Cost-effectiveness analysis of tislelizumab plus chemotherapy as the first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma in China.

OBJECTIVE: We aimed to investigate the cost-effectiveness of tislelizumab plus chemotherapy compared to chemotherapy alone as a first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (OSCC). METHODS: A partitioned survival model was developed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy versus chemotherapy alone in patients with advanced or metastatic OSCC over a 10-year lifetime horizon from the perspective of the Chinese healthcare system. Costs and utilities were derived from the drug procurement platform and published literature. The model outcomes comprised of costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were conducted to address uncertainty and ensure the robustness of the model. RESULTS: Tislelizumab plus chemotherapy yielded an additional 0.337 QALYs and incremental costs of $7,117.007 compared with placebo plus chemotherapy, generating an ICER of $21,116.75 per QALY, which was between 1 time ($12,674.89/QALY) and 3 times GDP ($38,024.67/QALY) per capita. In one-way sensitivity analysis, the ICER is most affected by the cost of oxaliplatin, paclitaxel and tislelizumab. In the probabilistic sensitivity analysis, when the willingness-to-pay threshold was set as 1 or 3 times GDP per capita, the probability of tislelizumab plus chemotherapy being cost-effective was 1% and 100%, respectively. CONCLUSION: Tislelizumab plus chemotherapy was probably cost-effective compared with chemotherapy alone as the first-line treatment for advanced or metastatic OSCC in China.

Individualized treatment decision model for inoperable elderly esophageal squamous cell carcinoma based on multi-modal data fusion.

BACKGROUND: This research aimed to develop a model for individualized treatment decision-making in inoperable elderly patients with esophageal squamous cell carcinoma (ESCC) using machine learning methods and multi-modal data. METHODS: A total of 189 inoperable elderly ESCC patients aged 65 or older who underwent concurrent chemoradiotherapy (CCRT) or radiotherapy (RT) were included. Multi-task learning models were created using machine learning techniques to analyze multi-modal data, including pre-treatment CT images, clinical information, and blood test results. Nomograms were constructed to predict the objective response rate (ORR) and progression-free survival (PFS) for different treatment strategies. Optimal treatment plans were recommended based on the nomograms. Patients were stratified into high-risk and low-risk groups using the nomograms, and survival analysis was performed using Kaplan-Meier curves. RESULTS: The identified risk factors influencing ORR were histologic grade (HG), T stage and three radiomic features including original shape elongation, first-order skewness and original shape flatness, while risk factors influencing PFS included BMI, HG and three radiomic features including high gray-level run emphasis, first-order minimum and first-order skewness. These risk factors were incorporated into the nomograms as independent predictive factors. PFS was substantially different between the low-risk group (total score ≤ 110) and the high-risk group (total score > 110) according to Kaplan-Meier curves (P < 0.05). CONCLUSIONS: The developed predictive models for ORR and PFS in inoperable elderly ESCC patients provide valuable insights for predicting treatment efficacy and prognosis. The nomograms enable personalized treatment decision-making and can guide optimal treatment plans for inoperable elderly ESCC patients.

Efficacy and cost-effectiveness analysis of pretreatment percutaneous endoscopic gastrostomy in unresectable locally advanced esophageal cancer patients treated with concurrent chemoradiotherapy (GASTO 1059).

