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One upside of cervical esophageal carcinoma is that radical surgery can be performed by laryngectomy, even for tumors with tracheal invasion. However, this approach drastically reduces the quality of life, such as by losing the vocal function. Cervical esophageal carcinoma is rare, and no comprehensive reports have described the current state of surgery. Using a Japanese nationwide web-based database, we analyzed the surgical outcomes of cervical esophageal carcinoma to evaluate the impact of larynx-preserving surgery.Based on the Japan National Clinical Database, 215 surgically treated cases of cervical esophageal carcinoma between January 1, 2018, and December 31, 2019, were enrolled. Clinical outcomes were compared between the larynx-preserved group and the laryngectomy group.Ninety-four (43.7%) patients underwent larynx-preserving surgery. A total of 177 (82.3%) patients underwent free jejunum reconstruction. More T4b patients and more patients who underwent preoperative radiotherapy were in the laryngectomy group. There were no significant differences in the frequency and the severity of morbidities between the two groups. However, in the laryngectomy group, in-hospital death within 30 days after surgery was observed in 1 patient, and the postoperative hospital stay was significantly longer (P = 0.030). In the larynx-preserved group, recurrent nerve paralysis was observed in 24.5%. Re-operation (35.3%, P = 0.016), re-intubation (17.6%, P = 0.019) and tracheal necrosis (17.6%, P = 0.028) were significantly more frequent in patients who underwent pharyngolaryngectomy with total esophagectomy and gastric tube reconstruction than in others.Larynx-preserving surgery was therefore considered to be feasible because it was equivalent to laryngectomy regarding the short-term surgical outcomes.

Cervical esophageal cancer is rare of esophageal cancers. Therefore, there is currently no survey for a large cohort of postoperative short-term outcomes. The gastric tube or the free jejunum are the two major reconstructed organs in esophageal reconstruction after esophagectomy for cervical esophageal cancer. This study aimed to clarify the current status of esophageal reconstruction by reconstructed organ after esophagectomy for cervical esophageal cancer, especially postoperative morbidities and mortality. Based on the Japan National Clinical Database, 807 surgically treated cases of cervical esophageal cancer between January 1, 2016, and December 31, 2019, were enrolled. Clinical outcomes were compared between the gastric tube group and the free jejunum group. The frequency of surgical site infection in organ space, anastomotic leakage, pneumonia, empyema, and chylothorax was significantly higher in the gastric tube group (10.0%, 17.9%, 16.7%, 2.0%, and 3.3%, respectively) than in the free jejunum group (2.9%, 6.7%, 11.1%, 0.0%, and 0.3%, respectively) (p = Although these two major reconstructed organs are often not oncologically selectable, our results suggested that the free jejunum reconstruction after esophagectomy for cervical esophageal cancer may be more desirable when confined resection of the cervical esophagus was oncologically acceptable.

The metabolism in tumors is reprogrammed to meet its energetic and substrate demands. However, this metabolic reprogramming creates metabolic vulnerabilities, providing new opportunities for cancer therapy. Metabolic vulnerability as a therapeutic target in esophageal squamous cell carcinoma (ESCC) has not been adequately clarified. Here, we identified pyruvate dehydrogenase (PDH) component X (PDHX) as a metabolically essential gene for the cell growth of ESCC. PDHX expression was required for the maintenance of PDH activity and the production of ATP, and its knockdown inhibited the proliferation of cancer stem cells (CSCs) and in vivo tumor growth. PDHX was concurrently upregulated with the CD44 gene, a marker of CSCs, by co‐amplification at 11p13 in ESCC tumors and these genes coordinately functioned in cancer stemness. Furthermore, CPI‐613, a PDH inhibitor, inhibited the proliferation of CSCs in vitro and the growth of ESCC xenograft tumors in vivo. Thus, our study provides new insights related to the development of novel therapeutic strategies for ESCC by targeting the PDH complex‐associated metabolic vulnerability., Inoue et al. found that pyruvate dehydrogenase (PDH) component X expression is necessary for PDH activity and is involved in the cancer stemness of esophageal squamous cell carcinoma (ESCC) cells, thereby being metabolically essential for the tumor growth of ESCC. This study provides new insights related to the development of novel therapeutic strategies for ESCC by targeting the PDH complex‐associated metabolic vulnerability.

