Prognostic factors in pulmonary metastases resection from colorectal cancer: impact of right-sided colon cancer and early recurrence.

OBJECTIVE: This retrospective cohort study aimed to explore the surgical outcomes and prognostic factors of resection of pulmonary metastases (PM) from colorectal cancer (CRC). METHODS: Overall, 60 patients who underwent resection of PM from CRC between 2015 and 2021 at two institutions were reviewed. The primary outcome were overall survival (OS) and early recurrence after PM resection. The association between OS and right-sided colon cancer (RCC) was investigated. Early recurrence after PM resection was defined as recurrence within one year. RESULTS: The 5-year OS after CRC resection was 83.8% (95% confidence interval [CI] 67.5-92.4) and after PM resection was 69.4% (95% CI 47.5-83.6). In total, 25 patients had recurrence after PM resection (16 within 1 year and 9 after 1 year). In multivariable analysis for OS, RCC (hazard ratio [HR] 4.370, 95% CI 1.020-18.73; p = 0.047) and early recurrence after resection of PM (HR 17.23, 95% CI 2.685-110.6; p = 0.003) were risk factors for poor OS. In multivariable analysis for early recurrence after PM resection, higher value of carcinoembryonic antigen (CEA) (> 5.0 mg/dL) before PM resection was a risk factor for early recurrence (HR 3.275, 95% CI 1.092-9.821; p = 0.034). CONCLUSION: The RCC and early recurrence after PM resection were poor prognosis factors of OS. Higher value of CEA before PM resection was an independent risk factor for early recurrence after resection of PM. Comparitive study between surgery and nonsurgery is necessary in patients with higher CEA values.

Compensatory expansion of the right middle lobe: volumetric and functional analysis of the changes after right upper or lower lobectomy.

The right middle lobe often poorly expands after right upper lobectomy. Postoperative pulmonary function may be inferior after right upper lobectomy than after right lower lobectomy due to poor expansion of the middle lobe. This study examined the difference in the postoperative right middle lobe expansion and pulmonary function between right upper and right lower lobectomy. Patients who underwent right upper or right lower lobectomy through video-assisted thoracic surgery (n = 82) were enrolled in this retrospective study. Pulmonary function tests and computed tomography were performed preoperatively and at 1 year postoperatively. Using three-dimensional computed tomography volumetry, the preoperative and postoperative lung volumes were measured, and the predicted postoperative forced expiratory volume in 1 s was calculated. Middle lobe volume ratio (i.e., ratio of the postoperative to the preoperative middle lobe volume) and the postoperative forced expiratory volume in 1 s ratio (i.e., ratio of the measured to the predicted postoperative forced expiratory volume in 1 s) were compared between right upper and right lower lobectomy. Compared with the patients who underwent right upper lobectomy (n = 50), those who underwent right lower lobectomy (n = 32) had significantly higher middle lobe volume ratio (1.15 ± 0.32 vs. 1.63 ± 0.52, p < 0.001) and postoperative forced expiratory volume in 1 s ratio (1.12 ± 0.12 vs. 1.19 ± 0.13, p = 0.010). The right middle lobe showed more expansion and better recovery of postoperative pulmonary function after right lower lobectomy than after right upper lobectomy.

Impact of intrapulmonary tumour location of non-small-cell lung cancer on surgical outcomes for segmentectomy.

