Prognostic Factors for Recovery from Left Recurrent Laryngeal Nerve Palsy After Minimally Invasive McKeown Esophagectomy: A Retrospective Study.

BACKGROUND: Recurrent laryngeal nerve (RLN) palsy is a serious complication of esophagectomy that affects the patient's phonation and the ability to prevent life-threatening aspiration events. The aim of this single-center, retrospective study was to investigate the clinical course of left RLN palsy and to identify the main prognostic factors for recovery. METHODS: The study cohort consisted of 85 patients who had developed left RLN palsy after minimally invasive McKeown esophagectomy. Vocal cord function was assessed in all participants through laryngoscopic examinations, both in the immediate postoperative period and during follow-up. Permanent palsy was defined as no evidence of recovery after 6 months. Univariate and multivariable logistic regression analyses were applied to evaluate the associations between different variables and the outcome of palsy. RESULTS: Twenty-two (25.8%) patients successfully recovered from left RLN palsy. On multivariable logistic regression analysis, active smoking (odds ratio [OR] 0.335, p = 0.038) and the use of thoracoscopic surgery (vs. robotic surgery; OR 0.264, p = 0.028) were identified as independent unfavorable predictors for recovery from palsy. The estimated rates of recovery derived from a logistic regression model for patients harboring two, one, or no risk factors were 13.16%, 31.15-34.75%, and 61.39%, respectively. CONCLUSION: Only one-quarter of patients who had developed left RLN palsy after minimally invasive McKeown esophagectomy were able to fully recover. Smoking habits and the surgical approach were identified as key determinants of recovery. Patients harboring adverse prognostic factors are potential candidates for early intervention strategies.

Survival Outcomes of Patients with Esophageal Cancer and Post-chemoradiotherapy Surgical T4b Disease: Is Palliative Resection Justified?

BACKGROUND: In patients with locally advanced esophageal cancer who had undergone chemoradiotherapy (CRT), the limitations of radiological evaluation may necessitate surgical exploration to ascertain disease resectability. Upon intraoperative confirmation of T4b disease (sT4b), the optimal management strategy remains unclear. While some surgeons may opt against resection, others advocate for palliative esophagectomy (PE). Regrettably, the current literature does not provide a consensus on the most effective approach for managing these intricate cases. METHODS: The study cohort consisted of 68 patients with esophageal squamous cell carcinoma (ESCC) who presented with sT4b disease following CRT. The perioperative outcomes and overall survival (OS) were compared between patients who underwent PE (n = 56) and those who received an open-close (OC) procedure (n = 12). RESULTS: Patients who underwent an OC procedure experienced a shorter hospital stay (16.5 vs. 28.8 days; p = 0.052) and showed a non-significant reduction in the rate of major complications (33.9% vs. 25%; p = 0.549) and in-hospital mortality (0% vs. 5.4%; p = 0.412) than those who received PE; however, PE was associated with a superior 2-year OS rate than OC (9.6% vs. 0%; p = 0.009). In multivariable analysis, a pretreatment clinical stage of II/III (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.31-0.87; p = 0.013) and PE with retrosternal reconstruction (HR 0.38, 95% CI 0.15-0.49; p = 0.010) were independently associated with a more favorable OS. CONCLUSION: PE with retrosternal reconstruction may be a feasible approach for patients with ESCC exhibiting sT4b disease after CRT.

Temporal Trends in Survival Outcomes for Patients with Esophageal Cancer Following Neoadjuvant Chemoradiotherapy: A 14-Year Analysis.

