Completely Resectable (cT1-2) Esophageal Squamous Cell Carcinoma with Minimal Lymph Node Involvement (cN1): Is Neoadjuvant Chemoradiation Therapy the Only Viable Treatment Option?

BACKGROUND: Neoadjuvant chemoradiation therapy (nCRT) is recommended when lymph node metastasis is evident or strongly suspected on preoperative imaging studies, even for a completely resectable (cT1-2) tumor with minimal lymph node involvement (cN1). We evaluated the validity of upfront surgical approach in this patient group. METHODS: We retrospectively reviewed data from 247 patients with cT1-2 esophageal squamous cell carcinoma (ESCC) who underwent upfront radical esophagectomy followed by the pathology-based adjuvant treatment. Oncologic outcomes of cN1 patients were compared with those of cN0 patients. RESULTS: There were 203 cN0 and 44 cN1 patients. The lymph node yield was 62.0 (interquartile range [IQR], 51.0-76.0) in cN0 and 65.5 (IQR, 57.5-85.0) in cN1 patients (p = 0.033). The size of metastatic node was 0.6 cm (IQR, 0.4-0.9 cm) in cN0 and 0.8 cm (IQR, 0.5-1.3 cm) in cN1 patients (p = 0.001). Nodal upstaging was identified in 29.1% of cN0 and 40.9% of cN1 patients, whereas 18.2% of the cN1 had no actual lymph node metastasis (pN0). The 5-year disease-free survival rate was not significantly different between the groups (cN0, 74.4%; cN1, 71.8%; p = 0.529). Survival rates were closely correlated with pN stage, and a multivariate analysis revealed that pN2-3 stage was a risk factor for poor disease-free survival. CONCLUSIONS: Upfront radical surgery provided accurate nodal staging information, potentially sparing some cN1 patients from unnecessary nCRT while demonstrating comparable survival rates. It might be a valid option for the treatment of cT1-2N1 ESCC.

Clinical Benefits of Lobe-Specific Lymph Node Dissection in Surgery for NSCLC: A Systematic Review and Meta-Analysis.

Introduction: The impact of lobe-specific lymph node dissection (LS-LND) in surgery for NSCLC remains controversial compared with that of systematic lymph node dissection (S-LND). This study aimed to compare clinical outcomes between the two strategies, including postoperative complications, and to explain the advantages of LS-LND. Methods: We searched for studies comparing LS-LND and S-LND up to April 14, 2022, using PubMed, EMBASE, and Web of Science. The primary outcomes were overall survival and recurrence-free survival. Secondary outcomes included postoperative complications, such as arrhythmia, chylothorax, and pneumonia. We evaluated the risk of bias and assessed the evidence quality using GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Results: A total of 13 studies, including one randomized controlled trial and 12 retrospective studies with 11,522 patients who underwent curative resections for lung cancer, were included. The results indicated that LS-LND had favorable overall survival (hazard ratio [HR] = 0.80, 95% confidence interval [CI]: 0.73-0.87) but no difference in recurrence-free survival (HR = 0.96, 95% CI: 0.84-1.09) on comparison with S-LND. In terms of postoperative complications, patients undergoing LS-LND had a lower rate of chylothorax (risk ratio [RR] = 0.54, 95% CI: 0.35-0.85) and arrhythmia (RR = 0.74, 95% CI: 0.57-0.97) than patients undergoing S-LND, but the risk of postoperative pneumonia was not different. The overall quality of evidence was low to moderate owing to the risk of bias related to heterogeneous study populations. Conclusions: Patients undergoing LS-LND had a comparable and favorable long-term prognosis and a lower rate of postoperative complications. Nevertheless, further standardized studies are necessary to improve the quality of evidence.

Proposal of a revised International Association for the Study of Lung Cancer grading system in pulmonary non-mucinous adenocarcinoma: The importance of the lepidic proportion.

OBJECTIVES: We aimed to measure the validity of the International Association for the Study of Lung Cancer (IASLC) grading system in Korean patients and propose a modification for an increase of its predictability, especially in grade 2 patients. MATERIALS AND METHODS: From 2012 to 2017, histopathologic characteristics of 1358 patients with invasive pulmonary adenocarcinoma (stage I-III) from two institutions were retrospectively reviewed and re-classified according to the IASLC grading system. Considering the amount of the lepidic proportion, the validity of the revised model (Lepidic-10), derived from the training cohort (hospital A), was measured using the validation cohort (hospital B). Its predictability was compared to that of the IASLC system. RESULTS: Of the 1358 patients, 259 had a recurrence, and 189 died during follow-up. The Harrell's concordance index and area under the curve of the IASLC system were 0.685 and 0.699 for recurrence-free survival (RFS) and 0.669 and 0.679 for death, respectively. From the training cohort, the IASLC grade 2 patients were divided into grades 2a and 2b (Lepidic-10 model) with a 10 % lepidic pattern. This new model further distinguished patients in both institutions that had better performance than the IASLC grading (Hospital A, p < 0.001 for RFS and death; Hospital B, p = 0.0215 for RFS, p = 0.0429 for death). CONCLUSION: The IASLC grading system was easily applicable; its clinical use in predicting the prognosis of Korean patients with pulmonary adenocarcinoma was validated. Furthermore, the introduction of the lepidic proportion as an additional criterion to differentiate grade 2 patients improved its predictability.

