Impact of Skeletal Muscle Loss and Sarcopenia on Outcomes of Locally Advanced Esophageal Cancer during Neoadjuvant Chemoradiation.

BACKGROUND: The impact of changes in skeletal muscle and sarcopenia on outcomes during neoadjuvant chemoradiotherapy (NACR) for patients with esophageal cancer remains controversial. PATIENTS AND METHODS: We retrospectively analyzed the data of patients with locally advanced esophageal squamous cell cancer who received NACR followed by esophagectomy between June 2013 and December 2021. The images at third lumbar vertebra were analyzed to measure the cross-sectional area and calculate skeletal muscle index (SMI) before and after NACR. SMI less than 52.4 cm2/m2 for men and less than 38.5 cm2/m2 for women were defined as sarcopenia. The nonlinearity of the effect of percent changes in SMI (ΔSMI%) to survival outcomes was assessed by restricted cubic splines. RESULTS: Overall, data of 367 patients were analyzed. The survival outcomes between sarcopenia and non-sarcopenia groups had no significant differences before NACR. However, patients in post-NACR sarcopenia group showed poor overall survival (OS) benefit (P = 0.016) and poor disease-free survival (DFS) (P = 0.043). Severe postoperative complication rates were 11.9% in post-NACR sarcopenia group and 5.0% in post-NACR non-sarcopenia group (P = 0.019). There was a significant non-linear relationship between ΔSMI% and survival outcomes (P < 0.05 for non-linear). On the multivariable analysis of OS, ΔSMI% > 12% was the independent prognostic factor (HR 1.76, 95% CI 1.03-2.99, P = 0.039) and significant difference was also found on DFS analysis (P = 0.025). CONCLUSIONS: Patients with post-neoadjuvant chemoradiotherapy sarcopenia have worse survival and adverse short-term outcomes. Moreover, greater loss in SMI is associated with increased risks of death and disease progression during neoadjuvant chemoradiotherapy, with maximum impact noted with SMI loss greater than 12%.

Increased resected lymph node stations improved survival of esophageal squamous cell carcinoma.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) and surgery have been recommended as the standard treatments for locally advanced esophageal squamous cell carcinoma (ESCC). In addition, nodal metastases decreased in frequency and changed in distribution after neoadjuvant therapy. This study aimed to examine the optimal strategy for lymph node dissection (LND) in patients with ESCC who underwent nCRT. METHODS: The hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) were calculated using the Cox proportional hazard model. To determine the minimal number of LNDs (n-LNS) or least station of LNDs (e-LNS), the Chow test was used. RESULTS: In total, 333 patients were included. The estimated cut-off values for e-LNS and n-LNS were 9 and 15, respectively. A higher number of e-LNS was significantly associated with improved OS (HR: 0.90; 95% CI 0.84-0.97, P = 0.0075) and DFS (HR: 0.012; 95% CI: 0.84-0.98, P = 0.0074). The e-LNS was a significant prognostic factor in multivariate analyses. The local recurrence rate of 23.1% in high e-LNS is much lower than the results of low e-LNS (13.3%). Comparable morbidity was found in both the e-LNS and n-LND subgroups. CONCLUSION: This cohort study revealed an association between the extent of LND and overall survival, suggesting the therapeutic value of extended lymphadenectomy during esophagectomy. Therefore, more lymph node stations being sampled leads to higher survival rates among patients who receive nCRT, and standard lymphadenectomy of at least 9 stations is strongly recommended.

Impact of deep muscle invasion on nodal status and survival in patients with pT2 esophageal squamous cancer.