BACKGROUND: The prognosis for patients with esophageal cancer who received neoadjuvant chemoradiotherapy (nCRT) followed by surgery has shown improvement in recent years. We sought to identify the critical factors contributing to enhanced survival outcomes. PATIENTS AND METHODS: We retrospectively examined 427 patients with esophageal cancer treated with nCRT and esophagectomy across two periods: P1 (from 1 January 2004 to 31 December 2011) and P2 (from 1 January 2012 to 31 December 2017). The introduction of the CROSS regimen and total meso-esophagectomy in P2 prompted an evaluation of their effects on perioperative outcomes and overall survival (OS). RESULTS: During P2, the occurrence of recurrent laryngeal nerve palsy increased significantly from 3.9 to 16.8% (p < 0.001), while pneumonia and in-hospital mortality rates remained unchanged. The median OS improved from 19.2 to 29.2 months (p < 0.001) between P1 and P2. Multivariable analysis identified higher nodal yields and the achievement of major response as favorable prognostic factors. Conversely, an involved circumferential resection margin (CRM), an advanced ypN stage, and pneumonia were independently associated with poor outcomes. Patients treated during P2 had a lower prevalence of involved CRM (10% vs. 25.1%, p < 0.001), a higher rate of major response (52.7% vs. 34.8%, p < 0.01), and a greater nodal yield (27.8 vs. 10.9, p < 0.001). CONCLUSIONS: The clinical outcomes following nCRT and surgery have improved significantly over time. This progress can be attributed to multiple factors, with the primary drivers being the refinement of nCRT protocols and the application of radical surgery.

Impact of prior thoracoscopic experience on the learning curve of robotic McKeown esophagectomy: a multidimensional analysis.

PURPOSE: Left upper mediastinal lymph node dissection (UMLND)-a technically demanding step of McKeown esophagectomy-is frequently complicated by recurrent laryngeal nerve (RLN) palsy. Under the hypothesis that robotic esophagectomy (RE) could increase the safety and feasibility of UMLND, we retrospectively investigated the degree to which a pre-existing experience in video-assisted thoracoscopic esophagectomy (VATE) may affect the learning curves of this critical part of RE. METHODS: Surgeon A had previously performed > 150 VATE procedures before transitioning to RE. While surgeon B had previously assisted to 50 RE, his pre-existing VATE experience consisted of less than five procedures. A total of 103 and 76 McKeown RE procedures were performed by surgeons A and B, respectively. The learning curve of left UMLND for each surgeon was examined using the cumulative sum method. RESULTS: The inflection point of RLN palsy for surgeon A occurred at patient 31. While the nerve palsy rate decreased from 32.3 to 4.2% (p < 0.001), the number of nodes harvested during left UMLND did not appreciably change. Surgeon B showed a bimodal learning curve for RLN palsy with primary and secondary inflection points at patients 15 and 49, respectively. The RLN palsy rate initially decreased from 66.7% (patients 1-15) to 14.7% (patients 16-49), followed by an additional decline to 3.7% (patients 50-76). However, the number of nodes harvested during left UMLND showed a downtrend which was paralleled by decreasing rates of RLN palsy. These results indicate that surgeon B has not yet reached an ideal balance between an extensive UMLND and nerve protection. CONCLUSION: The pre-existing VATE experience seems to affect the learning curves of left UMLND during RE.

Safety and oncological efficacy of bilateral recurrent laryngeal nerve lymph-node dissection after neoadjuvant chemoradiotherapy in esophageal squamous cell carcinoma: a propensity-matched analysis.