BACKGROUND: We launched a single-arm phase II study to determine the efficacy and cost-effectiveness of percutaneous endoscopic gastrostomy (PEG) before concurrent chemoradiotherapy (CCRT) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Eligible patients received pretreatment PEG and enteral nutrition during CCRT. The primary outcome was the change of weight during CCRT. The secondary outcome included nutrition status, loco-regional objective response rate (ORR), loco-regional progression-free survival (LRFS), overall survival (OS), and toxicities. A 3-state Markov model was applied for cost-effectiveness analysis. Eligible patients were matched and compared with those who had nasogastric tube feeding (NTF) or oral nutritional supplements (ONS). RESULTS: Sixty-three eligible patients received pretreatment PEG-based CCRT. The mean change of weight during CCRT was -1.4% (standard deviation, 4.4%), and after CCRT, 28.6% of patients gained weight and 98.4% had normal albumin levels. The loco-regional ORR and 1-year LRFS were 98.4% and 88.3%. The incidence of grade ≥3 esophagitis was 14.3%. After matching, another 63 patients were included in the NTF group and 63 in the ONS group. More patients gained weight after CCRT in the PEG group (p = 0.001). The PEG group showed higher loco-regional ORR (p = 0.036) and longer 1-year LRFS (p = 0.030). In cost analysis, the PEG group showed an incremental cost-effectiveness ratio of $3457.65 per quality-adjusted life-years (QALY) compared with the ONS group with a probability of cost-effectiveness of 77.7% at the $10,000 per QALY willingness-to-pay threshold. CONCLUSION: Pretreatment PEG is associated with better nutritional status and treatment outcome in ESCC patients treated with CCRT compared with ONS and NTF. Pretreatment of PEG can be cost-effective because of its significant clinical benefits.

Incidence and management of esophageal cancer recurrence to regional lymph nodes after curative esophagectomy.

Up to 50% of patients treated with curative esophagectomy for esophageal cancer will develop recurrence, contributing to the dismal survival associated with this disease. Regional recurrence may represent disease that is not yet widely metastatic and may therefore be amenable to more-aggressive treatment. We sought to assess all patients treated with curative esophagectomy for esophageal cancer who developed regional recurrence. We retrospectively identified all patients who underwent esophagectomy for esophageal adenocarcinoma and esophageal squamous cell carcinoma at a single institution from January 2000 to August 2019. In total, 1626 patients were included in the study cohort. As of June 2022, 595 patients had disease recurrence, which was distant or systemic in 435 patients (27%), regional in 125 (7.7%) and local in 35 (2.2%). On multivariable analysis, neoadjuvant chemoradiation with a total radiation dose <45 Gy (hazard ratio [HR], 3.5 [95% CI, 1.7-7.3]; P = .001), pathologic node-positive disease (HR, 1.9 [95% CI, 1.3-3.0]; P = .003) and lymphovascular invasion (HR, 1.6 [95% CI, 1.0-2.5]; P = .049) were predictors of isolated nodal recurrence, whereas increasing age (HR, 0.97 [95% CI, 0.96-0.99]; P = .001) and increasing number of excised lymph nodes (HR, 0.98 [95% CI, 0.95-1.00]; P = .021) were independently associated with decreased risk of regional recurrence. Patients treated with a combination of local and systemic therapies had better survival outcomes than patients treated with systemic therapy alone (P < .001). In patients with recurrence of esophageal cancer limited to regional lymph nodes, salvage treatment may be possible. Higher radiation doses and more-extensive lymphadenectomy may reduce the risk of regional recurrence.

Influences of intratumoral heterogeneity on assessment of tumor microenvironment in esophageal squamous cell carcinoma.

The intratumoral heterogeneity (ITH) of the tumor microenvironment (TME) has yet to be addressed in esophageal squamous cell carcinoma (ESCC). Here, we studied the ITH of CD8 and PD-L1 status in ESCC, and examined the potential of the tumor surface for representing the TME. In total, 67 surgically resected clinical Stage II ESCC specimens were analyzed. The CD8-cell density, PD-L1 tumor proportion score (TPS), and combined positive score (CPS) were calculated in three (superficial, middle, and deep) areas of each specimen. ITH was quantified by distance-standardized coefficient variations of the three values. The CD8 and PD-L1 status of each area was dichotomized and tumor-surface capabilities for predicting the entire tumor status were estimated. Variables were compared according to the presence of neoadjuvant chemotherapy (NAC). The ITH, especially PD-L1 heterogeneity, differed markedly among specimens. The concordance rates of CD8 and PD-L1 (CPS and TPS) status among the three different areas were 71.6%, 74.6%, and 73.1%, respectively. The sensitivity and the specificity of the tumor surface for predicting the CD8 status of the whole tumor were high, especially in the NAC- group (both 1.0). The tumor surface also showed high capabilities for representing the whole PD-L1 status, while yielding moderate positive predictive values (0.70). The ITH degrees and predictive capabilities did not differ according to NAC. Taken together, the ITH of CD8 and PD-L1 differed among ESCC specimens, while not being markedly affected by NAC. The use of a biopsy specimen from the tumor surface might be feasible for TME evaluation.