BACKGROUND: Whether T2 esophageal squamous cell carcinoma should be subclassified remains controversial. We aimed to investigate the impact of the depth of muscularis propria invasion on nodal status and survival outcomes. METHODS: We identified patients with pT2 esophageal squamous cell carcinoma who underwent primary surgery from January 2009 to June 2017. Clinical data were extracted from prospectively maintained databases. Tumor muscularis propria invasion was stratified into superficial or deep. Binary logistic regression was used to determine risk factors for lymph node metastases. The impact of the depth of muscularis propria invasion on survival was investigated using Kaplan‒Meier analysis and a Cox proportional hazard regression model. RESULTS: A total of 750 patients from three institutes were investigated. The depth of muscularis propria invasion (odds ratio [OR]: 3.95, 95% confidence interval [CI]: 2.46-6.35; p < 0.001) was correlated with lymph node metastases using logistic regression. T substage (hazard ratio [HR]: 1.37, 95% CI: 1.05-1.79; p < 0.001) and N status (HR: 1.51, 95% CI: 1.05-2.17; p < 0.001) were independent risk factors in multivariate Cox regression analysis. The deep muscle invasion was associated with worse overall survival (HR: 1.52, 95% CI: 1.19-1.94; p = 0.001) than superficial, specifically in T2N0 patients (HR: 1.38, 95% CI: 1.08-1.94; p = 0.035). CONCLUSIONS: We found that deep muscle invasion was associated with significantly worse outcomes and recommended the substaging of pT2 esophageal squamous cell carcinoma in routine pathological examination.

Mapping of lymph node metastasis from esophageal squamous cell carcinoma after neoadjuvant treatment: a prospective analysis from a high-volume institution in China.

The study aimed to describe the prevalence of lymph node metastases per lymph node station for esophageal squamous cell carcinoma (ESCC) after neoadjuvant treatment. Clinicopathological variables of ESCC patients were retrieved from the prospective database of the Surgical Esophageal Cancer Patient Registry in West China Hospital, Sichuan University. A two-field lymphadenectomy was routinely performed, and an extensive three-field lymphadenectomy was performed if cervical lymph node metastasis was suspected. According to AJCC/UICC 8, lymph node stations were investigated separately. The number of patients with metastatic lymph nodes divided by those who underwent lymph node dissection at that station was used to define the percentage of patients with lymph node metastases. Data are also separately analyzed according to the pathological response of the primary tumor, neoadjuvant treatment regimens, pretreatment tumor length, and tumor location. Between January 2019 and March 2023, 623 patients who underwent neoadjuvant therapy followed by transthoracic esophagectomy were enrolled. Lymph node metastases were found in 212 patients (34.0%) and most frequently seen in lymph nodes along the right recurrent nerve (10.1%, 58/575), paracardial station (11.4%, 67/587), and lymph nodes along the left gastric artery (10.9%, 65/597). For patients with pretreatment tumor length of >4 cm and non-pathological complete response of the primary tumor, the metastatic rate of the right lower cervical paratracheal lymph nodes is 10.9% (10/92) and 10.6% (11/104), respectively. For patients with an upper thoracic tumor, metastatic lymph nodes were most frequently seen along the right recurrent nerve (14.2%, 8/56). For patients with a middle thoracic tumor, metastatic lymph nodes were most commonly seen in the right lower cervical paratracheal lymph nodes (10.3%, 8/78), paracardial lymph nodes (10.2%, 29/285), and lymph nodes along the left gastric artery (10.4%, 30/289). For patients with a lower thoracic tumor, metastatic lymph nodes were most frequently seen in the paracardial station (14.2%, 35/247) and lymph nodes along the left gastric artery (13.1%, 33/252). The study precisely determined the distribution of lymph node metastases in ESCC after neoadjuvant treatment, which may help to optimize the extent of lymphadenectomy in the surgical management of ESCC patients after neoadjuvant therapy.

Longer Time Interval from Neoadjuvant Chemoradiation to Surgery is Associated with Poor Survival for Patients Without Clinical Complete Response in Oesophageal Cancer.