BACKGROUND: We sought to evaluate the safety and oncological efficacy of bilateral recurrent laryngeal nerve (RLN) lymph-node dissection (LND) in patients with esophageal squamous cell carcinoma (ESCC) who had undergone neoadjuvant chemoradiotherapy (nCRT). METHODS: We retrospectively examined the records of ESCC patients who were judged to be ycN-RLN(-) following nCRT. Patients were divided into two groups according to the extent of LND [standard two-field LND (STL group) versus total two-field LND (TTL group)]. Only lower mediastinal and upper abdominal lymph nodes were removed in the STL group. In addition to the standard procedure, patients in the TTL group underwent resection of upper mediastinal lymph nodes located along the bilateral RLN. Using propensity score matching, 29 pairs were identified and compared with regard to perioperative complications, lymph-node metastases rates, overall survival (OS), and disease-specific survival (DSS). RESULTS: No significant intergroup differences were identified in terms of in-hospital mortality and morbidity. Metastases to the RLN lymph nodes were identified in 20.7% (6/29) of TTL patients, being the only site of lymph-node metastases in three of them. TTL was associated with lower upper mediastinal lymph-node recurrence rate (6.5%) compared with STL (21.5%, p = 0.134), although the overall recurrence rate was similar (STL, 44.8% versus TTL, 46.4%). No significant intergroup differences were also evident with regard to 3-year DSS and OS rates. CONCLUSIONS: RLN LND can be safely performed in ESCC patients who had undergone nCRT, ultimately resulting in an improved local control, and should be practiced as part of the surgical routine.

Unexpected Microscopically Positive Proximal Resection Margins in Esophageal Squamous Cell Carcinoma After Chemoradiotherapy: Predictors and Prognostic Significance.

BACKGROUND: Esophageal cancer has the propensity to spread in a longitudinal manner (either proximally or distally), potentially resulting in the unexpected presence of microscopic disease at grossly tumor-free margins. The clinical significance of this phenomenon in patients treated with chemoradiotherapy (CRT) remains unclear. The purpose of this study was to investigate the prevalence, predictors, and prognostic impact of microscopically positive proximal resection margins (PPRMs) in patients with esophageal squamous cell carcinoma (ESCC) who received CRT. METHODS: Between 2000 and 2014, we identified 332 ESCC patients who underwent complete gross resection (R0/R1) following CRT. Patients were divided into two groups according to the status of the proximal resection margins on microscopic examination [negative proximal resection margins (NPRMs) vs PPRMs]. The occurrence of anastomotic leakage (AL) and anastomotic recurrence (AR) served as outcome measures. RESULTS: Sixteen (4.8 %) patients had PPRM. The presence of PPRM was not associated with AL but was a strong predictor of AR (PPRM vs NPRM, 23.1 vs 7 %, respectively, P = 0.033). Multivariate analysis identified a resection margin length <3.5 cm [odds ratio (OR) 4.473, P = 0.022] and salvage resection (OR 3.171, P = 0.045) as independent predictors of PPRM. The estimated PPRM rates were 16.7, 6.3, and 1.3 % for patients with 2, 1, and 0 predictors, respectively. CONCLUSIONS: PPRM occurred in 4.8 % of ESCC patients following CRT and was associated with AR. An intraoperative frozen section margin analysis should be performed in patients carrying risk factors to avoid unexpected PPRM.

Association between the thoroughness of the histopathological examination and survival in patients with esophageal squamous cell carcinoma who achieve pathological complete response after chemoradiotherapy.

The College of American Pathologists guidelines recommend examining at least four representative tumor blocks for determining pathological T stage in patients with primarily resected esophageal cancer. Whether the same pathological requirements are adequate in patients undergoing esophagectomy following neoadjuvant chemoradiotherapy (nCRT) remains unclear. We hypothesized that current examination protocols may underestimate the presence of microscopical residual disease after nCRT, potentially leading to under-staging. We retrospectively reviewed the records of patients with esophageal squamous cancer (ESCC) who were diagnosed as having pathological complete response (pCR) following nCRT. The thoroughness of the pathological examination in pCR patients was examined using (i) the number of blocks examined in suspicious tumor area (≤4 vs. >4), and (ii) the block quotient (calculated as the pretreatment tumor length divided by the number of blocks examined in suspicious tumor area). A total of 91 patients were enrolled. The mean number of blocks used to confirm pCR was 4.8 (range: 2-14). The 5-year overall survival (OS) and disease-free survival (DFS) in the entire cohort were 55% and 65%, respectively. Multivariate analyses identified the block quotient as the only independent predictor of OS and DFS. Receiver operating characteristic curve analysis indicated an optimal cutoff value of 1.4 for the block quotient. Among the patients who achieved pCR, the 5-year DFS differed significantly between subjects with a low (≤1.4) or high (>1.4) block quotient (76% vs. 47%, respectively, P = 0.03). The block quotient (calculated by the pretreatment tumor length divided by the number of blocks) - which reflects the meticulousness of the histopathological examination for confirming pCR - is associated with survival in ESCC patients.

