Clinical recommendations for perioperative immunotherapy-induced adverse events in patients with non-small cell lung cancer.

Perioperative adjuvant treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). In particular, the success of immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, in patients with lung cancer has increased our expectations for the success of these therapeutics as neoadjuvant immunotherapy. Neoadjuvant therapy is widely used in patients with resectable stage IIIA NSCLC and can reduce primary tumor and lymph node stage, improve the complete resection rate, and eliminate microsatellite foci; however, complete pathological response is rare. Moreover, because the clinical benefit of neoadjuvant therapy is not obvious and may complicate surgery, it has not yet entered the mainstream of clinical treatment. Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancellation of surgery, additional illness, and even death, and have therefore attracted much attention. In this article, we draw on several sources of information, including (i) guidelines on adverse reactions related to immune checkpoint inhibitors, (ii) published data from large-scale clinical studies in thoracic surgery, and (iii) practical experience and published cases, to provide clinical recommendations on adverse events in NSCLC patients induced by perioperative immunotherapy.

Icotinib as Adjuvant Treatment for Stage II-IIIA Lung Adenocarcinoma Patients with EGFR Mutation (ICWIP Study): Study Protocol for a Randomised Controlled Trial.

The efficacy and possible role of epidermal growth factor receptor tyrosine kinase inhibitors in treating early-stage non-small-cell lung cancer have yet to be established. Therefore, we aimed to explore the efficacy and safety of icotinib in completely resected EGFR-mutant stage II-IIIA lung adenocarcinoma patients who underwent standard chemotherapy. This is a randomised, double-blinded, placebo-controlled, multicentre, Phase III trial. A total of 124 patients aged 18-75 years who qualified the inclusion criteria were recruited. These patients were randomised (1:1) to receive either icotinib (125 mg 3 times per day) or placebo (the same dosage and frequency) for 36 months, followed by a further 36 months of observational window. The primary endpoint is disease-free survival (DFS), while the secondary endpoints are overall survival, 3-year and 5-year DFS, safety and tolerability of the medication, and health-related quality-of-life. Analyses will be conducted in a full analysis set and a per-protocol set as well. To our knowledge, the present study is the first randomised, double-blinded, placebo-controlled, multicenter trial designed to explore efficacy and safety of icotonib in this population. The results obtained in the near future may provide potential guidance in clinical practice. Trial Registration: This trial was registered on www.ClinicalTrail.gov as NCT02125240.

[Prognostic analysis of N2 non-small cell lung cancer].

OBJECTIVE: To evaluate the surgical therapeutic strategy and prognostic factors for non-small cell lung cancer (NSCLC) with mediastinal lymph node metastasis (N2). METHODS: The survival rate of 117 patients with N2 NSCLC treated surgically from January 1999 to May 2003 were analyzed. There were 88 male cases and 29 female cases, aged from 29 to 79 years. The procedure of operation (lobectomy, pneumonectomy and palliative resection), histological classification (squamous cell carcinoma, adenocarcinoma, mixed carcinoma, and large cell carcinoma and others), T primary tumor status, and adjuvant therapy were analyzed to determine their impact on the 5-year survival rate. RESULTS: The median survival time was 22 months, and the over-all 3- and 5-year survival rate was 28.1% and 19.0%. Survival was higher in patients with lobectomy than with palliative resection, with T1 and T2 than with T4. The 5-year survival rate had no deference in age, sex and different histological classification. The 5-year survival rates of lobectomy and pneumonectomy (22.2% and 25.0% respectively) was higher than palliative resection (9.1%). CONCLUSIONS: Surgical procedures (especially lobectomy) is the best choice for N2 NSCLC patients with T1 or T2. But it can not prolong T4 patients' life significantly.

[The cryosurgery of central lung cancer by rigid bronchoscopy].

