Role of bone single photon emission computed tomography/computed tomography in managing chronic fracture-related infections: Determining the depth of infection and avoiding unnecessary bone procedures.

PURPOSE: Fracture-related infections (FRIs) encompass a broad range of infections associated with bone fractures; they remain a significant clinical challenge. Here, we aimed to investigate the viability of focusing on soft-tissue management in patients suspected of chronic FRI, who exhibit no significant bony uptake on bone single photon emission computed tomography (SPECT)/computed tomography (CT) scans. METHODS: Between January 2016 and January 2022, we managed 25 patients with chronic FRI or post-traumatic osteomyelitis using technetium 99m-methyl diphosphonate bone SPECT/CT to assess infection depth. Among them, 13 patients showing negligible bony uptake were included and categorized into two groups based on wound discharge reaching the bone/implant (Criteria 1, n = 6) or not (Criteria 2, n = 7). RESULTS: Patients in the Criteria 1 group were treated with antibiotics and soft tissue debridement without bony procedure. The average duration of antibiotic therapy was 6.7 weeks. Treatments were individualized, including implant changes, local flaps, skin grafts, and negative pressure wound therapy. No recurrence was reported in the mean follow-up of 21.3 months. Patients in the Criteria 2 group were treated with oral antibiotics (mean duration: 5.9 weeks) and daily wound dressings. No recurrence was reported in the mean follow-up of 26.0 months, and no surgical interventions were required. CONCLUSION: This study demonstrates the feasibility of focusing on soft-tissue management in patients with chronic FRI showing minimal bony uptake on bone SPECT/CT. Our treatment protocol avoided unnecessary surgical bone procedures, resulting in successful clinical outcomes with no recurrences.

Practice pattern and risk of not receiving planned surgery after neoadjuvant chemoradiotherapy for locally advanced oesophageal squamous cell carcinoma.

OBJECTIVES: Unlike the initial plan, some patients with oesophageal squamous cell carcinoma cannot or do not receive surgery after neoadjuvant chemoradiotherapy (nCRT). This study aimed to report the epidemiology of patients not receiving surgery after nCRT and to evaluate the potential risk of refusing surgery. METHODS: We analysed patients with clinical stage T3-T4aN0M0 or T1-T4aN1-N3M0 oesophageal squamous cell carcinoma who underwent nCRT as an initial treatment intent between January 2005 and March 2020. Patients not receiving surgery were categorized using predefined criteria. To evaluate the risk of refusing surgery, a propensity-matched comparison with those who received surgery was performed. Recurrence-free (RFS) and overall survival (OS) was compared between groups, according to clinical response to nCRT. RESULTS: Among the study population (n = 715), 105 patients (14.7%) eventually failed to reach surgery. There were three major patterns of not receiving surgery: disease progression before surgery (n = 25), functional deterioration at reassessment (n = 47), and patient's refusal without contraindications (n = 33). After propensity-score matching, the RFS curves of the surgery group and the refusal group were significantly different (P < 0.001), while OS curves were not significantly different (P = 0.069). In patients who achieved clinical complete response on re-evaluation, no significant difference in the RFS curves (P = 0.382) and in the OS curves (P = 0.290) was observed between the surgery group and the refusal group. However, among patients who showed partial response or stable disease on re-evaluation, the RFS and OS curves of the refusal group were overall significantly inferior compared to those of the surgery group (both P < 0.001). The 5-year RFS rates were 10.3% for the refusal group and 48.2% for the surgery group, and the 5-year OS rates were 8.2% for the refusal group and 46.1% for the surgery group. CONCLUSIONS: Patient's refusal remains one of the major obstacles in completing the trimodality therapy for oesophageal squamous cell carcinoma. Refusing surgery when offered may jeopardize oncological outcome, particularly in those with residual disease on re-evaluation after nCRT. These results provide significant implications for consulting patients who are reluctant to oesophagectomy after nCRT.

Computed tomography characteristics of cN0 primary non-small cell lung cancer predict occult lymph node metastasis.

