Lack of evolutionary convergence in multiple primary lung cancer suggests insufficient specificity of personalized therapy.

Multiple primary lung cancer (MPLC) is an increasingly prevalent subtype of lung cancer. According to recent genomic studies, the different lesions of a single MPLC patient exhibit functional similarities that may reflect evolutionary convergence. We perform whole-exome sequencing for a unique cohort of MPLC patients with multiple samples from each lesion found. Using our own and other relevant public data, evolutionary tree reconstruction reveals that cancer driver gene mutations occurred at the early trunk, indicating evolutionary contingency rather than adaptive convergence. Additionally, tumors from the same MPLC patient are as genetically diverse as those from different patients, while within-tumor genetic heterogeneity is significantly lower. Furthermore, the aberrant molecular functions enriched in mutated genes for a sample show a strong overlap with other samples from the same tumor, but not with samples from other tumors or other patients. Overall, there is no evidence of adaptive convergence during the evolution of MPLC. Most importantly, the similar between-tumor diversity and between-patient diversity suggest that personalized therapies may not adequately account for the genetic diversity among different tumors in an MPLC patient. To fully exploit the strategic value of precision medicine, targeted therapies should be designed and delivered on a per-lesion basis.

Small nodules (≤ 6 mm in diameter) of multiple primary lung cancers: prevalence and management.

BACKGROUND: Synchronous multiple primary lung cancers associated with small non-dominant nodules are commonly encountered. However, the incidence, follow-up, and treatment of small non-dominant tumors have been but little studied. We explored the prevalence and management of small non-dominant tumors and factors associated with interval growth. METHODS: This observational, consecutive, retrospective single-center study enrolled patients diagnosed with synchronous multiple primary lung cancers and small non-dominant tumors (≤ 6 mm in diameter) who underwent resection of the dominant tumor. The incidence, follow-up, and management of small non-dominant tumors and predictors of nodule growth were analyzed. RESULTS: There were 88 patients (12% of all lung cancer patients) with pathological diagnoses of synchronous multiple primary lung cancers. A total of 131 (18%) patients were clinically diagnosed with at least one small (≤ 6 mm in diameter) multiple primary lung cancer non-dominant tumor. 94 patients with 125 small-nodule non-dominant tumors clinically diagnosed as multiple primary lung cancers were followed-up for at least 6 months. A total of 29 (29/125, 23.2%) evidenced small pulmonary nodules (≤ 6 mm in diameter) that exhibited interval growth on follow-up computed tomography (CT). On multivariate analysis, a part-solid nodule (compared to a pGGN) (OR 1.23; 95% CI 1.08-1.40) or a solid nodule (compared to a pGGN) (OR 3.50; 95% CI 1.94-6.30) predicted small nodule interval growth. CONCLUSION: We found a relatively high incidence of multiple primary lung cancers with small non-dominant tumors exhibiting interval growth on follow-up CT, suggesting that resection of non-dominant tumors at the time of dominant tumor resection, especially when the nodules are part-solid or solid, is the optimal treatment.

Application of Dynamic 18F-FDG PET/CT for Distinguishing Intrapulmonary Metastases from Synchronous Multiple Primary Lung Cancer.

It has been a big challenge to distinguish synchronous multiple primary lung cancer (sMPLC) from primary lung cancer with intrapulmonary metastases (IPM). We aimed to assess the clinical application of dynamic 18F-FDG PET/CT in patients with multiple lung cancer nodules. We enrolled patients with multiple pulmonary nodules who had undergone dynamic 18F-FDG PET/CT and divided them into sMPLC and IPM groups based on comprehensive features. The SUVmax, fitted K i value based on dynamic scanning, and corresponding maximum diameter (D max) from the two largest tumors were determined in each patient. We determined the absolute between-tumor difference of SUVmax/D max and K i /D max (ΔSUVmax/D max; ΔK i /D max) and assessed the between-group differences. Further, the diagnostic accuracy was evaluated by ROC analysis and the correlation between ΔSUVmax/D max and ΔK i /Dmax from all groups was determined. There was no significant difference for ΔSUVmax/D max between the IPM and sMPLC groups, while the IPM group had a significantly higher ΔK i /Dmax than the sMPLC group. The AUC of ΔK i /D max for differentiating sMPLC from IPM was 0.80 (cut-off value of K i = 0.0059, sensitivity 79%, specificity 75%, p < 0.001). There was a good correlation (Pearson r = 0.91, 95% CI: 0.79-0.96, p < 0.0001) between ΔSUVmax/D max and ΔK i /D max in the IPM group but not in the sMPLC group (Pearson r = 0.45, p > 0.05). Dynamic 18F-FDG PET/CT could be a useful tool for distinguishing sMPLC from IPM. K i calculation based on Patlak graphic analysis could be more sensitive than SUVmax in discriminating IPM from sMPLC in patients with multiple lung cancer nodules.

