Proposal of New ypStage Grouping System for Esophageal Squamous Cell Carcinoma Patients who Underwent Neoadjuvant Chemoradiotherapy followed by Surgery.

OBJECTIVE: To propose a new ypTNM grouping system to address these limitations and improve prognostic relevance. SUMMARY BACKGROUND DATA: The current 8th edition of the American Joint Committee on Cancer (AJCC) ypStage system shows unsatisfactory prognostic relevance in patients with esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy. METHODS: The study cohort included 501 ESCC patients who received nCRT followed by esophagectomy at the Samsung Medical Center in Korea between 1994 and 2018 (development cohort) and 422 patients treated at Asan Medical Center (validation cohort). Recursive partitioning with a tree-structured regression model was used to develop and validate a new ypStage grouping system. RESULTS: In the new ypStage grouping system, ypStage I includes ypT0N0 only; ypStage II includes ypTis-T2N0 or ypT0-T2N1; ypStage III includes ypT3N0-N1; and ypStage IV includes ypT4N0-N1 or ypTanyN2-3. This system adequately addressed the limitations of the existing AJCC classification system, including overlapping and reversal of survival rates. Moreover, the discrimination ability of the new system was higher than that of the existing system [concordance-index (C-index): 61.9%] in the development (C-index: 66.6%) and validation (C-index: 66.0%) cohorts. NRIe was 0.17 [95% confidence interval (CI): 0.09-0.26, P-<0.001) and 0.18 (95% CI: 0.10-0.27, P-<0.001)] in the development and validation cohorts, respectively. CONCLUSIONS: The current study proposes a clear revised version of the 8th edition of the AJCC ypStage grouping system that exhibits superior prognostic stratification in patients with ESCC treated with nCRT followed by esophagectomy.

Clinical and Pathologic Supraclavicular Lymph Node Metastases in Esophageal Squamous Cell Carcinoma Treated by Esophagectomy with Three-Field Lymph Node Dissection.

BACKGROUND: This study investigated the survival outcomes for surgically treated esophageal squamous cell carcinoma (ESCC) patients based on clinically suspicious supraclavicular lymph node (SCN) metastasis (cSCN+) and pathologically confirmed SCN metastasis (pSCN+). METHODS: Using an institutional registry between 1994 and 2018, this study retrospectively analyzed 611 patients who received curative-intent esophagectomy with 3-field lymph node dissection for ESCC. The study used computed tomography and positron emission tomography to define cSCN+. RESULTS: Among 611 patients, 24.4% had cSCN+ and 12.2% had pSCN+. The 5-year overall survival (OS) rates were 68.2% for cN0, 43.5% for cN+ without cSCN+, and 30.3% for cN+ with cSCN+ (p = 0.018). Although the univariable analysis showed that cSCN+ was associated with poorer survival than cN0 or cN+ with cSCN- (hazard ratio [HR], 1.818; p < 0.001), the multivariable analysis did not support this finding (HR, 1.281; p = 0.681). The 5-year OS rates were 64.2% for pN0, 41.5% for pN+ without pSCN+, and 25.6% for pN+ with pSCN+ (p = 0.054). Univariable analysis showed an association of pSCN+ with poor OS (HR, 1.830; p < 0.001), but the difference in the multivariable analysis was not significant (HR, 0.912; p = 0.587). CONCLUSIONS: The presence of SCN metastasis did not have a significant impact on the OS of ESCC patients with 3-field lymph node dissection regardless of clinical suspicion or pathologic confirmation.

PD-L1 expression in resected lung adenocarcinoma: prevalence and prognostic significance in relation to the IASLC grading system.