Combined assessment of clinical and pathological prognostic factors for deciding treatment strategies for esophageal squamous cell carcinoma invading into the muscularis mucosa or submucosa after endoscopic submucosal dissection.

OBJECTIVES: We aimed to clarify the prognostic factors for patients with esophageal squamous cell carcinoma (ESCC) invading into the muscularis mucosa (pT1a-MM) or submucosa (pT1b-SM) after endoscopic submucosal dissection (ESD). METHODS: This retrospective study enrolled such patients at 21 institutions in Japan between 2006 and 2017. We evaluated 15 factors, including pathological risk categories for ESCC-specific mortality, six non-cancer-related indices, and treatment strategies. RESULTS: In the analysis of 593 patients, the 5-year overall and disease-specific survival rates were 83.0% and 97.6%, respectively. In a multivariate Cox analysis, male sex (hazard ratio [HR] 3.56), Charlson comorbidity index (CCI) ≥3 (HR 2.53), ages of 75-79 (HR 1.61) and ≥80 years (HR 2.04), prognostic nutrition index (PNI) <45 (HR 1.69), and pathological intermediate-risk (HR 1.63) and high-risk (HR 1.89) were prognostic factors. Subsequently, we developed a clinical risk classification for non-ESCC-related mortality based on the number of prognostic factors (age ≥75 years, male sex, CCI ≥3, PNI <45): low-risk, 0; intermediate-risk, 1-2; and high-risk, 3-4. The 5-year non-ESCC-related mortality rates for patients without additional treatment were 0.0%, 10.2%, and 45.8% in the low-, intermediate-, and high-risk groups, respectively. Meanwhile, the 5-year ESCC-specific mortality rates for the pathological low-, intermediate-, and high-risk groups were 0.3%, 5.3%, and 18.2%, respectively. CONCLUSIONS: We clarified prognostic factors for patients with pT1a-MM/pT1b-SM ESCC after ESD. The combined assessment of non-ESCC- and ESCC-related mortalities by the two risk classifications might help clinicians in deciding treatment strategies for such patients.

Combined assessment of tumour cell nest size and desmoplastic reaction as an excellent prognostic predictor in oesophageal squamous cell carcinoma.

AIMS: Tumour budding (TB) activity, cell nest size (CNS), and desmoplastic reaction (DR) have been confirmed to be significantly correlated with prognosis in oesophageal squamous cell cancer (ESCC) recently. However, there are limited data on the prognostic significance of combined assessment of cellular dissociation and tumour stroma in ESCC. METHODS: In all, 265 cases with resected ESCCs diagnosed between January 2018 and August 2019 were retrospectively reviewed. All slides were reviewed for assessing TB, CNS, and DR. The Cellular Dissociation Grading and our Combined CNS and DR (CNS/DR) Grading systems were adopted to re-grade ESCCs. RESULTS: High TB activity, small CNS, and immature DR had a strong association with shorter overall survival (OS) and progression-free survival (PFS) (P < 0.001, respectively) in ESCC. Combined assessment of CNS and DR in a 4-tiered grading system displayed a prognostic excellence for survival (P < 0.001), and outperformed the Cellular Dissociation Grading for both OS (area under the curve [AUC], 0.728 versus 0.644, P = 0.043) and PFS (AUC, 0.763 versus 0.667, P = 0.018) by receiver operator characteristic curves. Also, Combined CNS/DR Grading showed superiority in recognizing a G4 subgroup with the worst outcome in our cohort, to whom the most urgent attention needs to be called. CONCLUSIONS: This is the first study to propose a novel Combined Grading system based on CNS and DR in ESCC, which has been demonstrated to be relatively superior to Cellular Dissociation Grading in predicting prognosis. The findings shed new light on the histopathological grading of ESCC and facilitates identifying biologically aggressive ESCCs.

