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.

Prognostic Impact of Inflammation-Based Factors in Patients with Esophageal Squamous Cell Carcinoma Achieving Pathological Complete Response After Neoadjuvant Chemoradiotherapy Followed by Surgery.

BACKGROUND: Patients achieving pathological complete response (pCR) post-neoadjuvant chemoradiotherapy (nCRT) and surgery for locally advanced esophageal squamous cell carcinoma (ESCC) have a favorable prognosis. However, recurrence occurs in approximately 20-30% of all patients, with few studies evaluating their prognostic factors. We identified these prognostic factors, including inflammation-based markers, in patients with ESCC showing pCR after nCRT and surgery. PATIENTS AND METHODS: Patients with ESCC undergoing esophagectomy post-nCRT (January 2007-August 2017) were studied. Survival analysis evaluated 5-year overall (OS) and recurrence-free survival (RFS). Risk factors, including inflammation factors, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR), were analyzed using Cox-proportional hazards model. RESULTS: Overall, 123patients participated herein. After a median follow-up duration of 67 months (44-86 months), 17 patients (12.3%) had recurrent disease. The 5-year OS and RFS rates were 71.6% and 68.0%, respectively. In the multivariable analysis, older age ( ≥ 60 years) [hazard ratio (HR) 3.228, 95% confidence interval (CI) 1.478-7.048, p = 0.003], higher pretreatment T stage (≥ T3; HR 2.563, 95% CI 1.335-4.922, p = 0.005), nonapplication of induction chemotherapy (HR 2.389, 95% CI 1.184-4.824, p = 0.015), and higher post-nCRT PLR (≥ 184.2; HR 2.896, 95% CI 1.547-5.420, p = 0.001) were poor independent prognostic factors for 5-year RFS. The patient group with three to four identified factors with poor outcomes exhibited a 5-year RFS rate of 46.2%. CONCLUSIONS: Significant prognostic factors include higher post-nCRT PLR, older age, higher clinical T stage, and nonapplication of induction chemotherapy. Identifying higher recurrence risk patients is crucial for tailored follow-up and treatment.

Stratifying non-small cell lung cancer patients using an inverse of the treatment decision rules: validation using electronic health records with application to an administrative database.

BACKGROUND: To validate a stratification method using an inverse of treatment decision rules that can classify non-small cell lung cancer (NSCLC) patients in real-world treatment records. METHODS: (1) To validate the index classifier against the TNM 7th edition, we analyzed electronic health records of NSCLC patients diagnosed from 2011 to 2015 in a tertiary referral hospital in Seoul, Korea. Predictive accuracy, stage-specific sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and c-statistic were measured. (2) To apply the index classifier in an administrative database, we analyzed NSCLC patients in Korean National Health Insurance Database, 2002-2013. Differential survival rates among the classes were examined with the log-rank test, and class-specific survival rates were compared with the reference survival rates. RESULTS: (1) In the validation study (N = 1375), the overall accuracy was 93.8% (95% CI: 92.5-95.0%). Stage-specific c-statistic was the highest for stage I (0.97, 95% CI: 0.96-0.98) and the lowest for stage III (0.82, 95% CI: 0.77-0.87). (2) In the application study (N = 71,593), the index classifier showed a tendency for differentiating survival probabilities among classes. Compared to the reference TNM survival rates, the index classification under-estimated the survival probability for stages IA, IIIB, and IV, and over-estimated it for stages IIA and IIB. CONCLUSION: The inverse of the treatment decision rules has a potential to supplement a routinely collected database with information encoded in the treatment decision rules to classify NSCLC patients. It requires further validation and replication in multiple clinical settings.

Comparison of Long-Term Outcomes Between Minimally Invasive Pulmonary Resection With and Without Video-Assisted Mediastinoscopic Lymphadenectomy for Left-Sided Lung Cancer.

