Risk factors for recurrence of esophageal squamous cell carcinoma after pathological complete response to neoadjuvant therapy followed by esophagectomy.

BACKGROUND: Prognosis of patients who achieve pathological complete response (pCR) with neoadjuvant therapy (NAT) is better than that of non-pCR patients. Currently, there is no indication for adjuvant immune checkpoint inhibitor therapy after achieving pCR. However, recurrence risk after pCR is reportedly 10%-20% with a poor prognosis. Therefore, we investigated the preoperative risk factors for recurrence in patients with pCR. METHODS: We analyzed 56 patients with esophageal squamous cell carcinoma who underwent esophagectomy after neoadjuvant chemoradiotherapy (NACRT) or neoadjuvant chemotherapy (NAC) and were histologically diagnosed with pCR. Preoperative factors were compared between patients with and without recurrence to identify the risk factors. RESULTS: Forty-eight patients who achieved pCR received NACRT and 8 received NAC. Ten patients who experienced recurrence (17.9%) had undergone NACRT. The cN2 lesions were more frequent, and pre-NAT blood hemoglobin (Hb) was lower in the recurrence group. In addition, the pre-NAT cross-sectional area (CSA) product of the major and minor diameters of the primary tumor before NAT was significantly higher in recurrent cases (p = 0.041). Multivariate analysis, including the cTNM stage, pre-NAT Hb, and pre-NAT CSA, identified high pre-NAT CSA as the only risk factor for recurrence (odds ratio 11.6, 95% confidence interval 1.3-104.1, and p = 0.028). Cox regression analysis of recurrence-free and overall survival identified only high pre-NAT CSA as a prognostic factor. CONCLUSIONS: The recurrence risk is relatively high even in patients who achieve pCR after NAT. High pre-NAT CSA of the primary tumor is a risk factor for recurrence necessitating close surveillance.

Association between prognosis and lymph node status using 18F-fluorodeoxyglucose-positron emission tomography in esophageal squamous cell carcinoma treated with esophagectomy post-neoadjuvant chemotherapy.

BACKGROUND: There are few reports on the associations between lymph node (LN) status, determined by preoperative 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET), and prognosis in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who underwent esophagectomy post-neoadjuvant chemotherapy (NCT). Additionally, details on the diagnostic performance of LN metastasis determination based on pathological examination versus FDG-PET have not been reported. In this study, we aimed to evaluate the associations among LN status using FDG-PET, LN status based on pathological examination, and prognosis in patients with locally advanced ESCC who underwent esophagectomy post-NCT. METHODS: We reviewed the data of 124 consecutive patients with ESCC who underwent esophagectomy with R0 resection post-NCT between December 2008 and August 2022 and were evaluated pre- and post-NCT using FDG-PET. The associations among LN status using FDG-PET, LN status based on pathological examination, and prognosis were assessed. RESULTS: Station-by-station analysis of PET-positive LNs pre- and post-NCT correlated significantly with pathological LN metastases (sensitivity, specificity, and accuracy pre- and post-NCT: 51.6%, 96.0%, and 92.1%; and 28.2%, 99.5%, and 93.1%, respectively; both p < 0.0001). Using univariate and multivariate analyses, LN status determined using PET post-NCT was a significant independent predictor of both recurrence-free survival and overall survival. CONCLUSION: The LN status assessed using FDG-PET post-NCT was significantly associated with the pathological LN status and prognosis in patients with ESCC who underwent esophagectomy post-NCT. Therefore, FDG-PET is a useful diagnostic tool for preoperatively predicting pathological LN metastasis and survival in these patients and could provide valuable information for selecting individualized treatment strategies.

Prognostic factors for esophageal squamous cell carcinoma without pathological lymph node metastasis after neoadjuvant therapy and surgery.

