Due to the phenotypic and genotypic heterogeneity of tumors, the efficacy of intraoperative indocyanine green (ICG) imaging in lung cancer exhibits significant inter-patient variability. This study identifies macrophage content as a critical predictive biomarker for ICG imaging outcomes, offering both mechanistic, and clinical insights into this variability. Mechanistically, macrophages are demonstrated to serve as the principal ICG reservoirs in tumor tissues, exhibiting seven-fold higher uptake capacity compared to cancer cells. This critical role is confirmed by significantly diminished ICG accumulation following macrophage depletion in patient-derived xenograft (PDX) models. Clinically, a strong correlation is observed between imaging quality and macrophage content, with solid nodules exhibiting superior ICG uptake compared to ground-glass nodules due to higher macrophage infiltration. Furthermore, the strong tumor-to-normal ratio (TNR) association with preoperative maximum Standardized Uptake Value (SUVmax) on PET-CT suggests the feasibility of predicting ICG-guided surgery outcomes through routine imaging. The substantial contribution of macrophages to this predictive capability is a significant discovery, offering a novel biomarker for patient stratification in ICG-guided surgery. These insights not only deepen our comprehension of the intricate interplay between ICG and the lung cancer microenvironment but also open new avenues for the development of more personalized and precise surgical strategies.
Chemoradiotherapy followed by consolidative immunotherapy is the standard-of-care for unresectable stage III non-small cell lung cancers (NSCLC), yet confers limited benefit in those with driver mutations, BRAF-V600x included. Here, we report two cases of unresectable stage III NSCLC harboring BRAF V600E mutation treated with induction dabrafenib, trametinib, and a PD-1 inhibitor. Both patients exhibited significant tumor regression, enabling surgical conversion and achieving pathological complete or major response, without significant adverse events. These cases suggest that targeted-immunotherapy combinations may present a promising treatment option for tumor downstaging and surgical conversion in unresectable stage III NSCLC with BRAF V600E mutation. However, prospective studies with larger cohorts and longer follow-up are warranted to validate this strategy.
Anomalous systemic arterial supply to the left basal segment of the lung is a rare congenital pulmonary vascular malformation, historically classified as a variant of intra-lobar pulmonary sequestration. The standard surgical approach has typically involved ligation of the anomalous artery in combination with lobectomy or segmentectomy. We present three cases of anomalous systemic arterial supply to the left basal segment of the lung, all successfully treated with thoracoscopic anomalous arterial ligation alone. In one case, indocyanine green was used to assess the blood supply, enhancing procedural safety. Thoracoscopic ligation of the anomalous artery alone may be a safe and lung-preserving surgical option for patients with this rare anomaly. The use of indocyanine green can further improve the safety of the procedure.
The optimal surgical approach for elderly patients with early-stage non-small cell lung cancer (NSCLC) remains a topic of debate. A retrospective analysis was conducted on patients who underwent pulmonary resection for early-stage NSCLC at our single institution between January 2018 and December 2022. Propensity score matching was used to balance baseline characteristics between the sublobar resection and lobectomy groups. Perioperative outcomes, pulmonary function recovery, postoperative quality of life, and survival were compared between the two groups. A total of 151 patients were included, with 42 undergoing sublobar resection and 109 undergoing lobectomy. After propensity score matching, baseline characteristics were well-balanced between the two groups. Sublobar resection was associated with shorter operative time (125.83 ± 33.56 min vs. 161.14 ± 61.54 min, p = 0.048), less intraoperative blood loss [65 (30, 75) ml vs. 120 (70, 170) ml, p < 0.001], shorter drainage duration [3 (2, 5) days vs. 5 (3, 6) days, p < 0.001], shorter hospital stay [6 (4, 8) days vs. 10 (7, 13) days, p < 0.001], and fewer postoperative complications (11.9