BACKGROUND: This study aimed to assess the long-term outcomes of video-assisted mediastinoscopic lymphadenectomy (VAMLA) combined with video-assisted thoracic surgery (VATS) for left-sided lung cancer pulmonary resection. PATIENTS AND METHODS: We retrospectively reviewed 1194 consecutive patients who underwent VATS anatomical resection for left-sided lung cancer between January 2007 and December 2016. Using propensity score-based inverse probability of treatment weighting (IPTW), perioperative outcomes and long-term survival outcomes were compared. RESULTS: Among 1194 patients, 295 (24.7%) underwent additional VAMLA (VATS + VAMLA group) and 899 patients (75.3%) underwent VATS only (VATS group). The proportion of patients with advanced N stage were higher in the VATS + VAMLA group (24.7%) than in the VATS group (18.3%). After IPTW adjustment, all baseline profiles between the two groups became similar. The long-term overall survival (OS) and recurrence-free survival (RFS) rates were similar between the VATS + VAMLA group and the VATS group (5-year OS, 77.8% versus 79.3%, p = 0.957; 5-year RFS, 69.6% versus 70.1%, p = 0.498). However, among patients with borderline pulmonary function (FEV1 ≤ 60% or DLCO ≤ 60%), the VATS + VAMLA group (n = 23) had a better prognosis than the VATS group (n = 36) (5-year OS, 67.4% versus 46.7%, respectively; p = 0.047; 5-year RFS, 74.6% versus 53.5%, respectively; p = 0.027). CONCLUSIONS: VAMLA might be a good complement to VATS for left-sided lung cancer, wherein optimal mediastinal lymph node dissection is not feasible under one-lung ventilation, such as when patients have borderline pulmonary function.

Influence of Preoperative Nutritional Status on Patients Who Undergo Upfront Surgery for Esophageal Squamous Cell Carcinoma.

Few studies have focused on preoperative nutritional status of esophageal cancer patients eligible for upfront surgery. We aimed to investigate the association of preoperative nutritional status with prognosis of patients who undergo upfront surgery for esophageal cancer. A total of 274 patients who underwent upfront surgery for esophageal squamous cell carcinoma between January 2012 and December 2016 were eligible. Preoperative nutritional status was evaluated using prognostic nutritional index (PNI) scoring system, nutritional risk screening 2002 (NRS 2002), and controlling nutritional status. The median age was 63 years (interquartile range, 58-70) and 94.7% of patients were male. The pathological stages were Stage I-74.5% (204/274), Stage II-20.4% (56/274), and Stage III-5.1% (14/274). Multivariate analysis revealed that advanced stage, a low PNI, and a high NRS 2002 were independent predictors of overall survival. During median follow-up period of 55 mo, overall survival rates were lower in the high NRS 2002 group (P < 0.001). A high NRS 2002 score was associated with frequent postoperative complications, especially pneumonia and anastomosis site leakage (P = 0.003). The poor preoperative nutritional status with a high NRS 2002 is associated with postoperative complications as well as poor overall survival in patients with upfront surgery for esophageal cancer.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2022.2042573.

Diagnostic and prognostic values of 2-[18F]FDG PET/CT in resectable thymic epithelial tumour.

OBJECTIVES: We aimed to evaluate the diagnostic ability for the prediction of histologic grades and prognostic values on recurrence and death of pretreatment 2-[18F]FDG PET/CT in patients with resectable thymic epithelial tumours (TETs). METHODS: One hundred and fourteen patients with TETs who underwent pretreatment 2-[18F]FDG PET/CT between 2012 and 2018 were retrospectively evaluated. TETs were classified into three histologic subtypes: low-risk thymoma (LRT, WHO classification A/AB/B1), high-risk thymoma (HRT, B2/B3), and thymic carcinoma (TC). Area under the receiver operating characteristics curve (AUC) was used to assess the diagnostic performance of PET/CT variables (maximum standardised uptake value [SUVmax], metabolic tumour volume [MTV], total lesion glycolysis [TLG], maximum diameter). Cox proportional hazards models were built using PET/CT and clinical variables. RESULTS: The tumours included 52 LRT, 33 HRT, and 29 TC. SUVmax showed good diagnostic ability for differentiating HRT/TC from LRT (AUC 0.84, 95% confidence interval [CI] 0.76 - 0.92) and excellent ability for differentiating TC from LRT/HRT (AUC 0.94, 95% CI 0.90 - 0.98), with significantly higher values than MTV, TLG, and maximum diameter. With an optimal cut-off value of 6.4, the sensitivity, specificity, and accuracy for differentiating TC from LRT/HRT were 69%, 96%, and 89%, respectively. In the multivariable Cox proportional hazards analyses for freedom-from-recurrence, SUVmax was an independent prognostic factor (p < 0.001), whereas MTV and TLG were not. SUVmax was a significant predictor for overall survival in conjunction with clinical stage and resection margin. CONCLUSION: SUVmax showed excellent diagnostic performance for prediction of TC and significant prognostic value in terms of recurrence and survival. KEY POINTS: • Maximum standardised uptake value (SUVmax) shows excellent performance in the differentiation of thymic carcinoma from low- and high-risk thymoma. • SUVmax is an independent prognostic factor for freedom-from-recurrence in the multivariable Cox proportional hazard model and a significant predictor for overall survival. • 2-[18F]FDG PET/CT can provide a useful diagnostic and prognostic imaging biomarker in conjunction with histologic classification and stage and help choose appropriate management for thymic epithelial tumours.