We determined the anastomotic site during gastric tube reconstruction in esophagectomy according to the "90-to 60-s rule" using indocyanine green (ICG) fluorescence angiography. We evaluated its safety and efficacy in a prospective multicenter setting. We enrolled 129 patients who underwent subtotal esophagectomy for esophageal cancer. ICG fluorescence angiography was performed after making a wide gastric tube, and the time from the initial enhancement of the right gastroepiploic artery to the tip of the gastric tube was used as a parameter. Esophago-gastro anastomosis was made at the area that was enhanced within 90 s (preferably within 60 s). The enhancement time and the incidence of anastomotic leakage were compared. In all cases, anastomosis was made at the site enhanced within 90 s. Anastomotic leakage was found in only 4 (3.1%) of 129 cases; specifically, it was detected in 3 (2.4%) of 126 cases whose anastomotic site was enhanced within 60 s and in 1 (33.3%) of 3 cases where the enhancement time exceeded 60 s (p = 0.09). Determining the anastomotic site using the 90-to 60-s rule with ICG imaging in gastric tube reconstruction helps reduce the rate of anastomotic leakage.

We previously reported on the thin membranous dense connective tissue around the esophagus in the upper mediastinum. This time, we histologically investigated the existence of similar structures in the middle and lower mediastinum, caudal to the bifurcation of the trachea. Semi-sequential transverse sections of the mediastinum were obtained from two cadavers. Hematoxylin and eosin staining and Elastica van Gieson staining were performed. In the middle mediastinum, the “visceral sheath” could not be observed completely around the esophagus. In the lower mediastinum, the thin membranous dense connective tissue was observed beneath the pericardium on the ventral side of the esophagus. On the dorsal side of the esophagus, two thin membranous dense connective tissues were similarly observed in two cadavers. One existed between the dorsal side of the esophagus and the three vessels (i.e., the descending aorta, the azygos vein and the thoracic duct) and was integrated with the thin membranous dense connective tissue of the ventral side of the esophagus at the bilateral side of the esophagus. This integrated dense connective tissue reached the left subpleural region and the adventitia of the aorta on the left side and the peripleural and pulmonary hilum on the right side. The other thin membranous dense connective tissue, which represents the “vascular sheath”, was observed between the descending aorta and the thoracic duct. These two thin membranous dense connective tissues, which are considered to represent the visceral sheath and vascular sheath, are thought to be available as optimal dissecting layers for radical esophagectomy.

Background Locoregional steroid injection prevents post-endoscopic submucosal dissection (ESD) esophageal stricture, but histological changes that occur following steroid injection in the human esophagus are unclear. This study investigated the histopathological characteristics caused by locoregional triamcinolone acetonide (TA) injection using human esophagectomy specimens. Methods From January 2014 to December 2019, among 297 patients (373 lesions) who underwent esophageal ESD, 13 patients who underwent additional esophagectomy after ESD were examined. Seven patients (TA group) with wide excisions were injected with TA after ESD and another six patients (Non-TA group) with smaller tumors were not injected with TA. The clinical background of these patients and histopathological features of ESD ulcer scar obtained from esophagectomy specimens were retrospectively investigated. Results The circumferential rate of ESD excision was more than three-quarters in all cases in the TA group, whereas it was less than three-quarters in the Non-TA group. No other statistical difference in the clinical background was found between the two groups. The subepithelial fibrous tissue of the ESD ulcer scar in the TA group was significantly thinner than that in the Non-TA group (P Conclusions Histological finding of thinning of the subepithelial fibrous tissue of ESD ulcer scar in the human esophagus after TA injection was obtained. This suggests that TA suppresses the proliferation of the fibrous tissue of the subepithelial layer to help prevent esophageal stricture after widespread ESD in the human esophagus.