BACKGROUND: The optimal interval between neoadjuvant therapy and oesophagectomy for oesophageal cancer remains controversial. METHODS: Patients with locally advanced oesophageal squamous cell carcinoma (ESCC) who received neoadjuvant chemoradiotherapy followed by oesophagectomy between June 2017 and December 2020 were prospectively enrolled and retrospectively analysed. Patients were divided into two groups: timely (group A; < 10 weeks) and delayed (group B; ≥ 10 weeks) surgery groups. Survival was the primary outcome, and tumour response and post-operative complications were the secondary outcomes. RESULTS: Overall, 224 patients were recruited; 116 patients (51.8%) underwent timely surgery within 10 weeks (group A), and 108 patients (49.2%) underwent delayed surgery over 10 weeks (group B) after chemoradiotherapy. In patients with clinical complete response (cCR), two groups had no significant difference of survival benefit (P = 0.618). However, in patients without cCR, delayed surgery was associated with poor survival (P = 0.035) and cancer progression (P = 0.036). A total of 40 patients (34.5%) in group A and 54 patients (50.0%) in group B achieved pCR (P = 0.019). pCR rates were significantly different across the four groups and increased over time (P = 0.006). CONCLUSIONS: Patients with a prolonged time interval from neoadjuvant chemoradiation to surgery had higher pCR rates. For patients with cCR to neoadjuvant chemoradiation, the time interval to surgery can be safely prolonged for at least 10 weeks. However, for patients with non-cCR to neoadjuvant chemoradiation, delayed surgery is associated with poor survival, and surgery should be performed within 10 weeks of neoadjuvant chemoradiation.

Pararespiratory and paradigestive lymph node metastases in esophageal squamous cell carcinoma: predicting survival and refining the N staging system.

BACKGROUND: The site of lymph node metastasis (LNM) may affect the prognosis of patients with esophageal squamous cell carcinoma (ESCC). To investigate the prognoses of pararespiratory and paradigestive LNM and to propose a novel N (nN) staging system that integrates both the LNM site and count. METHODS: This study was a multicenter, large-sample, retrospective cohort study that included ESCC patients with LNM between January 2014 and December 2019 from three Chinese institutes. Patients were set into training (two institutes) and external validation (one institute) cohorts. The primary outcomes were survival differences in LNM site and the development of novel nodal staging system. The overall survival (OS) of patients with pararespiratory LNM only (Group A), paradigestive LNM only (Group B), and both sites (Group C) was evaluated by Kaplan-Meier. Cox proportional hazards models were used to identify the independent prognostic factors. An nN staging system considering both the LNM site and count was developed and evaluated by the area under the receiver operating characteristic curve (AUC). RESULTS: In total, 1313 patients were included and split into training (n = 1033) and external validation (n = 280) cohorts. There were 342 (26.0%), 568 (43.3%) and 403 (30.7%) patients in groups A, B and C, respectively. The OS of patients with pararespiratory and patients with paradigestive LNM presented significant differences in the training and validation cohorts (P < 0.050). In the training cohort, LNM site was an independent prognostic factor (hazard ratio: 1.58, 95% confidence intervals: 1.41-1.77, P < 0.001). The nN staging definition: nN1 (1-2 positive pararespiratory/paradigestive LNs), nN2 (3-6 pararespiratory LNs or 1 pararespiratory with 1paradigestive LN), nN3 (3-6 LNs with ≥ 1 paradigestive LN), nN4 (≥ 7 LNs). Subsets of patients with different nN stages showed significant differences in OS (P < 0.050). The prognostic model of the nN staging system presented higher performance in the training and validation cohorts at 3-year OS (AUC, 0.725 and 0.751, respectively) and 5-year OS (AUC, 0.740 and 0.793, respectively) than the current N staging systems. CONCLUSIONS: Compared to pararespiratory LNM, the presence of paradigestive LNM is associated with worse OS. The nN staging system revealed superior prognostic ability than current N staging systems.

Safety and feasibility of a modularized procedure for trans-subxiphoid robotic extended thymectomy.