Effects of Multimodal Inpatient Rehabilitation vs Conventional Pulmonary Rehabilitation on Physical Recovery After Esophageal Cancer Surgery.

OBJECTIVE: To determine the effects of multimodal rehabilitation initiated immediately after esophageal cancer surgery on physical recovery compared with conventional pulmonary rehabilitation. DESIGN: Retrospective study. SETTING: Private quaternary care hospital. PARTICIPANTS: Fifty-nine inpatients (N=59) who participated in either conventional pulmonary rehabilitation (n=30) or in multimodal rehabilitation (n=29) after esophageal cancer surgery were included. INTERVENTIONS: Both groups performed pulmonary exercises, including deep breathing, chest expansion, inspiratory muscle training, coughing, and manual vibration. In the conventional pulmonary rehabilitation group, light-intensity mat exercise, stretching, and walking were performed. The multimodal rehabilitation group performed resistance exercises and moderate- to high-intensity aerobic interval exercises using a bicycle. MAIN OUTCOME MEASURES: The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 (EORTC QLQ-C30), pain, 6-minute walk test (6MWT), 30-second chair stand test, and grip strengths were assessed before and after the rehabilitation programs. RESULTS: Symptom scales of pain, dyspnea, and insomnia in the EORTC QLQ-C30 as well as 6MWT improved significantly after each program (P<.05). 6MWT (73.1±52.6 vs 28.4±14.3, P<.001, d=1.15), 30-second chair stand test (3.5±3.9 vs 0.35±2.0, P<.001, d=1.06), and left grip strength (1.2±1.3 vs 0.0±1.5, P=.002, d=0.42) improved significantly in the multimodal rehabilitation group compared with the pulmonary rehabilitation group. While right grip strength also showed more improvement for those undergoing the multimodal program, the mean strength difference was not clinically meaningful. CONCLUSIONS: A multimodal inpatient rehabilitation program instituted early after esophageal cancer surgery improved endurance for walking more than conventional pulmonary rehabilitation as measured by the 6MWT and the 30-second chair stand test.

Surgical Outcomes of Non-Small Cell Lung Cancer in Single-Zone N2 in the Aortopulmonary Zone.

OBJECTIVES: We evaluate the surgical outcome of clinically single-zone N2 lung cancer limited to aortopulmonary zone (AP zone; lymph node #5 or #6). PATIENTS AND METHODS: We performed a retrospective analysis of patients with non-small cell lung cancer, in whom mediastinal lymph node metastasis was confined to AP zone. RESULTS: A total of 84 patients who underwent upfront surgery were included in final analysis. Among these patients, pathological nodal outcomes were pN0-1 in 27 patients (32.1%), pN2a in 31 (36.9%), and pN2b in 26 (31.0%). In multivariate analysis, adenocarcinoma (p = 0.005) and staging workup without endobronchial ultrasound-transbronchial needle aspiration (p = 0.002) were independent risk factors for unexpected pN2b. The 5-year overall survival (OS) and disease-free survival (DFS) were 55.9 and 54.4%, respectively. There was no survival difference among patients with pN0-1, pN2a, and pN2b (p = 0.717). In survival analysis, there were no significant risk factors for OS. However, female sex and the ratio of positive lymph nodes to removed lymph nodes were significant risk factors for DFS in multivariate analysis (p = 0.032 and p = 0.009). CONCLUSION: In this study, cN2a in the AP zone with current diagnostic tool exhibited a relatively high false-positive rate (cN2/pN0-1; 32.1%). However, despite the possibility of pN2b, there were no significant differences in survival outcome according to the pathologic nodal stage.