Several recent studies suggest that serum anti-p53 antibodies (s-p53-Abs) may be combined with other markers to detect esophageal and colorectal cancer. In this study, we assessed the sensitivity and specificity of s-p53-Abs detection of a new electrochemiluminescence immunoassay (ECLIA; Elecsys anti-p53). Elecsys anti-p53 assay was used to analyze the level of s-p53-Abs in blood sera from patients with esophageal or colorectal cancer taken before treatment. Control blood sera from healthy volunteers, patients with benign diseases, and patients with autoimmune diseases served as a reference. In addition, squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragments (CYFRA21-1) were assessed in patients with esophageal cancer, and carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 were assessed in patients with colorectal cancer. Samples from 281 patients with esophageal cancer, 232 patients with colorectal cancer, and 532 controls were included in the study. The median value of s-p53-Abs in control samples was

Previous studies have evaluated the clinicopathological significance of carcinoembryonic antigen (CEA) of esophageal cancer in relatively small numbers of patients. Therefore, this study aimed to clarify the prognostic significance of CEA in 1822 patients with esophageal squamous cell carcinoma (SCC).Based on the Japanese Esophageal Society nationwide multi-institutional retrospective study, a total of 1,748 surgically treated ESCC from 15 hospitals were enrolled to evaluate prognostic impact of preoperative CEA values. Among them, 605 patients were categorized to up-front surgery group, and 1,217 patients were categorized to neoadjuvant therapy group. The CEA threshold for positivity was 3.7 ng/ml. The clinicopathological and prognostic impact of CEA was evaluated by univariate and multivariate analysis in each treatment modality groups.In total, the CEA positive rate was 25.8% (470/1822). CEA-positive status was significantly associated with distant metastasis (P = 0.004) but not associated with other factors. CEA-positive status was associated with poor overall survival (P 0.001) in univariate analysis as well as multivariate analysis (P = 0.003).CEA was an independent prognostic determinant of overall survival in esophageal SCC. Based on the subgroup analysis, regardless of the treatment modality, patients with high pretreatment CEA showed poor overall survival.

Currently, there is no consensus for an optimal minimally invasive esophagectomy (MIE) approach. This study aimed to compare hybrid MIE (hMIE) with neck-abdominal first approach to standard open esophagectomy (OE). Data from a cohort of 301 patients were retrospectively analyzed. All participants received either hMIE or OE for the treatment of esophageal squamous cell carcinoma at Tokyo Medical and Dental University between January 2003 and December 2013. Analyses included propensity score matching and the Kaplan–Meier statistical method to determine overall survival (OS) and disease-free survival (DFS) of the cohort. After one-to-one propensity score matching, there were 68 patient pairs. The hMIE group had significantly lower incidence of severe postoperative complications (20.1% vs. 7.4%; p = 0.026) and severe respiratory complications (7.4% vs. 0%; p = 0.058) than the OE group. The 5-year oncological outcomes of the two groups were almost equivalent (OS: OE, 55.0%; hMIE, 69.0%; p = 0.063 and DFS: OE, 54.0%; hMIE, 62.0%; p = 0.28). This study compared hMIE with neck-abdominal first approach to standard OE. The results showed significantly less severe postoperative complications for hMIE with neck-abdominal first approach in comparison with OE, without a compromise in long-term oncological outcomes.

We herein evaluated the hemodynamics of a gastric tube in esophagectomy using a new noninvasive blood flow evaluation device utilizing near-infrared spectroscopy. Thirty-two cases of subtotal esophagectomy and gastric tube reconstruction for esophageal cancer were studied. The new device measures the regional tissue saturation of oxygen (rSO2: 0–99%) and total hemoglobin index (T-HbI: 0–1.0) with a small sensor. We measured these values at the antrum (point A), final branch of the right gastroepiploic artery (point B) and planned anastomotic point (point C) before and after gastric tube formation. The values at the three points were compared, and the gradients at the three points from before to after gastric tube formation were compared. The mean values of rSO2 at point A, B, and C before gastric tube formation were 57.2%, 57.8% and 56.0%, and those after formation were 54.6%, 58.0% and 55.8%, respectively. There was no significant difference in the comparison of the rSO2 gradient before and after formation (p = 0.167). The mean values of T-HbI at point A, B, and C before formation were 0.126, 0.178 and 0.211, and those after formation were 0.167, 0.247 and 0.292, respectively. There was no significant difference in the gradient of the increase before and after formation (p = 0.461). A new device has shown that the gastric tube used in our facility is one that maintains tissue saturation of oxygen and does not cause excessive congestion at anastomosis.

