Significance of Surgery for Resectable M1 Lymph Node Metastases Without Organ Metastasis in Esophageal Carcinoma in the Era of Neoadjuvant Treatment.

BACKGROUND: M1 esophageal carcinoma goes beyond localized disease and requires treatment with systemic therapy. M1 status is primarily divided into two categories: M1 lymph node metastasis and distant organ metastasis. Oligometastasis is defined as a state of limited metastatic disease, and surgery for oligometastasis of distant organs is reported to be beneficial in limited conditions. The aim of this study was to investigate resected cases of M1 lymph node metastases as the only metastatic site in stage IVB esophageal carcinoma. PATIENTS AND METHODS: This study was a single-center retrospective cohort study. Patients with esophageal carcinoma who underwent esophagectomy with curative intent between April 2017 and December 2021 were examined. Neoadjuvant chemotherapy was our standard therapy and administered in almost all cases. We hypothesized that four sites of metastatic M1LN (supraclavicular (no. 104), pretracheal (no. 106pre), posterior thoracic para-aortic (no. 112aoP), and abdominal para-aortic (no. 16a2lat) LNs) were potentially resectable M1LN (rM1LN) metastases with curative intent and compared the prognosis of patients with and without rM1LN metastasis. RESULTS: Six hundred eight-two patients were included in the study. Among these patients, 80 had rM1LN metastasis and received surgery for curative intent. Short-term safety outcomes were equivalent between patients with and without rM1LN metastases. After propensity score matching, there were no significant differences in overall survival between patients with and without rM1LN metastasis. Multivariate analyses revealed that the only independent prognostic factor was ypN status. CONCLUSION: The present study suggests the feasibility and favorable OS in the patients with resection of rM1LN metastasis.

Neoadjuvant Chemotherapy Improves Feasibility of Larynx Preservation and Prognosis in Resectable Locally Advanced Cervical Esophageal Cancer.

BACKGROUND: The optimal strategy for cervical advanced esophageal cancer remains controversial in terms of oncologic outcome as well as vocal and swallowing function. Recently, in East Asian countries, neoadjuvant chemotherapy (NAC) has been a standard strategy for advanced esophageal cancer. METHODS: This study included 37 patients who underwent NAC, and 33 patients who underwent definitive chemoradiation therapy (dCRT) as larynx-preserving treatment for locally advanced cervical esophageal cancer from 2016 to 2021. This study retrospectively investigated outcomes, with comparison between NAC and dCRT for locally advanced cervical esophageal cancer. RESULTS: Larynx preservation was successful for all the patients with NAC and dCRT. After NAC, the rate of complete or partial response was 78.4%, and 30 patients underwent larynx-preserving surgery. On the other hand, after dCRT, the complete response rate was 71.9%, and 4 patients underwent larynx-preserving salvage surgery. Overall survival (OS) and progression free survival were similar between the two groups. However, for the patients with resectable cervical esophageal cancer (cT1/2/3), the 2-year OS rate was significantly higher with NAC (79.9%) than with dCRT (56.8%) (P = 0.022), and the multivariate analyses identified only NAC and cN0, one of the two as a significantly independent factor associated with a better OS (NAC: P = 0.041; cN0, 1: P = 0.036). CONCLUSION: The study showed that NAC as larynx-preserving surgery for resectable cervical esophageal cancer preserved function and had a better prognosis than dCRT. The authors suggest that NAC may be standard strategy for larynx preservation in patients with resectable cervical esophageal cancer.

Technical feasibility and oncological outcomes of robotic esophagectomy compared with conventional thoracoscopic esophagectomy for clinical T3 or T4 locally advanced esophageal cancer: a propensity-matched analysis.