BACKGROUND: Pathological lymph node metastasis (LNM) following multimodal therapy is an important indicator of poor prognosis in patients with esophageal cancer. However, a significant number of patients without LNM are still at high risk for recurrence. METHODS: We assessed prognostic factors in 143 patients without pathological LNM who were diagnosed with locally advanced esophageal squamous cell carcinoma (ESCC) and underwent neoadjuvant chemotherapy (NAC) or chemoradiotherapy (NACRT), followed by surgery. RESULTS: Using univariate and multivariate analyses of recurrence-free survival, carcinoembryonic antigen (CEA) levels (hazard ratio [HR]: 2.17, 95% confidence interval [CI]: 1.12-4.23, and p = 0.02) and neutrophil-to-lymphocyte ratio (NLR) (HR: 1.22, 95% CI: 1.04-1.43, and p = 0.02) were significant independent covariates. Furthermore, pretherapeutic LNM (HR: 1.94, 95% CI: 1.003-3.76, and p = 0.049), NACRT (HR: 3.29, 95% CI: 1.30-8.33, and p = 0.01), poorly differentiated tumors (HR: 2.52, 95% CI: 1.28-4.98, and p = 0.01), and lymphovascular invasion (LVI) (HR: 2.78, 95% CI: 1.27-6.09, and p = 0.01) were also significant independent covariates. The recurrence rates among patients with 0/1, 2, 3, and 4/5 poor prognostic factors were significantly different (5.0%, 25.0%, 35.7%, and 53.8%, respectively; p = 0.001); the survival rates were stratified among these prognostic groups. CONCLUSIONS: Pretherapeutic CEA and NLR levels, pretherapeutic LNM, NACRT, poorly differentiated tumors, and LVI were significantly correlated with survivals in patients without pathological LNM after neoadjuvant therapy and surgery. Postoperative therapy should be considered in patients with ESCC with several indicators of recurrence, even in those without pathological LNM who underwent surgery following neoadjuvant therapy.

The treatment efficacy and prognosis of each treatment in early postoperative recurrence of esophageal squamous cell carcinoma.

PURPOSE: Various treatments are used for early postoperative recurrence of esophageal cancer, which has a poor prognosis. We evaluated the differences in outcomes and prognoses of each treatment modality between patients with early and late recurrence. METHODS: Early and late recurrence were defined as recurrence within and after six postoperative months, respectively. Of the 351 patients with esophageal squamous cell carcinoma who underwent R0 resection esophagectomy, 98 experienced postoperative recurrence (early recurrence, n = 41; late recurrence, n = 57). We evaluated the characteristics of patients with early and late recurrence and compared their treatment responses and prognoses. RESULTS: Regarding treatment responses for chemotherapy or immunotherapy, the objective response rate was not significantly different between the early- and late-recurrence groups. For chemoradiotherapy, the objective response rate was significantly lower in the early-recurrence group than in the late-recurrence group. The overall survival was significantly worse in the early-recurrence group than in the late-recurrence group. An analysis by treatment type showed that the early-recurrence group had significantly worse overall survival for chemoradiotherapy, surgery, and radiotherapy than the late-recurrence group. CONCLUSIONS: Patients with early recurrence had particularly poor prognoses with worse post recurrence treatment efficacy than those with late recurrence. The differences in the treatment efficacy and prognosis were particularly pronounced for local therapy.

Real-world clinical outcomes of nivolumab and taxane as a second- or later-line therapy for recurrent or unresectable advanced esophageal squamous cell carcinoma.

Background: Nivolumab is approved in Japan as a second-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC) resistant to fluoropyrimidine and platinum-based drugs. It is also used in adjuvant and primary postoperative therapies. This study aimed to report real-world data on nivolumab use for esophageal cancer treatment. Methods: In total, 171 patients with recurrent or unresectable advanced ESCC who received nivolumab (n = 61) or taxane (n = 110) were included. We collected real-world data of patients treated with nivolumab as a second- or later-line therapy and evaluated treatment outcomes and safety. Results: Median overall survival was longer and progression-free survival (PFS) was significantly longer (p = 0.0172) in patients who received nivolumab than in patients who received taxane as a second- or later-line therapy. Furthermore, subgroup analysis for second-line treatment only showed the superiority of nivolumab in increasing the PFS rate (p = 0.0056). No serious adverse events were observed. Conclusions: In real-world practice, nivolumab was safer and more effective than taxane in patients with ESCC with diverse clinical profiles who did not meet trial eligibility criteria, including those with poor Eastern Cooperative Oncology Group performance status, comorbidities, and receiving multiple treatments.