Predicting Postoperative Complications and Long-Term Survival After Lung Cancer Surgery Using Eurolung Risk Score.

BACKGROUND: This study aimed to assess the clinical relevance of the parsimonious Eurolung risk scoring system for predicting postoperative morbidity, mortality, and long-term survival in Korean patients with surgically resected non-small cell lung cancer. METHODS: This retrospective analysis used the data of patients who underwent anatomical resection for non-small cell lung cancer between 2004 and 2018 at a single institution. The parsimonious aggregate Eurolung score was calculated for each patient. The Cox regression model was used to determine the ability of the Eurolung scoring system for predicting long-term outcomes. RESULTS: Of the 7,278 patients in the study, cardiopulmonary complications and mortality occurred in 687 (9.4%) and 53 (0.7%) patients, respectively. The rate of cardiopulmonary complications and mortality gradually increased with the increase in the Eurolung risk scores (all P < 0.001). When risk scores were grouped into four categories, the Eurolung scoring system showed a stepwise deterioration of overall survival with the increase in risk scores, and this association was statistically significant (P < 0.001). Multivariate Cox analysis showed that the Eurolung scoring system, classified into four categories, was a significant prognostic factor of overall survival even after adjusting for covariates such as tumor histology and pathological stage (P < 0.001). CONCLUSION: Stratification based on the parsimonious Eurolung scoring system showed good discriminatory ability for predicting postoperative morbidity, mortality, and long-term survival in South Korean patients with surgically resected non-small cell lung cancer. This might help clinicians to provide a detailed prognosis and decide the appropriate treatment option for high-risk patients with non-small cell lung cancer.

Blood Vessel Invasion Predicts Postoperative Survival Outcomes and Systemic Recurrence Regardless of Location or Blood Vessel Type in Patients with Lung Adenocarcinoma.

BACKGROUND: Presence of blood vessel invasion (BVI) is one of the prognostic indicators for lung cancer patients with surgical resection. However, prognostic roles of the location and the type of the involved blood vessel have not been fully evaluated yet. PATIENTS AND METHODS: We retrieved the data of 217 cases of surgically resected lung adenocarcinoma from Asan Medical Center. Clinicopathologic features, including BVI, were reassessed. The location (tumor center and/or periphery) and involved blood vessel types (large and/or small vessels; arteries and/or veins) of BVI were separately examined on standard hematoxylin-eosin slides and confirmed by van Gieson elastic staining. RESULTS: BVI was identified in 35% of cases (76/217), with the tumor center (intratumoral) as the location in more than half of the cases (42/76, 55.3%). The presence of BVI was significantly associated with higher pathologic stage, increased size of invasive components, frequent pleural invasion, lymphatic permeation, and spread through alveolar spaces. BVI was significantly associated with poor overall survival (OS) and recurrence-free survival (RFS) both in univariate and multivariate survival analyses [for OS, hazard ratio (HR) 1.92, 95% confidence interval (CI) 1.06-3.48, P = 0.031; for RFS, HR 2.65, 95% CI 1.64-4.28; P < 0.001]. BVI subgroups, according to location and type of the involved blood vessels, invariably displayed significantly poor RFS; however, the results for OS varied. CONCLUSION: Regardless of their location or blood vessel type, presence of BVI is a useful predictor for postoperative survival outcomes, which should be carefully evaluated on pathologic examination.

Pleuropulmonary Blastoma with Hotspot Mutations in RNase IIIb Domain of DICER 1: Clinicopathologic Study of 10 Cases in a Single-Institute Experience.