Prognosis of resected invasive mucinous adenocarcinoma compared with the IASLC histologic grading system for invasive nonmucinous adenocarcinoma: Surgical database study in the TKIs era in Korea.

BACKGROUND: The prognosis of invasive mucinous adenocarcinoma (IMA) remains controversial and should be clarified by comparison with the International Association for the Study of Lung Cancer (IASLC) histologic grading system for invasive nonmucinous adenocarcinoma (INMA). METHODS: This study included patients with IMA who underwent curative resection. Their clinicopathological outcomes were compared with those of patients with INMA. Propensity score matching was performed to compare the prognosis of IMA with IASLC grade 2 or 3. Kaplan-Meier survival curves and log-rank tests were used to analyze recurrence-free survival (RFS) and overall survival (OS). RESULTS: The prognoses of IMA and IASLC grade 2 were similar in terms of RFS and OS. Although patients with IMA had better RFS than patients with IASLC grade 3, the OS was not significantly different. After propensity score matching, IMA demonstrated similar RFS to IASLC grade 2 but superior to IASLC grade 3; there was no difference in the OS compared with grades 2/3. Multivariate analysis revealed that tumor size (hazard ratio [HR] = 1.20, p = 0.028), lymphovascular invasion (HR = 127.5, p = 0.003), and maximum standardized uptake value (HR = 1.24, p = 0.005) were poor prognostic predictors for RFS. Patients with IMA demonstrated RFS similar to and significantly better than that of patients with IASLC grades 2 and 3, respectively. For OS, IMA prognosis was between that of IASLC grades 2 and 3. CONCLUSIONS: Since the prognosis of IMA among lung adenocarcinomas appears to be relatively worse, further clinical studies investigating IMA-specific treatment and follow-up plans are necessary to draw more inferences.

Skeletonizing En Bloc Esophagectomy Revisited: Oncologic Outcome in Association with the Presence of Thoracic Duct Lymph Nodes.

BACKGROUND: Skeletonizing en bloc esophagectomy (SEBE) involves the removal of the esophagus en bloc with locoregional soft tissues and lymph nodes, including the thoracic duct (TD); however, its oncologic benefits remain unclear. We evaluated the impact of SEBE on oncologic outcomes in patients with esophageal squamous cell carcinoma. METHODS: Patients undergoing McKeown esophagectomy without neoadjuvant therapy between 2013 and 2019 were evaluated. Outcomes after SEBE were compared with those after conventional esophagectomy (CE) using propensity score-matched analysis. RESULTS: Overall, 232 patients were identified, including 133 patients with SEBE and 99 patients with CE. Lymph node metastasis along the TD was identified in 7.5% (10/133) of the SEBE group, and the incidence was closely related with the tumor invasion depth (2.2% in pT1 and 19.0% in pT2-3). Based on the propensity score, 180 patients (90 pairs) were analyzed. Tumor recurrence was identified in 24.4% and 12.2% of CE and SEBE cases, respectively (p = 0.036). The observed difference was due to the higher incidence of locoregional recurrence in CE (10.5% vs. 2.2%; p = 0.024), while the incidence of systemic recurrence was similar (18.6% vs. 12.2%; p = 0.240). The 5-year disease-free survival rate was 83.6% and 62.4% in the SEBE and CE groups, respectively (p = 0.022). Multivariate analysis revealed that SEBE could significantly reduce the risk of recurrence or death in patients with pT2-3 tumors (hazard ratio 0.173, 95% confidence interval 0.048-0.628; p = 0.008). CONCLUSIONS: SEBE could identify and eradicate lymphatic metastasis along the TD and positively impact disease-free survival, particularly in patients with pT2-3 tumors.

Postoperative bronchopleural fistula repair: Surgical outcomes and adverse factors for its success.