AIMS: Programmed death-ligand 1 (PD-L1) expression is a predictive biomarker for adjuvant immunotherapy and has been linked to poor differentiation in lung adenocarcinoma. However, its prevalence and prognostic role in the context of the novel histologic grade has not been evaluated. METHODS: We analysed a cohort of 1233 patients with resected lung adenocarcinoma where PD-L1 immunohistochemistry (22C3 assay) was reflexively tested. Tumour PD-L1 expression was correlated with the new standardized International Association for the Study of Lung Cancer (IASLC) histologic grading system (G1, G2, and G3). Clinicopathologic features including patient outcome were analysed. RESULTS: PD-L1 was positive (≥1%) in 7.0%, 23.5%, and 63.0% of G1, G2, and G3 tumours, respectively. PD-L1 positivity was significantly associated with male sex, smoking, and less sublobar resection among patients with G2 tumours, but this association was less pronounced in those with G3 tumours. PD-L1 was an independent risk factor for recurrence (adjusted hazard ratio [HR] = 3.25, 95% confidence intervals [CI] = 1.93-5.48, P < 0.001) and death (adjusted HR = 2.69, 95% CI = 1.13-6.40, P = 0.026) in the G2 group, but not in the G3 group (adjusted HR for recurrence = 0.94, 95% CI = 0.64-1.40, P = 0.778). CONCLUSION: PD-L1 expression differs substantially across IASLC grades and identifies aggressive tumours within the G2 subgroup. This knowledge may be used for both prognostication and designing future studies on adjuvant immunotherapy.

Prognostic role of pathologic status other than complete response after neoadjuvant therapy followed by surgery in esophageal squamous cell carcinoma.

BACKGROUND: This retrospective study was performed to investigate the survival differences according to the pathologic status after neoadjuvant chemotherapy followed by surgery in esophageal squamous cell carcinoma (ESCC), and to investigate whether current AJCC 8th ypStage can predict survival accurately. METHODS: Data of 563 patients who received neoadjuvant therapy and esophagectomy for ESCC between 1994 and 2018 were retrospectively reviewed. RESULTS: The mean age was 62.00 ± 8.01 years, of which 524 (93.1%) were males. The median follow-up period was 29.12 months. A total of 153 (27.1%) patients showed pathologic complete response (pCR) and 92 (16.3%) patients showed pCR of the primary lesion with residual metastatic lymph nodes (ypT0N +). A total of 196 (35%) and 122 (21.6%) patients showed ypT + N + and ypT + N, respectively. The 5-year overall survival (OS) of each group was 75.1% (CR), 42.4% (ypT + N0), 54.9% (ypT0N +), and 26.1% (ypT + N +); CR patients showed better survival than the other groups, and no survival differences were found in the 5-year OS between ypT + N0 and ypT0N + patients (p = 0.811). In ypStage I, there were survival differences between ypT0N0 and ypTis-2N0 patients, and ypT1N0 (ypStage I) and ypT0N1 (ypStageIIIA) showed similar OS (5-year OS in 49.3% vs. 67.1%, p = 0.623). CONCLUSIONS: pCR offers long-term survival in patients; however, survival significantly declines with the presence of residual primary lesion and nodal metastases.

Importance of Local Ablative Therapies for Lung Metastases in Patients With Colorectal Cancer.

OBJECTIVE: To assess the effect of local ablative therapy (LAT) on overall survival in patients with lung metastases from colorectal cancer (CRC) compared with patients treated with systemic therapy. SUMMARY BACKGROUND DATA: CRC affects approximately 1.4 million individuals worldwide every year. The lungs are commonly affected by CRC, and there is no treatment standard for a secondary lung metastasis from CRC. METHODS: This longitudinal, retrospective cohort study (2010-2018) quantified the pulmonary and extrapulmonary tumor burden of 1143 patients by retrospectively reviewing computed tomography images captured at diagnosis. A comprehensive multidisciplinary approach informed how and when surgery and/or stereotactic body radiotherapy was administered. RESULTS: Among 1143 patients, 473 patients (41%) received LAT, with surgery first (n = 421) or stereotactic ablative radiation therapy first (n = 52) either at the time of diagnosis (n = 288), within 1 year (n = 132), or after 1 year (n = 53). LAT was repeated in 158 patients (33.4%, 384 total sessions) when new lung metastases were detected. The 5- and 10-year survival rates for patients treated with LAT (71.2% and 64.0%, respectively) were significantly higher than those of patients treated with systemic therapy alone (14.2% and 10.0%, respectively; P <0.001). The overall survival of patients who received LAT intervention increased as the total tumor burden decreased. CONCLUSIONS: A high long-term survival rate was achievable in a significant portion of patients with lung metastasis from CRC by the timely administrations of LAT to standard systemic therapy. The tumor burden and LAT feasibility should be included in a discussion during the follow-up period.