Ability of Blood Cell Parameters to Predict Clinical Outcomes of Nivolumab Monotherapy in Advanced Esophageal Squamous Cell Carcinoma.

Purpose: Various blood cell parameters have been identified as predictive markers of tumor responses and the survival of patients with cancer treated with immune checkpoint inhibitors. The purpose of this study is to assess the ability of various blood cell parameters to predict therapeutic effects and survival in patients with esophageal squamous cell carcinoma (ESCC) treated with nivolumab monotherapy. Patients and Methods: We evaluated neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) and lymphocyte-to-monocyte (LMR) ratios as predictive markers of patients' survival and effects of nivolumab monotherapy after one or more prior chemotherapies for unresectable advanced or recurrent ESCC. Results: The objective response and disease control rates were 20.3% and 47.5%, respectively. The LMRs before, and 14 and 28 days after nivolumab initiation were significantly higher in patients with complete response (CR)/partial response (PR)/stable disease (SD) than those with progressive disease (PD). The NLRs at 14 and 28 days after nivolumab initiation were significantly lower in patients with CR/PR/SD than with PD. The optimal cutoffs for these parameters significantly discriminated patients with CR/PR/SD and PD. Univariate and multivariate analyses identified pretreatment NLRs as a significant independent factor for progression-free and overall survival (hazard ratio [HR]: 1.19, 95% confidence interval [CI]: 1.07-1.32, and HR 1.23, 95% CI: 1.11-1.37, respectively; p ≤ 0.001 for both). Conclusion: The pretreatment LMRs, and NLR and LMR at 14 and 28 days after starting nivolumab monotherapy were significantly associated with the clinical therapeutic effect. The pretreatment NLR was significantly associated with patients' survival. These blood cell parameters before and during the early days of nivolumab monotherapy can help to identify patients with ESCC who would most likely benefit from nivolumab monotherapy.

Correlation Between Tumor Uptake on FDG-PET and Malignant Features in Esophageal Squamous Cell Carcinoma After Neoadjuvant Chemotherapy Followed by Surgery.

BACKGROUND/AIM: To identify the correlations between the 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) images and the pathological features and recurrence among patients with esophageal squamous cell carcinoma (ESCC) who were administered neoadjuvant chemotherapy (NAC) followed by surgery. PATIENTS AND METHODS: We assessed the correlations between the maximum standardized uptake value (SUVmax) of primary tumors as reflected on preoperative FDG-PET images, the pathological features, and cancer recurrence in 124 patients with locally advanced ESCC, who were treated with NAC and esophagectomy. RESULTS: The pre-NAC SUVmax significantly differed for the ypT status and venous invasion (VI). The post-NAC SUVmax (post-SUVmax) significantly differed for the ypT and ypN status, VI, lymphatic invasion (LI), pathological tumor response, down-staging, and recurrence. The decrease in SUVmax before and after NAC (ΔSUVmax) significantly differed for ypT status, LI, VI, pathological tumor response, down-staging, and recurrence. The survivals were significantly stratified according to the optimal cutoffs of SUVmax for predicting recurrence (post- and ΔSUVmax cutoffs: 4.2 and 30, respectively; all p<0.0001). Moreover, multivariate analysis showed that the post- and ΔSUVmax were independent predictive factors for recurrence-free survival. CONCLUSION: The SUVmax on preoperative FDG-PET can predict the degree of aggressiveness of the tumor in locally advanced ESCC treated with NAC.

Blood biomarkers as predictors of pathological lymph node metastasis in clinical stage T1N0 esophageal squamous cell carcinoma.