BACKGROUND: Minimally invasive esophagectomy is the first-line approach for esophageal cancer; however, there has recently been a paradigm shift toward robotic esophagectomy (RE). We investigated the clinical outcomes of patients who underwent RE compared with those of patients who underwent conventional minimally invasive thoracoscopic esophagectomy (TE) for locally advanced cT3 or cT4 esophageal cancer using a propensity-matched analysis. METHODS: Overall, 342 patients with locally advanced cT3 or cT4 esophageal cancer underwent transthoracic esophagectomy with total mediastinal lymph node dissection between 2018 and 2022. The propensity-matched analysis was performed to assign the patients to either RE or TE by covariates of histological type, tumor location, and clinical N factor. RESULTS: Overall, 87 patients were recruited in each of the RE and TE groups according to the propensity-matched analysis. The total complication rate and the rates of the three major complications (recurrent laryngeal nerve paralysis, anastomotic leakage, and pneumonia) were not significantly different between the RE and TE groups. However, the peak C-reactive protein concentration on postoperative day 3, rate of surgical site infection, and intensive care unit length of stay after surgery were significantly shorter in the RE group than in the TE group. No significant differences were observed in the harvested total and mediastinal lymph nodes. The total operation time was significantly longer in the RE group, while the thoracic operation time was shorter in the RE group than in the TE group. There was no significant difference between the two groups in the recurrence rate of oncological outcomes after surgery. CONCLUSION: RE may facilitate early recovery after esophagectomy with total mediastinal lymph node dissection and has the same technical feasibility and oncological outcomes as TE.

Bilateral transcervical mediastinoscopic-assisted transhiatal laparoscopic esophagectomy compared with thoracolaparoscopic esophagectomy for esophageal cancer: a propensity score-matched analysis.

BACKGROUND: Transcervical mediastinoscopic esophagectomy for esophageal and esophagogastric junction cancer is indicated in select institutions because of the complex surgical technique required and the unfamiliar surgical view compared with the standard transthoracic esophagectomy approach. This study was performed to compare the feasibility and efficacy of bilateral transcervical mediastinoscopic-assisted transhiatal laparoscopic esophagectomy (BTC-MATLE) with thoracolaparoscopic esophagectomy (TLE) for esophageal cancer. METHODS: This study involved 392 consecutive patients with esophageal cancer who underwent curative minimally invasive esophagectomy with R0 resection (excluding salvage, conversion, and two-stage operations and open thoracotomy) at the National Cancer Center Hospital from 2017 to 2022. The patients underwent either BTC-MATLE or TE (32 and 360 consecutive patients, respectively). Propensity score-matching analysis was used to balance the baseline differences by covariates of age, performance status, and clinical stage. RESULTS: There were statistically significant differences in age, performance status, cT factor, cN factor, cStage, preoperative treatment, and surgical history for respiratory disease. After propensity score-matching, these significant differences (excluding a surgical history of respiratory disease) were no longer statistically significant, and 27 patients were assigned to each group. The total operation time and the postoperative intensive care unit stay were significantly shorter in the BTC-MATLE than TLE group. There were no significant differences in overall postoperative complications or the three major postoperative complications of recurrent laryngeal nerve paralysis, anastomotic leakage, and pneumonia, even for patients whose preoperative pulmonary function indices (vital capacity and forced expiratory volume in 1 s) were significantly lower in the BTC-MATLE than TLE group. The numbers of total and thoracic harvested lymph nodes were significantly higher in the TLE than BTC-MATLE group; however, there was no significant difference in the recurrence rate between the two groups. CONCLUSION: BTC-MATLE may provide the same feasibility and oncological outcomes as TLE even for patients with significantly lower pulmonary function.

Severe RAS-Associated Lymphoproliferative Disease Case with Increasing αß Double-Negative T Cells with Atypical Features.

Autoimmune lymphoproliferative syndrome (ALPS) is a disease of lymphocyte homeostasis caused by FAS-mediated apoptotic pathway dysfunction and is characterized by non-malignant lymphoproliferation with an increased number of TCRαß+CD4-CD8- double-negative T cells (αßDNTs). Conversely, RAS-associated leukoproliferative disease (RALD), which is caused by gain-of-functional somatic variants in KRAS or NRAS, is considered a group of diseases with a similar course. Herein, we present a 7-year-old Japanese female of RALD harboring NRAS variant that aggressively progressed to juvenile myelomonocytic leukemia (JMML) with increased αßDNTs. She eventually underwent hematopoietic cell transplantation due to acute respiratory distress which was caused by pulmonary infiltration of JMML blasts. In general, αßDNTs have been remarkably increased in ALPS; however, FAS pathway gene abnormalities were not observed in this case. This case with RALD had repeated shock/pre-shock episodes as the condition progressed. This shock was thought to be caused by the presence of a high number of αßDNTs. The αßDNTs observed in this case revealed high CCR4, CCR6, and CD45RO expressions, which were similar to Th17. These increased Th17-like αßDNTs have triggered the inflammation, resulting in the pathogenesis of shock, because Th17 secretes pro-inflammatory cytokines such as interleukin (IL)-17A and granulocyte-macrophage colony-stimulating factor. The presence of IL-17A-secreting αßDNTs has been reported in systemic lupus erythematosus (SLE) and Sjögren's syndrome. The present case is complicated with SLE, suggesting the involvement of Th17-like αßDNTs in the disease pathogenesis. Examining the characteristics of αßDNTs in RALD, JMML, and ALPS may reveal the pathologies in these cases.