PmrAB controls virulence-associated traits and outer membrane vesicle biogenesis in Acinetobacter baumannii.

The PmrAB two-component system modulates colistin resistance in Acinetobacter baumannii, but its association with the virulence traits of this bacterium remains uncharacterized. This study explored the role of A. baumannii PmrAB in surface motility, biofilm formation, and outer membrane vesicle (OMV) biogenesis using wild-type (WT) A. baumannii 17978 and ΔpmrA and ΔpmrB mutant strains. The two mutant strains exhibited significantly decreased surface motility compared with that of WT strain by the low expression of abaI, abaR, A1S_0113, A1S_0115, and A1S_0116. Biofilm mass also significantly decreased in the two mutant strains at 12 h of incubation, but restored at 24 h. Under static culture conditions for 12 h, the two mutant strains showed low pgaA expression. However, the other biofilm-associated genes, such as csuC, csuE, ompA, and bap, showed different expression between the two mutant strains. Although the size of OMVs was similar among the three strains, the number of OMVs secreted from the two mutant strains slightly decreased compared with that secreted from the WT strain. Protein concentrations in the OMVs of ΔpmrA mutant significantly decreased compared with those in the OMVs of WT and ΔpmrB strains. Overall, PmrAB modulates virulence traits and OMV biogenesis in A. baumannii.

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.

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.

Complementary Regulation of BfmRS Two-Component and AbaIR Quorum Sensing Systems to Express Virulence-Associated Genes in Acinetobacter baumannii.

Acinetobacter baumannii expresses various virulence factors to adapt to hostile environments and infect susceptible hosts. This study investigated the regulatory network of the BfmRS two-component and AbaIR quorum sensing (QS) systems in the expression of virulence-associated genes in A. baumannii ATCC 17978. The ΔbfmS mutant exhibited a significant decrease in surface motility, which presumably resulted from the low expression of pilT and A1S_0112-A1S_0119 gene cluster. The ΔbfmR mutant displayed a significant reduction in biofilm and pellicle formation due to the low expression of csu operon. The deletion of abaR did not affect the expression of bfmR or bfmS. However, the expression of abaR and abaI was upregulated in the ΔbfmR mutant. The ΔbfmR mutant also produced more autoinducers than did the wild-type strain, suggesting that BfmR negatively regulates the AbaIR QS system. The ΔbfmS mutant exhibited no autoinducer production in the bioassay system. The expression of the A1S_0112-A1S_0119 gene cluster was downregulated in the ΔabaR mutant, whereas the expression of csu operon was upregulated in this mutant with a high cell density. In conclusion, for the first time, we demonstrated that the BfmRS-AbaIR QS system axis regulated the expression of virulence-associated genes in A. baumannii. This study provides new insights into the complex network system involved in the regulation of virulence-associated genes underlying the pathogenicity of A. baumannii.

Association of early-onset diabetes, prediabetes and early glycaemic recovery with the risk of all-cause and cardiovascular mortality.