BACKGROUND: The purpose of this study was to investigate the results of postoperative bronchopleural fistula repair and to identify adverse factors for its success. METHODS: We retrospectively reviewed the surgical results of 39 patients who underwent surgical repair for postoperative bronchopleural fistula between January 2010 and June 2020. Success of bronchopleural fistula repair was defined as the visual closure of the bronchopleural fistula with the absence of an air leak, a recurrence of bronchopleural fistula and infection in the thoracic cavity. RESULTS: Twenty-five (64.1%) bronchopleural fistulas occurred after pulmonary resection and 14 (35.9%) after lung transplantation. Bronchopleural fistula was diagnosed 19 days (median) and repaired 28 days (median) after the initial operation by primary closure in 27 (69.2%) patients, and by additional resection in 12 (30.8%) patients. The overall success rate was 59% (23/39) and the overall mortality was 56.4% (22/39). Multivariable analysis revealed that the patients who were supported by mechanical ventilation at the time of repair had significantly lower success rates than those without (15.4%, 2/13 vs. 80.8%, 21/26, respectively, p < 0.001). The omental flap group tended to have a better success rate than the muscle flap group (p = 0.07). CONCLUSIONS: There was a high overall mortality rate after bronchopleural fistula repair and a low success rate. Mechanical ventilation at the time of bronchopleural fistula repair was significantly related to the failure of bronchopleural fistula repair.

Positive nodal status is still a risk factor for long-term survivors of non-small cell lung cancer 5 years after complete resection.

BACKGROUND: Lung cancer has a poor prognosis; the number of long-term survivors (LTSs) is small compared with that of other cancers. Few studies have focused on late recurrence in LTSs with lung cancer. The purpose of this study was to analyze the risk factors for survival and late recurrence in LTSs after disease-free period of 5 years. METHODS: A retrospective analysis of patients with a disease-free survival of at least 5 years after surgical resection for non-small cell lung cancer (NSCLC) between January 1998 and December 2012 was conducted. Patients who underwent neo-adjuvant therapy, had an incomplete resection, or had advanced stage (stages IIIb and IV) cancer were excluded. RESULTS: A total of 1,254 (53.2%) of 2,357 patients were enrolled. Of these, 759 (60.5%) were men, and the mean patient age was 61.9±10.1 (range, 10-87 years) years. Pathologic N0 (997 patients, 79.5%) and stage I (860 patients, 68.6%) were the dominant stages. Late recurrence occurred in 22 patients (1.8%) 5 years postoperatively. On multivariate analysis, male sex, older age, node-positive status, and late recurrence were found to be independent risk factors for overall survival (OS), while a node-positive status was the only independent risk factor for disease-free survival [hazard ratio (HR) =3.824; P=0.002; 95% confidence interval (CI): 1.658-8.821]. CONCLUSIONS: The nodal stage at the time of surgical resection was found to be an independent risk factor for both OS and disease-free survival 5 years after initial treatment in patients with completely resected NSCLC.

Effects of mediastinal lymph node dissection in colorectal cancer-related pulmonary metastasectomy.

BACKGROUND: The benefits of mediastinal lymph node dissection (MLND) in colorectal cancer-related pulmonary metastasectomy (PM) have been poorly reported. This study aimed to determine whether MLND affects survival in patients undergoing PM and to identify the prognostic factors for survival. METHODS: We retrospectively reviewed 275 patients who had undergone colorectal cancer-related PM from January 2010 to December 2016. MLND was defined as the resection of at least six mediastinal lymph node stations according to the International Association for the Study of Lung Cancer criteria (N1, ≥3 stations; N2, ≥3 stations). The propensity score matching method was used to reduce bias. RESULTS: Thirty-three (12%) patients underwent MLND, and 13 (4.7%) patients had mediastinal lymph node involvement. This study showed no difference in 5-year overall survival (no MLND, 52.7% vs. MLND, 53.5%; p = 0.81). On multivariable analysis, negative prognostic factors for overall survival were preoperative carcinoembryonic antigen (CEA) level (p < 0.001), a higher number of metastatic nodules (p < 0.001), metastatic nodule size ≥2 cm (p < 0.001), and lymph node involvement (p = 0.006). CONCLUSIONS: Mediastinal lymph node involvement, preoperative CEA level, higher metastatic nodule number, and nodule size negatively affected survival whereas MLND in PM was not associated with survival.

Video-Assisted Thoracic Surgery Segmentectomy.

Although lobectomy remains the gold-standard surgical treatment for non-small-cell lung cancer, the frequency of thoracoscopic segmentectomy is increasing. Multiple factors must be considered in the choice of the procedure, ranging from adequate surgical planning or simulation, tumor localization, and identification of the intersegmental plane to severing the intersegmental plane to achieve an oncologically safe surgical margin with no or minimal manual palpation and different landmarks. In this article, we present an overview of methods for each procedural step of thoracoscopic segmentectomy, from preoperative planning to division of the intersegmental plane.