Chylothorax is a serious complication after esophagectomy and there are unmet needs for new intraoperative navigation tools to reduce its incidence. The aim of this study is to explore the feasibility and effectiveness of near-infrared fluorescence imaging (NIR-FI) with indocyanine green (ICG) to identify thoracic ducts (TDs) and chyle leakage during video-assisted thoracoscopic esophagectomy. We recruited 41 patients who underwent thoraco-laparoscopic minimally invasive esophagectomy (MIE) for esophageal cancer in this prospective, open-label, single-arm clinical trial. ICG was injected into the right inguinal region before operations, after which TD anatomy and potential chyle leakage were checked under the near-infrared fluorescence intraoperatively. In 38 of 41 patients (92.7%) using NIR-FI, TDs were visible in high contrast. The mean signal-to-background ratio (SBR) value of all fluorescent TDs was 3.05 ± 1.56. Fluorescence imaging of TDs could be detected 0.5 hours after ICG injection and last up to 3 hours with an acceptable SBR value. The optimal observation time window is from about 1 to 2 hours after ICG injection. Under the guidance of real-time NIR-FI, three patients were found to have chylous leakage and the selective TD ligations were performed intraoperatively. No patient had postoperative chylothorax. NIR-FI with ICG can provide highly sensitive and real-time assessment of TDs as well as determine the source of chyle leakage, which might help reduce TD injury and direct selective TD ligation. It could be a promising navigation tool to reduce the incidence of chylothorax after minimally invasive esophagectomy.
Abstract Chylothorax is a serious complication after esophagectomy and an important reason for reoperation and prolonged hospital stay. A clear localization of thoracic ducts (TDs) and the potential leakage site is an ideal strategy to prevent postoperative chylothorax. In order to explore the feasibility and safety of near-infrared fluorescence imaging (NIR-FI) with indocyanine green (ICG) to identify TDs and potential chyle leakage during video-assisted thoracoscopic esophagectomy, a prospective clinical trial was conducted. We recruited 41 patients who underwent thoraco-laparoscopic minimally invasive esophagectomy for esophageal cancer in this prospective, single-arm clinical study between December 2020 and December 2021. The primary endpoint was the performance of NIR-FI in identifying TDs and chyle leakage. The ICG was injected subcutaneously into the right inguinal region 30 minutes before the thoracic operation, and it becomes fluorescent when excited by the light with a special wavelength in the NIR system. According to the intraoperative demands, surgeons can observe the position of the TDs under the real-time guidance of NIR-FI. In 38 of 41 patients (92.7%) using NIR-FI, TDs were clearly visible in high contrast. The mean signal-to-background ratio (SBR) of all fluorescent TDs was 3.05 ± 1.56. Fluorescence imaging of TDs could be detected 0.5 hours after ICG injection and last up to 3 hours with an acceptable SBR value. The optimal observation time window is from about 1 to 2 hours after ICG injection. Under the guidance of real-time NIR-FI, three patients were found to have chylous leakage and the selective TD ligation were performed intraoperatively. No patient had postoperative chylothorax. NIR-FI with ICG can provide highly sensitive and real-time assessment of TDs, as well as determine the source of chyle leakage, to prevent TD injury and direct selective TD ligation. It’s an effective navigation tool to minimize the incidence of chylothorax after minimally invasive esophagectomy.