RATIONALE: Occult lymph node metastasis (OLNM) is frequently found in patients with resectable non-small cell lung cancer (NSCLC), despite using diagnostic methods recommended by guidelines. OBJECTIVES: To evaluate the risk of OLNM in NSCLC patients using the radiologic characteristics of the primary tumor on computed tomography (CT). METHODS: We retrospectively reviewed clinicopathologic features of 2042 clinical T1-4N0 NSCLC patients undergoing curative intent pulmonary resection. Unique radiological features (i.e., air-bronchogram throughout the whole tumor, heterogeneous ground-glass opacity (GGO), mainly cystic appearance, endobronchial location), percentage of solid portion, and shape of tumor margin were analyzed via a stepwise approach. We used multivariable logistic regression to assess the relationship between OLNM and tumor characteristics. RESULTS: Compared with the other unique features, endobronchial tumors were associated with the highest risk of OLNM (OR = 3.9, 95% confidence interval (CI) = 2.29-6.62), and heterogeneous GGO and mainly cystic tumors were associated with a low risk of OLNM. For tumors without unique features, the percentage of the solid portion was measured, and solid tumors were associated with OLNM (OR = 2.49, 95% CI = 1.86-3.35). Among part-solid tumors with solid proportion > 50%, spiculated margin, and peri-tumoral GGO were associated with OLNM. CONCLUSIONS: The risk of OLNM could be assessed using radiologic characteristics on CT. This could allow us to adequately select optimal candidates for invasive nodal staging procedures (INSPs) and complete systematic lymph node dissection. CLINICAL RELEVANCE STATEMENT: These data may be helpful for clinicians to select appropriate candidates for INSPs and complete surgical systematic lymph node dissection in NSCLC patients. KEY POINTS: Lymph node metastasis status plays a key role in both prognostication and treatment planning. Solid tumors, particularly endobronchial tumors, were associated with occult lymph node metastasis (OLNM). The risk of OLNM can be assessed using radiologic characteristics acquired from CT images.

Predicting Brain Age and Gender from Brain Volume Data Using Variational Quantum Circuits.

The morphology of the brain undergoes changes throughout the aging process, and accurately predicting a person's brain age and gender using brain morphology features can aid in detecting atypical brain patterns. Neuroimaging-based estimation of brain age is commonly used to assess an individual's brain health relative to a typical aging trajectory, while accurately classifying gender from neuroimaging data offers valuable insights into the inherent neurological differences between males and females. In this study, we aimed to compare the efficacy of classical machine learning models with that of a quantum machine learning method called a variational quantum circuit in estimating brain age and predicting gender based on structural magnetic resonance imaging data. We evaluated six classical machine learning models alongside a quantum machine learning model using both combined and sub-datasets, which included data from both in-house collections and public sources. The total number of participants was 1157, ranging from ages 14 to 89, with a gender distribution of 607 males and 550 females. Performance evaluation was conducted within each dataset using training and testing sets. The variational quantum circuit model generally demonstrated superior performance in estimating brain age and gender classification compared to classical machine learning algorithms when using the combined dataset. Additionally, in benchmark sub-datasets, our approach exhibited better performance compared to previous studies that utilized the same dataset for brain age prediction. Thus, our results suggest that variational quantum algorithms demonstrate comparable effectiveness to classical machine learning algorithms for both brain age and gender prediction, potentially offering reduced error and improved accuracy.

Evaluating the Efficacy of the Erector Spinae Plane Block as a Supplementary Approach to Cardiac Anesthesia during Off-Pump Coronary Bypass Graft Surgery via Median Sternotomy: A Randomized Clinical Trial.

Background: Pain control after off-pump coronary artery bypass graft (OPCAB) facilitates mobilization and improves outcomes. The efficacy of the erector spinae plane block (ESPB) after cardiac surgery remains controversial. Methods: We aimed to investigate the analgesic effects of ESPB after OPCAB. Precisely 56 patients receiving OPCAB were randomly divided into ESPB and control groups. The primary outcome was visual analog scale (VAS) pain scores at 6, 12, 24, and 48 h postoperatively. Secondary outcomes were the dose of rescue analgesics in terms of oral morphine milligram equivalents, the dose of antiemetics, the length of intubation time, and the length of stay in the intensive care unit (ICU). Results: The VAS scores were similar at all time points in both groups. The incidence of severe pain (VAS score > 7) was significantly lower in the ESPB group (50% vs. 15.4%; p = 0.008). The dose of rescue analgesics was also lower in the ESPB group (19.04 ± 18.76, 9.83 ± 12.84, p = 0.044) compared with the control group. The other secondary outcomes did not differ significantly between the two groups. Conclusions: ESPB provides analgesic efficacy by reducing the incidence of severe pain and opioid use after OPCAB.

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.

