Esophagus最新文献

Background: Preoperative inspiratory muscle training (IMT) enhances diaphragmatic excursion (DE) in patients with esophageal cancer; however, the postoperative effects of IMT on DE have not yet been evaluated. This study aimed to investigate the effect of preoperative IMT on perioperative diaphragmatic function as measured by DE, inspiratory muscle strength, lung function, and exercise tolerance.

Methods: This was a parallel, randomized-controlled trial. Patients with thoracic or abdominal esophageal cancer scheduled for esophagectomy were randomized into either the incentive spirometry (IS) or IMT group. Each intervention was performed during preoperative neoadjuvant chemotherapy (NAC). The primary outcome was the DE, and the secondary outcomes were maximal inspiratory pressure (MIP), lung function, and exercise tolerance, which were measured before and 1-3 months after esophagectomy.

Results: Thirty-two patients were included in the analysis. The DE in the IMT group (n = 15) increased from baseline to pre-operation, and the rate of change was significantly greater than that in the IS group (n = 17). Although the DE and MIP decreased in both groups after esophagectomy, the decline in the DE after esophagectomy was significantly lower in the IMT group than that in the IS group (p < 0.05). Furthermore, significant differences in DE persisted at least until 3 months post-esophagectomy, whereas MIP did not differ significantly at any time point. Pulmonary function and exercise tolerance were not significantly different between the two groups.

Conclusions: The IMT before esophagectomy enhanced diaphragmatic function, which was preserved for more than 3 months after esophagectomy.

Background: Programmed cell death protein-1 (PD-1) blockade has improved survival for patients with esophageal squamous cell carcinoma (ESCC), but response rates are low. Biomarkers to predict who will benefit from PD-1 blockade are urgently needed.

Methods: This multicenter study involved 250 patients with recurrent/unresectable advanced ESCC receiving nivolumab as second- or later-line therapy. We assessed tumor-infiltrating T lymphocytes (TILs) and tertiary lymphoid structure (TLS) density using immunohistochemistry and hematoxylin/eosin staining in surgical specimens and pre-nivolumab endoscopic biopsies.

Results: In surgical specimens, clinical response (vs. non-response) to nivolumab correlated significantly with CD8⁺ lymphocyte count (160 vs. 95.2 cells/field, P = 0.0494), CD8/Foxp3 ratio (6.52 vs. 2.72, P = 0.0053), and TLS density (0.21/mm² vs. 0.10/mm², P = 0.0005). In terms of overall survival, multivariate analysis identified CD8/Foxp3 ratio (hazard ratio [HR] = 1.83, P = 0.0050) and TLS density (HR = 1.67, P = 0.0171 as independent prognostic parameters in surgical specimens. Similarly, in endoscopic biopsies, clinical response (vs. non-response) to nivolumab correlated significantly with CD8⁺ counts (254 cells/mm² vs. 124 cells/mm², P = 0.0344), CCR8⁺ lymphocyte count (62.6 cells/mm² vs. 140 cells/mm², P = 0.0355), CD8/Foxp3 ratio (2.09 vs. 0.89, P = 0.040), and CD8/CCR8 ratio (2.34 vs. 0.89, P = 0.0020). Multivariate analysis also identified CD8/CCR8 ratio in endoscopic biopsies (HR = 1.66, P = 0.0313) as an independent prognostic parameter.

Conclusions: CD8⁺ and CCR8⁺ cell counts, CD8/Foxp3 and CD8/CCR8 ratios, and TLS density may be predictive biomarkers of therapeutic efficacy and survival with PD-1 blockade for ESCC.

Background: Prehabilitation has been shown to prevent postoperative pneumonia and physical function decline after esophagectomy in recent systematic reviews and meta-analyses. However, the implementation status of prehabilitation for esophagectomy remains unknown. This nationwide survey was performed to investigate the current status of and barriers to prehabilitation before esophagectomy among Japanese hospitals.

Methods: This multicenter nationwide survey was performed using the postal mail method. The eligible facilities were 155 Japanese hospitals that had been certified as Authorized Institutes for Board-Certified Esophageal Surgeons by the Japan Esophageal Society within the past 10 years. We administered the original questionnaire to investigate the current status of prehabilitation before esophagectomy, excluding neoadjuvant therapy.

Results: The response rate was 75% (117/155 facilities). The number of facilities providing prehabilitation for esophagectomy was 77 (66%), including prehabilitation in the preoperative outpatient setting in 39 (33%) and in the preoperative inpatient setting in 53 (45%). Among the facilities that did not provide prehabilitation, the most common reasons for not providing prehabilitation (i.e., responses of "agree" and "strongly agree" on questionnaire) were a lack of human resources, preoperative period too short to provide prehabilitation, difficultly using reimbursed medical fees, and no establishment of a standard prehabilitation program.

Conclusions: We elucidated the current implementation status of prehabilitation, identified the critical gap between evidence and practice. This information will contribute to building an effective medical system and framework of prehabilitation for patients with esophageal cancer in Japan and other countries.