Accurate preoperative evaluation of lymph node (LN) metastasis is important for determining the treatment strategy for superficial esophageal cancer. Blood biomarkers, such as the neutrophil-lymphocyte, platelet-lymphocyte, and lymphocyte-monocyte ratios (NLR, PLR, and LMR, respectively), have clinical applications as predictors of LN metastasis for different cancers. Here, we investigated the use of these ratios as predictors of pathological LN metastasis and prognosis in patients with clinical stage T1N0M0 esophageal squamous cell carcinoma (ESCC). Patients (n = 185) with cT1N0M0 ESCC who underwent esophagectomy with R0 resection between April 2003 and August 2021 were enrolled. We investigated the ability of pretreatment NLR, PLR, and LMR to predict pathological LN metastasis. The optimal cutoff values of NLR, PLR, and LMR to predict pathological LN metastasis were 2.1, 122, and 4.8, respectively. Univariate and multivariate analyses revealed that the primary tumor length, depth of invasion, and NLR were significant predictors of LN metastasis. Furthermore, similar to the 5-year overall survival, the 5-year relapse-free survival was significantly better in the low NLR group than in the high NLR group. The NLR was the most useful predictor of pathological LN metastasis. Patients diagnosed with clinical stage I ESCC and with a high NLR require adequate LN dissection and may be good candidates for preoperative adjuvant therapy.

Prognostic value of quantitative parameters for esophageal squamous cell carcinoma determined by preoperative FDG-PET after trimodal therapy.

BACKGROUND: Associations between tumor metabolic and volumetric parameters determined by preoperative 18F-fluorodeoxyglucose-positron emission tomography and survival in patients with esophageal squamous cell carcinoma who underwent trimodal therapy have not been fully investigated. METHODS: We evaluated relationships between reductions in maximal standardized uptake value, metabolic tumor volume, and total lesion glycolysis in primary tumors on 18F-fluorodeoxyglucose-positron emission tomography images between before and after neoadjuvant chemoradiotherapy and the survival of 120 patients with esophageal squamous cell carcinoma who underwent neoadjuvant chemoradiotherapy followed by surgery. RESULTS: The optimal cutoffs of Δ maximal standardized uptake value, Δ metabolic tumor volume, and Δ total lesion glycolysis were defined to statistically yield the largest differences in recurrence-free survival for good and poor positron emission tomography responders to neoadjuvant chemoradiotherapy (cutoffs: 70%, 85%, and 90%, respectively). These cutoff values significantly stratified overall survival (Δ maximal standardized uptake value, P = .004; Δ metabolic tumor volume, P = .001; Δ total lesion glycolysis, P < .0001). Univariate analysis showed that Δ maximal standardized uptake value (hazard ratio, 0.50; 95% confidence interval, 0.32-0.79; P = .003), Δ metabolic tumor volume (hazard ratio, 0.50; 95% confidence interval, 0.31-0.81; P = .004), and Δ total lesion glycolysis (hazard ratio, 0.37; 95% confidence interval, 0.23-0.61; P < .001) were statistically significant for recurrence-free survival. Furthermore, Δ metabolic tumor volume (hazard ratio, 0.45; 95% confidence interval, 0.27-0.76; P = .003) and Δ total lesion glycolysis (hazard ratio, 0.37; 95% confidence interval, 0.22-0.63; P < .001) were independent factors for recurrence-free survival in multivariate analyses that included preoperative and pathological factors. CONCLUSION: Together with significant pathological prognostic factors, Δ metabolic tumor volume and Δ total lesion glycolysis were valuable for patients with esophageal squamous cell carcinoma who received trimodal therapy. Thus, preoperative 18F-fluorodeoxyglucose-positron emission tomography is a useful and noninvasive diagnostic tool that might facilitate tailoring optimal therapies for locally advanced esophageal squamous cell carcinoma.

Neutrophil-to-Lymphocyte Ratio as a Predictor of Postoperative Recurrence and Prognosis in Oesophageal Squamous Cell Carcinoma.