Metabolic dysfunction-associated steatotic liver disease and risk of esophageal cancer in patients with diabetes mellitus: a nationwide cohort study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with type 2 diabetes and a developing several cancers including esophageal cancer (EC). However, the association between MASLD and EC in diabetic patients has not been investigated. Therefore, we aimed to investigate the relation between MASLD and developing EC in diabetic patients. This was a population-based retrospective cohort study of data from the Korean National Health Insurance Service (NHIS). A total of 1,904,468 subjects diagnosed with diabetes who underwent NHIS-provided health checkups from 2009 to 2012 were included. We constructed a Cox proportional hazard model for the association of fatty liver index (FLI) and the risk of EC stratified by potential confounders. Over a mean follow-up duration of 6.9 years, the incidence of EC was higher in the high (≥60) FLI group compared to the low (<30) FLI group (14.4 vs. 13.7 event per 100,000 person-years). The risk of EC correlated with the degree of FLI, particularly in older (P = 0.002), female (P = 0.033), non-smoking (P = 0.002), and non-drinking patients (P = 0.025). Among obese patients, the risk of EC was not associated with FLI; however, the risk of EC was higher in the high FLI group in non-obese patients. Lean MASLD patients had the highest risk of EC (adjusted hazard ratio 1.78; 95% confidence interval, 1.5-2.13). MASLD was associated with an increased risk of EC in diabetic patients, and lean MASLD has the highest risk. Further studies are required to determine the causal relationship between MASLD and EC.

Preoperative DLco and FEV1 are correlated with postoperative pulmonary complications in patients after esophagectomy.

Limited information is available regarding the association between preoperative lung function and postoperative pulmonary complications (PPCs) in patients with esophageal cancer who undergo esophagectomy. This is a retrospective cohort study. Patients were classified into low and high lung function groups by the cutoff of the lowest fifth quintile of forced expiratory volume in 1 s (FEV1) %predicted (%pred) and diffusing capacity of the carbon monoxide (DLco) %pred. The PPCs compromised of atelectasis requiring bronchoscopic intervention, pneumonia, and acute lung injury/acute respiratory distress syndrome. Modified multivariable-adjusted Poisson regression model using robust error variances and inverse probability treatment weighting (IPTW) were used to assess the relative risk (RR) for the PPCs. A joint effect model considered FEV1%pred and DLco %pred together for the estimation of RR for the PPCs. Of 810 patients with esophageal cancer who underwent esophagectomy, 159 (19.6%) developed PPCs. The adjusted RR for PPCs in the low FEV1 group relative to high FEV1 group was 1.48 (95% confidence interval [CI] = 1.09-2.00) and 1.98 (95% CI = 1.46-2.68) in the low DLco group relative to the high DLco group. A joint effect model showed adjusted RR of PPCs was highest in patients with low DLco and low FEV1 followed by low DLco and high FEV1, high DLco and low FEV1, and high DLco and high FEV1 (Reference). Results were consistent with the IPTW. Reduced preoperative lung function (FEV1 and DLco) is associated with post-esophagectomy PPCs. The risk was further strengthened when both values decreased together.

Contralateral Pulmonary Resection after Pneumonectomy.

Background: Contralateral pulmonary resection after pneumonectomy presents considerable challenges, and few reports in the literature have described this procedure. Methods: We retrospectively reviewed the medical records of all patients who underwent contralateral lung resection following pneumonectomy for any reason at our institution between November 1994 and December 2020. Results: Thirteen patients (9 men and 4 women) were included in this study. The median age was 57 years (range, 35-77 years), and the median preoperative forced expiratory volume in 1 second was 1.64 L (range, 1.17-2.12 L). Contralateral pulmonary resection was performed at a median interval of 44 months after pneumonectomy (range, 6-564 months). Surgical procedures varied among the patients: 10 underwent single wedge resection, 2 were treated with double wedge resection, and 1 underwent lobectomy. Diagnoses at the time of contralateral lung resection included lung cancer in 7 patients, lung metastasis from other cancers in 3 patients, and tuberculosis in 3 patients. Complications were observed in 4 patients (36%), including acute kidney injury, pneumothorax following chest tube removal, pneumonia, and prolonged air leak. No cases of operative mortality were noted. Conclusion: In carefully selected patients, contralateral pulmonary resection after pneumonectomy can be accomplished with acceptable operative morbidity and mortality.

Role of invasive mediastinal nodal staging in survival outcomes of patients with non-small cell lung cancer and without radiologic lymph node metastasis: a retrospective cohort study.