Assessment of the Diagnostic Performance of Endoscopic Ultrasonography After Conventional Endoscopy for the Evaluation of Esophageal Squamous Cell Carcinoma Invasion Depth.

Importance: Distinguishing between mucosal and submucosal cancers is important for selecting the optimal treatment for patients with esophageal squamous cell carcinoma (ESCC); however, standard procedures for diagnosing cancer invasion depth have not yet been determined. Objective: To evaluate the diagnostic performance of endoscopic ultrasonography (EUS) after conventional endoscopy for the evaluation of ESCC invasion depth. Design, Setting, and Participants: This prospective single-arm confirmatory diagnostic study comprising 372 patients with T1 esophageal cancer was conducted at 41 secondary or tertiary hospitals in Japan. Enrollment began on July 20, 2017; patients were enrolled in 2 steps, with the first registration occurring from August 4, 2017, to December 11, 2019, and the second from August 9, 2017, to December 11, 2019. After the completion of all first and second registration examinations, patients received treatment and were followed up for 30 days, with follow-up ending on February 14, 2020. Patients were eligible for inclusion if they had pathologically or endoscopically diagnosed esophageal cancer with T1 clinical depth of invasion. Interventions: In the first registration, nonmagnifying endoscopy (non-ME) and magnifying endoscopy (ME) were used to diagnose cancer invasion depth. In the second registration, patients from the first registration who had cancers invading the muscularis mucosa or submucosa were enrolled and received EUS. After completion of the protocol examinations, patients received treatment with endoscopic resection or esophagectomy. The pathological results of the resected specimens were used as the reference standard for evaluating cancer invasion depth. Main Outcomes and Measures: The primary end point was the proportion of overdiagnosis of submucosal cancer (defined as invasion depth >200 µm) after receipt of non-ME and ME, with or without the addition of EUS. The secondary end points were underdiagnosis, sensitivity, and specificity. Results: Among 372 patients enrolled in the first registration, 371 received non-ME and ME. Of those, 300 patients were enrolled in the second registration, and 293 patients received EUS. A total of 269 patients (217 men [80.7%]; median age, 69 years; interquartile range, 62-75 years) were included in the final analysis. The addition of EUS was associated with a 6.6% increase in the proportion of overdiagnosis (from 16 of 74 patients [21.6%; 95% CI, 12.9%-32.7%] after non-ME and ME to 29 of 103 patients [28.2%; 95% CI, 19.7%-37.9%] after the addition of EUS; 1-sided P = .93). All subgroup analyses found similar increases in overdiagnosis of submucosal cancer. The addition of EUS was associated with a 4.5% reduction in the proportion of underdiagnosis (from 57 of 195 patients [29.2%; 95% CI, 23.0%-36.2%] after non-ME and ME to 41 of 166 patients [24.7%; 95% CI, 18.3%-32.0%] after the addition of EUS). After non-ME and ME, diagnostic sensitivity was 50.4% (95% CI, 41.0%-59.9%), specificity was 89.6% (95% CI, 83.7%-93.9%), and accuracy was 72.9% (95% CI, 67.1%-78.1%). After the addition of EUS, diagnostic sensitivity was 64.3% (95% CI, 54.9%-73.1%), specificity was 81.2% (95% CI, 74.1%-87.0%), and accuracy was 74.0% (95% CI, 68.3%-79.1%). Conclusions and Relevance: This study found that the addition of EUS was not associated with improvements in the diagnostic accuracy of cancer invasion depth. These findings do not support the routine use of EUS after conventional endoscopy for evaluating the invasion depth among patients with T1 ESCC.