BACKGROUND: The purpose of this study was to introduce an "eight-step modularized procedure (M-RET)" for trans-subxiphoid robotic extended thymectomy for patients with myasthenia gravis (MG). Its safety and feasibility were further verified in this study. MATERIALS AND METHODS: This retrospective study included 87 consecutive MG patients who underwent trans-subxiphoid robotic extended thymectomy at our institution between September 2016 and August 2021. According to different resection models, patients were divided into two groups: traditional trans-subxiphoid robotic extended thymectomy group (T-RET group) and eight-step modularized technique group (M-RET group). Baseline demographic characteristics and operation-related parameters were collected and compared between the two groups. RESULTS: There were 41 (47.1%) patients in the M-RET group and 46 (52.9%) patients in the T-RET group. The M-RET group resected a greater amount of mediastinal adipose tissues and required more dissection time (median and interquartile range: 135.0, 125.0 to 164.0 v. 120.0, 105.0 to 153.8, P = 0.006) compared with the T-RET group. There were no statistically significant differences in terms of the intraoperative blood loss, duration of chest drainage, length of hospital stay, and postoperative complications between the two groups. There was no mortality or conversion in each of the two groups and all patients recovered well upon discharge. CONCLUSION: The eight-step modularized technique of trans-subxiphoid robotic extended thymectomy was verified to be a safe, effective, radical procedure, which offers unique superiority over ectopic thymic tissue resection.

Limited-stage small cell carcinoma of the esophagus treated with curative esophagectomy: A multicenter retrospective cohort study.

BACKGROUND: This study aimed to investigate the efficacy of surgery in the treatment of small cell carcinoma of the esophagus (SCCE) and explore potential prognostic factors. METHODS: We screened patients with SCCE who underwent esophagectomy from 2010 to 2018 at three institutes. Differences in survival were analyzed using the Kaplan-Meier method and log-rank test. The prognostic factors were identified using univariate and multivariate analyses. RESULTS: A total of 69 patients were included. Multivariate analysis showed that TNM stage (hazard ratio [HR]: 4.10, 95% confidence interval [CI]: 1.57-10.75, p = 0.004) and adjuvant therapy (HR: 0.28, 95% CI: 0.16-0.51, p < 0.001) were independent prognostic factors. Stage I, stage IIA, and stage IIB disease were merged into the surgery response disease (SRD), whereas stage III disease into the surgery nonresponse disease (SNRD). The SRD group had significantly improved survival compared to the SNRD group (HR: 0.33, 95% CI: 0.19-0.58, p < 0.001). In addition, adjuvant therapy increased survival benefit in the SNRD group (p < 0.001) but not in the SRD group (p = 0.061). CONCLUSIONS: Surgery alone appears to be adequate for disease control in the SRD group, whereas multimodality therapy was associated with improved survival in the SNRD group.

Prognostic Role of Nodal Skip Metastasis in Thoracic Esophageal Squamous Cell Carcinoma: A Large-Scale Multicenter Study.

BACKGROUND: Nodal-skip metastasis (NSM) is found in esophageal squamous cell carcinoma (ESCC), but its prognostic role is controversial. This study aimed to investigate the prognostic value of NSM for thoracic ESCC patients. METHODS: Categorization of NSM was according to the N groupings of Japan Esophagus Society (JES) staging system, which is dependent on tumor location. Using the Kaplan-Meier method and Cox-regression analysis, this study retrospectively analyzed the overall survival (OS) for 2325 ESCC patients after radical esophagectomy at three high-volume esophageal cancer centers. Predictive models also were constructed. RESULTS: The overall NSM rate was 20% (229/1141): 37.4% in the in upper, 12.9% in the middle, and 22.2% in the lower thoracic ESCC. The patients with NSM always had a better prognosis than those without NSM. Furthermore, NSM was an independent prognostic factor for thoracic ESCC patients (hazard ratio [HR], 0.633; 95% confidence interval [CI], 0.499-0.803; P < 0.001). By integrating the prognostic values of NSM and N stage, the authors proposed the new N staging system. The categories defined by the new N staging system were more homogeneous in terms of OS than those defined by the current N system. Moreover, the new N system was shown to be an independent prognostic factor also for thoracic ESCC patients (HR, 1.607; 95% CI, 1.520-1.700; P < 0.001). Overall, the new N system had slightly better homogeneity, discriminatory ability, and monotonicity of gradient than the current N system. CONCLUSIONS: This study emphasized the prognostic power of NSM and developed a modified node-staging system to improve the efficiency of the current International Union for Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) N staging system.