BACKGROUND: Trimodal therapy is frequently used for patients with locally advanced, resectable oesophageal cancer. However, it does not provide a satisfactory prognosis. The neutrophil-to-lymphocyte ratio (NLR) is an important indicator of patients' inflammatory and immune statuses. We investigated the prognostic role of NLR values obtained at different treatment stages in patients with oesophageal squamous cell carcinoma. PATIENTS AND METHODS: We evaluated the correlation between NLR values or their change and prognosis at each treatment point (before chemoradiotherapy; before surgery; and at 14 days, and 1 and 2 months postoperatively) in 163 patients with oesophageal squamous cell carcinoma who underwent oesophagectomy after neoadjuvant chemoradiotherapy from April 2003 to August 2018. The outcomes studied were overall (OS) and relapse-free (RFS) survival. RESULTS: The NLR at 1 month postoperatively showed the strongest correlation with prognosis, with an optimal cut-off value of 4.5 (area under the curve=0.7878; 95% confidence interval=0.70-0.85; p<0.0001). Univariate and multivariate analyses showed that NLR ≥4.5 was a significant factor for both RFS (hazard ratio=4.44, 95% confidence interval=2.69-7.34) and OS (hazard ratio=3.88, 95% confidence interval=2.38-6.32). Furthermore, NLR significantly stratified patients for the RFS and OS regardless of the pathological response (complete/non-complete response) and postoperative complications (Clavien-Dindo grade

Prospective Randomized Trial of Early Postoperative Enteral and Total Parenteral Nutrition for Treating Esophageal Cancer.

BACKGROUND/AIM: Surgical stress significantly decreases serum diamine oxidase (DAO), a marker of intestinal mucosal maturation and integrity. This study aimed to determine the effects of postoperative enteral and total parenteral nutrition (EN and TPN, respectively) in patients with esophageal cancer. PATIENTS AND METHODS: This prospective randomized trial compared serum DAO activities, nutritional states, trace elements and complications between patients who underwent esophagectomy and received EN or TPN for seven days thereafter. RESULTS: Fifty-one patients were randomized to receive EN or TPN. The rates of change in serum DAO activity from the day before surgery were 0.79, 0.89 and 0.91 on postoperative days (POD) 1, 3 and 7, respectively, in the EN group, and 0.64, 0.76 and 1.06, respectively, in the TPN group, with no significant differences. Furthermore, the rates of changes in indicators of nutritional status, namely total protein, albumin, total cholesterol, trace element concentrations and infectious and non-infectious complications did not significantly differ between the groups. CONCLUSION: EN and/or TPN can be administered for early nutritional management until resumption of oral intake after esophagectomy according to the postoperative status of individual patients with esophageal cancer.

Comparison of Open and Thoracoscopic Esophagectomy in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma After Neoadjuvant Therapy.

BACKGROUND/AIM: The safety and effectiveness of thoracoscopic compared with open esophagectomy remain uncertain. We aimed to clarify the differences between these surgical modalities in patients with esophageal squamous cell carcinoma (ESCC) who underwent neoadjuvant therapy. PATIENTS AND METHODS: We reviewed surgical outcomes among 133 patients with locally advanced ESCC who underwent neoadjuvant therapy followed by esophagectomy. We compared the operative outcomes, postoperative complications and survival rates between 65 and 68 patients who were respectively treated by open and thoracoscopic esophagectomy. RESULTS: The surgical duration was longer, but blood loss was lower during thoracoscopic, compared with open esophagectomy. The numbers of dissected mediastinal lymph nodes and rates of postoperative complications did not significantly differ between open and thoracoscopic esophagectomy. However, the rates of postoperative pneumonia and recurrent laryngeal nerve paralysis were significantly lower and higher, respectively, after thoracoscopic, compared with open esophagectomy. Overall survival did not significantly differ between the groups. CONCLUSION: Thoracoscopic esophagectomy is feasible for patients with locally advanced ESCC who undergo neoadjuvant therapy.

Distribution of Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma After Trimodal Therapy.