Learning curve of uniportal video-assisted thoracoscopic lobectomy: an analysis of the proficiency of 538 cases from a single centre.

OBJECTIVES: Uniportal video-assisted thoracoscopic surgery (UniVATS) is widely used as a minimally invasive thoracic operation. The goal of our study was to analyse the effect of long-term experience with the UniVATS lobectomy on the learning curve. METHODS: The learning curves were quantitatively evaluated by the unadjusted cumulative sum, and they were segmented using joinpoint linear regression analysis. The variables were compared between subgroups using trend analysis, and linear regression analysis was applied to correlate clinical characteristics at different stages of the learning curve with the duration of the operation. RESULTS: The learning curve for the UniVATS lobectomy can be divided into 3 phases of proficiency at ∼200-300 procedures, with a fourth phase as the number of procedures increases. The 1st-52nd, 52nd-156th, 156th-244th and 244th-538th procedures comprised the preliminary learning stage, preliminary proficiency stage, proficiency stage and advanced proficiency stage, respectively. Surgical outcomes and their variability between stages improved with increasing case numbers, with the most significant addition of an auxiliary operating port and conversions. In multivariable analysis, as stages progressed, influences other than surgical experience increased the operative time, with male and extensive pleural adhesions in the preliminary proficiency stage; male and incomplete pulmonary fissures in the proficiency stage; and male, extensive pleural adhesions and incomplete pulmonary fissures in the advanced proficiency stage. CONCLUSIONS: As the number of procedures increases, there may be 4 different proficiency stages in the UniVATS lobectomy learning curve. The surgeon enters the fourth stage at approximately the 244th procedure. Moreover, at stage 4, the perioperative indicators tend to stabilize, and influences other than surgical experience become more significant.

Effect of single-port inflatable mediastinoscopy simultaneous laparoscopic-assisted radical esophagectomy on respiration and circulation.

BACKGROUND AND PURPOSE: We previously developed a new surgical method, namely, single-port inflatable mediastinoscopy simultaneous laparoscopic-assisted radical esophagectomy. The purpose of this study was to evaluate the effect of carbon dioxide inflation on respiration and circulation using this approach. METHODS: From April 2018 to October 2020, 105 patients underwent this novel surgical approach. The changes in respiratory and circulatory functions were reported when the mediastinal pressure and pneumoperitoneum pressure were 10 and 12 mmHg, respectively. Data on blood loss, operative time, and postoperative complications were also collected. RESULTS: 104 patients completed the operation successfully, except for 1 patient who was converted to thoracotomy because of intraoperative injury. During the operation, respectively, the heart rate, mean arterial pressure, central venous pressure, peak airway pressure, end-expiratory partial pressure of carbon dioxide and partial pressure of carbon dioxide increased in an admissibility range. The pH and oxygenation index decreased 1 h after inflation, but these values were all within a safe and acceptable range and restored to the baseline level after CO2 elimination. Postoperative complications included anastomotic fistula (8.6%), pleural effusion that needed to be treated (8.6%), chylothorax (0.9%), pneumonia (7.6%), arrhythmia (3.8%) and postoperative hoarseness (18.2%). There were no cases of perioperative death. CONCLUSIONS: When the inflation pressure in the mediastinum and abdomen was 10 mmHg and 12 mmHg, respectively, the inflation of carbon dioxide from single-port inflatable mediastinoscopy simultaneous laparoscopic-assisted radical esophagectomy did not cause serious changes in respiratory and circulatory function or increase perioperative complications.

Lymphadenectomy Along Bilateral Recurrent Laryngeal Nerves Under Single-Incision Mediastinoscopy.

This report proposes an approach for lymphadenectomy along bilateral recurrent laryngeal nerves (RLNs) under mediastinoscopy through a single left-neck incision. After pneumomediastinum is established, esophagectomy is begun over the aortic arch to the level of the lower edge of the left main bronchus, and lymphadenectomy along the left RLN is also accomplished. At the level of the lower edge of the right subclavian artery, between the trachea and the esophagus, the instruments can gain access to the right RLN. The lymphadenectomy may be performed up to 2 cm above the upper edge of the right subclavian artery.

Mediastinal lymphadenectomy under laparoscopic assisted single-port inflatable mediastinoscopy through left neck approach.