A rare Bochdalek hernia in an adult: a case report.

BACKGROUND: Symptomatic Bochdalek hernias are found mainly in infants in respiratory distress and occur rarely in adults. CASE PRESENTATION: We report a rare case of Bochdalek hernia associated with developmental abnormalities in an adult who exhibited acute chest pain and dyspnea on exertion. CONCLUSIONS: This case highlights the importance of the differential diagnosis of acute left-sided chest pain and antenatal examination.

Depth of Invasion into the Circular and Longitudinal Muscle Layers in T2 Esophageal Squamous Cell Carcinoma Does Not Affect Prognosis or Lymph Node Metastasis: A Multicenter Retrospective Study.

BACKGROUND: Although a greater depth of tumor invasion is correlated with a poorer prognosis in esophageal squamous cell carcinoma (ESCC), it remains controversial whether T2 ESCC should be subclassified by circular and longitudinal muscle invasion. We conducted a multicenter retrospective study to evaluate the relationship between the depth of invasion and long-term outcome and to identify the clinical significance of subclassifying T2 ESCC. METHODS: Patients with T2 ESCC who underwent esophagectomy at two different institutes between January 2009 and December 2017 were analyzed retrospectively. ESCC with circular and longitudinal muscle invasion was defined as T2 circular and T2 longitudinal ESCC, respectively. Survival outcomes and risk factors for lymph node metastasis (LNM) were evaluated by univariate and multivariate analyses. In addition, data from stage T1b ESCC cases during the same period were retrieved for use as a comparison cohort to evaluate the prognostic significance of the T2 substage. RESULTS: A total of 536 T2 ESCC patients were eligible, and 192 (36%) patients developed LNM. No significant difference was found in general characteristics between the T2 circular and T2 longitudinal ESCC groups (n = 219 and n = 317, P > 0.05), except for tumor location (P = 0.02). The T2 substage was not significantly correlated with survival on univariate or multivariate analysis (P = 0.30 and P = 0.34, respectively). Multivariate analysis also indicated that the T2 substage was not an independent risk factor for LNM (P = 0.15). When patients with stage T1b ESCC were considered, their survival time was significantly different from that of patients with T2 circular and T2 longitudinal disease (P = 0.01). CONCLUSIONS: The depth of tumor invasion into the circular and longitudinal muscle layers in T2 ESCC does not affect the prognosis or risk of LNM.

The Efficacy of Neoadjuvant Versus Adjuvant Therapy for Resectable Esophageal Cancer Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: Inconclusive results are available as to whether chemo/radiotherapy should be administered to resectable esophageal cancer patients before surgery (neoadjuvant therapy) or after surgery (adjuvant therapy). The paper, via a meta-analysis of effects of treatment modalities when administering chemo/radiotherapy, aims to systematically evaluate the effect of timing of chemo/radiotherapy and surgery. METHODS: We performed a systematic literature search for clinical trials of neoadjuvant and adjuvant therapy for patients with esophageal cancer. Using meta-analysis, we conducted direct and adjusted indirect comparisons of overall survival, complete resection rate (R0 resection), perioperative mortality, leakage rate and local recurrence in patients with resectable esophageal cancer. RESULTS: A total of 32 studies involving 7985 patients with esophageal cancer were included in the meta-analysis. Twenty-five randomized controlled studies indirectly compared neoadjuvant/adjuvant therapy with surgery alone, while five non-randomized controlled studies and two randomized controlled studies directly compared neoadjuvant with adjuvant therapy. Neoadjuvant therapy followed by surgery, compared with surgery along with adjuvant therapy, showed a significant overall survival advantage in our pooled analysis (HR 0.88; 95% CI 0.79-0.98). Directly compared with adjuvant therapy, neoadjuvant therapy demonstrated a lower local recurrence rate (OR 0.56; 95% CI 0.43-0.74) with low heterogeneity (I2 = 1%). Neoadjuvant therapy, comparing to surgery with or without adjuvant therapy, showed a significantly higher R0 resection rate (OR 2.86; 95% CI 2.02-4.04) with moderate heterogeneity (I2 = 38%) and no significant differences in postoperative anastomotic leakage (P = 0.50). However, neoadjuvant therapy, compared with surgery adjuvant therapy, significantly increased perioperative mortality in both direct and indirect comparisons (P < 0.01). CONCLUSIONS: We found that neoadjuvant therapy was associated with higher overall survival and R0 resection rate without increasing postoperative anastomotic leakage for patients with resectable esophageal cancer, whereas neoadjuvant therapy was associated with higher perioperative mortality after esophagectomy.