Impact of Radiation on Cardiovascular Outcomes in Older Resectable Esophageal Cancer Patients With Medicare.

OBJECTIVES: Preoperative radiotherapy improves outcomes for operable esophageal cancer patients, though the proximity of the heart to the esophagus puts patients at risk of radiation-induced cardiovascular disease. This study characterizes the impact of radiotherapy and different radiation techniques on cardiovascular morbidity among a cohort of esophageal cancer patients. MATERIALS AND METHODS: We identified 1125 patients aged 65 and older diagnosed between 2000 and 2011 with esophageal cancer who received surgery alone, or surgery preceded by either preoperative chemotherapy or preoperative chemoradiation from the Surveillance Epidemiology and End Results (SEER)-Medicare database. We used Medicare claims to identify severe perioperative and late cardiovascular events. Multivariable logistic regression and Fine-Gray models were used to determine the effect of presurgery treatment on the risk of perioperative and late cardiovascular disease. RESULTS: Preoperative chemotherapy or chemoradiation did not significantly increase the risk of perioperative cardiovascular complications compared with surgery alone. Patients treated with preoperative chemoradiation had a 36% increased risk of having a late cardiovascular event compared with patients treated with surgery alone (subdistribution hazard ratio [SDHR]: 1.36; P=0.035). There was no significant increase in late cardiovascular events among patients treated with preoperative chemotherapy (SDHR: 1.18; P=0.40). Among patients treated with preoperative chemoradiation, those receiving intensity modulated radiotherapy had a 68% decreased risk of having a late cardiovascular event compared with patients receiving conventional radiation (SDHR: 0.32; P=0.007). CONCLUSIONS: This study demonstrates an increased risk of cardiovascular complications among operative esophageal cancer patients treated with preoperative chemoradiation, though these risks might be reduced with more cardioprotective radiation techniques such as intensity modulated radiotherapy.

Pathologic assessment of endoscopic resection specimens with superficial carcinoma of the esophagus: current practice and practical issues.

Endoscopic resection (ER) has become the first-line therapy for early esophageal cancer and offers a treatment alternative to surgery, owing to less morbidity and better quality of life. ER techniques include endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). EMR is faster, simpler, and cheaper than ESD, but limited by its ability to resect lesions larger than 1.5 centimeters. Piecemeal EMR has limitations, including a high local recurrence rate and a suboptimal specimen for an accurate pathologic assessment. ESD, on the other hand, allows en bloc resections with negative (R0) margins, irrespective of lesion size, providing an excellent pathologic specimen, however, is technically challenging with a higher risk of complications. The evaluation of ER specimens in pathology varies slightly from institution to institution. Our review summarizes the current practices and issues in the pathologic assessment of esophageal ER specimens, which highlights the necessity of a systematic approach and standardization of both macroscopic and microscopic evaluation. There is a need for a comprehensive and standardized pathology report that will allow for uniform terminology for endoscopists, surgeons, and pathologists, which, in turn, will result in better treatment guidance.

Real-time assessment of video images for esophageal squamous cell carcinoma invasion depth using artificial intelligence.