Background: Circulating exosomal microRNAs are an easily obtained and minimally invasive biomarker for cancer treatment. Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive carcinomas. It would thus be extremely crucial to predict therapeutic sensitivity and the patient prognosis in advance.

Methods: A search for miRNAs with a therapeutic biomarker in ESCC was performed using the miRNA expression signatures obtained from ESCC plasma exosomes before chemoradiotherapy. miR-191-5p was selected based on a comparison of miRNA signatures and the findings of previous reports. We explored the utility of circulating exosomal miR-191-5p as a prognostic biomarker of chemoradiotherapy along with its target gene, molecular pathway and functions specifically related to radiotherapy in ESCC.

Results: Overexpression of miR-191-5p promoted ESCC cell proliferation, invasion and migration. miRNA-191-5p overexpression promoted cell survival and reduced cell apoptosis after irradiation. Mechanistically, miR-191-5p may downregulate death-associated protein kinase 1 (DAPK1) to induce radiation resistance via the MAPK-JNK pathway. The 5-year progression-free survival rate for ESCC patients who underwent treatment, including radiotherapy with high circulating exosomal miR-191-5p expression was significantly lower than in those with a low expression.

Conclusion: Tumor-derived exosomal miR-191-5p is a potential non-invasive biomarker for predicting the prognosis in esophageal cancer patients after radiotherapy.

Background: To ascertain the indication of endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC), accurate preoperative diagnosis of the tumor depth beyond cT1b-SM2 is crucial. This study aimed to assess the efficacy of the combined approach utilizing narrow-band imaging with magnifying endoscopy (NBI-ME) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for accurate discrimination of lesions of pT1b-SM2 or deeper.

Methods: Between 2016 and 2023, we retrospectively enrolled 127 cases (137 lesions) of superficial, treatment-naïve ESCC at Akita University Hospital, involving patients who underwent either ER alone or surgery alone. All patients underwent preoperative NBI-ME and FDG-PET. Preoperative tumor depth was estimated using type B vessels based on NBI-ME and SUVmax based on FDG-PET, and we confirmed the final tumor depth through histopathological evaluation of resected samples. The diagnostic performance of the tests in discriminating pT1b-SM2 or deeper was evaluated in terms of sensitivity, specificity, and accuracy.

Results: Treatment consisted of ER in 97 lesions and surgery in the remaining 40. Fifty-three lesions (44.7%) had pT1b-SM2 or deeper invasion. The sensitivity, specificity, and accuracy of NBI-ME using type B3 vessels were 41.5%, 97.6%, and 75.9%, respectively. For FDG-PET with a cutoff SUVmax of ≥ 2.4, these were 79.2%, 69.0%, and 73.0%, respectively. Combining both tests substantially improved diagnostic performance, with sensitivity, specificity, and accuracy of 83.0%, 89.3%, and 86.9%, respectively.

Conclusion: The combination of FDG-PET and NBI-ME offers enhanced diagnostic performance for ESCC with ≥ pT1b-SM2, thereby facilitating a more efficacious preoperative narrowing of the indications for ER of superficial ESCC.

Advanced esophageal cancer is treated by chemotherapy, radiation therapy, chemoradiotherapy, and immunotherapy. However, the stenosis caused by the tumor and cancer-related chronic inflammation leads to inadequate food intake, weight loss, and nutrition problems. Given that poor pre-treatment nutritional status increases the risks of treatment-related adverse events and a poor prognosis, the nutrition guidelines recommend a pre-treatment nutritional assessment. When malnutrition is present, nutritional interventions, such as dietary guidance and enteral nutrition supplements, provided by the medical team may reduce treatment-related adverse events. However, whether nutritional intervention improves the prognosis is a topic for future research, including randomized controlled trials. This review discusses the literature on nutritional management in patients undergoing chemotherapy and chemoradiotherapy for advanced esophageal cancer.

Background: Early response of the primary tumor (PT) to neoadjuvant chemotherapy (NAC) in patients with esophageal squamous cell carcinoma (ESCC) is considered a potential predictor of postoperative prognosis. However, the role of metastatic lymph nodes (LNs) remains poorly understood. This study aimed to compare the predictive value of early response in PT and LNs for postoperative prognosis.

Methods: We enrolled 124 consecutive patients who received NAC-docetaxel, cisplatin, 5-fluorouracil (DCF) followed by surgery for ESCC between April 2010 and March 2020. Initial tumor reduction of the PT (ITR-PT) and LN (ITR-LN), defined as the percentage decrease in tumor shorter diameter after the first course of NAC-DCF, was evaluated using computed tomography. The optimal cut-off values of ITRs were determined using receiver operating characteristic curves and Cox regression models, and their relationship with recurrence-free survival (RFS) was analyzed.