BACKGROUND: Although metastatic tumors in lymph nodes (LN) are potentially affected by neoadjuvant chemoradiotherapy (NCRT), the distribution of LN metastases of esophageal squamous cell carcinoma (ESCC) after trimodal therapy has never been sufficiently estimated. PATIENTS AND METHODS: We evaluated the distribution of LN metastases, relationships between LN metastases and radiation fields, risk factors for LN metastasis, and the influence of LN metastasis on the survival of 184 patients with ESCC who underwent NCRT followed by esophagectomy. RESULTS: Neoadjuvant chemoradiotherapy resulted in down-staged LN status in 74 (49.3%) patients. Pathological LN metastases were extensive in 177 LN stations in the cervical, mediastinal, and abdominal fields, and 162 (91.5%) metastases were located inside the radiation fields. Multivariate analysis showed that clinical N stage [N0 vs. 1/2/3: hazard ratio (HR), 2.69; 95% confidence interval (CI), 1.22-5.92; p = 0.01] and clinical response of primary tumor (complete vs. noncomplete: HR, 2.93; 95% CI, 1.50-5.69; p = 0.002) were statistically significant for pathological LN metastasis. Recurrence-free and overall survivals were significantly stratified according to the number of pathological LN metastases, associations between clinical and pathological LN metastases, and presence or absence of pathological LN metastases outside radiation field. CONCLUSIONS: About 50% of patients who were clinically diagnosed with LN metastasis before treatment were downstaged by NCRT, and their prognoses were relatively good. However, LN metastases were extensive at the cervical, mediastinal, and abdominal areas, even within the radiation field. Thus, systematic and adequate lymphadenectomy is required for ESCC treated by NCRT.

Risk Factors for Recurrence in Esophageal Squamous Cell Carcinoma Without Pathological Complete Response After Trimodal Therapy.

BACKGROUND/AIM: Intensive trimodal therapy is needed for locally advanced esophageal squamous cell carcinoma (ESCC). The prediction of recurrence is especially required for patients with pathological residual tumors in the resected primary sites and/or lymph nodes [non-pathological complete response (pCR)] who have a high possibility of recurrence after trimodal therapy. We aimed to determine the risk factors for cancer recurrence in ESCC patients diagnosed with non-pCR after trimodal therapy. PATIENTS AND METHODS: We evaluated the risk factors for recurrence-free survival (RFS) using the multivariate Cox proportional hazards analysis, based on data from 105 ESCC patients diagnosed with non-pCR after neoadjuvant chemoradiotherapy followed by esophagectomy. RESULTS: Univariate analysis revealed that RFS was significantly associated with postoperative complications, pathological T, N, M stage after therapy (ypT, ypN, ypM), tumor differentiation, lymphovascular invasion (LVI), and pathological response of the primary tumor. Subsequent multivariate analysis revealed postoperative complications ypN, tumor differentiation, and LVI as independent variables for RFS. The RFSs significantly differed between patients with and without these risk factors. CONCLUSION: Severe postoperative complications, ypN 2/3, poor tumor differentiation, and LVI were significantly associated with poor RFS. These factors may be used as prognostic factors in patients with non-pCR after trimodal therapy.

Successful Management of Esophageal Cancer With Perforation Using Bypass Surgery Followed by Definitive Chemoradiotherapy.

BACKGROUND: Esophageal perforation in advanced esophageal cancer requires immediate treatment. However, no clear treatment protocol has been established for this condition. We report a case of advanced esophageal cancer with esophageal perforation treated with esophageal bypass surgery and definitive chemoradiotherapy (CRT). CASE REPORT: A 45-year-old woman was diagnosed with locally advanced esophageal cancer with esophageal perforation. Although the patient's general condition was relatively stable, no improvement was expected through conservative treatment. Esophageal gastric bypass surgery was performed; her symptoms improved postoperatively and oral ingestion became possible. Definitive CRT with 66 Gy radiotherapy and chemotherapy with cisplatin and 5-fluorouracil was administered. A complete clinical response was achieved. The patient is alive and well without recurrence 20 months after treatment. CONCLUSION: Definitive CRT after esophageal bypass surgery is a potential treatment option for locally advanced esophageal cancer with esophageal perforation to improve treatment response and quality of life.

Predictions of Pathological Features and Recurrence Based on FDG-PET Findings of Esophageal Squamous Cell Carcinoma after Trimodal Therapy.