AIMS/HYPOTHESIS: The increasing incidence of diabetes among young adults is a disease burden; however, the effects of early-onset diabetes, prediabetes and glycaemic recovery on CVD or mortality remain unclear. We aimed to investigate the association of these factors with 10 year all-cause mortality, CVD mortality and CVD incidence in Korean young adults. METHODS: This large and longitudinal cohort study included data from the Korean National Health Insurance Service-National Health Information Database; 2,502,375 young adults aged 20-39 years without diabetes mellitus and CVD at baseline were included. Glycaemic status was measured twice, first in 2002-2003 and second in 2004-2005. Changes in fasting glucose levels were evaluated according to fasting glucose status: normal fasting glucose (NFG; <5.5 mmol/l), impaired fasting glucose (IFG; 5.5-6.9 mmol/l), and diabetic fasting glucose (DFG; ≥7.0 mmol/l). Primary outcomes were all-cause and CVD mortality risk. The secondary outcome was incidence of CVD, including acute myocardial infarction and stroke. All outcomes arose from the 10 year follow-up period 1 Jan 2006 to 31 December 2015. RESULTS: Individuals with NFG at baseline, who were subsequently newly diagnosed with diabetes and prediabetes (IFG), had increased all-cause mortality (HR [95% CI] 1.60 [1.44, 1.78] and 1.13 [1.09, 1.18], respectively) and CVD incidence (1.13 [1.05, 1.23] and 1.04 [1.01, 1.07], respectively). In those with DFG at baseline, early recovery to NFG and IFG was associated with decreased all-cause mortality (0.57 [0.46, 0.70] and 0.65 [0.53, 0.81], respectively) and CVD incidence (0.70 [0.60, 0.81] and 0.78 [0.66, 0.91], respectively). Among patients with IFG at baseline, early recovery to NFG was associated with decreased CVD mortality (0.74 [0.59, 0.93]). CONCLUSIONS/INTERPRETATION: Early-onset diabetes or prediabetes increased CVD risks and all-cause mortality after the 10 year follow-up. Furthermore, recovery of hyperglycaemia could reduce the subsequent 10 year risk for CVD incidence and all-cause mortality. Graphical abstract.

Prognostic factors for resected non-small cell lung cancer in patients with type 2 diabetes mellitus.

BACKGROUND: For diabetic patients with lung cancer, blood glucose levels and medications such as metformin and statins may influence survival. OBJECTIVES: This study aimed to determine prognostic survival factors for diabetic patients with resected non-small cell lung cancer. PATIENTS AND METHODS: Between January 2005 and December 2013, 301 patients with type 2 diabetes mellitus who underwent curative resection for non-small cell lung cancer were identified and reviewed retrospectively. RESULTS: The median follow-up period was 48 months. In multivariate analysis for lung cancer-specific survival, older age, forced expiratory volume in 1 s (FEV1) <80% predicted, and advanced pathologic stage were significant negative prognostic factors; statin use was a positive prognostic factor (hazard ratio (HR), 0.468). In multivariate analysis for overall survival, male sex, older age, comorbidity index, and advanced pathologic stage were significant negative prognostic factors and proper glycemic control (HR, 0.621) and statin use (HR, 0.585) were positive prognostic factors. CONCLUSIONS: Proper glycemic control (glycated hemoglobin A1c <7%) is recommended for diabetic patients undergoing lung cancer operations. Further studies are required to elucidate associations between type 2 diabetes mellitus and antineoplastic effects of statins and to evaluate statins as a novel adjuvant treatment for lung cancer.

Association of Blood Pressure Classification in Korean Young Adults According to the 2017 American College of Cardiology/American Heart Association Guidelines With Subsequent Cardiovascular Disease Events.