BACKGROUND: Although optimal treatment of superficial esophageal squamous cell carcinoma (SCC) requires accurate evaluation of cancer invasion depth, the current process is rather subjective and may vary by observer. We, therefore, aimed to develop an AI system to calculate cancer invasion depth. METHODS: We gathered and selected 23,977 images (6857 WLI and 17,120 NBI/BLI images) of pathologically proven superficial esophageal SCC from endoscopic videos and still images of superficial esophageal SCC taken in our facility, to use as a learning dataset. We annotated the images with information [such as magnified endoscopy (ME) or non-ME, pEP-LPM, pMM, pSM1, and pSM2-3 cancers] based on pathologic diagnosis of the resected specimens. We created a model using a convolutional neural network. Performance of the AI system was compared with that of invited experts who used the same validation video set, independent of the learning dataset. RESULTS: Accuracy, sensitivity, and specificity with non-magnified endoscopy (ME) were 87%, 50%, and 99% for the AI system and 85%, 45%, 97% for the experts. Accuracy, sensitivity, and specificity with ME were 89%, 71%, and 95% for the AI system and 84%, 42%, 97% for the experts. CONCLUSIONS: Most diagnostic parameters were higher when done by the AI system than by the experts. These results suggest that our AI system could potentially provide useful support during endoscopies.

Cost-effectiveness analysis of nivolumab in the second-line treatment for advanced esophageal squamous cell carcinoma.

Background: To investigate the cost-effectiveness of nivolumab versus chemotherapy in the second-line treatment for advanced esophageal squamous cell carcinoma. Materials & methods: A Markov model reflecting the patients in the ATTRACTION-3 trial was established. Weibull survival model was employed to fit the Kaplan-Meier progression-free survival and overall survival probabilities of the nivolumab and chemotherapy strategy, respectively. Meanwhile, one-way and PSA were performed to test the uncertainty in the model. Results: Overall, the incremental effectiveness and cost of nivolumab versus chemotherapy were 0.107 quality-adjusted life-years and $14,627.90, resulting in an incremental cost-effectiveness ratio of $136,709.35/quality-adjusted life-year. Conclusion: Nivolumab is not a cost-effective treatment option compared with chemotherapy from the perspective of Chinese society.

Histopathological Assessment for Esophageal Squamous Cell Carcinoma.

Histological assessment of esophageal squamous malignancies is crucial for management of patients with the cancer as well as working in research on the cancer. The squamous malignancies in the esophagus comprise squamous dysplasia and squamous cell carcinoma. Current classification of squamous dysplasia in the esophagus is to divide it into low grade and high grade. Most of the esophageal squamous cell carcinomas are of conventional type and divided into well, moderately, and poorly differentiated. The variants of esophageal squamous cell carcinoma include basaloid squamous carcinoma, spindle cell carcinoma, and verrucous carcinoma. Preoperative chemoradiation is used commonly in the treatment of esophageal squamous cell carcinoma and induces changes in morphology. Tumor regression grading systems based on the percentage of the remaining carcinoma cells are used to assess the response to the neoadjuvant therapy in the cancer. Additional histological parameters including lymphovascular invasion, perineural invasion, clearance of resection margins, and carcinoma in the nodal and distant metastatic sites provide essential information for the management of the patient with the cancer.

Macroscopic Assessment and Sampling of Endoscopic Resection Specimens for Squamous Epithelial Malignancies with Superficial Involvement of Esophagus.

Endoscopic resection is commonly used for superficial squamous cell carcinoma or high-grade dysplasia of esophageal squamous cell carcinoma. The depth of invasion, clearance from resection margins, and other pathological parameters are important parameters to be examined. The depth of invasion by carcinoma is associated with the risk of lymph node metastases. In endoscopic resection of superficial squamous malignancies of the esophagus, proper pathological examination of the resected specimen could guide the management of the patients in terms of the need for additional treatment, including lymph node dissection, chemotherapy, and radiation therapies.

Cost-effectiveness of chemoradiation followed by esophagectomy versus chemoradiation alone in squamous cell carcinoma of the esophagus.

