Clinical efficacy and immune response of neoadjuvant camrelizumab plus chemotherapy in resectable locally advanced oesophageal squamous cell carcinoma: a phase 2 trial.

BACKGROUND: Neoadjuvant immunotherapy is under intensive investigation for esophageal squamous cell carcinoma (ESCC). This study assesses the efficacy and immune response of neoadjuvant immunochemotherapy (nICT) in ESCC. METHODS: In this phase II trial (ChiCTR2100045722), locally advanced ESCC patients receiving nICT were enrolled. The primary endpoint was the pathological complete response (pCR) rate. Multiplexed immunofluorescence, RNA-seq and TCR-seq were conducted to explore the immune response underlying nICT. RESULTS: Totally 42 patients were enrolled, achieving a 27.0% pCR rate. The 1-year, 2-year DFS and OS rates were 89.2%, 64.4% and 97.3%, 89.2%, respectively. RNA-seq analysis highlighted T-cell activation as the most significantly enriched pathway. The tumour immune microenvironment (TIME) was characterised by high CD4, CD8, Foxp3, and PD-L1 levels, associating with better pathological regression (TRS0/1). TIME was categorised into immune-infiltrating, immune-tolerant, and immune-desert types. Notably, the immune-infiltrating type and tertiary lymphoid structures correlated with improved outcomes. In the context of nICT, TIM-3 negatively influenced treatment efficacy, while elevated TIGIT/PD-1 expression post-nICT correlated positively with CD8+ T cell levels. TCR-seq identified three TCR rearrangements, underscoring the specificity of T-cell responses. CONCLUSIONS: Neoadjuvant camrelizumab plus chemotherapy is effective for locally advanced, resectable ESCC, eliciting profound immune response that closely associated with clinical outcomes.

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.

MTHFD1L confers a poor prognosis and malignant phenotype in esophageal squamous cell carcinoma by activating the ERK5 signaling pathway.

MTHFD1L, a key enzyme of folate metabolism, is seldom reported in cancer. In this study, we investigate the role of MTHFD1L in the tumorigenicity of esophageal squamous cell carcinoma (ESCC). ESCC tissue microarrays (TMAs) containing 177 samples from 109 patients were utilized to evaluate whether MTHFD1L expression, determined using immunohistochemical analysis, is a prognostic indicator for ESCC patients. The function of MTHFD1L in the migration and invasion of ESCC cells was studied with wound healing, Transwell, and three-dimensional spheroid invasion assays in vitro and a lung metastasis mouse model in vivo. The mRNA microarrays and Ingenuity pathway analysis (IPA) were used to explore the downstream of MTHFD1L. Elevated expression of MTHFD1L in ESCC tissues was significantly associated with poor differentiation and prognosis. These phenotypic assays revealed that MTHFD1L significantly promote the viability and metastasis of ESCC cell in vivo and in vitro. Further detailed analyses of the molecular mechanism demonstrated that the ESCC progression driven by MTHFD1L was through up-regulation ERK5 signaling pathways. These findings reveal that MTHFD1L is positively associated with the aggressive phenotype of ESCC by activating ERK5 signaling pathways, suggesting that MTHFD1L is a new biomarker and a potential molecular therapeutic target for ESCC.

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.

The development and progress of nanomedicine for esophageal cancer diagnosis and treatment.

Esophageal cancer (EC) is a common gastrointestinal malignancy with poor prognosis and high mortality. Although combined therapeutic strategies have been developed, the 5-year survival rate of patients with EC remains relatively poor. Conventional anti-cancer drug delivery techniques have some shortcomings, such as nontargeted delivery and nonspecific toxicity. Nanoparticles (NPs) provide a promising platform for delivering drugs in various therapeutic modalities for EC, which possess several remarkable advantages in cancer therapy, such as reduced side effects, prolonged circulation time, and preferential accumulation at the tumor site. In this review, we summarized various types of NPs applied in the treatment of EC, including polymers, micelles, liposomes, inorganic NPs and organic NPs. Meanwhile, we discussed the efficacy and safety of newly designed nanomedicine in various treatments of EC, including chemotherapy, radiotherapy, gene therapy, photodynamic therapy (PDT), photothermal therapy (PTT), and their synergetic therapy. In addition, nanomedicine applied in tumor imaging and diagnoses were also reviewed. Current studies have suggested the potential advantages of nanoformulations over conventional formulations. More researches to promote clinical translation of nanomedicine for EC are anticipated in the future.