Minimally invasive esophagectomy (MIE) has been developed for decades. However, conventional MIE requires transthoracic surgery, which can increase the risk of many perioperative cardiopulmonary complications. Therefore, mediastinoscopy-assisted transhiatal esophagectomy has been proposed, but the traditional surgical methods have shortcomings, such as unclear vision, especially during the dissection of mediastinal lymph nodes (LNs). A new approach for mediastinal lymphadenectomy under single-port inflatable mediastinoscopy with one left-neck incision is proposed. There are three difficulties in this procedure. (I) LNs along the left recurrent laryngeal nerve (RLN). After establishing pneumomediastinum, esophagectomy is performed over the aortic arch to the level of the lower edge of the left main bronchus, and lymphadenectomy along the left RLN is also accomplished during this process. (II) LNs along the right RLN. At the level of the lower edge of the right subclavian artery (RSA), between the trachea and the esophagus, instruments are used to access the right RLN. Lymphadenectomy of up to 2 cm can be accomplished at the upper edge of the RSA. (III) Subcarinal LNs. Between the trachea and esophagus, the left and right main bronchi are exposed along the trailing edge of the trachea down to the carina, and lymphadenectomy can be performed here. The surgical procedure described here in detail is the first mediastinal lymphadenectomy under mediastinoscopy with one single left-neck incision.

A meta-analysis of adjuvant EGFR-TKIs for patients with resected non-small cell lung cancer.

OBJECTIVES: We performed this meta-analysis to compare adjuvant EGFR-TKIs with a placebo or adjuvant chemotherapy among patients with resected non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: A literature search was performed using relevant keywords. All randomized controlled trials (RCTs) that compared the survival benefits of adjuvant EGFR-TKIs with those of placebo or adjuvant chemotherapy for resected NSCLC were eligible for inclusion. RESULTS: The literature search yielded five eligible RCTs including three RCTs that compared adjuvant EGFR-TKIs with a placebo, and two RCTs that compared adjuvant EGFR-TKIs with chemotherapy. For unselected intent-to-treat patients who received adjuvant EGFR-TKIs versus a placebo, the hazard ratio (HR) of disease-free survival (DFS) was 0.88 (95% confidence interval (CI): 0.59-1.32; P = 0.54). For patients with an EGFR mutation, the DFS after adjuvant EGFR-TKIs was superior to that after a placebo, with a HR of 0.59 (95% CI: 0.40-0.88; P = 0.009). For patients with an EGFR mutation, the DFS after EGFR-TKIs was greater than that after chemotherapy, with a HR of 0.42 (95% CI: 0.19-0.93; P = 0.03). For patients with wild-type EGFR, the DFS of adjuvant EGFR-TKIs was similar to the placebo, with a RR of 1.00 (95% CI: 0.62-1.60; P = 0.99). Treatment with EGFR-TKIs resulted in more adverse events compared with the placebo, with a risk ratio (RR) of 2.72, (95% CI: 2.23-3.33; P < 0.00001), but fewer adverse events compared with chemotherapy, with an RR of 0.26 (95% CI: 0.18-0.38; P < 0.00001). CONCLUSIONS: For patients with resected NSCLC harboring EGFR mutations, treatment with an adjuvant EGFR-TKI was superior to that of a placebo or chemotherapy in terms of DFS. Treatment with adjuvant EGFR-TKIs were not effective among patients with wild type EGFR NSCLC.

Predictive Value of Anastomotic Blood Supply for Anastomotic Stricture After Esophagectomy in Esophageal Cancer.

BACKGROUND: Insufficient blood supply in the gastric tube is considered as a risk factor for postoperative anastomotic strictures in patients receiving esophagectomy, but the direct evidence is lacking. AIMS: We aimed to investigate the correlation between perioperative blood supply in the anastomotic area of the gastric tube and the formation of anastomotic strictures in the patients undergoing esophagectomy. METHODS: This prospective study included 60 patients with esophageal squamous cell carcinoma undergoing Ivor Lewis esophagectomy between March 2014 and February 2016, which were divided into stricture group (n = 13) and non-stricture group (n = 47) based on their severity of anastomotic strictures at 3 months post-operation. The perioperative anastomotic blood supply was measured using a laser Doppler flowmetry. The gastric intramucosal pH (pHi) was measured by a gastric tonometer within 72 h post-operation. The perfusion index and gastric pHi were compared between groups. RESULTS: The stricture group had a significantly lower blood flow index (P < 0.001) and gastric pHi values from day 1 to day 3 post-operation than the non-stricture group (all P < 0.001). In addition, Pearson correlation analysis showed that both the perfusion index and gastric pHi were significantly correlated with stricture size and stricture scores, respectively (r = 0.65 - 0.32, all P < 0.05). Furthermore, the multivariate logistic regression analysis showed that perfusion index was an influential factor associated with postoperative anastomotic strictures (OR 0.84. 95% CI 0.72-0.98, P = 0.026). CONCLUSION: These results suggested that poor blood supply in the anastomotic area of the gastric tube in the perioperative period was a risk factor for postoperative anastomotic strictures.