Mechanistic insights into the alternative translation termination by ArfA and RF2.

During cellular translation of messenger RNAs by ribosomes, the translation apparatus sometimes pauses or stalls at the elongation and termination steps. With the exception of programmed stalling, which is usually used by cells for regulatory purposes, ribosomes stalled on mRNAs need to be terminated and recycled to maintain adequate translation capacity. Much ribosome stalling originates in aberrant mRNAs that lack a stop codon. Transcriptional errors, misprocessing of primary transcripts, and undesired mRNA cleavage all contribute to the formation of non-stop mRNAs. Ribosomes stalled at the 3' end of non-stop mRNAs do not undergo normal termination owing to the lack of specific stop-codon recognition by canonical peptide release factors at the A-site decoding centre. In bacteria, the transfer-messenger RNA (tmRNA)-SmpB-mediated trans-translation rescue system reroutes stalled ribosomes to the normal elongation cycle and translation termination. Two additional rescue systems, ArfA-RF2 (refs 13, 14, 15, 16) and ArfB (formerly known as YaeJ), are also present in many bacterial species, but their mechanisms are not fully understood. Here, using cryo-electron microscopy, we characterize the structure of the Escherichia coli 70S ribosome bound with ArfA, the release factor RF2, a short non-stop mRNA and a cognate P-site tRNA. The C-terminal loop of ArfA occupies the mRNA entry channel on the 30S subunit, whereas its N terminus is sandwiched between the decoding centre and the switch loop of RF2, leading to marked conformational changes in both the decoding centre and RF2. Despite the distinct conformation of RF2, its conserved catalytic GGQ motif is precisely positioned next to the CCA-end of the P-site tRNA. These data illustrate a stop-codon surrogate mechanism for ArfA in facilitating the termination of non-stop ribosomal complexes by RF2.

Non-curative resection for surgical T4b esophageal cancer: esophagectomy or non-esophagectomy?

BACKGROUND: Recently, with the development of multidisciplinary treatment, the treatment outcomes of esophageal cancer (EC) have improved. However, despite advances in diagnostic imaging modalities, preoperative diagnosis of T4 EC is still difficult, and the prognosis of T4 EC remains very poor. In addition, the prognosis of surgical T4b EC (sT4b EC) after surgery remains unclear. In this study, we retrospectively reviewed sT4b EC. METHODS: We evaluated the clinical course of sT4b EC and compared palliative esophagectomy with R2 resection (PE group) with other procedures without esophagectomy (NE group) (e.g., only esophagostomy) for sT4b EC. RESULTS: Forty-seven patients with thoracic EC underwent R2 resection at our institution between January 2009 and December 2020. Thirty-four patients were in the PE group, and 13 patients were in the NE group. The 2-year overall survival rate was 0% in the PE group and 20.2% in the NE group (p = 0.882). There was one case of long-term survival in the NE group that underwent surgery followed by definitive chemoradiation. Postoperative complications (Clavien-Dindo grade ≥ 3) were observed in 25 patients (73.5%) in the PE group and in three patients (23.1%) in the NE group (p = 0.031). The median time to the initiation of postoperative treatment was 68.1 days in the PE group and 18.6 days in the NE group (p = 0191). CONCLUSIONS: If EC is diagnosed as sT4b, palliative esophagectomy should be avoided because of the high complication rate and the lack of long-term survival.

Perioperative Decrease in Tongue Pressure is an Intervenable Predictor of Aspiration After Esophagectomy.