BACKGROUND: The degree of metabolic activity in tumor cells can be determined by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). Associations between FDG uptake by primary tumors of locally advanced esophageal squamous cell carcinoma (ESCC) under trimodal therapy and the pathological features of such tumors have not been fully investigated. PATIENTS AND METHODS: We evaluated relationships between the maximal standardized uptake (SUVmax) in primary tumors on preoperative PET images and pathological features as well as cancer recurrence in 143 patients with ESCC who underwent neoadjuvant chemoradiotherapy (NCRT) followed by surgery. RESULTS: The post-SUVmax significantly differed after NCRT for ypT and ypN status, lymphatic invasion (LI), venous invasion (VI), and recurrence. Furthermore, the %ΔSUVmax (rate of decrease between before and after NCRT) for LI, VI, and recurrence significantly differed. Univariate and multivariate analyses selected post-SUVmax and %ΔSUVmax as independent preoperative predictors of recurrence-free survival [hazard ratio (HR) 1.46; 95% confidence interval (CI) 1.24-1.72 and HR 0.97; 95% CI 0.96-0.99, respectively; p < 0.001 for both]. Recurrence-free and overall survival were significantly stratified according to optimal SUVmax cutoffs for predicting recurrence (post- and %ΔSUVmax: 2.8 and 70, respectively). CONCLUSIONS: The post- and %ΔSUVmax of primary tumors were significantly associated with the pathological features and recurrence of ESCC under trimodal therapy. Therefore, FDG-PET can preoperatively predict the degree of aggressive tumor behavior in ESCC under trimodal therapy.

Circulating microRNA/isomiRs as novel biomarkers of esophageal squamous cell carcinoma.

BACKGROUND: MicroRNA (miR)s are promising diagnostic biomarkers of cancer. Recent next generation sequencer (NGS) studies have found that isoforms of micro RNA (isomiR) circulate in the bloodstream similarly to mature micro RNA (miR). We hypothesized that combination of circulating miR and isomiRs detected by NGS are potentially powerful cancer biomarker. The present study aimed to investigate their application in esophageal cancer. METHODS: Serum samples from patients with esophageal squamous cell carcinoma (ESCC) and age and sex matched healthy control (HC) individuals were investigated for the expression of miR/isomiRs using NGS. Candidate miR/isomiRs which met the criteria in the 1st group (ESCC = 18 and HC = 12) were validated in the 2nd group (ESCC = 30 and HC = 30). A diagnostic panel was generated using miR/isomiRs that were consistently confirmed in the 1st and 2nd groups. Accuracy of the panel was tested then in the 3rd group (ESCC = 18 and HC = 18). Their use was also investigated in 22 paired samples obtained pre- and post-treatment, and in patients with esophageal adenocarcinoma (EAD) and high-grade dysplasia (HGD). RESULTS: Twenty-four miR/isomiRs met the criteria for diagnostic biomarker in the 1st and 2nd group. A multiple regression model selected one mature miR (miR-30a-5p) and two isomiRs (isoform of miR-574-3p and miR-205-5p). The index calculated from the diagnostic panel was significantly higher in ESCC patients than in the HCs (13.3±8.9 vs. 3.1±1.3, p<0.001). The area under the receiver operating characteristics (ROC) curves of the panel index was 0.95. Sensitivity and specificity were 93.8%, and 81% in the 1st and 2nd groups, and 88.9% and 72.3% in the 3rd group, respectively. The panel index was significantly lower in patients with EAD (6.2±4.5) and HGD (4.2±1.7) than in those with ESCC and was significantly decreased at post-treatment compared with pre-treatment (6.2±5.6 vs 11.6±11.5, p = 0.03). CONCLUSION: Our diagnostic panel had high accuracy in the diagnosis of ESCC. MiR/isomiRs detected by NGS could serve as novel biomarkers of ESCC.

Predicting the presence of breast cancer using circulating small RNAs, including those in the extracellular vesicles.