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.

The Prognostic Value of Nodal Skip Metastasis in Patients with Esophageal Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Esophageal cancer (EC) is the sixth leading cause of cancer deaths worldwide. Nodal skip metastasis (NSM), a common form of lymphatic spread in EC, can be defined as the metastatic involvement of distant lymph nodes (LNs) without prior involvement of adjacent LNs. The results of the previous studies investigating the association between NSM and survival outcomes in patients with EC were inconsistent and even contradictory. The aim of this systematic review and meta-analysis is to investigate the prognostic value of NSM and to summarize the NSM definitions of EC in previous studies. METHODS: Four databases were used in this meta-analysis. The association between NSM and overall survival (OS) was evaluated by using pooled HRs and their 95% confidence interval (CI). The sensitivity analysis and funnel plot were used to assess the publication bias. RESULTS: Nine studies were included in this meta-analysis. The pooled results of meta-analysis indicated that there was no significant association between NSM and OS (HR = 0.99, 95% CI: 0.75-1.31; P = 0.951). Meanwhile, according to the results of sub-group analysis on the basis of histological feature, method of lymphadenectomy, node staging system, and NSM definitions, no significant association was found between NSM and OS. CONCLUSIONS: On the basis of available evidences, NSM could not be used as a prognostic factor for patients with EC. For future studies investigating the prognostic value of NSM, only three-field lymphadenectomy with adequate harvested LNs can be performed. NSM definitions based on lymph node station and anatomical compartment could both be feasible classification for EC.

Overexpressed COL3A1 has prognostic value in human esophageal squamous cell carcinoma and promotes the aggressiveness of esophageal squamous cell carcinoma by activating the NF-κB pathway.

Alpha-1 Type Ⅲ Collagen (COL3A1) encodes the Collagen alpha-1(Ⅲ) chain, which is a fibrillar collagen that exists in extensile connective tissues. Few studies have reported its role in tumorigenicity. In the present study, we identified that COL3A1 protein and mRNA expression levels were considerably up-regulated in esophageal squamous cell carcinoma (ESCC) cells in comparison with normal esophageal squamous epithelial cells (P < 0.05). Immunohistochemical (IHC) analysis of 114 paraffin-embedded archived ESCC tissues demonstrated that COL3A1 expression was positively correlated with the postoperative T stage. Univariate and multivariable analysis demonstrated that COL3A1 expression was an independent poor prognostic factor for overall survival in the whole cohort. Silencing COL3A1 inhibited, while overexpressing COL3A1 promoted, the proliferation, migration, and invasion of ESCC cells. Furthermore, down-regulation of COL3A1 expression also suppressed the growth of ESCC in subcutaneous xenograft mouse models and inhibited ESCC metastasis in lung metastasis mouse models. In addition, we proved that the tumor-promoting effect of COL3A1 on ESCC cells was related to the activation of NF-κB signaling pathway. These findings indicate that COL3A1 confers a poor prognosis and malignant phenotype by activating the NF-κB pathway in ESCC, potentially representing a novel biomarker and/or providing a new curative target for ESCC.

Acid-Responsive Aggregated Gold Nanoparticles for Radiosensitization and Synergistic Chemoradiotherapy in the Treatment of Esophageal Cancer.