Deep learning based decision tree ensembles for incomplete medical datasets.

BACKGROUND: In practice, the collected datasets for data analysis are usually incomplete as some data contain missing attribute values. Many related works focus on constructing specific models to produce estimations to replace the missing values, to make the original incomplete datasets become complete. Another type of solution is to directly handle the incomplete datasets without missing value imputation, with decision trees being the major technique for this purpose. OBJECTIVE: To introduce a novel approach, namely Deep Learning-based Decision Tree Ensembles (DLDTE), which borrows the bounding box and sliding window strategies used in deep learning techniques to divide an incomplete dataset into a number of subsets and learning from each subset by a decision tree, resulting in decision tree ensembles. METHOD: Two medical domain problem datasets contain several hundred feature dimensions with the missing rates of 10% to 50% are used for performance comparison. RESULTS: The proposed DLDTE provides the highest rate of classification accuracy when compared with the baseline decision tree method, as well as two missing value imputation methods (mean and k-nearest neighbor), and the case deletion method. CONCLUSION: The results demonstrate the effectiveness of DLDTE for handling incomplete medical datasets with different missing rates.

Trainability for cardiopulmonary fitness is low in patients with peripheral artery disease.

AIMS: In patients with peripheral arterial disease (PAD), exercise therapy is recommended to relieve leg symptoms, as noted in the 2016 AHA/ACC and 2017 ESC/ESVS guidelines. We assessed the trainability for cardiopulmonary fitness (CPF) and quality of life (QOL); three distinct patient types, namely, PAD, heart failure (HF), and stroke, were compared. METHODS AND RESULTS: This is a multicentre, retrospective analysis of prospectively collected data from three clinical studies. Data collected from 123 patients who completed 36 sessions of supervised aerobic training of moderate intensity were analysed, with 28 PAD, 55 HF, and 40 stroke patients totalling 123. Before and after training, cardiopulmonary exercise testing with non-invasive cardiac output monitoring and QOL evaluation using a 36-Item Short Form Survey (SF-36) were performed. Non-response was defined as a negative change in the post-training value compared with that in the pre-training value. The result showed an improvement in CPF in all three groups. However, cardiorespiratory fitness (CRF) increased by a lesser extent in the PAD group than in the HF and stroke groups; the physical and mental component scores (MCS) of SF-36 exhibited a similar pattern. Non-response rates of peak V˙O2, oxygen uptake efficiency slope, and MCS were higher in the PAD group. In the PAD group, non-responders regarding peak V˙O2 had a higher pulse wave velocity than responders. CONCLUSION: In patients with PAD following exercise therapy, CRF and QOL improved to a lesser extent on average; their non-response rate was also higher compared with that of HF or stroke patients. Therefore, a higher dose of exercise might be needed to elicit adaptation in PAD patients, especially those with high pulse wave velocity.

Incidence and Predictors of Textbook Outcome after Minimally Invasive Esophagectomy for Cancer: A Two-Center Study.