Emerging evidence indicates that small RNAs, including microRNAs (miRNAs) and their isoforms (isomiRs), and transfer RNA fragments (tRFs), are differently expressed in breast cancer (BC) and can be detected in blood circulation. Circulating small RNAs and small RNAs in extracellular vesicles (EVs) have emerged as ideal markers in small RNA-based applications for cancer detection. In this study, we first undertook small RNA sequencing to assess the expression of circulating small RNAs in the serum of BC patients and cancer-free individuals (controls). Expression of 3 small RNAs, namely isomiR of miR-21-5p (3' addition C), miR-23a-3p and tRF-Lys (TTT), was significantly higher in BC samples and was validated by small RNA sequencing in an independent cohort. Our constructed model using 3 small RNAs showed high diagnostic accuracy with an area under the receiver operating characteristic curve of 0.92 and discriminated early-stage BCs at stage 0 from control. To test the possibility that these small RNAs are released from cancer cells, we next examined EVs from the serum of BC patients and controls. Two of the 3 candidate small RNAs were identified, and shown to be abundant in EVs of BC patients. Interestingly, these 2 small RNAs are also more abundantly detected in culture media of breast cancer cell lines (MCF-7 and MDA-MB-231). The same tendency in selective elevation seen in total serum, serum EV, and EV derived from cell culture media could indicate the efficiency of this model using total serum of patients. These findings indicate that small RNAs serve as significant biomarkers for BC detection.

Tumor Response in Esophageal Squamous Cell Carcinoma Treated With Neoadjuvant Chemotherapy Followed by Surgery.

BACKGROUND/AIM: Neoadjuvant therapy followed by surgery is the standard treatment for advanced esophageal cancer. This study aimed to evaluated the potential of 18F-fluorodeoxyglucose positron-emission tomography to predict the pathological therapeutic effect of neoadjuvant chemotherapy. PATIENTS AND METHODS: We enrolled 68 patients with advanced esophageal squamous cell carcinoma who underwent 18F-fluorodeoxyglucose positron-emission tomography before and after neoadjuvant chemotherapy, followed by surgery. Retrospective analysis of the pathological therapeutic effects was performed. RESULTS: The pathological therapeutic effect of good responders was significantly inversely associated with the maximum standardized uptake value (SUVmax) after neoadjuvant chemotherapy and with SUVmax reduction (both p<0.0001). Univariate and multivariate analyses revealed that lower post therapy SUVmax and reduction in SUVmax were independent prognostic factors for relapse-free (p=0.02) and overall survival (p<0.0001). CONCLUSION: Post-neoadjuvant chemotherapy SUVmax and SUVmax reduction can predict the pathological therapeutic effect of neoadjuvant chemotherapy.

Three-step surgical treatment of aortoesophageal fistula after thoracic endovascular aortic repair: A case report.

INTRODUCTION: Aortoesophageal fistula (AEF) is a fatal complication results in sudden massive hematemesis. Although thoracic endovascular aortic repair (TEVAR) is an established method of treating aortic aneurysms or aortic dissection, the number of AEF after TEVAR is recently increasing due to the spread of TEVAR. However, the therapeutic strategy for AEF remains controversial. PRESENTATION OF CASE: We describe a 71-year-old man with Stanford B aortic dissection and aortic aneurysm rupture treated by TEVAR who developed AEF between the thoracic aorta and upper thoracic esophagus 20 months thereafter. We applied a three-step surgical procedure for this patient comprising resection of the esophagus as the infectious source, removal of an aortic aneurysm with stent-graft and replacement of the aorta, and final reconstruction of the esophagus. Thereafter, the patient resumed oral intake and has remained relapse-free for 24 months without adverse events. DISCUSSION: Previous reports have described simultaneous resection of the esophagus and aortic stent-graft via a left thoracotomy followed by a two-step surgical reconstruction of the esophagus. We applied a three-step procedure consisting of resections of the esophagus and aortic stent-graft on separate occasions followed by esophageal reconstruction in this patient. The first procedure in the three-step approach is less stressful than that of the two-step approach. CONCLUSION: The three-step surgical approach to treating AEF after TEVAR resulted in a good outcome for this patient. Thus, this surgical strategy is a useful option for treating AEF after TEVAR.