OBJECTIVE: To evaluate the method and effectiveness of rigid-bronchoscopic cryosurgery for advanced central lung cancer. METHODS: Forty-eight patients were enrolled in this study from June 2002 to December 2008, including 33 male and 15 female. The average age was 70 years (ranged from 45 to 83 years old). For the 48 patients, 38 cases were patients with advanced central lung cancer who were not suitable for surgery, and the remaining 10 cases were patients with local recurrence in trachea or main bronchus postoperatively. Cryosurgery was performed 120 times for all patients, 2.5 times per patient on average. The trachea or bronchus station, symptom such as dyspnea, hemoptysis, respiratory function and quality of life were observed. RESULTS: The unblocked ratio of trachea and bronchi was 97%. All patients got satisfied improvement ratio of symptoms, 87.5% for dyspnea, 72.9% for cough, 93.8% for hemoptysis and 62.5% for chest pain. Respiratory function tests showed that both the mean forced expiratory volume in first second and forced vital capacity got an improvement from (1.03+/-0.05) L to (1.85+/-0.13) L and from (1.69+/-0.18) L to (2.96+/-0.14) L respectively (P<0.01). Karnofsky score also got no less than 20 scores improvement. The Follow-up time was 6 to 62 months. The longest survival was 62 months. The median survival time was 20 months. There was no severe perioperative complications and mortality except for 3 cases of moderate exeduation. CONCLUSIONS: Cryosurgery is easy to perform with minimal complications. Not only could it provide an effective and rapid control of symptoms caused by central lung cancer, it could also unobstructed bronchus promptly and improve patients' quality of life.

Lymph node metastasis in Chinese patients with clinical T1 non-small cell lung cancer: A multicenter real-world observational study.

BACKGROUND: Approximately 8.3-15.9% of patients with clinical stage I non-small cell lung cancer are subsequently shown to have lymph node metastasis. However, the clinical characteristics of patients with lymph node metastasis in China are not fully understood. METHODS: This is a multicenter retrospective analysis of pathological T1 non-small cell lung cancer patients who underwent surgical resection from 2 January 2014 to 27 December 2017. Clinical and pathological information was collected with the assistance of the Large-scale Data Analysis Center of Cancer Precision Medicine-LinkDoc database. The clinical and pathological factors associated with lymph node metastasis were analyzed by univariate and multivariate logistic regression. RESULTS: A total of 10 885 participants (51.6% women; 15.3% squamous cell carcinoma) were included in the analysis. The median age was 60.0 years (range 12.9-86.6 years). A total of 1159 patients (10.6%) had metastases in mediastinal nodes (N2), and 640 patients (5.9%) had metastasis in pulmonary lymph nodes (N1). Most patients had T1b lung cancer (4766, 43.8%). Of the patients, 3260 (29.9%) were current or former smokers. The univariate and multivariate analyses showed that younger age, squamous cell carcinoma, poor differentiation, larger tumor size, carcinoembryonic antigen level ≥5 ng/mL, and vascular invasion (+) were significantly associated with higher percentages of lymph node metastases (P < 0.001 for all). CONCLUSION: This real-world study showed the significant association of lymph node metastasis with age, tumor size, histology and differentiation, carcinoembryonic antigen levels, and status of vascular invasion. Female patients with T1a adenocarcinoma in the right upper lobe barely had lymph node metastasis.

[Results of myasthenia gravis treated with thymectomy].

OBJECTIVE: To evaluate the effectiveness of thymectomy for myasthenia gravis (MG) and the relative risk factors for postoperative myasthenic crisis. METHODS: The clinic data of 78 cases with MG who underwent thymectomy from June 1985 to June 2005 were analyzed retrospectively. The relative risk factors of postoperative myasthenic crisis were analyzed and the differences between new and old region of perioperative management were compared. RESULTS: The symptom of MG was complete remission in 21 cases, significantly improved in 38 cases, improved in 11 cases and unchanged in 8 cases, respectively. The symptom duration before operation, preoperative serum level of anti-acetylcholine receptor antibody, Osserman stage and pathological type of thymoma were independent relative risk factors for postoperative myasthenic crisis. The new region of perioperative management was significant better than the old one. CONCLUSION: Surgical treatment shows significant clinical benefits for patients with MG.

For non-small cell lung cancer with T3 (central) disease, sleeve lobectomy or pneumonectomy?

BACKGROUND: Pneumonectomy (PN) has traditionally been the treatment of choice for central lung tumors for which the alternative is sleeve lobectomy (SL). The aim of this study was to compare early and long-term results after SL and PN in focusing on T3 central non-small cell lung cancer (NSCLC). METHODS: Patients who underwent SL (n=58) or PN (n=42) were retrospectively analyzed. For bias reduction, these 100 patients had been selected according to the following criteria: (I) tumor located in the main bronchus less than 2 cm distal to the carina; (II) there were no N2 disease; (III) no induction therapy was applied; (IV) complete resection (R0) was achieved. RESULTS: SL and PN patients had comparable mean ages, gender distribution, mean forced expiratory volume in 1 second (FEV1), stage and tumor grade. Postoperative mortality (3.4% vs. 4.8%, P=1.0) and morbidity (41% vs. 38%, P=0.74) were similar between the two groups. Recurrences occurred in 48% of patients after SL and in 31% of those after PN (P=0.08). The 5-year survival after SL (64.8%) and PN (61.4%) was not significantly different (P=0.20). Multivariable survival analysis showed that there were no independent prognostic factors. CONCLUSIONS: SL does not compromise survival for NSCLC with T3 central disease compared with PN. It is an adequate oncologic resection and should be treated as the first line intervention whenever complete resection can be achieved.