Purpose Esophagectomy with three-field lymphadenectomy (3FLD) is a potentially curative treatment option for resectable esophageal cancer (EC), which is associated with significant morbidity. Risk scores are useful for patient assessment; this study compares 7 different scores and indexes to find the best model for predicting morbidity in patients undergoing 3FLD. Methods Six years of data from January 2010 to January 2016 were reviewed, patients with EC who underwent 3FLD were retrospectively scored using 4 predictive scores and 3 predictive index models. Postoperative morbidity was assessed according to the extended Clavien-Dindo classification. The outcomes were the presence and severity of morbidity. Validation was performed by calculating the area under the ROC curve and by the assessment of collinearity among the variables independently associated with morbidity in the overall model to determine the best predictive model. Results We included 230 patients were included in the final analysis. Complications after 3FLD occurred in 168 patients (73%; minor complications, n = 96 [41%]; major complications, n=72 [31%]). The AUC values ( Conclusion No score or index could predict the presence or severity of morbidity after 3FLD with good discrimination power. Age (>68 years) was the most critical factor affecting morbidity. The Steyerberg score model, based on the addition and subtraction of risk values was the best model for predicting morbidity after 3FLD.

Background and Aim: The aim of the present study was to evaluate the clinical usefulness of the ¹³C breath test in postoperative patients who underwent gastric tube reconstruction following esophagectomy. Methods: Postoperative patients (POs; n=26) and healthy volunteers (HVs; n=10) were included as subjects. Of the 26 POs, the 7 with late dumping symptoms were regarded as the dumping group (DG), and the remaining were considered the non-dumping group (NDG). Semisolid test meal mixed with 100 mg of ¹³C-sodium acetate was given to each subject. Breath samples for the ¹³C gas analysis and blood samples were collected. Results: The Cmax was 37 ± 13(‰) in the HVs and 49 ± 11(‰) in POs, being significantly higher in POs (p=0.019). The Cmax was 56 ± 14(‰) for DG and 47 ± 8.9(‰) for NDG, indicating that the Cmax in the DG tended to be higher than that in the NDG, although not to a significant degree (p=0.12). The change in the C value and each glucose metabolism-related marker showed a general correlation. Conclusion: The present results suggest that the ¹³C-acetate breath test reflects changes in glucose homeostasis after esophagectomy, making it useful for objectively and simply assessing late dumping symptoms in postoperative esophageal cancer patients.

Postoperative feeding is administered relatively early in gastric surgery, especially distal gastrectomy, but its feasibility and safety for proximal gastric surgery remains unclear. We retrospectively analyzed 91 consecutive patients who underwent total or proximal gastrectomy between 2014 and 2019. Baseline and perioperative results were prospectively recorded in our dataset. In our clinical pathway, sips of water and a soft diet were allowed on postoperative days 1 and 3. Discharge was set at days 6–8, and clinical pathway completion was defined as discharge by postoperative day 8. Median patient age was 69 years, and 25 patients (27%) were aged ≥ 75 years. Fifty-nine patients (65%) had comorbidities. Esophageal involvement occurred in 12 patients (13%), and there were 28 cases (31%) of pathological stage IA. The open approach was applied in 22 patients (24%), laparoscopy was applied in 53 patients (58%), and the robotic approach was applied in 16 patients (18%). Total gastrectomy was performed in 56 patients (62%) and proximal gastrectomy was performed in 35 patients (38%). Overall and severe (Clavien–Dindo grade III or higher) complications occurred in 24 (26%) and 9 (10%) patients, respectively. There were four cases (4%) of esophagojejunal leakage (three with esophagogastric junction cancer, one with long-term corticosteroid use). Clinical pathway completion was achieved in 66 patients (73%), with readmission of five cases (5%). Early feeding and discharge for total or proximal gastrectomy is feasible and safe as long as it is carefully applied to high-risk patients, but we must be aware of the relatively higher readmission rate of this patient group.

The standard treatment for locally advanced gastric cancer differs across the world. In western countries, perioperative chemotherapy or postoperative adjuvant chemoradiotherapy are the preferred treatment options, whereas in Asia, D2 gastrectomy followed by postoperative adjuvant chemotherapy is standard. In Japan, adjuvant chemotherapy with S-1 is the standard treatment for pStage II gastric cancer, whereas adjuvant chemotherapy with a doublet regimen is preferred for pStage III gastric cancer. The efficacy of preoperative neoadjuvant chemotherapy using S-1 plus cisplatin, has been investigated in selected patients with expected poor survival outcomes. To expand the indications for neoadjuvant chemotherapy, a clinical trial investigating the efficacy of preoperative S-1 plus oxaliplatin in patients with cStage III (cT3-4N1-3) gastric cancer (JCOG1509) is ongoing in Japan. The addition of immune checkpoint inhibitors to cytotoxic chemotherapy also seems promising and is being investigated in international randomized clinical trials. Although we have to await the final results of these studies, preoperative neoadjuvant chemotherapy is a promising treatment strategy and likely to become standard treatment for locally advanced gastric cancer in Japan.