Importance: Among young adults, the association of the 2017 American College of Cardiology/American Heart Association (ACC/AHA) High Blood Pressure Clinical Practice Guidelines with risk of cardiovascular disease (CVD) later in life is uncertain. Objective: To determine the association of blood pressure categories before age 40 years with risk of CVD later in life. Design, Setting, and Participants: This population-based cohort study from the Korean National Health Insurance Service consisted of 2 488 101 adults aged 20 through 39 years with blood pressure measurements taken twice from 2002 through 2005. Starting from January 1, 2006, participants were followed up until the date of CVD diagnosis, death, or December 31, 2015. Exposures: Participants were categorized by blood pressure readings: normal (systolic, <120 mm Hg; diastolic, <80 mm Hg), elevated (sytolic, 120-129 mm Hg; diastolic, <80 mm Hg), stage 1 hypertension (systolic, 130-139 mm Hg; diastolic, 80-89 mm Hg), and stage 2 hypertension (systolic, ≥140 mm Hg; diastolic, ≥90 mm Hg). Main Outcomes and Measures: The primary outcome was CVD defined as 2 or more days of hospitalization due to CVD or death due to CVD. The secondary outcomes were coronary heart disease (CHD) and stroke. Results: The study population consisted of 2 488 101 participants (median age, 31 years [interquartile range, 27-36 years], 789 870 women [31.7%]). A total of 44 813 CVD events were observed during a median follow-up duration of 10 years. Men with baseline stage 1 hypertension compared with those with normal blood pressure had higher risk of CVD (incidence, 215 vs 164 per 100 000 person-years; difference, 51 per 100 000 person-years [95% CI, 48-55]; adjusted hazard ratio [HR], 1.25 [95% CI, 1.21-1.28]), CHD (incidence, 134 vs 103 per 100 000 person-years; difference, 31 per 100 000 person-years [95% CI, 28-33]; adjusted HR, 1.23 [95% CI, 1.19-1.27]), and stroke (incidence, 90 vs 67 per 100 000 person-years; difference, 23 per 100 000 person-years [95% CI, 21-26]; adjusted HR, 1.30 [95% CI, 1.25-1.36]). Women with baseline stage 1 hypertension compared with those with normal blood pressure had increased risk of CVD (incidence, 131 vs 91 per 100 000 person-years; difference, 40 per 100 000 person-years [95% CI, 35-45]; adjusted HR, 1.27 [95% CI, 1.21-1.34]), CHD (incidence, 56 vs 42 per 100 000 person-years; difference, 14 per 100 000 person-years [95% CI, 11-18]; adjusted HR, 1.16 [95% CI, 1.08-1.25]), and stroke (incidence, 79 vs 51 per 100 000 person-years; difference, 28 per 100 000 person-years [95% CI, 24-32]; adjusted HR [1.37, 95% CI, 1.29-1.46]). Results for state 2 hypertension were consistent. Conclusions and Relevance: Among Korean young adults, stage 1 and stage 2 hypertension, compared with normal blood pressure, were associated with increased risk of subsequent cardiovascular disease events. Young adults with hypertension, defined by the 2017 ACC/AHA criteria, may be at increased risk of cardiovascular disease.

Prognostic value of the neutrophil-to-lymphocyte ratio for overall and disease-free survival in patients with surgically treated esophageal squamous cell carcinoma.

Although increasing evidence indicates that cancers are associated with inflammation, the prognostic role of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) in patients with esophageal squamous cell carcinoma remains controversial. We determined the prognostic roles of NLR and PLR in patients with esophageal squamous cell carcinoma who underwent surgical treatment. We retrospectively reviewed 119 patients with esophageal squamous cell carcinoma who underwent surgical resection and complete lymph node dissection from 2004 to 2012. The preoperative NLR and PLR were measured. The patients included 112 (94.1 %) males (mean age, 63.64 ± 8.42 years) of whom 37 (31.1 %) were pathological stage I, 33 (27.7 %) were stage II, and 49 (41.2 %) were stage III. The median follow-up period was 28.68 months. Recurrence was reported in 48 (40.3 %) patients. Mean NLR and PLR were 2.35 ± 1.39 and 140.77 ± 70.47, respectively. A multivariate analysis revealed that NLR was a risk factor for disease-free survival (DFS) (hazard ratio [HR], 1.194; p = 0.031) and overall survival (OS) (HR, 1.230; p = 0.011), whereas PLR was not a risk factor for DFS or OS. The 3-year OS rates were 51.0 % in low-NLR (<2.97) patients and 17.4 % in high-NLR (≥2.97) patients (p = 0.007). Akaike's information criterion decreased when the NLR was included in the multivariate model compared to the multivariate model without NLR. A high NLR was a significant prognostic factor for OS and DFS in patients with surgically treated esophageal squamous cell carcinoma, whereas PLR showed no prognostic significance.