OBJECTIVES: While segmentectomy is considered a viable option for small peripheral non-small-cell lung cancer, its efficacy for central lesions remains uncertain. This study aimed to assess the oncological outcomes of segmentectomy for central lesions compared to peripheral ones. METHODS: We retrospectively examined 338 clinical stage IA non-small-cell lung cancer patients who underwent thoracoscopic anatomical segmentectomy at our institution from January 2013 to December 2021. Patients were divided into 2 groups based on intrapulmonary tumour location: inner two-thirds (central group, n = 82) and outer one-third (peripheral group, n = 256). RESULTS: The gender, body mass index, performance score, smoking, comorbidities and preoperative pulmonary function were similar in both groups. On computed tomography images, tumour diameter and consolidation-to-tumour ratio were comparable between the groups. The central group had significantly greater tumour-to-pleura distances [mm, 23 (18-27) vs 11 (8-14); P < 0.001], shorter margin distances [mm, 20 (15-20) vs 20 (20-20); P < 0.001] and larger resected lung volumes based on subsegment count [4 (3-6) vs 3 (3-5); P = 0.004] than the peripheral group. Surgery duration, bleeding, hospitalization or drainage period, mortality, readmission and pathological stage were equivalent between the groups. The central group showed significantly more postoperative pleural effusions (5% vs 1%; P = 0.03) than the peripheral group, with no adverse impact on postoperative pulmonary functions. During the follow-up period, local-only recurrence rates were 0% and 8% in the respective groups (Gray test P = 0.07), and total recurrence rates were 6% and 11% (Gray test P = 0.70), with no significant differences. Moreover, no significant inter-group difference in overall survival rates was observed (82% vs 93%; P = 0.15). CONCLUSIONS: Segmentectomy may be a promising therapeutic option for early-stage non-small-cell lung cancer located in the inner two-thirds of the parenchyma.

Weight loss of 5% or more after lobectomy for lung cancer via minimally invasive approaches is associated with poor prognosis.

INTRODUCTION: We analyzed the association between postoperative weight loss (WL), preoperative body mass index (BMI), and prognosis in patients with lung cancer who underwent lobectomy using minimally invasive approaches. METHODS: Weight change in 325 patients who underwent radical lobectomy for non-small cell lung cancer was assessed at 3, 6, and 12 months postoperatively and compared to preoperative weight. Patients were divided into three groups according to their preoperative BMI interquartile range: low BMI ≤20.3 kg/m2 , middle BMI 20.4-24.4 kg/m2 , and high BMI ≥24.5 kg/m2 . Postoperative WL ≥5% was evaluated with reference to frailty. RESULTS: There were no significant differences in pathological findings, postoperative complications, or postoperative hospital stay among the three groups. Thirty all-cause deaths and 39 cancer recurrences occurred. Within the first year after surgery, WL of any grade was observed in 229 patients (70.5%) and WL ≥5% in 86 patients (26.5%). Postoperative WL of any grade within 1 year after surgery was not associated with OS and RFS (both p > .05). However, WL ≥5% within 1 year after surgery was associated with worse OS and RFS (p = .007 and .006, respectively). WL ≥5% within 1 year after surgery was more common in the low BMI group (p = .045). There was no difference in OS and RFS among the BMI groups in patients with WL ≥5% and those without WL ≥5% (all p > .05). CONCLUSION: WL ≥5% was associated with poor prognosis after lobectomy via minimally invasive approaches. Weighing is a useful prognostic marker that can be easily self-checked.

Thoracoscopic Anatomical Sublobar Resection Including Subsegmentectomy for Non-Small Cell Lung Cancer.

BACKGROUND: Among anatomical sublobar resection techniques for non-small cell lung cancer (NSCLC), the clinical benefit of subsegmentectomy remains unclear. We investigated whether anatomical sublobar resection including subsegmentectomy-segmental resection with subsegmental additional resection or subsegmental resection alone-is an effective and feasible surgical procedure for NSCLC. METHODS: We retrospectively reviewed data of 285 patients with clinical stage I NSCLC who underwent anatomical sublobar resection at our institution from January 2013 to March 2021 and compared surgical outcomes between patients who underwent anatomical sublobar resection including (IS; n = 50) and excluding (ES; n = 235) subsegmentectomy. RESULTS: No significant intergroup differences were noted in terms of age, sex, smoking, comorbidities, tumor size or location, consolidation tumor ratio, and preoperative pulmonary function. The IS group had more preoperative computed tomography-guided markings (34 vs. 15%; p = .004) and smaller resected lung volumes converted to the total subsegment number [3 (2-4) vs. 3 (3-6); p = .02] than the ES group. No significant differences in margin distance [mm, 20 (15-20) vs. 20 (20-20); p = .93], readmission rate (2% vs. 3%; p > .99), and intraoperative (8% vs. 7%; p = .77) or postoperative (8% vs. 10%; p = .80) complication rates were observed, and the 5-year local recurrence-free survival (91% vs. 90%; p = .92) or postoperative pulmonary function change were comparable between both groups. CONCLUSIONS: Although further investigations are required, anatomical sublobar resection including subsegmentectomy for clinical stage I NSCLC could be an acceptable therapeutic option.