Single-Port Inflatable Mediastinoscopy Combined With Laparoscopic-Assisted Small Incision Surgery for Radical Esophagectomy Is an Effective and Safe Treatment for Esophageal Cancer.

BACKGROUND: We previously developed a novel non-trans thoracic esophagectomy, the single-port inflatable mediastinoscopy combined with laparoscopy for the radical esophagectomy of esophageal cancer. The purpose of this study was to report its therapeutic efficacy and safety. METHODS: From May 2016 to August 2017, we have completed 80 cases of radical resection of esophageal carcinoma using this novel surgical technique. The intraoperative findings and postoperative complications were reported. RESULTS: The operation was successfully performed in all patients except for one patient switched from laparoscopic-assisted operation to open surgery. The mean operation duration was 191.4 ± 27 min, and the mean intraoperative blood loss was 147.3 ± 28.9 mL. The mean number of removed lymph node was 21.9 ± 4.1. Five patients (6.4%) who had preoperative type I respiratory failure needed to stay in the intensive care unit for 24 h postoperatively. Postoperative complications included anastomotic leakage (8.9%), anastomotic stricture (21.25%), pleural effusion (9%), and hoarseness postoperative hoarseness (18.8%). The incidence of hoarseness at 3 months postoperation was reduced to 3.8%. All the complications were Clavien-Dindo grades I-III. There were no perioperative death and postoperative cardiopulmonary complications. CONCLUSION: These results showed that the single-port inflatable mediastinoscopy combined with laparoscopy is feasible for radical esophagectomy and possesses good therapeutic efficacy and safety.

The procedure of single-port inflatable mediastinoscopy and laparoscopic surgery for radical esophagectomy.

It has been described as a new non-transthoracic esophagectomy that the single-port inflatable mediastinoscopy and laparoscopic surgery is safe and effective for the radical esophagectomy of esophageal cancer. This report describes the whole procedure in detail. The patient lies in the supine position with the legs apart. The procedure is performed under general anesthesia with a single lumen endotracheal tube. For upper mediastinal operation, a lateral incision of the clavicle was made about 3 cm; for laparoscopic operation, the incisions of 5 ports for the laparoscopic operation. CO2 insufflation is performed into the mediastinum with 10 mmHg to make artificial mediastinal emphysema. The Maryland forceps is used to perform separation before dissection. In the non-transthoracic esophagectomy, it is essential to expose the recurrent laryngeal nerve and the azygos vein. The lymph nodes around the esophagus were removed in en bloc. Maintaining double lung ventilation during surgery can significantly reduce carbon dioxide accumulation, especially for those with reduced lung function or severe pleural adhesion. Furthermore, it saves much time that upper mediastinal operation and laparoscopic operation are undergone simultaneously. It is a perfect surgical technique that is worth to promote.

Expression of periostin in small cell lung cancer and its effect on chemoresistance / 中国胸心血管外科临床杂志

@#Objective    To detect the difference of periostin expression in small cell lung cancer (SCLC) cell, and explore its effect on chemoresistance of SCLC patients. Methods    The expression of periostin in mRNA and protein was detected by RT-PCR and Western blot analysis in SCLC H69 and multidrug resistant strain H69AR. The expression of periostin was up-regulated by recombinant plasmid-periostin in H69 cell. The survival rate in the transfected group was different from that of the negative control group and uninterrupted group. Results    The expression of periostin mRNA and protein in the sensitive strain H69 was lower than that of the multidrug resistant strain H69AR (P<0.05). The recombinant periostin-plasmid was transfected into H69 cells and at the same concentration of chemotherapeutic drugs (cisplatin, etoposide) the survival rate increased significantly (P<0.05). The positive expression rate of periostin in SCLC tissues was 67.44%, and the sensitivity of the chemotherapy group was lower than that of the drug resistant group (P<0.05). Conclusion    The expression of periostin in SCLC cell H69 is significantly lower than that of the multidrug resistant strain H69AR and overexpression of periostin increases resistance of the sensitive strain H69 and hence periostin may be involved in SCLC chemoresistance.