PURPOSE: The textbook outcome (TBO), a multidimensional indicator that reflects an optimal perioperative course, has emerged as a significant prognostic variable in surgical oncology. Our study aimed to assess the occurrence and determinants of TBO following minimally invasive esophagectomy (MIE) for cancer. METHODS: A total of 945 patients who had undergone MIE at two high-volume centers between 2008 and 2022 were analyzed. Multivariable logistic regression analysis was applied to identify the independent predictors of TBO. The potential selection bias associated with choosing between different MIE techniques-namely, robotic esophagectomy (RE) and video-assisted thoracoscopic esophagectomy (VATE)-was addressed by applying inverse probability of treatment weighting (IPTW). RESULTS: TBO was realized in 46.6% of cases (n = 440), correlating with markedly better overall and disease-free survival. Multivariable analysis showed that treatment with RE (odds ratio (OR) = 1.527; 95% confidence interval (CI) = 1.149-2.028) was associated with a higher likelihood of achieving TBO, whereas a Charlson Comorbidity Index (CCI) of 2 or higher showed an opposite association (CCI2: OR = 0.687, 95% CI = 0.483-0.977; CCI ≥ 3: OR = 0.604, 95% CI = 0.399-0.915). The advantage of RE in attaining a higher rate of TBO, compared to VATE, remained statistically significant after applying IPTW, with rates of 53.3% for RE and 42.2% for VATE. Notably, RE contributed to a greater probability of thorough lymph node dissection, resection with negative margins, and the avoidance of major complications. CONCLUSION: TBO was realized in 46.6% of the patients who underwent MIE for cancer. Patients with a lower CCI and those who received RE were more likely to achieve TBO.

Esophageal stenting with minimally-invasive surgical intervention for delayed spontaneous esophageal perforation.

Background: Spontaneous esophageal perforation is a challenging surgical emergency with significant morbidity and mortality, and timely primary repair carries good outcomes. However, direct repair for a delayed spontaneous esophageal perforation is not always feasible and is associated with high mortality. Esophageal stenting can provide therapeutic benefits in the management of esophageal perforations. In this study, we review our experience with placing esophageal stents in combination with minimally-invasive surgical drainage to treat delayed spontaneous esophageal perforations. Methods: We retrospectively analyzed patients with delayed spontaneous esophageal perforations between September 2018 and March 2021. All patients were treated using a hybrid approach, including esophageal stenting across the gastroesophageal junction (GEJ) to reduce continued contamination, gastric decompression with extraluminal sutures to prevent stent migration, early enteral nutrition, and aggressive minimally-invasive thoracoscopic debridement and drainage of infected material. Results: There were 5 patients with delayed spontaneous esophageal perforation treated with this hybrid approach. The mean duration between symptoms and diagnosis was 5 days, and the interval between symptoms and esophageal stent insertion was 7 days. The median time to oral nutrition and to esophageal stent removal was 43 and 66 days. There was no stent migration or hospital mortality. Three patients (60%) had postoperative complications. All patients were successfully resumed on oral nutrition with esophageal preservation. Conclusions: A hybrid approach combining endoscopic esophageal stent placement with extraluminal sutures to prevent stent migration, thoracoscopic decortication with chest tube drainage, gastric decompression, and jejunostomy tube placement for early nutrition was feasible and effective in the treatment of delayed spontaneous esophageal perforations. This technique offers a less invasive treatment approach for a challenging clinical problem which has traditionally carried a high rate of morbidity and mortality.

Prediction for blood lactate during exercise using an artificial intelligence-Enabled electrocardiogram: a feasibility study.

Introduction: The acquisition of blood lactate concentration (BLC) during exercise is beneficial for endurance training, yet a convenient method to measure it remains unavailable. BLC and electrocardiogram (ECG) both exhibit variations with changes in exercise intensity and duration. In this study, we hypothesized that BLC during exercise can be predicted using ECG data. Methods: Thirty-one healthy participants underwent four cardiopulmonary exercise tests, including one incremental test and three constant work rate (CWR) tests at low, moderate, and high intensity. Venous blood samples were obtained immediately after each CWR test to measure BLC. A mathematical model was constructed using 31 trios of CWR tests, which utilized a residual network combined with long short-term memory to analyze every beat of lead II ECG waveform as 2D images. An artificial neural network was used to analyze variables such as the RR interval, age, sex, and body mass index. Results: The standard deviation of the fitting error was 0.12 mmol/L for low and moderate intensities, and 0.19 mmol/L for high intensity. Weighting analysis demonstrated that ECG data, including every beat of ECG waveform and RR interval, contribute predominantly. Conclusion: By employing 2D convolution and artificial neural network-based methods, BLC during exercise can be accurately estimated non-invasively using ECG data, which has potential applications in exercise training.