Recurrence Risk-Scoring Model for Stage I Adenocarcinoma of the Lung.

PURPOSE: The aim of this retrospective, multicenter study was to develop a recurrence risk-scoring model in patients with curatively resected stage I lung adenocarcinoma (ADC). METHODS: Clinicopathologic and outcome data for a development cohort of 1,700 patients with pathologic stage I ADC from four institutions resected between January 2000 and December 2009 were evaluated. A phantom study was performed for correction of inter-institutional differences in positron emission tomography-standardized uptake value (PET-SUV). A nomogram for recurrence prediction was developed using Cox proportional hazards regression. This model was validated in a cohort of 460 patients in two other hospitals. The recurrence rate was 21.0 % for the development cohort and 22.1 % for the validation cohort. RESULTS: In multivariable analysis, three independent predictors for recurrence were identified: pathologic tumor size (hazard ratio [HR] 1.03, 95 % CI 1.017-1.048; p < 0.001), corrected PET-SUV (HR 1.08, 95 % CI 1.051-1.105; p < 0.001), and lymphovascular invasion (HR 1.65, 95 % CI 1.17-2.33; p = 0.004). The nomogram was made based on these factors and a calculated risk score was accorded to each patient. Kaplan-Meier analysis of the development cohort showed a 5-year recurrence-free survival (RFS) of 83 % (95 % CI 0.80-0.86) in low-risk patients and 59 % (95 % CI 0.54-0.66) in high-risk patients with the highest 30 percentile scores. The concordance index was 0.632 by external validation. CONCLUSIONS: This recurrence risk-scoring model can be used to predict the RFS for pathologic stage I ADC patients using the above three easily measurable factors. High-risk patients need close follow-up and can be candidates for adjuvant chemotherapy.

Relationship Between the Size of Metastatic Lymph Nodes and Positron Emission Tomographic/Computer Tomographic Findings in Patients with Esophageal Squamous Cell Carcinoma.

BACKGROUND: We measured the sizes of metastatic lymph nodes and the relationships thereof by (18)F-fluorodeoxyglucose positron emission tomography/computer tomography (PET/CT). We identified risk factors for nodal upstaging in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Eighty-five patients with ESCC who underwent esophagectomy with extensive mediastinal lymphadenectomy were assessed. Two radiologists blinded to pathology data reviewed PET/CT scans, evaluating both primary tumors and lymph node involvement. A pathologist examined all metastatic lymph nodes in terms of maximal diameter (LNmax), the size of the metastatic focus (Fmax), and the metastasis occupation ratio (MOR = Fmax/LNmax). RESULTS: The maximal tumor length averaged 2.9 ± 0.2 cm and the mean SUVmax of the primary lesion 5.3 ± 0.5. On PET/CT scans, 26 (30.6 %) patients exhibited nodal metastasis and 59 (69.4 %) did not. Pathology grades of pN0, pN1, pN2, and pN3 were assigned to 45 (52.9 %), 24 (28.2 %), 13 (15.3 %), and 3 (3.5 %) patients, respectively. Nodal upstaging was evident in 29 (34.1 %) cases. In 123 metastatic nodes of 4212 nodes dissected, the LNmax was 6.60 ± 0.39 mm, the Fmax 4.47 ± 0.35 mm, and the MOR 0.68 ± 0.03. Of 123 nodes, 85 (69.1 %) were retrieved from PET-negative stations, and the LNmax and Fmax values of these nodes were 5.88 ± 0.42 and 3.75 ± 0.31 mm, respectively. Upon multivariate analysis, tumor length (OR 1.666, p = 0.019) and lymphovascular invasion (OR 41.038, p < 0.001) were risk factors for nodal upstaging. CONCLUSION: A significant proportion of nodal metastases were too small to detect via PET/CT imaging. Therefore, meticulous lymph node dissection might be helpful in ESCC patients.