Despite the increasing use of minimally invasive esophagectomies, aspiration pneumonia remains the most serious complication. This study clarified the association between perioperative tongue pressure and postoperative aspiration after thoracoscopic-laparoscopic esophagectomy in patients with esophageal cancer. This retrospective, single-center, observational study evaluated data of 216 patients scheduled for thoracoscopic-laparoscopic esophagectomy. Tongue pressure was measured before the procedure and on postoperative day 6; perioperative changes were assessed. Patients were divided into non-aspiration and aspiration groups according to penetration-aspiration scale scores. Hierarchical and stratified logistic regression analyses were performed to identify factors associated with aspiration. Receiver operating characteristic curves were used to assess the cut-off value of perioperative changes in tongue pressure for aspiration. Perioperative changes in tongue pressure (odds ratio 0.92; 95% confidence interval 0.88-0.96, P < 0.001), age (odds ratio 1.07; 95% confidence interval 1.01-1.13, P = 0.013), and postoperative recurrent laryngeal nerve palsy (odds ratio 3.04; 95% confidence interval 1.15-8.03, P = 0.025) were significantly associated with aspiration. The cut-off value of perioperative changes in tongue pressure for postoperative aspiration was - 6.58%. In addition, decreases in tongue pressure were associated with aspiration regardless of recurrent laryngeal nerve palsy and age. The perioperative decrease in tongue pressure, higher age, and postoperative recurrent laryngeal nerve palsy were significant factors strongly associated with aspiration in the acute phase post-esophagectomy. Decreased tongue pressure is the only intervenable predictor of aspiration. Rehabilitation for preventing decreases in tongue pressure may reduce the risk of aspiration.

The evaluation of the association between preoperative sarcopenia and postoperative pneumonia and factors for preoperative sarcopenia in patients undergoing thoracoscopic-laparoscopic esophagectomy for esophageal cancer.

PURPOSE: This study identified the relationship between postoperative pneumonia and preoperative sarcopenia as well as the factors for preoperative sarcopenia in patients with esophageal cancer. METHODS: In this retrospective, single-center, observational study, we evaluated the data of 274 patients who were scheduled for thoracoscopic-laparoscopic esophagectomy. Sarcopenia was defined using the skeletal muscle index, handgrip strength, and gait speed. The physical activity and nutritional status were evaluated. A multivariate logistic regression analysis was performed to confirm the association between sarcopenia and postoperative pneumonia and identify sarcopenia-related factors. A Spearman's correlation analysis was used to identify the relationship between physical activity and nutritional status. RESULTS: Age, male sex, sarcopenia, and postoperative recurrent laryngeal nerve palsy were significantly associated with postoperative pneumonia. Age, male sex, physical activity, and nutritional status were significantly associated with preoperative sarcopenia. There was a significant correlation between physical activity and nutritional status. CONCLUSIONS: Preoperative sarcopenia was confirmed to be a predictor of postoperative pneumonia. Furthermore, age, sex, physical activity, and nutritional status were significantly associated with preoperative sarcopenia. Physical activity and nutritional status are closely associated with each other in patients with esophageal cancer. A multidisciplinary approach to preoperative sarcopenia, taking exercise and nutrition into account, is recommended.

Significance of lymphovascular invasion in esophageal squamous cell carcinoma undergoing neoadjuvant chemotherapy followed by esophagectomy.

BACKGROUND: Lymphovascular invasion (LVI) was previously reported to be an independent factor associated with survival in locally advanced esophageal squamous cell carcinoma (LAESCC) patients receiving neoadjuvant chemotherapy (NAC); however, the detailed clinicopathological significance of LVI remains unclear. This study evaluated the prognostic impact of LVI in patients with LAESCC after NAC with cisplatin and 5-fluorouracil (CF) or docetaxel, cisplatin and 5-fluorouracil (DCF) followed by surgery and in LAESCC patients with recurrence after NAC and surgery. METHODS: 438 patients with thoracic LAESCC who had undergone NAC followed by an esophagectomy with three-field lymphadenectomy were assessed using a propensity score matched analysis, and their long-term outcomes were retrospectively reviewed. RESULTS: In matched cohort, a multivariate analysis of relapse-free survival (RFS) in the NAC-CF group suggested that ypN (≥ 1, HR = 3.715, p = 0.004) and LVI (positive, HR = 3.366, p = 0.012) were independent factors associated with RFS; in the NAC-DCF group, ypN (≥ 1, HR = 4.829, p < 0.001) was the only independent factor associated with RFS. Comparisons of overall survival (OS) between the ypN + /LVI + group and other groups among patients with recurrence in each NAC regimen showed significant differences in both of NAC groups (p < 0.001, respectively). The ypN + /LVI + group had a significantly poor OS in both an oligometastatic recurrence (OMR) group (p < 0.001) and a non-OMR group (p < 0.001). CONCLUSIONS: The present study suggested that the independent factor associated with prognosis of patients with LAESCC after NAC and surgery may differ according to the NAC regimen, and the presence of both ypN and LVI was a prognostic factor for patients with recurrence, including those with OMR. These results might be helpful when deciding on an additional treatment strategy for LAESCC patients.