Baseline and interim [18F]FDG-PET/MRI to assess treatment response and survival in patients with M0 esophageal squamous cell carcinoma treated by curative-intent therapy.

BACKGROUND: To investigate the value of [18F]FDG-PET/MRI in predicting treatment response and survival in patients with primary M0 esophageal squamous cell carcinoma. METHODS: Patients with esophageal squamous cell carcinoma received [18F]FDG-PET/MRI at baseline and during neoadjuvant or definitive chemoradiotherapy. The treatment response was classified according to the Response Evaluation Criteria for Solid Tumors 1.1. We used Kaplan-Meier and Cox regression analyses to assess the association between PET/MRI parameters and overall survival (OS) or progression-free survival (PFS). RESULTS: We included 40 M0 patients in the final analysis. The volume transfer constant (Ktrans) from baseline PET/MRI (area under the curve (AUC) = 0.688, P = 0.034) and total lesion glycolysis (TLG) from baseline PET/MRI (AUC = 0.723, P = 0.006) or interim PET/MRI (AUC = 0.853, P < 0.001) showed acceptable AUC for predicting treatment response. The TLG from interim PET/MRI (interim TLG, P < 0.001) and extracellular volume fraction (Ve) on interim PET/MRI (interim Ve, P = 0.001) were identified as independent prognostic factors for OS. Baseline Ve (P = 0.044) and interim TLG (P = 0.004) were significant predictors of PFS. The c-indices of the prognostic models combining interim TLG with Ve for predicting OS, and baseline Ve and interim TLG for predicting PFS were 0.784 and 0.699, respectively. These values were significantly higher than the corresponding c-indices of the TNM staging system (P = 0.002 and P = 0.047, respectively). CONCLUSIONS: Combining the baseline and interim [18F]FDG-PET/MRI qualitative imaging parameters aids in predicting the prognosis of patients with M0 esophageal squamous cell carcinoma. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov (identifier: NCT05855291 and NCT05855278).

The impact of surgical learning curve on short-term outcomes after bilateral lung transplantation: results from a multidisciplinary surgical team.

OBJECTIVES: The aim of this study was to examine the impact of surgical learning curve on short-term clinical outcomes of patients after bilateral lung transplantation (LTx) performed by a surgical multidisciplinary team (MDT). METHODS: Forty-two patients underwent double LTx from December 2016 to October 2021. All procedures were performed by a surgical MDT in a newly established LTx program. The time required for bronchial, left atrial cuff and pulmonary artery anastomoses was the main end point to assess surgical proficiency. The associations between the surgeon's experience and procedural duration were examined by linear regression analysis. We employed the simple moving average technique to generate learning curves and evaluated short-term outcomes before and after achieving surgical proficiency. RESULTS: Both total operating time and total anastomosis time were inversely associated with the surgeon's experience. On analysing the learning curve for bronchial, left atrial cuff and pulmonary artery anastomoses using moving averages, the inflection points occurred at 20, 15 and 10 cases, respectively. To assess the learning curve effect, the study cohort was divided into early (cases 1-20) and late (cases 21-42) groups. Short-term outcomes-including intensive care unit stay, in-hospital stay and severe complications-were significantly more favourable in the late group. Furthermore, there was a notable tendency for patients in the late group to experience a decreased duration of mechanical ventilation along with reduced instances of grade 3 primary graft dysfunction. CONCLUSIONS: A surgical MDT can perform double LTx safely after 20 procedures.