Comparative study of local versus general anesthesia in video-assisted thoracoscopic surgery for empyema.

OBJECTIVE: This study evaluated the feasibility of performing non-intubated video-assisted thoracoscopic surgery (VATS) with local anesthesia for parapneumonic effusion and empyema resistant to conservative treatment. METHODS: We retrospectively reviewed 80 patients who underwent surgery for parapneumonic effusions and empyema between 2015 and 2021. Patients were divided into those who received non-intubated local anesthesia and general anesthesia during surgery. Patient demographics, characteristics, laboratory findings, treatment progress, and treatment outcomes were compared. The primary outcomes were duration of postoperative drainage, postoperative complication rate, and postoperative mortality rate within 30 days. RESULTS: Among patients who received local (n = 21) and general anesthesia (n = 59), there was a significant difference in age (median 79.0 years [interquartile range (IQR) 77.0-80.0] vs. 68.0 years [IQR 54.5-77.5]; p < 0.001), preoperative performance status (3.0 [IQR 2.0-4.0] vs. 2.0 [IQR 1.0-3.0]; p < 0.001), and operative time (69 min [IQR 50-128] vs. 150 min [IQR 107-198]; p < 0.001) but not in preoperative white blood cell count (12,100/µL [IQR 8,400-18000] vs. 12,220/µL [IQR 8,950-16,724]; p = 0.840), C-reactive protein (15.2 mg/dL [8.8-21.3] vs. 17.9 mg/dL [IQR 9.5-23.6]; p = 0.623), postoperative drainage period (11 days [IQR 7-14] vs. 9 days [7-13]; p = 0.216), postoperative hospital stay (22 days [IQR 16-53] vs. 18 days [IQR 12-26]; p = 0.094), reoperation rate (9.5% vs. 15.3%; p = 0.775), postoperative complication rate (19.0% vs. 18.6%; p = 0.132), or postoperative 30-day mortality rate (4.8% vs. 0%; p = 0.587). CONCLUSIONS: VATS using local anesthesia is feasible for patients with treatment-resistant parapneumonic effusion and empyema with poor general condition.

Three-Arm Robotic Lung Resection via the Open-Thoracotomy-View Approach Using Vertical Port Placement and Confronting Monitor Setting: Focusing on Segmentectomy.

To perform robotic lung resections with views similar to those in thoracotomy, we devised a vertical port placement and confronting upside-down monitor setting: the three-arm, robotic "open-thoracotomy-view approach (OTVA)". We described the robotic OTVA experiences focusing on segmentectomy and its technical aspects. We retrospectively reviewed 114 consecutive patients who underwent robotic lung resections (76 lobectomies and 38 segmentectomies) with OTVA using the da Vinci Xi Surgical System between February 2019 and June 2022. To identify segmental boundaries, we administered indocyanine green intravenously and used the robotic fluorescence imaging system (Firefly). In all procedures, cranial-side intrathoracic structures, which are often hidden in the conventional look-up-view method, were well visualized. The mean durations of surgery and console operation were 195 and 140 min, respectively, and 225 and 173 min, for segmentectomy and lobectomy, respectively. In segmentectomy, console operation was significantly shorter (approximately 30 min, p < 0.001) and two more staplers (8.2 ± 2.3) were used compared with lobectomy (6.6 ± 2.6, p = 0.003). In both groups, median postoperative durations of chest tube placement and hospitalization were 0 and 3 days, respectively. This three-arm robotic OTVA setting offers natural thoracotomy views and can be an alternative for segmentectomy and lobectomy.

Postoperative surveillance using low-dose computed tomography for non-small-cell lung cancer.