Impact of pre-diabetes, well-controlled diabetes, and poorly controlled diabetes on anastomotic leakage after esophagectomy for esophageal cancer: a two-center retrospective cohort study of 1901 patients.

BACKGROUND: Diabetes is known to be associated with anastomotic leakage (AL) after esophagectomy. However, it is unknown whether well-controlled diabetes is also associated with AL. METHODS: We conducted a two-center retrospective cohort database study of patients who underwent oncological esophagectomy (2011-2019). Patients were divided into four groups: normoglycemia, pre-diabetes, well-controlled diabetes (hemoglobin A1c [HbA1c] < 7.0%), and poorly controlled diabetes (HbA1c ≥ 7.0%). The occurrence of AL and length of stay were compared between groups using multivariable analyses. The relationship between categorical HbA1c levels and AL was also investigated in patients stratified by diabetes medication before admission. RESULTS: Among 1901 patients, 1114 (58.6%) had normoglycemia, 480 (25.2%) had pre-diabetes, 180 (9.5%) had well-controlled diabetes, and 127 (6.7%) had poorly controlled diabetes. AL occurred in 279 (14.7%) patients. Compared with normoglycemia, AL was significantly associated with both well-controlled diabetes (odds ratio 1.83, 95% confidence interval [CI] 1.22-2.74) and poorly controlled diabetes (odds ratio 1.95, 95% CI 1.23-3.09), but not with pre-diabetes. Preoperative HbA1c levels showed a J-shaped association with AL in patients without diabetes medication, but no association in patients with diabetes medication. Compared with normoglycemia, only poorly controlled diabetes was significantly associated with longer hospital stay after surgery, especially in patients with operative morbidity (unstandardized coefficient 14.9 days, 95% CI 5.6-24.1). CONCLUSIONS: Diabetes was associated with AL after esophagectomy even in well-controlled patients, but pre-diabetes was not associated with AL. Operative morbidity, including AL, in poorly controlled diabetes resulted in prolonged hospital stays compared with normoglycemia.

Does Preoperative Corticosteroid Administration Improve the Short-Term Outcome of Minimally Invasive Esophagectomy for Esophageal Cancer? A Propensity Score-Matched Analysis.

BACKGROUND: In open esophagectomy for esophageal cancer, steroid administration is associated with attenuated postoperative inflammation and reduced complications. However, the efficacy of steroids in minimally invasive esophagectomy (MIE) is uncertain. This study aimed to investigate the impact of steroid administration on short-term postoperative outcomes in MIE. METHODS: The study compared 458 patients who underwent MIE between April 2017 and December 2021. The patients were divided into steroid (n = 206) and non-steroid (n = 252) groups, and 160 paired cases were compared by 1:1 propensity score-matching. RESULTS: In the steroid group versus the non-steroid group, the intensive care unit stay was significantly shorter (2.6 vs 3.3 days; P = 0.001), and the incidence of surgical-site infection (SSI) was significantly lower (1.2 % vs 13.1 %; P < 0.001). The incidence of pneumonia tended to be lower in the steroid group, but not significantly lower (19.3 % vs 29.3 %; P = 0.065). Multivariate analysis showed that steroid administration independently affected SSI (odds ratio, 11.6; 95 % confidence interval, 3.3-73.6; P < 0.001). Compared with the non-steroid group, the steroid group had more favorable arterial partial pressure of oxygen/fraction of inspired oxygen ratio (503 ± 178 vs 380 ± 104; P < 0.001) and body temperature (37.2 ± 0.54 °C vs 38.3 ± 0.66 °C; P < 0.001) on postoperative day (POD) 0, heart rate (beats per minute) (74.6 ± 8.9 vs 84 ± 11.4; P < 0.001) on POD 1, and C-reactive protein concentration (7.07 ± 3.4 vs 13.7 ± 6.4 mg/dL; P < 0.001) on POD 3. CONCLUSIONS: In MIE, steroid administration was associated with reduced SSI, suggesting an attenuated inflammatory response to surgical stress.