INTRODUCTION: Pleuropulmonary blastoma (PPB) is a rare sarcomatous malignancy involving the lung and pleura which occurs in early childhood. Cystic PPB in the early stage can be misdiagnosed as other cystic diseases. Early detection of this entity is important for appropriate treatment and prevention of disease progression. Hotspot mutations in the ribonuclease IIIb (RNase IIIb) domain of DICER1 have been reported to have a crucial role as genetic factors of PPB and DICER1 familial syndrome. We reviewed the clinicopathologic findings of PPB and the status of DICER1 hotspot mutation and patients' clinical course. METHODS: We retrospectively reviewed all patients with histologically confirmed PPB at Asan Medical Center between 2000 and 2017. Ten cases were identified in the database, and their clinicopathologic parameters were evaluated. PPB was classified into the following 3 pathologic subtypes: type I (purely cystic), type II (mixed cystic and solid), and type III (entirely solid). The status of DICER1 mutation in 2 hotspot regions of the RNase IIIb domain was evaluated by Sanger sequencing. RESULTS: The most frequent PPB type was II (6 cases), followed by I and III (2 cases each). The age at diagnosis ranged from 16 months to 15 years. All patients underwent surgery, and all patients received adjuvant or neoadjuvant chemotherapy. Four of 7 patients had missense mutations in the RNase IIIb hotspot; the base and predicted corresponding amino acid changes were c.5113 G>A (p.E1705K), c.5407 G>A (p.E1803K), c.5425 G>A (p.G1809R), and c.5428 G>T (p.D1810Y). There was no particular association between the presence of the hotspot mutation and histologic type. Nine patients survived with no evidence of disease for a median interval of 93 (range, 13-199) months. Only 1 patient diagnosed with type III PPB at the age of 18 years had recurrence after 20.8 months and eventually died 66 months after the initial diagnosis. CONCLUSIONS: Late detection of solid PPB is associated with poor prognosis. Considering the rarity of PPB disease and the importance of DICER1 hotspot mutation in pathogenesis, DICER1 hotspot mutation testing and identification in the early cystic stage can improve patient outcomes.

Close Observation versus Additional Surgery after Noncurative Endoscopic Resection of Esophageal Squamous Cell Carcinoma.

INTRODUCTION: After noncurative endoscopic submucosal dissection (ESD) of superficial esophageal squamous cell carcinoma (SESCC), additional esophagectomy is generally recommended. However, considering its high mortality and morbidity, it is uncertain if additional surgery improves the clinical outcomes. This study aimed to compare the clinical outcomes between patients who were observed without additional treatment and those who underwent radical esophagectomy. METHODS: A total of 52 patients with SESCC who underwent complete but noncurative ESD from January 2008 to December 2016 at the Samsung Medical Center and Asan Medical Center in Korea were retrospectively analyzed. Clinicopathologic characteristics and oncologic outcomes were compared between the observation group (n = 23) and the additional surgery group (n = 29). RESULTS: During a mean follow-up of 34.4 and 41.7 months, respectively, the rates of death (observation vs. surgery, 17.4 vs. 10.3%; p = 0.686), recurrence (observation vs. surgery, 13 vs. 17.2%; p = 1.000), and disease-specific death (observation vs. surgery, 4.3 vs. 6.9%; p = 1.000) did not significantly differ between the 2 groups. The 3-year overall survival was 86.3 and 96.4%, respectively (p = 0.776). The 3-year recurrence-free survival (observation vs. surgery, 85.0 vs. 88.7%; p = 0.960) and disease-specific survival (observation vs. surgery, 95.2 vs. 96.4%; p = 0.564) also did not significantly differ. CONCLUSIONS: The clinical outcomes of close observation of noncuratively resected SESCC are comparable to those of additional surgery, at least in the midterm. The wait-and-see strategy could be a feasible management option after noncurative ESD of SESCC in selected patients.

Surgical outcomes of pulmonary metastasectomy in hepatocellular carcinoma patients according to approach method: thoracoscopic versus open approach.

