieving pCR, and 16.7% and 66.7% for patients with PD-L1 ≥ 50% in N and N/C groups, respectively. Thirteen (25.0%) patients experienced grade 3 or higher immune-related adverse events during neoadjuvant treatment. Patients with post-neoadjuvant ctDNA negativity was more likely to have pCR (39.1%) compared with those remained positive (6.7%, odds ratio = 6.14, 95% CI 0.84-Inf, p = 0.077). With a median follow-up of 25.1 months, the 18-month EFS rate was 64.8% (95% CI 51.9-81.0%). For patients with ctDNA- vs. ctDNA + , the 18m-EFS rate was 93.8% vs 47.3% (HR, 0.15; 95% CI 0.04, 0.94; p = 0.005). Immunochemotherapy may serve as an optimal neoadjuvant treatment even for patients with PD-L1 expression ≥ 50%. ctDNA negativity following neoadjuvant treatment and surgery could help identify superior pathological and survival benefits, which requires further confirmation in a prospective clinical trial (NCT04015778).

Pathological Responses of the Primary Tumor and Locoregional Lymph Nodes After Neoadjuvant Immunochemotherapy in Esophageal Squamous Cell Cancer.

Background: The current study attempted to describe the specific patterns of pathological tumor response and locoregional node metastases from surgically resected esophageal squamous cell carcinoma after neoadjuvant immunochemotherapy (NAIC), as well as to explore the association between clinicopathological characteristics and such oncological patterns. Methods: Fifty-one patients with cT3 or deeper esophageal squamous cell cancer underwent subtotal esophagectomy after NAIC. The NAIC regimen included intravenous administration of platinum-based and docetaxel- and taxane-based chemotherapeutics along with a 200 mg fixed dose of one programmed death 1 (PD-1) inhibitor, given every 3 weeks. We divided patients into tumor/nodal good-responders and poor-responders based on the pathological observation of the tumor or nodal responses. We also examined the association between clinicopathological factors and tumor/nodal responses. Further, significant baseline predictors for tumor and nodal good-responders were identified using multivariate binary logistic regression. Results: Of the 51 patients, 68.6% achieved marked primary tumor response. Notably, 21.6% of patients achieved complete pathological response. Significant differences in treatment cycles between tumor good-responders and tumor poor-responders (P = 0.019) were observed. For locoregional nodal responses, only 33.3% of patients achieved down-staged nodal disease. Of the investigated variables, neoadjuvant cycles (odds ratio (OR): 5.271, 95% confidence interval (CI): 1.278 - 21.740, P = 0.022) and pretreatment platelets (OR: 0.979, 95% CI: 0.962 - 0.996, P = 0.017) were identified as independent predictors for good tumor and nodal responses. Conclusions: We conclusively noted that most patients receiving NAIC were tumor good-responders, whereas only one-third of patients were nodal good-responders. Furthermore, we identified that treatment cycle number and baseline platelet counts were independent predictors of combined tumor and nodal responses.

Multiple-bar Nuss operation: an individualized treatment scheme for patients with significantly asymmetric pectus excavatum.