Chyle Leakage after Esophageal Cancer Surgery.

Surgeons recommend dissecting lymph nodes in the thorax, abdomen, and neck during surgery for esophageal cancer because of the possibility of metastasis to the lymph nodes in those areas through the lymphatic plexus of the esophageal submucosal layer. Extensive lymph node dissection is essential for accurate staging and is thought to improve survival. However, it can result in several complications, including chyle leakage, which refers to continuous lymphatic fluid leakage and can occur in the thorax, abdomen, and neck. Malnutrition, fluid imbalance, and immune compromise may result from chyle leakage, which can be potentially life-threatening if it persists. Therefore, various treatment methods, including conservative treatment, pharmacological treatment such as octreotide infusion, and interventions such as thoracic duct embolization and surgical thoracic duct ligation, have been applied. In this article, the risk factors, diagnosis, and treatment methods of chyle leakage after esophagectomy are reviewed.

Factors Affecting the Number of Stapler Cartridges in Complete Video-Assisted Thoracoscopic Surgery Lobectomy for Non-small Cell Lung Cancer.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) lobectomy has become the major surgical option for the treatment of non-small cell lung cancer (NSCLC). Endoscopic instruments such as stapler cartridges are essential for VATS procedures. In this study, we investigated the factors that affect the number of stapler cartridges used in VATS lobectomy. METHODS: A retrospective analysis was conducted of patients who underwent complete VATS lobectomy for NSCLC from January 2013 to December 2015. RESULTS: In total, 596 patients underwent complete VATS lobectomy. The average number of stapler cartridges used for VATS lobectomy was 5.3±1.9. The number of stapler cartridges used for VATS lobectomy was higher in men (5.5±1.9 vs. 5.0±18, p=0.006), those aged older than 70 years (5.5±2.1 vs. 5.1±1.7, p=0.038), those who underwent upper or middle lobectomy procedures (5.7±1.9 vs. 4.1±1.2, p<0.001), those with a higher fissure sum average (p<0.001), and those in whom surgery was performed by a surgeon with a preference for staplers (5.6±2.0 vs. 4.9±1.6, p<0.001). CONCLUSION: The number of stapler cartridges required to perform VATS lobectomy in NSCLC patients appears to be influenced by sex, age, the location of the tumor, the degree of fissure development, and the surgeon's preference.

Emergency Pulmonary Artery-to-Systemic Artery Shunt to Break the Positive Feedback Loop of a Pulmonary Hypertensive Crisis after Neonatal Coarctation Repair.

A 2.5-kg neonate with coarctation of the aorta and a small left ventricle experienced a severe pulmonary hypertensive crisis. An emergency pulmonary artery-to-systemic artery shunt was placed to break the positive feedback loop caused by pulmonary hypertension and functional mitral stenosis. This shunt provided immediate relief of suprasystemic pulmonary hypertension and the resultant low cardiac output.

Mutation analysis of the APC gene in unrelated Korean patients with FAP: four novel mutations with unusual phenotype.

Germline mutations within the adenomatous polyposis coli (APC) gene are responsible for most cases of familial adenomatous polyposis (FAP), an autosomal dominantly inherited predisposition to colorectal cancer. To date more than 900 different APC germline mutations have been characterized worldwide demonstrating allelic heterogeneity. Here, we analyzed the APC gene in 23 DNA samples from unrelated Korean patients with the typical clinical symptoms of FAP by denaturing high-performance liquid chromatography (DHPLC) and direct sequencing. We identified 20 different APC sequence variants, including 9 truncating mutations, 1 missense mutation, 7 polymorphisms, and 3 intronic variants. Nine different truncating mutations, including four novel mutations (p.Leu180TyrfsX5, p.Gly567X, p.Ser1275PhefsX13, p.Leu1280CysfsX8), were detected. The most common mutation was a 5 bp deletion at codon 1,309 (p.Glu1309AspfsX4) as in Western studies. The next most common mutation was p.Ser1275PhefsX13 with a severe form of FAP with many extracolonic manifestations; this was a novel mutation identified in our study and may represent the second hot-spot mutation in a Korean population. Novel mutations are of particular interest because of the unusual phenotypic features shown by patients. In present study, we found new positions associated with thyroid cancer (codon 180) and desmoid tumor (codon 1,280), which have not been previously reported. The results of this molecular study have revealed the existence of novel pathogenic mutations in Korean patients with FAP. In addition to allowing phenotype-genotype correlations to be performed, these results are currently being used in genetic counseling and in patient care.