Background: Lung cancer diagnostic guidelines advocate for invasive mediastinal nodal staging (IMNS), but the survival benefits of this approach in patients with non-small cell lung cancer (NSCLC) without radiologic evidence of lymph node metastasis (rN0) remain uncertain. We aimed to investigate the impact of IMNS in patients with rN0 NSCLC by comparing the long-term survival between patients who underwent IMNS and those who did not (non-IMNS). Methods: In this retrospective cohort study, we included patients with NSCLC but without radiologic evidence of lymph node metastasis from the Registry for Thoracic Cancer Surgery and the clinical data warehouse at the Samsung Medical Centre, Republic of Korea between January 2, 2008 and December 31, 2016. We compared the 5-year overall survival (OS) rate as the primary outcome after propensity score matching between the IMNS and non-IMNS groups. The age, sex, performance statue, tumor size, centrality, solidity, lung function, FDG uptake in PET-CT, and histological examination of the tumor before surgery were matched. Findings: A total of 4545 patients (887 in the IMNS group and 3658 in the non-IMNS group) who received curative treatment for NSCLC were included in this study. By the mediastinal node dissection, the overall incidence of unforeseen mediastinal node metastasis (N2) was 7.2% (317/4378 patients). Despite the IMNS, 67% of pathological N2 was missed (61/91 patients with unforeseen N2). Based on propensity score matching, 866 patients each for the IMNS and non-IMNS groups were assigned. There was no significant difference in 5-year OS and recurrence-free survival (RFS) between two groups: 5-year OS was 73.9% (95% confidence interval, CI: 71%-77%) for IMNS and 71.7% (95% CI: 68.6%-74.9%; p = 0.23), for non-IMNS (hazard ratio, HR 0.90, 95% CI: 0.77-1.07), while 5-year RFS was 64.7% (95% CI: 61.5%-68.2%) and 67.5% (95% CI: 64.3%-70.9%; p = 0.35 (HR 1.08, 95% CI: 0.92-1.27), respectively. Moreover, the timing and locations of recurrence were similar in both groups. Interpretation: IMNS might not be required before surgery for patients with NSCLC without LN suspicious of metastasis. Further randomised trials are required to validate the findings of the present study. Funding: None.

Surgical outcomes and survival following esophagectomy for squamous cell carcinoma with or without liver cirrhosis: retrospective cohort study.

BACKGROUND AND AIMS: Esophageal squamous cell carcinoma (ESCC) shares common risk factors with liver cirrhosis (LC). The influence of LC in patients with ESCC has not been fully investigated. This study aimed to investigate the postoperative and long-term survival outcomes of esophagectomy for ESCC according to LC presence. METHODS: Among patients who underwent curative-intent surgery for ESCC between 1994 and 2018, 121 patients with Child-Pugh class A LC and 2810 patients without LC were compared. RESULTS: Among the LC patients, 73 (60.3%) were diagnosed with LC before surgery and 48 (39.7%) were diagnosed intraoperatively. There were no significant differences in baseline characteristics between patients with LC and those without LC. However, intraoperative blood loss was higher, and operation time, hospital stay, and ICU stay were longer in patients with LC than in those without LC. Moreover, the reoperation, 30-day morbidity (60.6 vs. 73.6%, P =0.006) and 90-day mortality (2.2 vs. 4.9%, P =0.049) were significantly higher in patients with LC. The 5-year overall survival (OS) rate was significantly higher in patients without LC than in those with LC. After adjusting the confounding variables, LC was an adverse risk factor of OS (hazard ratio 1.402, P =0.004). Among patients with LC, the Model of End-Stage Liver Disease score was related to the development of complications of grade more than III (odds ratio 1.459, P =0.013). CONCLUSION: ESCC patients with Child-Pugh class A LC have high incidences of postoperative morbidity and mortality, and poor OS. Thus, careful patient selection, meticulous operation, and careful postoperative care are needed.

Treatment Patterns and Outcomes of Anastomotic Leakage after Esophagectomy for Esophageal Cancer.