School of Earth and Atmospheric Sciences, Georgia Institute of Technology, Atlanta, Georgia, USA 8 National Center for Atmospheric Research, Boulder, Colorado, USA 9 University of Maryland Baltimore County JCET, Baltimore, Maryland, USA 10 Royal Netherlands Meteorological Institute, De Bilt, the Netherlands 11 Wageningen University, Meteorology and Air Quality Group, Wageningen, the Netherlands 12 NASA Goddard Space Flight Center, Greenbelt, Maryland, USA 13 Universities Space Research Association, Columbia, Maryland, USA 14 National Exposure Research Laboratory, Office of Research and Development, U.S. Environmental Protection 15
IMPORTANCE Exhaled breath is an attractive option for cancer detection. A sensitive and reliable breath test has the potential to greatly facilitate diagnoses and therapeutic monitoring of lung cancer. OBJECTIVE To investigate whether the breath test is able to detect lung cancer using the highly sensitive high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS). DESIGN, SETTING, AND PARTICIPANTS This diagnostic study was conducted with a prospective-specimen collection, retrospective-blinded evaluation design. Exhaled breath samples were collected before surgery and detected by HPPI-TOFMS. The detection model was constructed by support vector machine (SVM) algorithm. Patients with pathologically confirmed lung cancer were recruited from Peking University People's Hospital, and healthy adults without pulmonary noncalcified nodules were recruited from Aerospace 731 Hospital. Data analysis was performed from August to October 2020. EXPOSURES Breath testing and SVM algorithm. MAIN OUTCOMES AND MEASURES The detection performance of the breath test was measured by sensitivity, specificity, accuracy, and area under the receiver-operating characteristic curve (AUC). RESULTS Exhaled breath samples were from 139 patients with lung cancer and 289 healthy adults, and all breath samples were collected and tested. Of all participants, 228 (53.27%) were women and the mean (SD) age was 57.0 (11.4) years. After clinical outcomes were ascertained, all participants were randomly assigned into the discovery data set (381 participants) and the blinded validation data set (47 participants). The discovery data set was further broken into a training set (286 participants) and a test set (95 participants) to construct and test the detection model. The detection model reached a mean (SD) of 92.97%(4.64%) for sensitivity, 96.68%(2.21%) for specificity, and 95.51% (1.93%) for accuracy in the test set after 500 iterations. In the blinded validation data set (47 participants), the model revealed a sensitivity of 100%, a specificity of 92.86%, an accuracy of 95.74%, and an AUC of 0.9586. CONCLUSIONS AND RELEVANCE This diagnostic study's results suggest that a breath test with HPPI-TOFMS is feasible and accurate for lung cancer detection, which may be useful for future lung cancer screenings.
Background: To explore the different metastatic patterns between esophageal squamous-cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Methods: For this propensity-matched analysis, we used data from the latest iteration of the Surveillance, Epidemiology, and End Results (SEER) database and included patients diagnosed with esophageal cancer from 2010 to 2017. Results: A total of 20,189 patients were identified, including 6,610 ESCC and 13,579 EAC. After propensity score matching, 4597 pairs were selected. Compared with ESCC, EAC had a higher rate of liver metastasis (P < 0.001) and brain metastasis (P < 0.001), and a lower rate of lung metastasis (P < 0.001), with no significant difference in bone metastasis (P = 0.255). The liver preferentially co-metastasized with lung in both cohorts. Brain metastasis was commonly observed in combination with other organ metastases in EAC. Conclusions: There are major differences in metastatic patterns between ESCC and EAC. The patterns identified may reflect the underlying biology of metastatic esophageal cancer and have potential to influence future monitoring strategies depending on clinical settings.
Objective:To investigate the application of low-dose chest CT(LDCT) in the screening of pulmonary subsolid nodules in population and the application value of artificial intelligence.Methods:People who received chest LDCT screening between January 2015 and December 2017 were included. A retrospective study was developed to analyze the enrolled population features , detection of pulmonary subsolid nodules and independent predictors of subsolid nodules , and to evaluate the accuracy of the artificial intelligence reading method.Results:Result of three cross-sectional studies reveals that the detection rates of pulmonary subsolid nodules were 0.42%, 0.69% and 0.92% in three rounds. 726 cases who completed the three rounds of screening were included in the cohort study. The cohort population was predominantly male(83.2%), with a median age of 43 years, and nearly half of the subjects(47.0%) had a history of smoking. GEE revealed that the patient's family history of lung cancer( OR=8.753, 95% CI: 1.877-40.816, P=0.006) was an independent predictor of the detection of subsolid nodules. In the 110 kVp tube voltage group, AUC of AI model was 0.740, and AUC of the manual reading method was 0.721, no significant differences were observed( P=0.502); when the preseted cutoff value of AI model was 0.75, the NRI was -0.15, indicating the accuracy of AI model was inferior to manual method( P=0.006). In the 130 kVp tube voltage group, AUC of the model was 0.888, and AUC of the manual reading method was 0.756, no significant differences were observed( P=0.128); and the NRI was 0.19, indicating the accuracy of AI model was not inferior to manual method( P=0.123). Conclusion:This population' s detection rates of pulmonary subsolid nodules were 0.42%-0.92%. Family history of lung cancer was an independent predictor of subsolid pulmonary nodules. The result of AI pulmonary nodule detection model could be a reference when the training set data parameters match the actual application parameters.