Predictive Ability of the Five-time Chair Stand Test for Postoperative Pneumonia after Minimally Invasive Esophagectomy for Esophageal Cancer.

BACKGROUND: The revised sarcopenia guidelines proposed handgrip strength (HGS) and five-time chair stand test (5-CST) as the primary parameters of muscle function. HGS and 5-CST are associated with pulmonary function among community-dwelling people, although few reports have described an association between these parameters and surgical outcomes in carcinomas. We examined the predictive ability of 5-CST for postoperative pneumonia after minimally invasive esophagectomy (MIE) compared with that of HGS. METHODS: This retrospective, single-center, observational study evaluated 222 male patients who underwent MIE for esophageal cancer between February 2018 and October 2020. Sarcopenia parameters included 5-CST, HGS, and skeletal muscle index. Postoperative pneumonia predictors were determined by using multivariate logistic regression analysis. We assessed the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) to analyze the predictive ability of 5-CST and HGS. RESULTS: MIE was performed for squamous cell carcinoma (n = 179), adenocarcinoma (n = 38), and other cancers (n = 5). Forty-nine (22.1%) patients developed postoperative pneumonia. Multivariate logistic regression showed that age (odds ratio [OR] 1.05; 95% confidence interval [CI] 1.01-1.10; p = 0.027), 5-CST (OR, 1.19; 95% CI 1.00-1.40; p = 0.046), and recurrent laryngeal nerve palsy (RLNP) (OR, 3.37; 95% CI 1.60-7.10; p = 0.001) significantly predicted postoperative pneumonia. Category-free NRI and IDI showed that adding 5-CST in the prediction model with age and RLNP resulted in significantly greater reclassification and discrimination abilities than did HGS. CONCLUSIONS: The 5-CST significantly predicted postoperative pneumonia after MIE. NRI and IDI analyses suggested that 5-CST had significantly better predictive ability for postoperative pneumonia than did HGS.

Surveillance Strategy after Curative Resection for Oesophageal Squamous Cell Cancer Using the Hazard Function.

BACKGROUND: The optimal surveillance period and frequency after curative resection for oesophageal squamous cell carcinoma (OSCC) remain unclear, and current guidelines are mainly based on traditional Kaplan-Meier analyses of cumulative incidence rather than risk analysis. The aim of this study was to determine a suitable follow-up surveillance program following oesophagectomy for OSCC using the hazard function. METHODS: A total of 1187 patients who underwent curative resection for OSCC between 2000 and 2014 were retrospectively analyzed. The changes in the estimated hazard rates (HRs) of recurrence over time were analyzed according to tumour-node-metastasis stage. RESULTS: Four hundred seventy-eight (40.2%) patients experienced recurrence during the follow-up period (median, 116.5 months). The risk of recurrence peaked at 9.2 months after treatment (HR = 0.0219) and then decreased to half the peak value at 24 months post-surgery. The HRs for Stage I and II patients were low (< 0.007) post-treatment. The HR for Stage III patients peaked at 9.9 months (HR = 0.031) and the hazard curve declined to a plateau at 30 months. Furthermore, the HR peaked at 10.8 months (HR = 0.052) in Stage IV patients and then gradually declined from 50 months. CONCLUSIONS: According to tumour-node-metastasis stage, changes in the HRs of postoperative recurrence in OSCC varied significantly. Intensive surveillance should be undertaken for 3 years in Stage III patients and for 4 years in Stage IV patients, followed by annual screening. For Stage I OSCC patients, a reduction in the surveillance intensity could be taken into consideration.

Salvage minimally invasive esophagectomy after definitive chemoradiotherapy for esophageal cancer can improve postoperative complications compared with salvage open esophagectomy.