Tracheostomy and venovenous extracorporeal membrane oxygenation for difficult airway patient with carinal melanoma: A case report and literature review.

BACKGROUND: Anesthesia for tracheal tumor resection is challenging, particularly in patients with a difficult upper airway. We report a case of a difficult upper airway with a metastatic tracheal tumor causing near-total left bronchial obstruction and requiring emergency tracheostomy and venovenous extracorporeal membrane oxygenation (VV-ECMO) support for rigid bronchoscopy-assisted tumor resection. CASE SUMMARY: A 41-year-old man with a history of right retromolar melanoma treated by tumor excision and myocutaneous flap reconstruction developed progressive dyspnea on exertion and syncope episodes. Chest computed tomography revealed a 3.0-cm tracheal mass at the carinal level, causing 90% tracheal lumen obstruction. Flexible bronchoscopy revealed a pigmented tracheal mass at the carinal level causing critical carinal obstruction. Because of aggravated symptoms, emergency rigid bronchoscopy for tumor resection and tracheal stenting were planned with standby VV-ECMO. Due to limited mouth opening, tracheostomy was necessary for rigid bronchoscopy access. While transferring the patient to the operating table, sudden desaturation occurred and awake fiberoptic nasotracheal intubation was performed for ventilation support. Femoral and internal jugular vein were catheterized to facilitate possible VV-ECMO deployment. During tracheostomy, progressive desaturation developed and VV-ECMO was instituted immediately. After tumor resection and tracheal stenting, VV-ECMO was weaned smoothly, and the patient was sent for intensive postoperative care. Two days later, he was transferred to the ward for palliative immunotherapy and subsequently discharged uneventfully. CONCLUSION: In a difficult airway patient with severe airway obstruction, emergency tracheostomy for rigid bronchoscopy access and standby VV-ECMO can be life-saving, and ECMO can be weaned smoothly after tumor excision. During anesthesia for patients with tracheal tumors causing critical airway obstruction, spontaneous ventilation should be maintained at least initially, and ECMO deployment should be prepared for high-risk patients, such as those with obstructive symptoms, obstructed tracheal lumen > 50%, or distal trachea location.

Factors related to quality of life after video-assisted thoracoscopic surgery in patients with stage I adenocarcinoma lung cancer: A longitudinal study.

PURPOSE: This study aimed to assess the 5-year survival, quality of life for cancer- and lung-specific symptoms, and to identify predictive factors of quality of life during a 12-month period after video-assisted thoracic surgery (VATS) for early-stage lung adenocarcinoma. METHODS: A convenience sample of 53 patients who had undergone VATS for lung cancer was used for this longitudinal, prospective study. All participants provided responses to the cancer-specific quality-of-life European Organization for Research and Treatment of Cancer questionnaire as well as a questionnaire for lung cancer-specific symptoms using structured interviews at baseline (T0) and 3-, 6-, 9-, and 12-months post-surgery (T1, T2, T3, and T4, respectively). Generalized estimating equation models were used to investigate whether quality of life scores improved from baseline measures and to determine characteristics associated with changes in scores for quality-of-life post-surgery. RESULTS: The mean age of participants was 58.5 years (SD = 8.76), and most were female (64.2%). Participants received either a wedge or sublobular lobectomy (47.2%) or a lobectomy (52.8%). The size of the primary tumour for most participants was <2 cm (78.7%). The five-year survival rate was 90%. Lung-specific symptoms of insomnia were worse at T1 compared with baseline. Significant improvements in scores for function and cancer symptoms were seen at T4 compared with scores at T0. Age, marital status, smoking, alcohol consumption, and a history of previous cancer were significantly associated with quality of life. CONCLUSIONS: Surgical resection with VATS resulted in good 5-year survival rates and long-term improvements in quality of life. Our findings suggest VATS for patients with early-stage lung adenocarcinoma should be considered as a means of improving long-term survival and quality of life.