Combined electro-acupuncture with liver artery intubation in treatment of massive liver cancer.

OBJECTIVE: To investigate the clinical effectiveness of electro-acupuncture therapy (EAT) in combination with liver artery intubation chemotherapy for massive liver cancer. METHODS: A total of 106 patients were divided into 3 groups. In group A, patients underwent EAT in combination with invasive therapy. In group B, patients received EAT alone. In group C, patients underwent liver artery intubation chemotherapy. In group A and B, subcostal oblique incision was performed to expose liver cancer, and electrodes were inserted into the tumor under direct vision. In group A, liver artery intubation was performed during operation, followed by chemotherapy through the tube. Liver artery intubation chemotherapy was performed only in group C. RESULTS: The effective rate was 73.7% (28/38), 55.6% (20/36) and 28.1% (9/32) in group A, B and C, respectively. CONCLUSIONS: Electro-acupuncture therapy in combination with liver artery intubation chemotherapy achieves best results. It is an effective therapy for massive liver cancer.

[Results of unilateral lung volume reduction surgery in twenty-five patients with chronic obstructive pulmonary disease].

OBJECTIVE: To evaluate the effectiveness of unilateral lung volume reduction surgery (LVRS) in patients with chronic obstructive pulmonary disease (COPD). METHODS: The follow-up data of 25 patients with COPD who had underwent unilateral LVRS between January 1996 to December 2002 in department of thoracic surgery, China-Japan friendship hospital were analyzed retrospectively. The operative target was determined by pre-operative CT and pulmonary ventilation-perfusion (V/Q) scintigraphy. LVRS was performed in 21 patients through video assisted thoracoscopy surgery (VATS) or VATS with adjuvant small lateral thoracotomy. In 4 patients LVRS was performed through posterolateral thoracotomy. Destroyed pulmonary tissue was resected by liner stapler or Endo GIA. To evaluate the effectiveness of unilateral LVRS, the changing of dyspnea score, pulmonary function and the quality of life were analyzed. RESULTS: The postoperative follow-up interval range was 2 years. The mean postoperative FEV(1) increased by (35 +/- 9)%, and six minute walking distance (6MWD) increased by (88 +/- 22)%. For dyspnea score, among 16 patients with a preoperative grade of IV, 4 patients improved to grade I, 12 improved to grade II; among 9 patients with a preoperative grade of V, 1 improved to grade I, 1 improved to grade II, 4 improved to grade III, and the other 3 improved to grade IV. Karnofsky score increased by (44 +/- 10) in average. One and two year survival rates was 96% and 92%, respectively. There was no perioperative death in this group, and the total postoperative morbidity was 32%. CONCLUSIONS: Unilateral LVRS shows significant clinical benefits for the majority of patients with COPD. It is associated with lower operative mortality and morbidity, and has a wide range of indications. The key points of the operation are to resect dysfunctional lung tissues as much as possible and to prevent pulmonary air leak. Preoperative and postoperative breathing training plays a very important role in the postoperative recovering of lung function.

[Replacement of artificial tracheal prosthesis by two-stage procedure with memory-alloy mesh].

OBJECTIVE: To design an artificial trachea which can totally heal with the native trachea. METHODS: Using memory-alloy mesh as the skeleton to construct an artificial trachea by two-stage operation. After 2-year animal experiment we successfully performed the operation in a patient with recurrent carcinoid of the trachea, radically resected the tumor and primarily reconstructed the trachea. RESULTS: The inner side of this "sandwich" artificial tracheal prosthesis was coated with skin and outside the memory-alloy mesh was muscle and vessel pedicle with good blood supply. The upper and lower anastomosis completely healed with recipient's trachea with a full recovery of trachea. Six-month follow-up showed that the patients resumed their normal life. CONCLUSION: The artificial trachea completely healed with the native trachea and became a part of the human trachea. The inner side of artificial trachea is coated with intact native skin tissue with ample blood supply, totally alive without rejection. Therefore, the pedicled artificial tracheal prosthesis is an real artificial trachea.