Results: The median ITR-PT and ITR-LN were 21.77% and -0.88%, respectively. The optimal cut-off values for predicting prognosis were approximately 10% for ITR-PT (hazard ratio [HR], 3.23; 95% confidence interval [CI], 1.84-5.64) and -10% for ITR-LN (HR, 2.20; 95% CI, 1.27-3.80). ITR-PT showed a greater impact on RFS (3-year RFS: ITR-PT ≥ 10%, 66.1%; ITR-PT < 10%, 18.4%; log-rank P < 0.001) compared with ITR-LN (3-year RFS: ITR-LN ≥ -10%, 64.1%; ITR-PT < -10%, 34.3%; log-rank P = 0.004). Multivariate analysis of RFS identified ypN, ITR-PT, and ITR-LN as independent prognostic factors.

Conclusions: Both ITR-PT and ITR-LN are promising predictors of survival in patients with ESCC who underwent NAC-DCF plus surgery. ITR-PT may be a stronger prognostic factor than ITR-LN.

Background: Gastric tube prolapse into the thoracic cavity in retrosternal route reconstruction during esophagectomy is known as intrathoracic herniation of the gastric tube (IHGT). However, few reports have determined whether a correlation exists between IHGT and postoperative complications. Moreover, the optimal procedure for avoiding IHGT remains unclear.

Methods: This retrospective study included 200 patients who had undergone subtotal esophagectomy and retrosternal gastric tube reconstruction at a single institution. The diagnosis of IHGT was defined as a gastric tube herniation length of ≥ 5 cm on plain chest radiography. The frequency of postoperative complications in patients with IHGT was measured to determine any correlation. The incidence of IHGT in a laparoscopic retrosternal route creation group was also measured and the efficacy of this procedure was investigated.

Results: The overall incidence of IHGT was 7.5%. The incidence of grade II or higher anastomotic leakage and atelectasis was significantly higher in the IHGT( +) (anastomotic leakage, 26.7% vs. 4.3%, P = 0.007; atelectasis, 40.0% vs. 13.5%, P = 0.016). In univariate analysis, IHGT( +) showed a significantly higher incidence of anastomotic leakage (OR 7.88, P = 0.007). In multivariate analysis, IHGT was an independent risk factor for atelectasis (OR 5.03, P = 0.005). Furthermore, the incidence of IHGT was significantly lower in the laparoscopic group (2.0% vs. 13.0%, P = 0.005).

Conclusion: Our findings show that IHGT may be correlated with grade II or higher anastomotic leakage and atelectasis. Laparoscopic retrosternal route creation may be effective in avoiding IHGT and contributes to a reduction in postoperative complications.

Background: Upper extremity deep vein thrombosis (UEDVT) is a fatal postoperative complication that can cause pulmonary embolism (PE). There have been few reports on the relationship between esophageal cancer and UEDVT. The aim of this study is to analyze the risk factors for UEDVT in esophageal cancer.

Methods: Seventy-five cases of thoracic esophageal cancer who underwent one-stage curative resection and reconstructive surgery from May 2019 to June 2022 were included. The stomach or ileocolon was selected as the reconstructive graft. All cases requiring chemotherapy were treated with a peripheral central venous catheter (PICC). To evaluate the width of the retrosternal space, the retrosternal ratio and the cross-sectional area of the graft intestine were measured at the level of the left brachiocephalic vein.

Results: UEDVT was observed in 11 patients (14.7%) and occurred only with gastric tube reconstruction (p = 0.02). The width of the retrosternal space was significantly different between the UEDVT and non-UEDVT groups (p = 0.002). The cross-sectional area of reconstructive organ was larger in the stomach than in the ileocolon (p < 0.01). Patients with a history of PICC insertion from the left side had a higher incidence of UEDVT (p = 0.025).

Conclusions: In esophagectomy, gastric tube reconstruction, a retrosternal ratio less than 0.16, and history of PICC insertion from the left side are risk factors for UEDVT.

Background: Oligometastases, defined as a limited metastatic disease, have been considered potential therapeutic targets of cancers. This study aimed to clarify the characteristics of oligometastatic recurrence and therapeutic strategy after curative esophagectomy for esophageal cancer.

Methods: Clinical details, such as recurrence site, timing and contents of therapies for recurrence, and prognosis, were examined in 138 patients who experienced recurrence among 366 who underwent curative esophagectomy for esophageal cancer. Oligometastases were defined as three or fewer metastatic recurrence lesions within a single organ or lymph node (LN) station.

Results: Oligometastases were identified in 36 patients (26%). The most common oligometastatic recurrence site was the LN (21 patients), followed by the lung (14 patients). In addition, the oligometastases group had a significantly better prognosis than the multiple metastasis group (P < 0.0001). Analysis for prognostic factors revealed that surgical resection for oligometastases had a significant prognostic impact on long-term survival after treatment for initial recurrence of esophageal cancer (P = 0.012).

Conclusion: Oligometastases serve as a prognostic factor for recurrent esophageal cancer after curative esophagectomy. The surgical resection of isolated oligometastatic recurrences, particularly pulmonary and cervical node metastases, combined with chemotherapy or radiotherapy, represents a promising treatment strategy with a survival benefit in recurrent esophageal cancer.