BACKGROUND: Standard treatment for locally advanced esophageal cancer usually includes a combination of chemotherapy, radiation, and surgery. In squamous cell carcinoma (SCC), recent studies have indicated that esophagectomy after chemoradiation does not significantly improve survival but may reduce recurrence at the cost of treatment-related mortality. This study aims to evaluate the cost-effectiveness of chemoradiation with and without esophagectomy. METHODS: We developed a decision tree and Markov model to compare chemoradiation therapy alone (CRT) versus chemoradiation plus surgery (CRT+S) in a cohort of 57-year-old male patients with esophageal SCC, over 25 years. We used information on survival, cancer recurrence, and side effects from a Cochrane meta-analysis of two randomized trials. Societal utility values and costs of cancer care (2017, USD) were from medical literature. To test robustness, we conducted deterministic (DSA) and probabilistic sensitivity analyses (PSA). RESULTS: In our base scenario, CRT resulted in less cost for more quality-adjusted life years (QALYs) compared to CRT+S ($154 082 for 1.32 QALYs/patient versus $165 035 for 1.30 QALYs/patient, respectively). In DSA, changes resulted in scenarios where CRT+S is cost-effective at thresholds between $100 000-$150 000/QALY. In PSA, CRT+S was dominant 17.9% and cost-effective at willingness-to-pay of $150 000/QALY 38.9% of the time, and CRT was dominant 30.6% and cost-effective 61.1% of the time. This indicates that while CRT would be preferred most of the time, variation in parameters may change cost-effectiveness outcomes. CONCLUSIONS: Our results suggest that more data is needed regarding the clinical benefits of CRT+S for treatment of localized esophageal SCC, although CRT should be cautiously preferred.

Prediction of lymph node metastatic status in superficial esophageal squamous cell carcinoma using an assessment model combining clinical characteristics and pathologic results: A retrospective cohort study.

BACKGROUND: It is important to identify the risk of lymph node metastasis (LNM) in patients with superficial esophageal squamous carcinoma (SESC) who have received endoscopic resection (ER). We aimed to develop a risk-predicting model for metastasis of SESC to lymph nodes using clinicopathological features and pathological results. METHODS: Clinical data on 539 consecutive patients who underwent esophagectomy for SESC in our hospital were collected. Their post-surgical pathological results were assessed and analyzed. Multivariate logistic regression was used to identify all independent risk factors associated with LNM that then were incorporated into the prediction model. RESULTS: LNM was identified in 53 of 366 patients and 30 of 173 patients by positive histopathological results in the training and validation cohorts. The risk factors associated with LNM were large tumor size, poor tumor grade, deep invasion, and presence of angiolymphatic invasion. The model achieved good discriminatory ability of 0.80 (95%CI, 0.74-0.86) and 0.81 (95%CI, 0.75-0.86) in predicting LNM in the training and validation cohorts respectively. A LNM-predicting nomogram was formed with an area under curve of 0.80 (95% CI, 0.74-0.86), which had well-fitted calibration curves. CONCLUSIONS: A prediction model was constructed to generates 3 categories for estimated LNM risk in SESC patients. It provides a practical way of estimation of LNM risk in SESC patients who had received ER.

Assessment of apelin, apelin receptor, resistin, and adiponectin levels in the primary tumor and serum of patients with esophageal squamous cell carcinoma.

BACKGROUND: Disturbances in adipokine secretion are associated with the risk of cancer growth and progression. OBJECTIVES: The aim of the study was to evaluate the mRNA expression and protein levels of apelin, the apelin receptor, resistin, and adiponectin in the tumor tissues of surgically treated esophageal squamous cell carcinoma (ESCC) patients. Concentrations of serum adipokines were assessed in relation to ESCC progression. MATERIAL AND METHODS: The study group consisted of 53 patients with ESCC and 27 controls. In the ESCC group, 27 patients were surgically treated and 26 were treated with palliative procedures. RT-PCR and ELISA tests were used to measure the mRNA expression and protein level of adipokines in tissues and their concentration in serum. RESULTS: We found that mRNA expression and protein concentrations of apelin, the apelin receptor and resistin were significantly higher in tumor tissue than in control tissue. The protein concentration of apelin were significantly increased in the tumors of patients with lymph node metastasis (p < 0.005). Circulating levels of apelin, the apelin receptor and resistin were significantly higher in the cancer patients than in controls (p < 0.05 for all). The concentration of serum apelin receptor significantly decreased in patients with stage IV cancer, the presence of lymph node or distant metastasis (p < 0.05). CONCLUSIONS: Apelin may participate in lymphangiogenesis and the progression of ESCC. The apelin receptor is intensely produced in the early stage of cancer development and it may take part in the carcinogenic processes of ESCC.