Thymoma is a potential malignant disease with a recurrence rate of 10% to 30% after complete resection. There is no agreement on the treatment strategy and standard for recurrent thymoma. The treatment methods include reoperation, chemotherapy, radiotherapy, targeted therapy and immunotherapy. In this article, we review the previous literature and summarize the indications, efficacy and prognosis of different treatments for recurrent thymoma, so as to provide some reference for treatment criteria for recurrent thymoma.
OBJECTIVESVideo-assisted thoracoscopic thymectomy is becoming the preferable approach for early-stage thymoma. However, large thymomas are still recognized as a relative contraindication due to the possible risk of incomplete resection or capsular disruption. Thus, the aim of this study is to evaluate the feasibility of video-assisted thoracoscopic thymectomy for large thymomas.METHODSPatients diagnosed with Masaoka stage I-IV thymoma between April 2001 and December 2018 were retrospectively reviewed. All patients were divided into 2 groups: thymoma <5.0 cm (group A) and thymoma ≥5.0 cm (group B). Propensity score matching analysis was performed to compare postoperative results. Recurrence-free survival and overall survival were compared for oncological evaluation.RESULTSA total of 346 patients were included in this study. In the propensity score matching analysis, 126 patients were included both in group A and group B. There was no significant difference between these 2 groups in terms of the R0 resection rate (95.2% vs 94.4%, P = 1.000), conversion rate (1.6% vs 3.2%, P = 0.684), operation time (119.4 ± 48.4 vs 139.1 ± 46.6 min, P = 0.955), blood loss (93.2 ± 231.7 vs 100.5 ± 149.3 ml, P = 0.649), duration of chest drainage (2.7 ± 1.6 vs 2.8 ± 2.0 days, P = 0.184), length of hospitalization (5.0 ± 3.9 vs 5.2 ± 2.9 days, P = 0.628) or postoperative complications (5.9% vs 8.5%, P = 0.068). There was no significant difference between these 2 groups in terms of the overall survival (P = 0.271) and recurrence-free survival (P = 0.288).CONCLUSIONSVideo-assisted thoracoscopic thymectomy is a safe and effective approach for large thymomas (≥5 cm) with comparable surgical and oncological results.
Objective To determine the long-term impacts of major pulmonary complications ( MPCs) and identify the in-dependent risk factors in those non-small cell lung cancer(NSCLC)patients who underwent VATS lobectomy.Methods A ret-rospective study was developed to analyze the pulmonary complications of 574 non-small cell lung cancer patients who under-went VATS lobectomy in Peking University Hospital , the complications were graded according to TMM classification criteria . The effects of PCs on the long-term prognosis were analyzed by using the Kaplan-Meier method.Multivariate logistic regression analysis was used to determine the risk factors of MPCs.Results Of 574 patients, 106 had PCs, including 50(8.7%) MPCs, Postoperative pulmonary complications were associated with significantly longer drainage time (P<0.001) and hospital stays(P<0.001).Perioperative mortality was significantly increased in patients with PCs (4.0% vs 0.6%; P =0.021). Those who develop a MPC had a reduced 3-year DFS and 5-year DFS(61.3% vs.77.4%、42.2% vs.69.3%;P=0.003), as well as the reduced 3-year OS and 5-year OS(78.5%vs.88.2%、62.4% vs.79.2%;P=0.047).MPCs were independ-ent prognostic factors of patients with lung cancer .Multivariate logistic regression analysis showed that the independent risk fac-tors for MPCs were age, male, ASA grade.Conclusion Major pulmonary complications after VATS lobectomy are associated with a poorer long-time outcome.The independent risk factors for MPCs are age, male, and ASA grade.