BACKGROUND: The role of surgical intervention as a treatment for pulmonary metastasis (PM) from hepatocellular carcinoma (HCC) has not been established. In this study, we investigated the clinical outcomes of pulmonary metastasectomy. Using propensity score matching (PSM) analysis, we compared the results according to the surgical approach: video-assisted thoracic surgery (VATS) versus the open method. METHODS: A total of 134 patients (115 men) underwent pulmonary metastasectomy for isolated PM of HCC between January 1998 and December 2010 at Seoul Asan Medical Center. Of these, 84 underwent VATS (VATS group) and 50 underwent thoracotomy or sternotomy (open group). PSM analysis between the groups was used to match them based on the baseline characteristics of the patients. RESULTS: During the median follow-up period of 33.4 months (range, 1.8-112.0), 113 patients (84.3%) experienced recurrence, and 100 patients (74.6%) died of disease progression. There were no overall survival rate, disease-free survival rate, and pulmonary-specific disease-free survival rate differences between the VATS and the open groups (p = 0.521, 0.702, and 0.668, respectively). Multivariate analysis revealed local recurrence of HCC, history of liver cirrhosis, and preoperative alpha-fetoprotein level as independent prognostic factors for overall survival (hazard ratio, 1.729/2.495/2.632, 95% confidence interval 1.142-2.619/1.571-3.963/1.554-4.456; p = 0.010/< 0.001/< 0.001, respectively). CONCLUSIONS: Metastasectomy can be considered a potential alternative for selected patients. VATS metastasectomy had outcomes comparable to those of open metastasectomy.

Natural Progression of Ground-glass Nodules after Curative Resection for Non-small Cell Lung Cancer.

BACKGROUND: This retrospective study investigated the natural course of synchronous ground-glass nodules (GGNs) that remained after curative resection for non-small-cell lung cancer (NSCLC). METHODS: Prospectively collected retrospective data were reviewed concerning 2,276 patients who underwent curative resection for NSCLC between 2008 and 2017. High-resolution computed tomography or thin-section computed tomography data of 82 patients were included in the study. Growth in size was considered the most valuable outcome, and patients were grouped according to GGN size change. Patient demographic data (e.g., age, sex, and smoking history), perioperative data (e.g., GGN characteristics, histopathology and pathological stage of the resected tumours), and other medical history were evaluated in a risk factor analysis concerning GGN size change. RESULTS: The median duration of follow-up was 36.0 months (interquartile range, 23.0-59.3 months). GGN size decreased in 6 patients (7.3%), was stationary in 43 patients (52.4%), and increased in 33 patients (40.2%). In univariate analysis, male sex, the GGN size on initial CT, part-solid GGN and smoking history (≥ 10 pack-years) were significant risk factors. Among them, multivariate analysis revealed that lager GGN size, part-solid GGN and smoking history were independent risk factors. CONCLUSION: During follow-up, 40.2% of GGNs increased in size, emphasising that patients with larger GGNs, part-solid GGN or with a smoking history should be observed.

A nomogram for predicting recurrence after complete resection for thymic epithelial tumors based on the TNM classification: A multi-institutional retrospective analysis.

OBJECTIVES: This study aimed to compare the predictive ability between the Masaoka-Koga (M-K) staging system and the 8th TNM staging system for the recurrence of thymic epithelial tumors (TETs). In addition, a nomogram was developed on the basis of the proposed TNM classification to predict individual recurrence rate. METHODS: A retrospective study was performed on 445 patients who underwent complete resection (R0) of TETs between January 2000 and February 2013. Concordance index (C-index) was used as a statistical indicator to quantify the prediction power of the prediction models. RESULTS: In multivariate analysis, tumor stage and WHO classification were independent recurrence factors in a predictive model on the basis of M-K and TNM stage. The TNM model showed higher C-index than the M-K model (0.837 vs 0.817). The nomogram, on the basis of the TNM model, revealed a highly predictive performance, with a bootstrap-corrected C-index of 0.85 (95% CI, 0.76 to 0.93). CONCLUSIONS: A predictive model based on the 8th TNM stage was slightly better than that based on M-K stage with respect to recurrence after R0 of TETs. The proposed nomogram could be applied to estimate the individual recurrence rate and make decisions for proper surveillance.

Genomic profiles of lung cancer associated with idiopathic pulmonary fibrosis.