BACKGROUND: Although the advantage of minimally invasive esophagectomy (MIE) over open esophagectomy (OE) in planned esophagectomy is being established, the utility of salvage MIE (S-MIE) remains unclear. We aimed to investigate the feasibility and advantage of S-MIE compared with salvage OE (S-OE). METHODS: We retrospectively assessed 82 patients who underwent salvage esophagectomy after definitive chemoradiotherapy for thoracic esophageal cancer between January 2007 and April 2020. Perioperative factors and postoperative complications were compared between the S-OE group (n = 62) and the S-MIE group (n = 20). Logistic regression analysis was performed to analyze the factors associated with postoperative complications. RESULTS: Regarding the patients' preoperative characteristics, the S-OE group had a significant number of grade ≥ cT3 patients vs the S-MIE group (69% vs 35%, respectively; p = 0.006), whereas ycT rates were comparable. Compared with S-OE, S-MIE had comparable operative time, number of harvested thoracic lymph nodes, and R0 resection, but significantly less estimated blood loss (150 ml and 395 ml, respectively; p = 0.003). Regarding postoperative complications, total complications (79% vs 50%; p = 0.01) and pneumonia (48.3% vs 20%; p = 0.02) rates were significantly lower with S-OE vs S-MIE, respectively. On multivariate analysis, S-MIE was an independent factor associated with postoperative pneumonia (odds ratio: 0.29, 95% confidence interval: 0.06-0.99; p = 0.04) and total complications (odds ratio: 0.26, 95% confidence interval: 0.07-0.86; p = 0.02). CONCLUSION: S-MIE was feasible for salvage esophagectomy, with favorable short-term outcomes vs S-OE regarding postoperative pneumonia and total complications.

Handgrip strength predicts early postoperative dysphagia after thoracoscopic-laparoscopic esophagectomy in male patients with esophageal cancer.

BACKGROUND: Dysphagia after esophagectomy, especially in the early postoperative period, remains a severe complication. The association between sarcopenia and dysphagia has received attention in geriatric non-cancer populations. This study aimed to determine the associations between sarcopenia parameters and early postoperative dysphagia after esophagectomy. METHODS: This retrospective observational study included 201 consecutive male patients undergoing thoracoscopic-laparoscopic esophagectomy (TLE) for esophageal cancer between October 2018 and December 2020. We used three sarcopenia parameters: handgrip strength (HGS), skeletal muscle index, and gait speed. Postoperative swallowing function was assessed by videofluoroscopy using the penetration-aspiration scale (PAS; range 1-8). Logistic regression analyses were used to predict factors associated with postoperative aspiration (PAS 6-8). Furthermore, we compared values in patients with symptomatic aspiration (PAS 6-7) and with silent aspiration (PAS 8). RESULTS: Aspiration occurred in 38 of 201 patients (18.9%). On multivariate analysis, significant predictors of aspiration included age [odds ratio (OR) 1.11; 95% confidence interval (CI) 1.05-1.17; p < 0.001], low HGS (OR 3.05; 95% CI 1.06-8.78; p = 0.039), upper third esophageal cancer (OR 2.79; 95% CI 1.03-7.54; p = 0.044) and recurrent laryngeal nerve palsy (OR 2.98; 95% CI 1.26-7.06; p = 0.013). Furthermore, among patients with aspiration (PAS 6-8), low HGS was significantly associated with silent aspiration (OR 6.43; 95% CI 1.06-39.00; p = 0.043). CONCLUSIONS: Low HGS was significantly associated with early postoperative aspiration and impairment of airway protective reflexes after TLE.

Novel pathological staging for patients with locally advanced esophageal squamous cell carcinoma undergoing neoadjuvant chemotherapy followed by surgery.

BACKGROUND: The aim of the present study was to clarify an appropriate staging system for patients with locally advanced esophageal squamous cell carcinoma (LAESCC) after neoadjuvant chemotherapy (NAC) prior to surgery. METHODS: A total of 388 patients with clinical stage II or III LAESCC who had undergone NAC followed by an esophagectomy with three-field lymphadenectomy were retrospectively reviewed. RESULTS: The relapse-free survival (RFS) curves plotted using ypN grading and ypTNM staging both monotonically decreased as the classification number increased, and the groups were more clearly separated than when the Japanese Classification (JC) was applied. A multivariate analysis of relapse free survival (RFS) suggested that ypN (HR = 2.911, P < 0.001), lymphovascular invasion (LVI) (HR = 2.608, P < 0.001) were independent factors associated with OS. The LVI+/ypN+ group had a significantly poorer outcome than the other groups (P < 0.001). The 5-year RFS rates for patients with ypStage IIIA or higher among the LVI-negative cases and ypStage II or higher among the LVI-positive cases were around 0.6 or under. The novel pathological staging which was based on the present results was proposed and RFS curves of each novel stage suggested the suitability of these staging for our cohort. CONCLUSIONS: The present results suggest that a novel pathological staging system using the ypTNM classification, in which the supraclavicular lymph node was regarded as a regional lymph node and the presence of LVI was included as a category, was appropriate for patients with LAESCC after NAC prior to surgery.