FAM3B promotes progression of oesophageal carcinoma via regulating the AKT-MDM2-p53 signalling axis and the epithelial-mesenchymal transition.

FAM3B has been suggested to play important roles in the progression of many cancers, such as gastric, oral, colon and prostate cancer. However, little is known about the role of FAM3B in human esophageal squamous cell carcinoma (ESCC). In the present study, we found that FAM3B expression was higher in ESCC tissues than in adjacent normal tissues. Using quantitative real-time polymerase chain reaction, we found similar results in cell lines. FAM3B expression was significantly related to T/TNM stage. Importantly, Kaplan-Meier analysis revealed that a high expression level of FAM3B predicted a poor outcome for ESCC patients. Overexpression of FAM3B inhibits ESCC cell death, increases oesophageal tumour growth in xenografted nude mice, and promotes ESCC cell migration and invasion. Further studies confirmed that FAM3B regulates the AKT-MDM2-p53 pathway and two core epithelial-to-mesenchymal transition process markers, Snail and E-cadherin. Our results provide new insights into the role of FAM3B in the progression of ESCC and suggest that FAM3B may be a promising molecular target and diagnostic marker for ESCC.

The Role and Prognostic Significance of Aortopulmonary, Anterior Mediastinal, and Tracheobronchial Lymph Nodes in Esophageal Cancer: Update of the Eighth-Edition TNM Staging System (2018).

BACKGROUND: The eighth edition of TNM staging for esophageal cancer will be implemented at 2018. The stations 5, 6, and 10 lymph nodes (LNs) have been omitted from the regional lymph node map for the new TNM staging. However, the role and prognostic significance of these LN stations were not clear. The purpose of this study was to investigate whether the revised nodal staging is appropriate and to verify the role, prognostic significance, and therapeutic value of these LNs in esophageal cancer. METHODS: The records of patients who underwent esophagectomy for cancer in our department between 2007 and 2013 were retrospectively analyzed. The rate of metastases was calculated for stations 5, 6, and 10 LNs. LN metastasis and patient survival were analyzed. RESULTS: A total of 1637 patients were included. The calculated rate of metastasis to stations 5, 6, and 10 was 3.2%, 2.3%, and 4.9%, respectively. No difference was found in the N stage determined by the seventh and eighth edition N staging systems. The status of station 5, 6, or 10 was not associated with long-term survival according to Cox proportional hazards model analysis. CONCLUSIONS: Metastasis to stations 5, 6, or 10 LNs was infrequent. Omitting of stations 5, 6, and 10 LNs in the eighth edition TNM staging did not influence the accuracy and survival-predicting efficacy. The therapeutic value of lymphadenectomy of stations 5, 6, and 10 was limited. The status of stations 5, 6, and 10 LNs was not associated with long-term survival.

End-to-End Versus End-to-Side Hand-Sewn Anastomosis for Minimally Invasive McKeown Esophagectomy.