BACKGROUND: Research into multiple-bar Nuss operations for the treatment of wide-range or significantly asymmetric pectus excavatum is rarely reported. This paper aims to explore the curative effects of multiple-bar Nuss operations on wide-range or significantly asymmetric pectus excavatum. METHODS: We reviewed the clinical data of 153 patients with pectus excavatum who were treated in our hospital from September 2006 to August 2014. All the patients had wide-range or significantly asymmetric pectus excavatum and underwent multiple-bar Nuss operations performed by the author. RESULTS: All 153 patients agreed to undergo the operation. The median age was 17 y (10.2-41 y). The median Haller index was 3.98 (3.2-25). One hundred and fifty-one patients accepted treatment with two bars, and 2 cases accepted treatment with three bars. The median operation time was 123 min (65-500 min), the median blood loss was 20 mL (2-200 mL), and the median postoperative hospital stay was 6 days (3-33 days). The incidence rates of pleural effusion, pneumothorax and hydropneumothorax that required drainage treatment were 0.7% (1/153), 1.3% (2/153) and 3.3% (5/153), respectively. Displacement of a bar occurred in one case, and bar exposure occurred in 7 cases. Therefore, 2 cases had the bars removed early, within 2 years postoperation. One patient with severe depression (Haller index: 8.8) had an unhealed auxiliary incision of the xiphoid process, and although the incision was cured after the early removal of the inferior bar, the deformity recurred. There were no cases of death. Currently, 51.6% (79/153) of the cases have had the bars removed. The most recent follow-up revealed that patients' median satisfaction score for the surgical correction effect was 9 points (10 points indicated full satisfaction). CONCLUSIONS: For patients with significantly asymmetric and severely deformed pectus excavatum, the multiple-bar Nuss operation not only is safe and effective but can also achieve a better cosmetic appearance. However, we should continue to explore technical improvements.

TCF19 contributes to cell proliferation of non-small cell lung cancer by inhibiting FOXO1.

Transcription factor 19 (TCF19) harbors a forkhead association (FHA) domain, a proline-rich region, a PHD or RING finger region, suggesting that TCF19 possesses a powerful function. However, its expression and function remains unknown in non-small-cell lung cancer (NSCLC). The function cluster analysis was carried out using Metascape website. 3-(4,5-Dimethyl-2-thiazolyl)2,5-diphenyl-2H-tetrazolium bromide (MTT), colony formation, and anchorage-independent growth ability assay were carried out to detect the effect of TCF19 on cell proliferation. Bromodeoxyuridine (Brdu) labeling and flow cytometry assay were used to evaluate the effect of TCF19 on cell-cycle progression. Quantitative polymerase chain reaction and chromatin immunoprecipitation assay were performed to investigate the mechanism by which TCF19 is involved in cell-cycle transition. By analyzing the publicly available dataset, The Cancer Genome Atlas (TCGA), we found that TCF19 is significantly increased in the lung adenocarcinoma (LAC) and squamous cell carcinoma (SCC), two primary histological subtype of NSCLC. Besides, further function cluster analysis exhibited that TCF19 may mainly participate in cell cycle. MTT, colony formation, and anchorage-independent growth ability assay confirmed that overexpression of TCF19 enhances the proliferation of both LAC and SCC cells. Besides, further experiments revealed that TCF19 contributes to cell cycle G1/S transition. Not only that, upregulation of TCF19 can inhibit the expression of p21, p27, and p57, while promote the expression of cyclin D1 by inhibiting FOXO1. Our research offers important evidence that TCF19 can promote cell-cycle progression of NSCLC cells, and TCF19 may served as novel therapeutic targets.

A randomised phase II clinical trial of nab-paclitaxel and carboplatin compared with gemcitabine and carboplatin as first-line therapy in advanced squamous cell lung carcinoma (C-TONG1002).

BACKGROUND: Nab-paclitaxel/carboplatin (nab-PC) and gemcitabine/carboplatin (GC) are the standard first-line chemotherapy in non-small cell lung carcinoma. Up to now, there is no head to head trial to compare nab-PC with GC in advanced squamous cell lung carcinoma. PATIENTS AND METHODS: A multicentre randomised phase II trial was performed to compare the efficacy and safety for nab-PC with GC in previously untreated patients with advanced squamous cell lung carcinoma. The primary end-point was objective response rate (ORR). Progression-free survival (PFS), overall survival (OS), treatment-related adverse events and quality of life (QoL) were also analysed. RESULTS: Totally 127 participants were eligible for this study (62/65 nab-PC/GC). Nab-PC has higher ORR than GC without statistical significance (42% versus 27%, P > 0.05). After a median follow-up of 14.5 months, both PFS and OS had no difference between the two arms (6.7 versus 5.8 months, hazard ratio [HR] 0.75, P = 0.143; 11.6 versus 14.4 months, HR 0.92, P = 0.846). Both regimens were well tolerated; however, more dose reduction occurred after cycle 2 in GC (27%) than in nab-PC (12%) (P < 0.05). Significant QoL improvement measured by trial outcome index was seen in nab-PC than in GC (P < 0.05). CONCLUSIONS: The first-line nab-PC and GC had the same response, PFS, and OS in patients with advanced squamous cell lung carcinoma. Nab-PCM has advantage over GC in QoL improvement. TRIAL REGISTRATION NUMBER: NCT01236716.