Purpose The prognostic significance of pretreatment serum C-terminus of cytokeratin 19 (CYFRA21-1, CYFRA) status was evaluated in the patients with surgically treated esophageal squamous cell carcinoma. Methods A total of 1047 patients with surgically treated esophageal cancer were enrolled in a multi-institutional study promoted by the Japanese Esophageal Society. This study included an up-front surgery group (n = 412), a neoadjuvant chemotherapy (NAC) group (n = 486), and a neoadjuvant chemoradiation/radiation therapy (NACRT/RT) group (n = 149). The pretreatment CYFRA status was analyzed to assess prognostic significance using multivariate analysis according to treatment modalities. Results The CYFRA-positive group was significantly associated with deep tumor. Univariate analysis showed that the overall survival of the CYFRA-positive group was significantly worse than that of the CYFRA-negative group, but the difference was not significant in the multivariate analysis. CYFRA was an independent risk factor for poor prognosis just in the NACRT/RT group. Conclusions The CYFRA-positive group was associated with deep tumor and poor survival. Pretreatment CYFRA was not an independent risk factor for poor prognosis in the up-front surgery group or NAC group. It was an independent risk factor for poor prognosis just in the NACRT/RT group.

Although previous reports showed clinicopathological and diagnostic significance of serum p53 antibody in esophageal squamous cell carcinoma, all those reports analyzed only 100 to 200 patients at single institute. This study was designed as a multi-institutional study promoted by the Japan Esophageal Society to elucidate the clinical significance of serum p53 antibody in esophageal cancer treatment. Methods A total of 1,487 patients, from 15 hospitals of Japan, with esophageal carcinoma surgically treated between 2008 and 2016 were enrolled in this retrospective study. We used 1.30 U/ml as a cutoff for classifying patients into positive and negative groups. And we attempted to analyze only positive cases. A receiver operating characteristic curve was constructed to assess serum p53 antibody cutoff levels to differentiate poor prognosis. We used 9.82 U/ml as a cutoff for classifying patients into low and high groups. Univariate and multivariate analyses were used to evaluate the clinicopathological and prognostic significance of pretreatment level of serum p53 antibody. Results There were significant relationships between serum p53 antibody level and tumor depth (p = 0.002), nodal status (p = 0.027) and pathological stage (p = 0.002). The positive serum p53 antibody group had a no significantly worse overall survival than that of the negative group (p = 0.699). The high serum p53 antibody group had a significantly worse overall survival than that of the low group (p = 0.024). However, the difference was not significant in the multivariate analysis (p = 0.137). Conclusion Although high level (>9.82 U/ml) of pretreatment serum p53 antibody might be associated with poor prognosis for patients with esophageal cancer, high serum p53 antibody was not an independent risk factor.

Several authors have reported on the left trans-cervical and transhiatal approaches under pneumomediastinum and right cervical open surgery for mediastinoscopic esophagectomy. However, with these approaches, sufficient dissection of the right upper mediastinal paraesophageal lymph nodes, right recurrent nerve lymph nodes and the subaortic arch to the left tracheobronchial lymph nodes is thought to be difficult. We herein report the usefulness of the ‘bilateral’ trans-cervical pneumomediastinal approach. Methods Ten patients with thoracic esophageal cancer were treated using this approach. Under pneumomediastinum via a right neck incision, the right cervical and upper mediastinal paraesophageal lymph nodes were dissected. The left recurrent nerve lymph nodes were dissected using a left trans-cervical pneumomediastinal approach. The subaortic arch to the left tracheobronchial lymph nodes was dissected with a combined right and left trans-cervical crossover approach. After this approach, thoracoscopic observation was then performed in the left decubitus position, and if the lymph nodes were not sufficiently dissected, the remnant lymph nodes were retrieved thoracoscopically. Results The average total number of dissected lymph nodes among the right cervical and upper mediastinal paraesophageal lymph nodes identified with a right cervical open/right trans-cervical mediastinoscopic/right thoracoscopic approach was 3.2/4.0/0.6, respectively. The average total number of dissected lymph nodes among the subaortic arch to the left tracheobronchial lymph nodes with a right trans-cervical mediastinoscopic/right thoracoscopic approach was 1.5/0.6, respectively. These findings indicate that, without the right trans-cervical pneumomediastinal approach, roughly four of the right cervical and upper mediastinal paraesophageal lymph nodes and one or two of the subaortic arch to the left tracheobronchial lymph nodes could not have been retrieved. Conclusion A bilateral trans-cervical pneumomediastinal approach is useful for achieving sufficient upper mediastinal lymph node dissection and esophagectomy.