OBJECTIVES: We retrospectively analysed the surgical prognosis of patients with pathological stage I non-small-cell lung cancer (NSCLC) who after complete resection underwent low-dose computed tomography (LDCT) or conventional CT as postoperative surveillance. METHODS: We investigated 416 patients who underwent lobectomy or segmentectomy between January 2013 and December 2016. We compared the prognosis between the LDCT and conventional CT groups using the propensity score-matched analysis. RESULTS: The median follow-up period was 57 months. Cancer recurrence occurred in 47 patients (11.3%). In the entire cohort (n = 416), recurrence-free survival (RFS) and overall survival (OS) were better in the LDCT group (P = 0.001 and 0.002, respectively). Both intrathoracic recurrence and distant metastasis were higher in the conventional group (P = 0.015 and 0.009, respectively). However, there was no statistical difference in the factors leading to recurrence detection (routine radiological examination, symptoms and elevated tumour markers: all P > 0.05). Both groups were matched using a ratio of 1:1. The area under the receiver operating characteristic curve was 0.788. A total of 226 patients were successfully matched. After matching, there was no statistical difference between the 2 groups for RFS and OS (P = 0.263 and 0.226). There were also no statistical differences in recurrence rate, the factors leading to recurrence detection or recurrence site (all P > 0.05). CONCLUSIONS: After using propensity score matched, RFS and OS did not differ significantly between LDCT and conventional CT groups. Retrospective comparisons suggest no disadvantages of using LDCT for postoperative surveillance of pathological stage I NSCLC. Further validation will be needed in the future.

Effect of resected lung lobe on the prediction of postoperative pulmonary function.

OBJECTIVES: This study examined whether a resected lung lobe can affect the accuracy of postoperative forced expiratory volume in 1 s (FEV1) predicted using the subsegment counting method and three-dimensional computed tomography (3D-CT) volumetry. METHODS: Overall, 125 patients who underwent lobectomy through video-assisted thoracic surgery were enrolled in this retrospective study. Pulmonary function tests were performed preoperatively and postoperatively at 3 months. We defined the accuracy index as the ratio of predicted postoperative FEV1 to measured postoperative FEV1 and compared the accuracy index of the subsegment counting method and 3D-CT volumetry. Factors affecting the accuracy index were also examined. RESULTS: The accuracy index of the subsegment counting method was 0.94 ± 0.12, versus 0.93 ± 0.11 for 3D-CT volumetry (P = 0.539). There was a significant difference among the resected lobes in the accuracy index of the subsegment counting method (P < 0.001) but not in that of 3D-CT volumetry (P = 0.370). The resected lobe, the number of staples used for interlobar dissection and interstitial pneumonia were significantly associated with the accuracy index of the subsegment counting method (all P < 0.001). The number of staples and interstitial pneumonia were significantly associated with the accuracy index of 3D-CT volumetry (P < 0.001, respectively), whereas the resected lobe was not a significant factor (P = 0.240). CONCLUSIONS: The resected lobe affected the accuracy of the subsegment counting method but not that of 3D-CT volumetry. Furthermore, 3D-CT volumetry predicted postoperative FEV1 independent of the resected lobe.

Analysis of postoperative weight loss associated with prognosis after lobectomy for lung cancer.

OBJECTIVES: Weight assessment is an easy-to-understand method of health checkup. The present study investigated the association between weight loss (WL) after lung cancer (LC) surgery and short-mid-term prognosis. METHODS: The data of patients who underwent radical lobectomy for primary LC were assessed between December 2017 and June 2021. Percentage weight gain or loss was determined at 3, 6 and 12 months postoperatively based on preoperative weight. The timing of decreased weight was divided into 0-3, 3-6 and 6-12 months. We also evaluated the relationship between severe WL (SWL) and prognosis. RESULTS: We reviewed 269 patients, of whom 187 (69.5%) showed WL within 1 year after surgery. The interquartile range for maximal WL was 2.0-8.2% (median 4.0%). Furthermore, we defined SWL as WL ≥8%. Twenty-five patients (9.3%) died: 9 from primary LC and 16 from non-LC causes. Cancer recurrences occurred in 45 patients (16.7%). WL occurred from 6 to 12 months postoperatively was associated with poor overall survival and recurrence-free survival (P < 0.05, both). Body mass index <18.5 kg/m2 and idiopathic pulmonary fibrosis were predictive factors (P < 0.05, all). In the SWL group, overall survival, recurrence-free survival and non-cancer-specific were worse (P = 0.001, 0.005 and 0.019, respectively). Age ≥70 years and severe postoperative complications were predictive factors for SWL (P < 0.05, all). CONCLUSIONS: WL from 6 to 12 months postoperatively and SWL were associated with poor prognosis. Ongoing nutritional management is important to prevent life-threatening WL in patients with predictive factors.