Background Thoracoscopic R4 sympathectomy has been recommended as a safe and effective surgical treatment procedure for primary palmar hyperhidrosis (PPH). However, approximately half of patients presented postoperative moist hands (PMH), and recurrence occurred individually. Therefore, more thorough long-term results should be evaluated. Methods Between January 2005 and December 2014, 506 consecutive patients with palmar hyperhidrosis treated with either R4 or R4+5 were retrospectively reviewed and followed-up. Results A total of 451 patients (89.1%) completed the follow-up with an average follow-up time of 30.7±25.4 months. Palmar sweating completely ceased in 178 patients (39.5%), whereas 215 (47.7%) achieved greater than 50% improvement, 43 (9.5%) achieved 20-50% improvement. Fifteen individuals (3.3%) experienced recurrence. The frequency of individuals achieving 100% improvement was significantly higher in the group R4+5 than in the group R4 (60.9% vs. 27.8%, respectively; P<0.001). A total of 321 patients (71.2%) showed compensatory hyperhidrosis with 290 (64.3%) and 29 (6.4%) experiencing mild or moderate types respectively. Two individuals (0.4%) suffered from severe type. The incidence of compensatory hyperhidrosis in the group R4+5 was significantly lower than the group R4 (63.8% vs. 73.7%, respectively; P=0.037). Regarding satisfaction, 345 (76.5%) and 83 (18.4%) patients were highly satisfied and partially satisfied with their surgical results, respectively. Six patients (1.3%) were dissatisfied, and 17 (3.8%) expressed regret for surgery. Conclusions PMH occurred in over half of patients after R4 or R4+5 sympathectomy, but most of these patients were satisfied with the surgical results. R4+5 appears to be a better option for palmar hyperhidrosis with lower incidence of PMH and compensatory hyperhidrosis.
BACKGROUND:The use of video-assisted thoracic surgery (VATS) in the treatment of thymoma is becoming more and more common. The aim of this study was to evaluate safety and effectiveness of thoracoscopic treatment of thymoma and, more importantly, to report long-term follow-up results of a large single-center cohort.METHODS:A retrospective review of a prospective database was performed. In total, 150 patients who underwent VATS resection for thymoma at Peking University People's Hospital from April 2001 to November 2014 were retrospectively reviewed.RESULTS:Average operation time was 140.1±54.2 min, median blood loss was 50 mL (range, 10-700 mL), median post-operative drainage time was 3 days (range, 1-11 days), and median length of post-op stay was 5 days (range, 2-20 days); 134 patients (89.3%) were followed up successfully. Median follow-up was 59.5 months (range, 2-187 months). Five- and 10-year recurrence free survival (RFS) rates of entire group were 96.5% and 94.4%, respectively; 5- and 10-year RFS rates for Masaoka stages I + II were 98.1% and 98.1%, respectively; 5- and 6-year RFS rates for Masaoka stage III were 90% and 60%, respectively. One case of recurrence in five Masaoka stage IV patients was observed, and 4-year RFS was 80%. Multivariable analysis indicated that recurrence tended to occur in Masaoka stages III + IV patients (P=0.037, HR =12.69, 95% CI: 1.17-138.22) and older patients had a lower risk of recurrence (P=0.029, HR =0.87, 95% CI: 0.77-0.99). Myasthenia gravis (MG) presented in 44 patients (29.3%), of which 36 patients (81.8%) were followed up. Nine patients achieved complete remission, and 19 patients had symptom improvement after surgery. Overall response rate of MG was 77.8% (28/36).CONCLUSIONS:VATS was a safe and effective procedure for treatment of thymomas with satisfactory prognosis. MG with thymoma treated by VATS had comparable neurological outcome to that associated with the trans-sternal approach.