Aim: Psychotherapy is an effective intervention for depressive cancer patients. However, there are barriers to applying psychotherapy in clinical settings. This study assessed cancer patients’ preferences for psychotherapy using a conjoint analysis.Methods: We conducted a single-center, cross-sectional study using a self-reported questionnaire between March 2018 and March 2020. The questionnaire asked for patients’ preferences for 48 psychotherapy scenarios according to a combination of type, length, price, and frequency. We conducted a conjoint analysis, calculating the relative importance and part worth value of each factor.Results: Cancer patients consider type as the most important factor when deciding whether to undergo psychotherapy (relative importance: 37.5%), followed by frequency (23.4%), price (19.6%), and length (19.5%). Cancer patients value life reviews highly among the four psychotherapy types. Conclusion: Cancer patients consider the type of psychotherapy to be the most important factors when choosing it, although their preferences do depend on their individual characteristics.

In cadavers, even Thiel-embalmed cadavers, the arteries (especially the thoracic aorta) are extremely collapsed. This is in marked contrast to the state of the arteries in a living body. Aortic inflation is necessary to improve this unfavorable situation for anatomical observation or dissection. To inflate the aorta, we injected 500 ml of hot liquid agar into the aorta using a 18-Fr catheter inserted into the common femoral artery and subclavian artery. The injected agar then rapidly cools to room temperature and solidifies. As a result, the thoracic aorta remains sufficiently and constantly inflated in the mediastinum. This method is not only easy and inexpensive, but also useful and effective for achieving a life-like anatomy in cadavers used in surgical training for operations involving mediastinal organs, with the exception of the heart and great vessels.

We investigated the merits and demerits of right cervical open surgery with right trans-cervical pneumomediastinal approach in mediastinoscopic esophagectomy. Ten thoracic esophageal cancer patients were treated using this approach. Under pneumomediastinum via a right neck incision, the right cervical and upper mediastinal paraesophageal lymph nodes were dissected. The left recurrent nerve lymph nodes were dissected using a left trans-cervical pneumomediastinal approach. The subaortic arch to the left tracheobronchial lymph nodes was dissected with a combined right and left trans-cervical crossover approach. The average number of dissected lymph nodes among the right cervical and upper mediastinal paraesophageal lymph nodes identified with a right cervical open/right trans-cervical mediastinoscopic/right thoracoscopic approach was 3.2/4.0/0.6, respectively. The average number of dissected lymph nodes among the subaortic arch to the left tracheobronchial lymph nodes with a right trans-cervical mediastinoscopic/right thoracoscopic approach was 1.5/0.6, respectively. These findings indicate that, without using the right trans-cervical pneumomediastinal approach, it might be impossible to successfully remove some of the right cervical and upper mediastinal paraesophageal lymph nodes and the subaortic arch to the left tracheobronchial lymph nodes lymph nodes. Regarding surgical complications, one case of bilateral recurrent nerve palsy as well as two cases on the right and two cases on the left were noted. Although the rate of recurrent nerve palsy should still be reduced, a bilateral (especially right-sided) trans-cervical pneumomediastinal approach is an available option for achieving sufficient upper mediastinal lymph node dissection and esophagectomy.