Feasibility of a robot-assisted thoracoscopic lymphadenectomy along the recurrent laryngeal nerves in radical esophagectomy for esophageal squamous carcinoma.

BACKGROUND: Lymph node dissection along bilateral recurrent laryngeal nerves (RLNs) is an essential component of radical esophagectomy for esophageal squamous carcinoma. However, it is associated with significant morbidity and requires a great deal of skill when performed with minimally invasive surgery. METHODS: Between October 2010 and July 2012, 40 consecutive patients underwent a robot-assisted thoracoscopic esophagectomy and total mediastinal lymphadenectomy. The lymph nodes along the dorsal side of the RLNs were removed in the initial 18 patients (group 1), and the RLNs were skeletonized by dissection of all the lymph nodes and surrounding fatty tissues in the following 22 patients (group 2). RESULTS: All but one patient underwent a successful robot-assisted, thoracoscopic esophagectomy. The mean operation time was 428.6 ± 75.0 min, and the mean robot console time was 186.7 ± 52.1 min. An average of 42.6 ± 14.1 nodes was retrieved, and the mean number of dissected nodes from the mediastinum and the RLN chains were 25.5 ± 9.6 and 9.6 ± 6.5, respectively. One mortality occurred (2.5%), and the incidences of pneumonia and RLN palsy were 12.5 and 20%, respectively. The mean robot console time was longer in group 2 (211.4 ± 49.5 min) than in group 1 (156.6 ± 38.2 min) (p < 0.001), and group 2 had higher mean numbers of dissected nodes from the mediastinum (30.3 ± 7.9 vs 19.6 ± 8.2; p < 0.001) and the RLN chains (13.5 ± 5.7 vs 4.8 ± 3.6; p < 0.001). Although RLN palsy was more common in group 2 (31.8 vs 5.6%; p = 0.054), all palsies resolved within 1 year. CONCLUSIONS: Robot-assisted thoracoscopic lymphadenectomy along bilateral RLNs was technically feasible and safe. Skeletonization of the RLNs yields more lymph nodes, but efforts should be made to decrease the incidence of RLN palsy.

Surgical Outcomes of Cervical Esophageal Cancer: A Single-Center Experience.

Background: Cervical esophageal cancer is a rare malignancy that requires specialized care. While definitive chemoradiation is the standard treatment approach, surgery remains a valuable option for certain patients. This study examined the surgical outcomes of patients with cervical esophageal cancer. Methods: The study involved a retrospective review and analysis of 24 patients with cervical esophageal cancer. These patients underwent surgical resection between September 1994 and December 2018. Results: The mean age of the patients was 61.0±10.2 years, and 22 (91.7%) of them were male. Furthermore, 21 patients (87.5%) had T3 or T4 tumors, and 11 (45.8%) exhibited lymph node metastasis. Gastric pull-up with esophagectomy was performed for 19 patients (79.2%), while 5 (20.8%) underwent free jejunal graft with cervical esophagectomy. The 30-day operative mortality rate was 8.3%. During the follow-up period, complications included leakage at the anastomotic site in 9 cases (37.5%) and graft necrosis of the gastric conduit in 1 case. Progression to oral feeding was achieved in 20 patients (83.3%). Fifteen patients (62.5%) displayed tumor recurrence. The median time from surgery to recurrence was 10.5 months, and the 1-year recurrence rate was 73.3%. The 1-year and 3-year survival rates were 75% and 33.3%, respectively, with a median survival period of 17 months. Conclusion: Patients with cervical esophageal cancer who underwent surgical resection faced unfavorable outcomes and relatively poor survival. The selection of cases and decision to proceed with surgery should be made cautiously, considering the risk of severe complications.