BACKGROUND: Standard anastomotic configuration for esophagogastric anastomosis is not conclusive. This study aimed to compare the short-term outcomes of end-to-end (ETE) cervical double-layer hand-sewn anastomoses with those of end-to-side (ETS) anastomoses for minimally invasive McKeown esophagectomy. METHODS: Between January 2016 and December 2017, the clinical data of 252 consecutive patients who underwent minimally invasive esophagectomy were reviewed retrospectively. The 252 patients comprised 130 patients in the ETS group and 122 patients in the ETE group. The same surgical procedures were applied in both groups, except for esophagogastric reconstruction. Short-term outcomes including leakage, stricture, reflux, operative features, and other surgical complications were analyzed for a comparison of the two configurations. RESULTS: The ETS and ETE groups did not differ significantly in terms of leakage rate (P = 0.34), anastomotic stricture rate (P = 0.70), or postoperative reflux (P = 0.66). However, the ETS group had a longer operation time (P = 0.011), a longer anastomosis time (P < 0.001), and a longer postoperative hospital stay (P = 0.009) than the ETE group, and the postoperative gastric dilation rates were lower in ETE group than in the ETS group (P = 0.025). The two groups did not differ significantly in terms of other postoperative complications. CONCLUSIONS: The major postoperative complications were comparable for the two anastomotic configurations. However, the patients with ETE anastomosis showed a favorable outcome in terms of a decreasing postoperative thoracic gastric dilation rate. End-to-end anastomosis also seemed to have slight advantages in terms of shorter operation and anastomosis times as well as a shorter postoperative hospital stay.

Lymph Node Station-Based Nodal Staging System for Esophageal Squamous Cell Carcinoma: A Large-Scale Multicenter Study.

BACKGROUND: The American Joint Committee on Cancer (AJCC) nodal staging for esophageal squamous cell carcinoma (ESCC) has been defined by the number of metastatic lymph nodes (N system). However, the precise counting of individual positive lymph nodes is difficult and unreliable in some clinical settings, which calls for a more available and reliable system. This study examined the performance of a newly proposed nodal staging category, termed the S system, based on the number of metastatic lymph node stations. METHODS: Using the Kaplan-Meier method and Cox-regression analysis, this study retrospectively analyzed the overall survival (OS) of 2285 ESCC patients who underwent esophagectomy in three major China hospitals. Predictive models were constructed, and C-indices were computed to evaluate the discriminatory power of the S system, and to compare it with the N system. RESULTS: The categories defined by the S system were more homogeneous in terms of OS than those defined by the N system. Overall, the S system had a slightly better C-index (p = 0.659) than the N system ((p = 0.658). Subgroup analyses also showed that the C-index of the S system was slightly better than that of the N system for each subgroup of sex and age, but the two were comparable for each subgroup defined by the tumor location. CONCLUSION: The S system demonstrated a competing prognostic performance compared with the current AJCC N system. Due to the relatively easy accessibility of the number of metastatic lymph node stations, the S system may offer an easier option for cancer staging without a loss of discriminative power.

Clinical significance of LOXL4 expression and features of LOXL4-associated protein-protein interaction network in esophageal squamous cell carcinoma.

Lysyl oxidase-like 4 (LOXL4), a member of the LOX family proteins, catalyzes oxidative deamination of lysine residues in collagen and elastin, which are responsible for maintaining extracellular matrix homeostasis. In this study, the mRNA expression of LOXL4 in seven esophageal squamous cell carcinoma (ESCC) cell lines and 15 ESCC pairs of clinical samples were examined. Furthermore, LOXL4 protein levels in the ESCC cell lines were determined using western blotting. With the use of immunofluorescence, LOXL4 was observed to be localized primarily in the cytoplasm, but was also present in the nucleus. In addition, the results indicated that the upregulated expression of LOXL4 was associated with poor survival in patients with ESCC even following curative resection (P = 0.010). Similar Kaplan-Meier estimator curves for proteins that interact with LOXL4, SUV39H1 (P = 0.014) and COL2A1 (P = 0.011), were plotted. The analyses based on the protein-protein interaction network depicted the expression of LOXL4 and its associated proteins as well as their functions, suggesting that LOXL4 and its associated proteins may serve a significant role in the development and progression of ESCC. In conclusion, the results of the present study suggest that LOXL4 is a potential biomarker for patients with ESCC, as well as SUV39H1 and COL2A1, and high expression levels of these genes are associated with poor prognosis in patients with ESCC.