Molecular determinants of release factor 2 for ArfA-mediated ribosome rescue.

Translation termination in bacteria requires that the stop codon be recognized by release factor RF1 or RF2, leading to hydrolysis of the ester bond between the peptide and tRNA on the ribosome. As a consequence, normal termination cannot proceed if the translated mRNA lacks a stop codon. In Escherichia coli, the ribosome rescue factor ArfA releases the nascent polypeptide from the stalled ribosome with the help of RF2 in a stop codon-independent manner. Interestingly, the reaction does not proceed if RF1 is instead provided, even though the structures of RF1 and RF2 are very similar. Here, we identified the regions of RF2 required for the ArfA-dependent ribosome rescue system. Introduction of hydrophobic residues from RF2 found at the interface between RF2 and ArfA into RF1 allowed RF1 to associate with the ArfA-ribosome complex to a certain extent but failed to promote peptidyl-tRNA hydrolysis, whereas WT RF1 did not associate with the complex. We also identified the key residues required for the process after ribosome binding. Our findings provide a basis for understanding how the ArfA-ribosome complex is specifically recognized by RF2 and how RF2 undergoes a conformational change upon binding to the ArfA-ribosome complex.

Feasibility of conversion thoracoscopic esophagectomy after induction therapy for locally advanced unresectable esophageal squamous cell carcinoma.

BACKGROUND: Recently, patients with cT4b esophageal cancer often require conversion surgery following induction therapy, for which the standard procedure is open esophagectomy. However, thoracoscopic esophagectomy, including thoracoscopic esophagectomy in the prone position, is increasingly used. We compared short-term outcomes of thoracoscopic esophagectomy and open esophagectomy in this setting. METHODS: We retrospectively analyzed 14 patients who underwent thoracoscopic esophagectomy, and 10 who underwent open esophagectomy, for locally advanced unresectable esophageal cancer after induction therapy between March 2007 and July 2020. RESULTS: The two groups did not significantly differ in patient background. Median total and thoracic surgical times were both significantly longer for open esophagectomy than for thoracoscopic esophagectomy. Median blood loss was also greater in the open esophagectomy group than in the thoracoscopic esophagectomy group. The thoracoscopic esophagectomy group also had significantly shorter median chest drain duration; and lower C-reactive protein levels on the second and third postoperative days. The two groups did not significantly differ in total complications or postoperative hospital stay. CONCLUSIONS: Thoracoscopic esophagectomy is as safe and feasible as open esophagectomy for conversion surgery after induction therapy for locally advanced unresectable esophageal squamous cell carcinoma.

Does staged surgical training for minimally invasive esophagectomy have an impact on short-term outcomes?

BACKGROUND: sophageal cancer has a low incidence, and the anatomy is difficult to understand during esophagectomy. This necessitates a precise and lengthy operation. Therefore, the establishment of a training system in esophageal surgery is of critical importance. In this study, we compared the short-term outcomes of minimally invasive esophagectomy (MIE) performed by consultants versus trainees and explored the factors that impacted the thoracic operation time for each group. METHODS: We have introduced standardized MIE surgical techniques to our trainees in 2016. Our procedure consists of a laparoscopic phase and a thoracoscopic phase and is systematically designed to be learned in a step-by-step manner in each phase. We retrospectively identified 308 patients who underwent MIE from April 2016 to April 2018. The patients were divided into those who underwent MIE by consultants and those who underwent MIE by trainees. The preoperative background factors, operation-related factors, and postoperative complications were compared between the two groups. We also assessed the association between a prolonged thoracic operation time and tumor-and patient-related factors in each of the consults and trainees. RESULTS: Significantly more patients had stage ≥ III cancer in the consultant than trainee group. However, the postoperative complications were comparable, specifically pneumonia (11% vs. 18%), anastomotic leakage (11% vs. 13%), and mortality (0.6% vs. 1.3%). There was no significant difference in the lymph node yield (20 vs. 17) or R0 resection rate (94% vs. 91%) between the two groups. However, the trainees had a significantly longer thoracic operation time (143 ± 34 vs. 190 ± 28 min) and significantly greater blood loss (93 vs. 183 ml). Oncological factors were correlated with a prolonged thoracic operation time in the consultants, but not in the trainees. CONCLUSIONS: Under standardized surgical management using a stepwise educational program, performance of MIE by trainees has no impact on short-term outcomes.