Risk Factor Analysis of Morbidity and 90-Day Mortality of Curative Resection in Patients with Stage IIIA-N2 Non-Small Cell Lung Cancer after Induction Concurrent Chemoradiation Therapy.

Background: Major pulmonary resection after neoadjuvant concurrent chemoradiation therapy (nCCRT) is associated with a substantial risk of postoperative complications. This study investigated postoperative complications and associated risk factors to facilitate the selection of suitable surgical candidates following nCCRT in stage IIIA-N2 non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective analysis of patients diagnosed with clinical stage IIIA-N2 NSCLC who underwent surgical resection following nCCRT between 1997 and 2013. Perioperative characteristics and clinical factors associated with morbidity and mortality were analyzed using univariable and multivariable logistic regression. Results: A total of 574 patients underwent major lung resection after induction CCRT. Thirty-day and 90-day postoperative mortality occurred in 8 patients (1.4%) and 41 patients (7.1%), respectively. Acute respiratory distress syndrome (n=6, 4.5%) was the primary cause of in-hospital mortality. Morbidity occurred in 199 patients (34.7%). Multivariable analysis identified significant predictors of morbidity, including patient age exceeding 70 years (odds ratio [OR], 1.8; p=0.04), low body mass index (OR, 2.6; p=0.02), and pneumonectomy (OR, 1.8; p=0.03). Patient age over 70 years (OR, 1.8; p=0.02) and pneumonectomy (OR, 3.26; p<0.01) were independent predictors of mortality in the multivariable analysis. Conclusion: In conclusion, the surgical outcomes following nCCRT are less favorable for individuals aged over 70 years or those undergoing pneumonectomy. Special attention is warranted for these patients due to their heightened risks of respiratory complications. In high-risk patients, such as elderly patients with decreased lung function, alternative treatment options like definitive CCRT should be considered instead of surgical resection.

Clonal Distribution and Its Association With the Carbapenem Resistance Mechanisms of Carbapenem-Non-Susceptible Pseudomonas aeruginosa Isolates From Korean Hospitals.

Background: Carbapenem resistance in Pseudomonas aeruginosa is a serious global health problem. We investigated the clonal distribution and its association with the carbapenem resistance mechanisms of carbapenem-non-susceptible P. aeruginosa isolates from three Korean hospitals. Methods: A total of 155 carbapenem-non-susceptible P. aeruginosa isolates collected between 2011 and 2019 were analyzed for sequence types (STs), antimicrobial susceptibility, and carbapenem resistance mechanisms, including carbapenemase production, the presence of resistance genes, OprD mutations, and the hyperproduction of AmpC ß-lactamase. Results: Sixty STs were identified in carbapenem-non-susceptible P. aeruginosa isolates. Two high-risk clones, ST235 (N=41) and ST111 (N=20), were predominant; however, sporadic STs were more prevalent than high-risk clones. The resistance rate to amikacin was the lowest (49.7%), whereas that to piperacillin was the highest (92.3%). Of the 155 carbapenem-non-susceptible isolates, 43 (27.7%) produced carbapenemases. Three metallo-ß-lactamase (MBL) genes, blaIMP-6 (N=38), blaVIM-2 (N=3), and blaNDM-1 (N=2), were detected. blaIMP-6 was detected in clonal complex 235 isolates. Two ST773 isolates carried blaNDM-1 and rmtB. Frameshift mutations in oprD were identified in all isolates tested, regardless of the presence of MBL genes. Hyperproduction of AmpC was detected in MBL gene-negative isolates. Conclusions: Frameshift mutations in oprD combined with MBL production or hyperproduction of AmpC are responsible for carbapenem resistance in P. aeruginosa. Further attention is required to curb the emergence and spread of new carbapenem-resistant P. aeruginosa clones.