Background: Anastomotic leakage (AL) following esophagectomy represents a serious complication that often results in prolonged hospitalization and necessitates repeated interventions, including nothing-by-mouth (NPO) restriction, endoscopic vacuum therapy (EVT), or surgical repair. In this study, we evaluated the patterns and outcomes of AL treatment. Methods: We retrospectively reviewed the medical records of patients who underwent esophagectomy for esophageal cancer at a single center between 2003 and 2020. Of 3,096 examined cases, 181 patients (5.8%) with AL were included in the study: 114 patients (63%) with cervical anastomosis (CA) and 67 (37%) with intrathoracic anastomosis (TA). Results: The incidence of AL was 11.9% in the CA and 3.2% in the TA group (p<0.001). Among patients with CA who developed AL, 87 (76.3%) were managed with NPO, 15 (13.2%) with EVT, and 12 (10.5%) with surgical repair. Over 90% of patients with cervical AL resumed an oral diet by the time of discharge, regardless of treatment method. Among patients with TA and AL, 36 (53.7%) received NPO, 25 (37.7%) underwent EVT, and 6 (9%) required surgery. Of these, 34 patients who were managed with NPO and 19 with EVT could resume an oral diet. However, only 2 patients who underwent surgery resumed an oral diet, and 2 patients required additional EVT. Conclusion: Although patients with CA displayed a higher incidence of AL, their rate of successful oral intake exceeded that of those with TA, regardless of treatment method. Among patients exhibiting AL with TA, EVT was more commonly employed than in CA cases, and it appears effective.

Outcomes of Completion Lobectomy for Locoregional Recurrence after Sublobar Resection in Patients with Non-small Cell Lung Cancer.

Background: This retrospective study aimed to determine the treatment patterns and the surgical and oncologic outcomes after completion lobectomy (CL) in patients with locoregionally recurrent stage I non-small cell lung cancer (NSCLC) who previously underwent sublobar resection. Methods: Data from 36 patients who initially underwent sublobar resection for clinical, pathological stage IA NSCLC and experienced locoregional recurrence between 2008 and 2016 were analyzed. Results: Thirty-six (3.6%) of 1,003 patients who underwent sublobar resection for NSCLC experienced locoregional recurrence. The patients' median age was 66.5 (range, 44-77) years at the initial operation, and 28 (77.8%) patients were men. Six (16.7%) patients underwent segmentectomy and 30 (83.3%) underwent wedge resection as the initial operation. The median follow-up from the initial operation was 56 (range, 9-150) months. Ten (27.8%) patients underwent CL, 22 (61.1%) underwent non-surgical treatments (chemotherapy, radiation, concurrent chemoradiation therapy), and 4 (11.1%) did not receive treatment or were lost to follow-up after recurrence. Patients who underwent CL experienced no significant complications or deaths. The median follow-up time after CL was 64.5 (range, 19-93) months. The 5-year overall survival (OS) and post-recurrence survival (PRS) were higher in the surgical group than in the non-surgical (p<0.001) and no-treatment groups (p<0.001). Conclusion: CL is a technically demanding but safe procedure for locoregionally recurrent stage I NSCLC after sublobar resection. Patients who underwent CL had better OS and PRS than patients who underwent non-surgical treatments or no treatments; however, a larger cohort study and long-term surveillance are necessary.

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.

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.

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 Validation of the Unparalleled Sensitivity of the Novel Allele-Discriminating Priming System Technology-Based EGFR Mutation Assay in Patients with Operable Non-Small Cell Lung Cancer.

PURPOSE: Recently, we developed allele-discriminating priming system (ADPS) technology. This method increases the sensitivity of conventional quantitative polymerase chain reaction up to 100 folds, with limit of detection, 0.01%, with reinforced specificity. This prospective study aimed to develop and validate the accuracy of ADPS epidermal growth factor receptor (EGFR) Mutation Test Kit using clinical specimens. MATERIALS AND METHODS: In total 189 formalin-fixed paraffin-embedded tumor tissues resected from patients with non-small cell lung cancer were used to perform a comparative evaluation of the ADPS EGFR Mutation Test Kit versus the cobas EGFR Mutation Test v2, which is the current gold standard. When the two methods had inconsistent results, next-generation sequencing-based CancerSCAN was utilized as a referee. RESULTS: The overall agreement of the two methods was 97.4% (93.9%-99.1%); the positive percent agreement, 95.0% (88.7%-98.4%); and the negative percent agreement, 100.0% (95.9%-100.0%). EGFR mutations were detected at a frequency of 50.3% using the ADPS EGFR Mutation Test Kit and 52.9% using the cobas EGFR Mutation Test v2. There were 10 discrepant mutation calls between the two methods. CancerSCAN reproduced eight ADPS results. In two cases, mutant allele fraction was ultra-low at 0.02% and 0.06%, which are significantly below the limit of detection of the cobas assay and CancerSCAN. Based on the EGFR genotyping by ADPS, the treatment options could be switched in five patients. CONCLUSION: The highly sensitive and specific ADPS EGFR Mutation Test Kit would be useful in detecting the patients who have lung cancer with EGFR mutation, and can benefit from the EGFR targeted therapy.