Proposed clinical phases for the improvement of personalized treatment of checkpoint inhibitor-related pneumonitis.

Background: Checkpoint inhibitor-related pneumonitis (CIP) is a lethal immune-related adverse event. However, the development process of CIP, which may provide insight into more effective management, has not been extensively examined. Methods: We conducted a multicenter retrospective analysis of 56 patients who developed CIP. Clinical characteristics, radiological features, histologic features, and laboratory tests were analyzed. After a comprehensive analysis, we proposed acute, subacute, and chronic phases of CIP and summarized each phase's characteristics. Results: There were 51 patients in the acute phase, 22 in the subacute phase, and 11 in the chronic phase. The median interval time from the beginning of CIP to the different phases was calculated (acute phase: ≤4.9 weeks; subacute phase: 4.9~13.1 weeks; and chronic phase: ≥13.1 weeks). The symptoms relieved from the acute phase to the chronic phase, and the CIP grade and Performance Status score decreased (P<0.05). The main change in radiologic features was the absorption of the lesions, and 3 (3/11) patients in the chronic phase had persistent traction bronchiectasis. For histologic features, most patients had acute fibrinous pneumonitis in the acute phase (5/8), and most had organizing pneumonia in the subacute phase (5/6). Other histologic changes advanced over time, with the lesions entering a state of fibrosis. Moreover, the levels of interleukin-6, interleukin-10 and high-sensitivity C-reactive protein (hsCRP) increased in the acute phase and decreased as CIP progressed (IL-6: 17.9 vs. 9.8 vs. 5.7, P=0.018; IL-10: 4.6 vs 3.0 vs. 2.0, P=0.041; hsCRP: 88.2 vs. 19.4 vs. 14.4, P=0.005). Conclusions: The general development process of CIP can be divided into acute, subacute, and chronic phases, upon which a better management strategy might be based devised.

Esophagobronchial fistula successfully managed with a self-expandable metallic stent followed by fixation using a silicon Y stent.

Esophagobronchial fistula (EBF) formation is a severe complication of advanced thoracic malignancies, that affects the prognosis and quality of life of patients. This study reports the case of an 80-year-old man with advanced esophageal cancer, complicated by EBF formation in the left main bronchus proximal to the carina following chemoradiation therapy. A fully covered stent was placed in the left main bronchus but was dislocated on the oral side. The attempt to place a partially covered self-expandable metallic stent (SEMS) also failed due to stent dislocation on the oral side. To avoid stent dislocation, a partially covered SEMS with a length of 40 mm and a diameter of 16 mm was placed to cover the EBF in the left main bronchus. Then, a silicone Y stent (16 × 13 × 13 mm in outer diameter) was inserted to support the SEMS from the inside. After placing the SEMS and Y stent, the position of the SEMS was stabilized. The patient remained stable with adequate oral intake.

Efficacy of a combined tool for stage I non-small cell lung cancer against lymph node metastasis.

In patients with clinical stage I non-small cell lung cancer (NSCLC), the prediction of occult lymph node metastasis (LNM) based on a combination of morphology using high-resolution computed tomography (HRCT) and metabolism using positron emission tomography (PET)-CT is unknown. The present study evaluated the use of predictive radiological tools, chest CT and PET-CT, for occult LNM in patients with clinical stage I NSCLC. The records of patients who underwent lobectomy between July 2014 and November 2021 were retrospectively reviewed. The differences in clinicopathological parameters, including CT and PET, between the LNM and non-LNM groups were assessed. Pure solid tumor was defined as a consolidation-to-tumor ratio of 1. The optimal cut-off value for predictive radiological tools for LNM was assessed according to the area under the receiver operating characteristic (ROC) curve. The present study included 288 patients, of whom 39 (13.5%) had LNM; of these 38 (97.4%) were pure solid type. Larger consolidation size (CS), higher maximal standardized uptake (SUVmax) value and histological type were statistically associated with LNM (all P<0.05). The optimal cutoff values of CS and SUVmax for predicting LNM were 19 mm and 5.5 respectively, as assessed using the area under the ROC curve. The combination of CS ≥19 mm and SUVmax ≥5.5 demonstrated a markedly higher odds ratio (9.184; 95% CI, 4.345-19.407) than each parameter individually. The minimum values of CS and SUVmax associated with LNM were 10 mm and 0.8 respectively. Pure solid formation and CS as morphology and SUVmax as metabolism were useful tools that complemented each other in predicting LNM. The combined method of evaluating SUVmax and CS may identify eligibility for LN dissection. However, considering the minimum values of CS and SUVmax in LNM, it cannot affirm the omission of LN dissection for cases that do not meet the combined criteria using HRCT and PET-CT.