[Predictive value of c-met for long-term mortality in patients with esophageal squamous cell carcinoma].

OBJECTIVE: To explore the correlation of c-met protein with the clinical staging and cell differentiation of esophageal squamous cell carcinoma (ESCC). METHODS: A total of 100 patients with ESCC were enrolled were examined for expression of c-met protein using immunohistochemistry, and the patients in negative and positive c-met expression groups were compared for clinicopathological characteristics and overall survival. RESULTS: s The 100 ESCC patients included 67 male and 33 female patients with a median age of 59 years; 49 of the patients were negative and 51 were positive for c-met expression. Positive c-met expression was significantly correlated with advanced TMN stages and lower tumor differentiation. Kaplan-Meier survival curve showed that the median survival time of c-met-positive patients was significantly reduced compared with that of c-met-negative patients (30.9 vs 48.2 months, P<0.05). COX regression analysis showed that c-met was a independent risk factor for the overall survival of the patients (HR: 2.34, 95% CI: 1.63-4.54, P<0.05). CONCLUSION: A positive expression of c-met protein is significantly correlated with an advanced TMN stage, lower tumor differentiation and a poor prognosis, and may serve as a indicator for predicting the prognosis of ESCC.

Surgical correction of 639 pectus excavatum cases via the Nuss procedure.

BACKGROUND: To review the clinical experience and short- to middle-term effects of the Nuss procedure for correction of pectus excavatum (PE). METHODS: From September 2006 to August 2014, 639 patients with PE were treated using the Nuss procedure. Of these, 546 were male and 93 were female. The mean age was 15.3±5.8 years (2.5-49 years). Preoperative chest CT scans Haller index (HI) was 4.3±1.7 (2.9-17.4), with 75 cases of mild PE (HI <3.2), 114 cases of moderate PE (HI 3.2-3.5), 393 cases of severe PE (HI 3.6-6.0), and 57 cases of extremely severe PE (HI >6.0). RESULTS: A total of 638 patients successfully completed the surgery, an 11-year-old male patient who died after the surgery had undergone ventricular septal defect closure surgery through a sternal incision 7 years ago. The mean operative time was 64.3±41.7 min (40-310 min). Excluding the patient who died, the average blood loss was 24.5±17.8 mL (10-160 mL). The average length of postoperative hospital stay was 5.2±2.9 days (4-36 days). A total of 484 cases (75.7%) required 1 steel bar insertion, 153 cases (24.0%) required 2 steel bars, and 2 cases (0.3%) required 3 bars. Postoperative evaluation of the surgery outcomes revealed the following: excellent in 504 cases, good in 105, fair in 28 and poor in 2, good quality rate was 95.3%. CONCLUSIONS: Correction of PE via the Nuss procedure is minimally invasive and simple to perform with good short and mid-term effects, while long-term efficacy remains to be determined.

Robotic thoracic surgery versus video-assisted thoracic surgery for lung cancer: a meta-analysis.