Robotic Side-to-Side and End-to-Side Stapled Esophagogastric Anastomosis of Ivor Lewis Esophagectomy for Cancer.

BACKGROUND: Both linear-stapled side-to-side esophagogastric anastomosis (LSEA) and circular-stapled end-to-side esophagogastric anastomosis (CEEA) are frequently used following esophagectomy. The aims of the present study were to review our experience of robotic intrathoracic alimentary tract reconstruction and to compare the short-term surgical outcomes of LSEA and CEEA in robotic Ivor Lewis esophagectomy. METHODS: A prospectively collected dataset from 79 consecutive patients who underwent robot-assisted Ivor Lewis esophagectomy from February 2016 to December 2018 was retrospectively analyzed. Two groups (LSEA and CEEA) were classified according to the anastomotic mode. Demographic data, intraoperative characteristics and short-term surgical outcomes were compared between the two groups. RESULTS: Two patients were converted to laparotomy. The remaining 77 patients (68 males and 9 females, mean age of 61.7 years) were successfully treated with completely robotic Ivor Lewis esophagectomy. According to the anastomotic procedure performed, 35 patients were categorized into the LSEA group and 42 patients were categorized into the CEEA group. The mean anastomotic time in the LSEA group was longer than that in the CEEA group (63.0 ± 9.0 vs. 44.2 ± 8.5 min, p < 0.001). No significant difference was detected in anastomotic complications, including leakage (8.6% with LSEA and 4.8% with CEEA, p = 0.83) and postoperative dysphagia (5.7% with LSEA and 16.7% with CEEA, p = 0.26). No statistical difference was observed for the other surgical outcomes. There was no incidence of in-hospital mortality and 30-day mortality in both groups. CONCLUSIONS: In robotic Ivor Lewis esophagectomy, both LSEA and CEEA were feasible and safe to be performed and surgeons can select either LSEA or CEEA based on their own technical expertise.

Modified Intrathoracic Esophagogastrostomy with Minimally Invasive Robot-Assisted Ivor-Lewis Esophagectomy for Cancer.

BACKGROUND: Intrathoracic esophagogastrostomy plays an important role in minimally invasive Ivor-Lewis esophagectomy for cancer. Intrathoracic anastomosis with robot-assisted Ivor-Lewis esophagectomy (RAILE) includes hand-sewn and circular stapler methods, which remain technically challenging. In this study, we modified the techniques for intrathoracic anastomosis at RAILE, in order to simplify the complex procedures. METHODS: "Side-insertion" technique was used for anvil placement and purse string suture for intrathoracic anastomosis at RAILE. Medical records for consecutive patients who had undergone robot-assisted minimally invasive Ivor-Lewis esophagectomy for cancer between January 2015 and June 2018 were analyzed. RESULTS: A total of consecutive 31 patients were enrolled. There was no conversion to open thoracotomy in this cohort. Mean operation duration in the robotic group was 387.4 ± 68.2 min. Median estimated blood loss was 110 mL (range 50-400 mL). Two patients (6.5%) had postoperative anastomotic leak. No postoperative reoperation was needed and there were no mortality. Six patients (19.4%) had anastomotic stricture and 2 patients of them needed endoscopic dilation. CONCLUSION: RAILE is safe and feasible. Our modified procedure highlighting the "side-insertion" method may simplify the process of intrathoracic anvil placement and purse string suture for anastomosis at RAILE.