Preoperative percutaneous needle indigo carmine and lipiodol mixture marking in lung segmentectomy.

OBJECTIVES: For successful nodule localization and appropriate surgical margin distances in pulmonary segmentectomy for patients with lung malignancies, the effectiveness and feasibility of preoperative marking using an indigo carmine and lipiodol mixture remain unclear. METHODS: Patients who underwent thoracoscopic pulmonary segmentectomy with (marking group, n = 69) and without (non-marking group, n = 265) preoperative marking at our institution from January 2013 to March 2020 were retrospectively reviewed and compared in terms of surgical outcomes. All markings were performed using a fine needle to percutaneously inject an indigo carmine and lipiodol mixture under the guidance of computed tomography fluoroscopy. RESULTS: Successful localization was achieved in 66 (96%) patients, of whom 62 (94%) underwent dye pigmentation and 4 (6%) underwent intraoperative fluoroscopy. On images, the marking group showed a significantly longer distance between the lung surface and tumour [mm, 9 (1-17) vs 0 (0-10); P < 0.01] and smaller maximum tumour size [mm, 16 (11-21) vs 17 (13-23); P = 0.03] and consolidation tumour ratio [0.4 (0.3-1) vs 0.8 (0.4-1); P < 0.01] than the non-marking group. Both groups had comparable operative outcomes, perioperative complications, pulmonary function changes and surgical margin distances [mm, 20 (15-21) vs 20 (15-20); P = 0.96] without any local recurrence on the surgical margin. Propensity score-matching analysis also showed similar findings for both groups. CONCLUSIONS: Thoracoscopic pulmonary segmentectomy with preoperative marking using an indigo carmine and lipiodol mixture may be an acceptable therapeutic option for small malignancies located in deep lung parenchyma.

A nomogram for predicting hyperprogressive disease after immune checkpoint inhibitor treatment in lung cancer.

Background: Immune checkpoint inhibitor (ICI) therapy is an emerging type of treatment for lung cancer (LC). However, hyperprogressive disease (HPD) has been observed in patients treated with ICIs that lacks a prognostic prediction model. There is an urgent need for a simple and easily implementable predictive model to predict the occurrence of HPD. This study aimed to establish a novel scoring system based on a nomogram for the occurrence of HPD. Methods: We retrospectively identified 1473 patients with stage III-IV LC or inoperable stage I-II LC (1147 in training set, and 326 in testing set), who had undergone ICI therapy at the Shanghai Chest Hospital between January 2017 and March 2022. Available computed tomography (CT) data from the previous treatment, before ICI administration, and at least 2 months after the first the course of ICI administration is collected to confirm HPD. Data from these patients' common blood laboratory test results before ICI administration were analyzed by the univariable and multivariable logistic regression analysis, then used to develop nomogram predictive model, and made validation in testing set. Results: A total of 1,055 patients were included in this study (844 in the training set, and 211 in the testing set). In the training set, 93 were HPD and 751were non-HPD. Multivariate logistic regression analyses demonstrated that lactate dehydrogenase [LDH, P<0.001; odds ratio (OR) =0.987; 95% confidence interval (CI): 0.980-0.995], mean corpuscular hemoglobin concentration (MCHC, P=0.038; OR =1.021; 95% CI: 1.003-1.033), and erythrocyte sedimentation rate (ESR, P=0.012; OR =0.989; 95% CI: 0.977-0.997) were significantly different. The prediction model was established and validated based on these 3 variables. The concordance index were 0.899 (95% CI: 0.859-0.918) and 0.924 (95% CI: 0.866-0.983) in training set and testing set, and the calibration curve was acceptable. Conclusions: This model, which was developed from a laboratory examination of LC patients undergoing ICI treatment, is the first nomogram model to be developed to predict HPD occurrence and exhibited good sensitivity and specificity.