Clinical Utility of Circulating Tumor Cells for Predicting Major Histopathological Response after Neoadjuvant Chemoradiotherapy in Patients with Esophageal Cancer.

BACKGROUND: A "surgery as needed" approach may be offered to patients with esophageal cancer (EC) who achieve major histopathological response (MaHR) after neoadjuvant chemoradiotherapy (nCRT). However, the utility of clinical response assessment (CRE) for predicting histopathological response to nCRT remains limited. Circulating tumor cells (CTCs) hold promise as biomarkers of response to nCRT. METHODS: We analyzed the clinical utility of post-nCRT CTCs, alone or in combination with CRE, in the prediction of MaHR. We defined MaHR as either the lack or a limited presence (≤10%) of vital residual tumor cells in the resected esophageal specimen in the absence of nodal involvement. RESULTS: Of the 48 study patients, 27 (56%) achieved MaHR. Patients with MaHR had a significantly lower CTCs count compared with those without (3.61 ± 4.53 versus 6.83 ± 5.22 per mL of blood, respectively; P = 0.027). Using a cutoff for positivity of 5 CTCs per mL of blood, the combination of CTCs and CRE allowed achieving a negative predictive value for MaHR of 93% (95% confidence interval [CI] = 70-99%) along with a false negative rate of 5% (95% CI = 1-33%). CONCLUSION: CTCs count assessed in combination with CRE can potentially help identify patients with EC who achieved MaHR after nCRT.

Adjuvant Chemoradiotherapy Associated with Improved Overall Survival in Resected Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy in Intensity-Modulated Radiotherapy Era.

BACKGROUND: The prognosis of patients with resected esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy is particularly poor in those who were staged as ypT3/T4 and/or ypN+. This study investigated whether adjuvant chemoradiotherapy was associated with improved clinical outcomes in these patients. METHODS: we identified patients with esophageal squamous cell carcinoma who were staged as ypT3/T4 and/or ypN+ after being treated with neoadjuvant chemoradiotherapy followed by esophagectomy between the years 2013 and 2019. Patients were divided into two groups based on whether they received adjuvant chemoradiotherapy. The Kaplan-Meier method and Cox regression modeling were performed for survival analyses and multivariable analysis, respectively. RESULTS: 76 eligible patients were included in the analyses. The median follow-up for the study cohort was 43.4 months. On Kaplan-Meier analyses of the overall population, adjuvant chemoradiotherapy was associated with significantly improved median overall survival (31.7 months vs. 16.3 months, p = 0.036). On Kaplan-Meier analyses of the 35 matched pairs generated by propensity score matching, adjuvant chemoradiotherapy was associated with significantly longer median overall survival (31.7 months vs. 14.3 months; p = 0.004) and median recurrence-free survival (18.9 months vs. 11.7 months; p = 0.020). In multivariable analysis, adjuvant chemoradiotherapy was independently associated with a 60% reduction in mortality (p = 0.003) and a 48% reduction in risk of recurrence (p = 0.035) after adjusting for putative confounders. In addition, microscopic positive resection margin and Mandard tumor regression grade 3-4 were independently associated with increased mortality and risk of recurrence. While a greater number of lymph nodes dissected was independently associated with significantly improved overall survival, the number of positive lymph nodes was independently associated with significantly worse overall survival and a trend (p = 0.058) towards worse recurrence-free survival. CONCLUSIONS: This study demonstrated that adjuvant CRT was independently associated with a significantly improved survival and lower risk of recurrence than observation in esophageal squamous cell carcinoma patients staged as ypT3 and/or ypN+ after receiving neoadjuvant chemoradiotherapy and radical surgery. The results of this study have implications for the design of future clinical trials and may improve treatment outcomes of patients in this setting who cannot afford or are without access to adjuvant nivolumab.