Little is known about the pathogenesis or molecular profiles of idiopathic pulmonary fibrosis-associated lung cancer (IPF-LC). This study was performed to investigate the genomic profiles of IPF-LC and to explore the possibility of defining potential therapeutic targets in IPF-LC. We assessed genomic profiles of IPF-LC by using targeted exome sequencing (OncoPanel version 2) in 35 matched tumour/normal pairs surgically resected between 2004 and 2014. Germline and somatic variant calling was performed with GATK HaplotypeCaller and MuTect with GATK SomaticIndelocator, respectively. Copy number analysis was conducted with CNVkit, with focal events determined by Genomic Identification of Significant Targets in Cancer 2.0, and pathway analysis (KEGG) with DAVID. Germline mutations in TERT (rs2736100, n = 33) and CDKN1A (rs2395655, n = 27) associated with idiopathic pulmonary fibrosis risk were detected in most samples. A total of 410 somatic mutations were identified, with an average of 11.7 per tumour, including 69 synonymous, 177 missense, 17 nonsense, 1 nonstop and 11 splice-site mutations, and 135 small coding indels. Spectra of the somatic mutations revealed predominant C > T transitions despite an extensive smoking history in most patients, suggesting a potential association between APOBEC-related mutagenesis and the development of IPF-LC. TP53 (22/35, 62.9%) and BRAF (6/35, 17.1%) were found to be significantly mutated in IPF-LC. Recurrent focal amplifications in three chromosomal loci (3q26.33, 7q31.2, and 12q14.3) and 9p21.3 deletion were identified, and genes associated with the JAK-STAT signalling pathway were significantly amplified in IPF-LC (P = 0.012). This study demonstrates that IPF-LC is genetically characterized by the presence of somatic mutations reflecting a variety of environmental exposures on the background of specific germline mutations, and is associated with potentially targetable alterations such as BRAF mutations. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Recent Trends in Demographics, Surgery, and Prognosis of Patients with Surgically Resected Lung Cancer in a Single Institution from Korea.

BACKGROUND: Over the past few decades, demographics information has changed significantly in patients with surgically resected lung cancer. Herein, we evaluated the recent trends in demographics, surgery, and prognosis of lung cancer surgery in Korea. METHODS: Patients with surgically resected primary lung cancer from 2002 to 2016 were retrospectively analyzed. Multivariable Cox regression analysis was conducted to identify prognostic factors for overall survival. The annual percent change (APC) and statistical significance were calculated using the Joinpoint software. RESULTS: A total of 7,495 patients were enrolled. Over the study period, the number of lung cancer surgeries continued to increase (P < 0.05). The proportion of women to total subjects has also increased (P < 0.05). The proportion of elderly patients (≥ 70 years) as well as those with tumors measuring 1-2 cm and 2-3 cm significantly increased in both genders (all P < 0.05). The proportion of patients with adenocarcinoma, video-assisted thoracic surgery, sublobar resection, and pathological stage I significantly increased (P < 0.05). The 5-year overall survival rate of lung cancer surgery increased from 61.1% in 2002-2006 to 72.1% in 2012-2016 (P < 0.001). The operative period was a significant prognostic factor in multivariable Cox analysis (P < 0.001). CONCLUSION: The mean age of patients with lung cancer surgery increased gradually, whereas tumor size reduced. Prognosis of lung cancer surgery improved with recent increases in the frequency of adenocarcinoma, video-assisted thoracic surgery, sublobar resection, and pathological stage I. The operation period itself was also an independent prognostic factor for overall survival.

Effect of restrictive fluid therapy with hydroxyethyl starch during esophagectomy on postoperative outcomes: a retrospective cohort study.

BACKGROUND: To improve prognosis after esophageal surgery, intraoperative fluid optimization is important. Herein, we hypothesized that hydroxyethyl starch administration during esophagectomy reduce the total amount of fluid infused and it could have a positive effect on postoperative complication occurrence and mortality. METHODS: All consecutive adult patients who underwent elective esophageal surgery for cancer were studied. The primary outcome was the development of composite complications including death, cardio-cerebrovascular complications, respiratory complications, renal complications, gastrointestinal complications, sepsis, empyema or abscess, and multi-organ failure. The relationship between perioperative variables and composite complication was evaluated using multivariable logistic regression. RESULTS: Of 892 patients analyzed, composite complications developed in 271 (30.4%). The higher hydroxyethyl starch ratio in total fluid had a negative relationship with the total fluid infusion amount (r = - 0.256, P <  0.001). In multivariable analysis, intraoperatively administered total fluid per weight per hour (odds ratio, 1.248; 95% CI, 1.153-1.351; P <  0.001) and HES-to-crystalloid ratio (odds ratio, 2.125; 95% CI, 1.521-2.969; P <  0.001) were associated with increased risks of postoperative composite outcomes. CONCLUSIONS: Although hydroxyethyl starch administration reduces the total fluid infusion amount during esophageal surgery for cancer, intravenous hydroxyethyl starch infusion is associated with an increasing risk of postoperative composite complications.