OBJECTIVES: There are two different minimally invasive approaches, robotic thoracic surgery (RTS) and video-assisted thoracic surgery (VATS), which are performed for lung cancer resection. This meta-analysis aimed to compare the perioperative outcomes of RTS with those of VATS for patients with lung cancer. METHODS: We searched articles indexed in the PubMed and ScienceDirect databases that met our predefined criteria, published up to January 2015. A meta-analysis was performed by combining the results of reported incidences of perioperative morbidity and mortality. The relative risk (RR) was used as a summary statistic. RESULTS: Eight eligible articles with 3379 subjects were considered in the analysis (8 articles for morbidity, while 4 articles for mortality). Overall, pooled analysis indicated that perioperative morbidity and mortality were similar between RTS and VATS (morbidity: RR, 1.02; 95% CI, 0.94-1.10; P = 0.605; mortality: RR, 0.28; 95% CI, 0.06-1.25; P = 0.095). No evidence of publication bias was observed. CONCLUSIONS: This meta-analysis showed that RTS resulted in similar outcomes compared with VATS cases. RTS appears to be an appropriate alternative to VATS, which is associated with improved outcomes compared with open thoracotomy. RTS should be studied further in selected centres and compared with VATS in a randomized fashion to better define its potential advantages and disadvantages.

[Thoracoscopy assisted Nuss procedure for pectus excavatum correction].

OBJECTIVE: To evaluate the short-term effect and experience of Nuss procedure on 120 cases of patients with pectus excavatum. METHODS: Thoracoscopy assisted Nuss procedure with different ways of anesthesia were applied to 120 cases of patients with pectus excavatum, including 7 cases of recurrence after traditional surgical procedure (6 cases) and Nuss method (another one). The patients ranged in age from 2.5 to 43 (mean 14.1) years and in Haller index from 2.91 to 29. Of the 120, 73 had symmetric and 47 had asymmetric pectus excavatum. The Nuss procedure is performed with general anesthesia and a convex steel bar is inserted under the sternum with thoracoscopy through small bilateral thoracic incisions. The steel bar is inserted with the convexity facing posteriorly, and when it is in position, the bar is turned over, thereby correcting the deformity. RESULTS: The operation was successfully accomplished without severe complications in all the 120 cases. The mean operative time was 58 minutes and the mean volume of blood loss was 30 ml. 103 patients had one bar inserted while the other 17 cases with more extremely diffuse depression required 2 or even 3 bars to get a satisfactory correction. Such methods as modifications to the fixing points and the shape of the bar, partial osteotomy, were developed to deal with asymmetric ones. CONCLUSION: The Nuss procedure is a minimally invasive technique for correction of pectus excavatum. It can lead to a satisfactory outcome and surgical time is less.

[Diagnosis and treatment of cervical anastomotic fistula contaminating mediastinum or pleural cavity after esophagogastrostomy: a report of five cases with literature review].

BACKGROUND & OBJECTIVE: A special kind of fistula will be formed when cervical gastroesophageal anastomotic fistula occurs and its contents contaminate mediastinum or pleural cavity after esophagogastrostomy. The diagnosis and treatment are difficult to made. It is very dangerous if the treatment is incorrect. This study was to analyze the causes, preventive measures, diagnosis methods and standard, and appropriate treatments of this kind of fistula. METHODS: Clinical data of 5 patients who suffered cervical anastomotic fistula contaminating mediastinum or pleural cavity after esophagogastrostomy, treated in our hospital, were retrospectively analyzed; the related literature was reviewed. RESULTS: The morbidity of this kind fistula was 1.83%(4/219) in our hospital. All the 5 patients suffered fistula 1-13 days after esophagogastrostomy; bronchopleural fistula occurred in 2 patients. The main causes of this kind of anastomotic fistula were hypertensive anastomosis, low anastomotic location, incomplete suture of thorax-esophagus outlet, defection of surgical technique, and so on. The fistula could be diagnosed correctly when the patient suffered high fever, dyspnea and thoracalgia after operation, with cervical anastomotic external fistula which could not been healed when the wound was opened, X-ray-showed widened mediastinum and hydropneumothorax, and drainage, esophagoraphy and CT-confirmed anastomotic fistula. All patients were cured in a short term with sufficient drainage and irrigation, enough nutrition, appropriate use of antibiotics, and pyothorax dissection and muscle flaps transplantation for bronchopleural fistula. CONCLUSION: Most cervical anastomotic fistulas happen 1-13 days after esophagogastrostomy with critical conditions; timely diagnosis and proper treatment including operation could shorten the disease course and greatly decrease the mortality.