Radiotherapy and chemotherapy are limited by insufficient therapeutic efficacy of low-dose radiation and nonspecific drug biodistribution. Herein, an acid-responsive aggregated nanosystem (AuNPs-D-P-DA) loaded with doxorubicin (DOX) is designed for radiosensitization and synergistic chemoradiotherapy. In response to the acid microenvironment of esophageal cancer (EC), small-sized AuNPs-D-P-DA forms large-sized gold nanoparticle (AuNPs) aggregates in tumor tissues to hinder the backflow of AuNPs to the circulation, resulting in enhanced tumor accumulation and retention. Simultaneously, the AuNPs-based radiosensitization is significantly improved because of the high concentration and large size of intratumoral AuNPs, while DOX are delivered and released specifically into tumor cells triggered by the acid microenvironment for chemo-radio synergistic therapy. Acid-responsive AuNPs exacerbate radiation-induced DNA damage, cell apoptosis, cell cycle arrest, and low colony formation ability in vitro and enhance anti-tumor efficacy in vivo compared to un-responsive control. When combined with acid-responsive DOX, the therapeutic efficacy of the formulation is further improved by their synergistic effect. After the treatment of acid-responsive AuNPs plus radiotherapy, fatty acid metabolism is reprogrammed in xenograft models, which provides potential targets for further improvement of radiosensitization. In summary, the acid-responsive AuNPs-D-P-DA nanosystem leverages the radio- and chemotherapeutic synergies of AuNPs-sensitized X-ray irradiation and acid-responsive DOX in the treatment of EC.

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.

The emerging role of long noncoding RNAs in esophageal carcinoma: from underlying mechanisms to clinical implications.

Long noncoding RNAs (lncRNAs), a type of transcriptional product more than 200 nucleotides in length, have emerged as crucial regulators in human cancers. Accumulating data have recently indicated relationships between lncRNAs and esophageal carcinoma (EC). Of note, lncRNAs act as decoys/sponges, scaffolds, guides, and signals to regulate the expression of oncogenes or tumor suppressors at epigenetic, post-transcriptional, and protein levels, through which they exert their unique EC-driving or EC-suppressive functions. Moreover, the features of EC-related lncRNAs have been gradually exploited for developing novel diagnostic and therapeutic strategies in clinical scenarios. LncRNAs have the potential to be used as diagnostic and prognostic indicators individually or in combination with other clinical variables. Beyond these, although the time is not yet ripe, therapeutically targeting EC-related lncRNAs via gene editing, antisense oligonucleotides, RNA interference, and small molecules is likely one of the most promising therapeutic strategies for the next generation of cancer treatment. Herein, we focus on summarizing EC-driving/suppressive lncRNAs, as well as discussing their different features regarding expression profiles, modes of action, and oncological effects. Moreover, we further discuss current challenges and future developing possibilities of capitalizing on lncRNAs for EC early diagnosis and treatment.

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.

Fatal congenital lobar emphysema in a puerpera: a case report and literature review.

BACKGROUND: Congenital lobal emphysema (CLE) is a developmental lung abnormality usually diagnosed in the neonatal period and is rarely observed in adults. Adults with CLE are usually asymptomatic and only a small fraction may present with coughing, recurrent pneumonia and respiratory distress. In imaging studies, the most frequently affected lobe of CLE is the left upper lobe, followed by the right middle lobe. However, multilobar involvement with severe mediastinal shift is extremely rare. CASE PRESENTATION: We report a case of fatal CLE in a 28-year-old puerpera with postpartum respiratory failure. Chest computed tomography (CT) revealed emphysema of the right upper, middle and lower lobes resulting in adjacent atelectasis. Hyperinflation of the right upper lobe crossed the midline, leading to a deviation of the mediastinal structure to the left hemithorax and severe compression of the left lung. CONCLUSIONS: Early and timely diagnosis of CLE with routine follow-up is necessary for patients. CLE, especially with multilobar involvement or mediastinal shift, could be life-threatening and should be promptly and aggressively treated to prevent severe complications.

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.

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.