Surgical Outcome of Colon Interposition in Esophageal Cancer Surgery: Analysis of Risk Factors for Conduit-Related Morbidity.

BACKGROUND: We aimed to assess the feasibility, surgical outcomes, and conduit-related complications of colon interposition in patients with esophageal cancer. METHODS: Patients with esophageal cancer who underwent colon interposition for esophageal reconstruction between June 2000 and June 2013 were retrospectively reviewed. RESULTS: A total of 67 consecutive patients (mean age, 62.2 ± 7.9 years) were enrolled. During this time period, 944 patients underwent esophageal reconstruction using gastric conduit. Twelve patients (17.9%) also received neoadjuvant chemoradiotherapy (nCRT). The median follow-up duration was 44 months (range, 1-168 months); median survival duration was 63 months (range, 1-168 months); and 3- and 5-year overall survival rates were 61.6 and 49.4%, respectively. A total of 43 patients (64.2%) experienced at least 1 postoperative morbidity. According to the Clavien-Dindo grading system, 36 patients (54%) experienced postoperative morbidity of higher than Grade III. Pulmonary complications were most commonly observed complications among the patients (18 patients, 26.9%). Anastomosis site leakage developed in 11 patients (16.4%), and 3 of these patients (6.0%) eventually experienced graft failure. On multivariate analysis, nCRT was determined as a significant risk factor for conduit-related complications (leakage, graft failure, fistula, and stricture). CONCLUSION: Colon interposition is associated with relatively high complication rates, whereas nCRT is associated with conduit morbidity.

Surgical Outcomes after Pulmonary Resection for Non-Small Cell Lung Cancer with Localized Pleural Seeding First Detected during Surgery.

OBJECTIVES: Curative resection is not indicated for non-small cell lung cancer (NSCLC) with pleural seeding, which is classified as stage IV (M1a) disease. However, some patients with a presumably resectable main tumor are diagnosed with localized pleural seeding during surgery. METHODS: A retrospective analysis was performed of 3,975 patients who underwent surgery for NSCLC from 2000 to 2011. Among these cases, 78 (2.0%) patients had unexpected pleural seeding detected during surgery. Exploration with pleural biopsy was performed in 42 of these patients (exploration-only group) and pulmonary resection, including for the main tumor, was performed in 36 cases (resection group; sublobar resection in 12, lobectomy in 21, and pneumonectomy in 3 patients). Survival and cancer progression rates were estimated using the Kaplan-Meier method. Cox proportional hazard regression was used to evaluate prognostic factors associated with survival. RESULTS: Adenocarcinoma was the predominant histological type in both the exploration and resection groups (88.1 and 86.1%, respectively). Epidermal growth factor receptor expression was detected in 22 (52.4%) patients of the exploration group and 21 (58.3%) patients of the resection group. Baseline characteristics including age, sex, comorbidity, pulmonary function, and clinical T/N status were not significantly different between the two groups. There were no postoperative deaths in either group but postoperative complications occurred in two (4.8%) patients of the exploration group and three (8.3%) patients of the resection group. The overall 3- and 5-year survival rates in the exploration group were 41.1 and 15.2%, respectively, with a median survival time (MST) of 33 months, whereas they were 66.7 and 42.7%, respectively, in the resection group, with a 52-month MST (p = 0.012). Local and regional progression-free rates were significantly different (p < 0.001 and p = 0.029, respectively) between groups, whereas no difference was seen in the distant metastasis rates (p = 0.957). In multivariate survival analysis, surgical resection was the only significant prognostic factor (p = 0.01). CONCLUSIONS: Pulmonary resection including the main tumor, regardless of resection extent, may increase long-term survival for NSCLC patients with localized pleural seeding first detected during surgery, without a significant increase in hospital mortality or morbidity.