Retrospective Assessment of the Diagnostic Accuracy of the Depth of Invasion by Narrow Band Imaging Magnifying Endoscopy in Patients with Superficial Esophageal Squamous Cell Carcinoma.

PURPOSE: Treatment strategies for superficial esophageal squamous cell carcinoma (S-ESCC) are determined mainly on the basis of the depth of invasion. We retrospectively studied the accuracy of the depth of tumor invasion, comprehensively assessed using the Japan Esophageal Society (JES) classification. METHODS: The study group comprised 256 patients who underwent narrow band imaging (NBI) magnifying endoscopy, and endoscopic submucosal dissection for S-ESCC. The depth of invasion of S-ESCC was classified into three groups: EP/LPM, MM/SM1, and SM2. The following variables were studied retrospectively: (1) the diagnostic accuracy of non-magnifying white-light endoscopy, (2) the diagnostic accuracy of type B vessels, (3) the diagnostic accuracy of avascular area (AVA), (4) the diagnostic accuracy of the JES classification, and (5) the diagnostic accuracy of comprehensive diagnosis. The depth of invasion was assessed by white-light non-magnifying endoscopy, followed by NBI magnifying endoscopy. RESULTS: The positive predictive value (PPV) of white-light non-magnifying endoscopy was 86% for EP/LPM, 53% MM/SM1, and 74% for SM2. The PPV of the diagnosis of type B vessels was 93% for EP/LPM, 62% for MM/SM1, and 74% for SM2. The PPV of the AVA diagnosis was 73% for EP/LPM, 89% for MM/SM1, and 100% for SM2. The PPV of diagnosis according to the JES classification was 93% for EP/LPM, 65% for MM/SM1, and 77% for SM2. The PPV of the comprehensive diagnosis was 94% for EP/LPM, 63%, for MM/SM1, and 75% for SM2. CONCLUSIONS: The additional use of NBI magnifying endoscopy can enhance the diagnostic accuracy of the depth of invasion in patients with S-ESCC.

Preclinical assessment of histone deacetylase inhibitor quisinostat as a therapeutic agent against esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most serious life-threatening malignancies. Although chemotherapeutic targets and agents for ESCC have made much progress recently, the efficacy is still unsatisfactory. Therefore, there is still an unmet medical need for patients with ESCC. Here, we report the expression status of HDAC1 in human ESCC and matched paracancerous tissues, and the results indicated that HDAC1 was generally upregulated in ESCC specimens. Furthermore, we comprehensively assessed the anti-ESCC activity of a highly active HDAC1 inhibitor quisinostat. Quisinostat could effectively suppress cellular viability and proliferation of ESCC cells, as well as induce cell cycle arrest and apoptosis even at low treatment concentrations. The effectiveness was also observed in KYSE150 xenograft model when quisinostat was administered at tolerated doses (3 mg/kg and 10 mg/kg). Meanwhile, quisinostat also had the ability to suppress the migration and invasion (pivotal steps of tumor metastasis) of ESCC cells. Western blot analysis indicated that quisinostat exerted its anti-ESCC effects mainly through blockade of Akt/mTOR and MAPK/ERK signaling cascades. Overall, HDAC1 may serve as a potential therapeutic target for ESCC, and quisinostat deserves to be further assessed as a promising drug candidate for the treatment of ESCC.