New evaluation of the tumor immune microenvironment of non-small cell lung cancer and its association with prognosis.

BACKGROUND: A better understanding of the tumor immune microenvironment (TIME) will facilitate the development of prognostic biomarkers and more effective therapeutic strategies in patients with lung cancer. However, little has been reported on the comprehensive evaluation of complex interactions among cancer cells, immune cells, and local immunosuppressive elements in the TIME. METHODS: Whole-exome sequencing and RNA sequencing were carried out on 113 lung cancers. We performed single sample gene set enrichment analysis on TIME-related gene sets to develop a new scoring system (TIME score), consisting of T-score (tumor proliferation), I-score (antitumor immunity) and S-score (immunosuppression). Lung cancers were classified according to a combination of high or low T-score, I-score, and S-scores (eight groups; G1-8). Clinical and genomic features, and immune landscape were investigated among eight groups. The external data sets of 990 lung cancers from The Cancer Genome Atlas and 76 melanomas treated with immune checkpoint inhibitors (ICI) were utilized to evaluate TIME scoring and explore prognostic and predictive accuracy. RESULTS: The representative histological type including adenocarcinoma and squamous cell carcinoma, and driver mutations such as epidermal growth factor receptor and TP53 mutations were different according to the T-score. The numbers of somatic mutations and predicted neoantigens were higher in Thi (G5-8) than Tlo (G1-4) tumors. Immune selection pressure against neoantigen expression occurred only in Thi and was dampened in Thi/Ilo (G5-6), possibly due to a reduced number of T cells with a high proportion of tumor specific but exhausted cells. Thi/Ilo/Shi (G5) displayed the lowest immune responses by additional immune suppressive mechanisms. The T-score, I-score and S-scores were independent prognostic factors, with survival curves well separated into eight groups with G5 displaying the worst overall survival, while the opposite group Tlo/Ihi/Slo (G4) had the best prognosis. Several oncogenic signaling pathways influenced on T-score and I-scores but not S-score, and PI3K pathway alteration correlated with poor prognosis in accordance with higher T-score and lower I-score. Moreover, the TIME score predicted the efficacy of ICI in patients with melanoma. CONCLUSION: The TIME score capturing complex interactions among tumor proliferation, antitumor immunity and immunosuppression could be useful for prognostic predictions or selection of treatment strategies in patients with lung cancer.

Emergency rollout and conversion procedures during the three-arm robotic open-thoracotomy-view approach.

OBJECTIVES: To conduct robotic lung resections (RLRs) with views similar to those in open-thoracotomy surgery (OTS), we adopted a vertical port placement and confronting upside-down monitor setting: the robotic open-thoracotomy-view approach (OTVA). We herein discuss the procedures for emergency rollout and conversion from the robotic OTVA to OTS or video-assisted thoracoscopic surgery (VATS). METHODS: We retrospectively reviewed the cases of 88 patients who underwent RLR with three-arm OTVA using the da Vinci Xi Surgical System between February 2019 and July 2021. Robotic ports were vertically placed along the axillary line, and 2 confronting monitors and 2 assistants were positioned on each side of the patient. Three possible conversions were prepared: (i) emergency thoracotomy using an incision along the ribs in a critical situation, (ii) cool conversion using vertical incision thoracotomy in a calmer condition and (iii) conversion to confronting VATS. All staff involved in the surgery repeatedly rehearsed the emergency rollout in practice. RESULTS: No emergent or cool conversion to OTS occurred. Two patients (2.3%) experienced confronting VATS conversions. One patient underwent an urgent conversion for a moderate haemorrhage from a pulmonary artery branch during left upper lobectomy in the introduction phase. Another patient underwent a calmer conversion during an extended RS6 + S10a segmentectomy, where staples could not be inserted appropriately due to lung lacerations. In all patients, postoperative courses were uneventful. CONCLUSIONS: The OTVA setting is a possible option for RLRs. This report describes the emergent rollout and subsequent conversion procedures for this method.