Background and study aims Endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) are promising therapeutic options for early esophageal cancer (EC). The factors that can affect mid- and long-term survival in patients with submucosal EC (SM1 and SM2) have not been described in the literature. We aim to describe clinicopathological outcomes and factors that can affect the mid- and long-term survival in patients with resected submucosal tumors. Patients and methods We performed a retrospective analysis of patients who underwent endoscopic resection (ER) for submucosal tumors over a 20-year period. The final study population included 119 cases with 137 lesions. Information was collected according to the Japanese Classification of Esophageal Cancer 11-edition and factors affecting survival for 2 and 5 years after ER were analyzed. Results EMR was performed in 99 cases (72.3 %), ESD in 38 cases (27.7 %). There were no significant complications. Two- and 5-year survival rates were 91 % and 82 %, respectively. Mean age was 67.22 years (± 9.49 years), mortality caused by EC occurred in 13 cases (11 %). Factors that had a significant impact on long-term survival were age > 65 years (P = 0.0026), number of resected specimens (P = 0.0031), presence of another progressive disease (not EC) (P ≤ 0.001), recurrence (P = 0.0002), and relation between histopathological positive vertical margin and recurrence (P = 0.0112). Conclusions ER is viable treatment for esophageal submucosal cancer, selection between ESD/EMR can depend on tumor size and patient condition, and en bloc ER is the recommended technique for submucosal tumors. Long-term survival factors were identified.

A prospective trial evaluated the feasibility and safety of “mediastinoscopic esophagectomy with lymph node dissection” (MELD). Eligible patients had thoracic esophageal squamous cell carcinoma, excluding T4, a bulky primary lesion or distant metastasis. Ten patients were enrolled and treated between September 2015 and March 2018. Additionally, to verify the integrity of the mediastinal lymph node dissection, thoracoscopic observation and lymph node dissection were followed. The primary end point was the integrity of mediastinal lymph node dissection. The secondary end points were the short-term outcomes, including mortality and morbidity. The median number of dissected lymph nodes in the upper mediastinal to cervical region and middle to lower mediastinal region by mediastinoscopy/thoracoscopy was 27/0.5 and 11.5/0, respectively. The median total operation time was 615 min, the median bleeding amount was 476 ml, and the median postoperative hospital stay was 15.5 days. Regarding complications of more than grade III according to the Clavien–Dindo classification, four had sputum excretion difficulty, one had pneumothorax and one had bilateral recurrent nerve palsy, but none required conversion to thoracotomy, and no operative deaths occurred. Although the rate of recurrent nerve palsy still should be reduced, our mediastinoscopic lymphadenectomy technique is closely similar to radical esophagectomy.

Molecular motions taking place in the nanospace of metal–organic frameworks (MOFs) are an interesting research subject, although not yet fully investigated. In this work, we utilized in situ Raman spectroscopy in the ultralow-frequency region to investigate the libration motion (including the rotational motion of phenylene rings) of MOFs, in particular [Cu2(bdc)2(dabco)] (Cu-JAST-1), where bdc = 1,4-benzenedicarboxylate and dabco = 1,4-diazabicyclo[2.2.2]octane. The libration mode of Cu-JAST-1 was found to be significantly suppressed by the adsorption of various guest molecules, such as CO2, Ar, and N2. In addition, an appreciable correlation between the libration mode and adsorption equilibrium time was identified, which provides useful novel tools in the design of MOFs acting as molecular adsorption and separation materials.

Background High levels of periodontopathic bacteria as well as Streptococcus anginosus were detected in cancer tissue from patients with esophageal cancer. An association between oral infectious bacteria and esophageal cancer has been reported. Methods Characteristics of the oral microbiota and periodontal conditions were studied as clinicopathologic factors in patients with esophageal cancer. The study included 61 patients with esophageal cancer and 62 matched individuals without any cancers. Samples of subgingival dental plaque and unstimulated saliva were collected to evaluate the prevalence and abundance of the following oral bacteria using a real-time polymerase chain reaction assay: Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, Treponema denticola, and S. anginosus. Results In the cancer group, the prevalence of all bacteria, with the exception of F. nucleatum, in dental plaque; the prevalence of A. actinomycetemcomitans in saliva; the abundance of all bacteria, with the exception of F. nucleatum and P. intermedia, in dental plaque; and the abundance of A. actinomycetemcomitans and S. anginosus in saliva were significantly higher. Furthermore, a logistic regression analysis suggested that the prevalence of T. forsythia and S. anginosus in dental plaque and of A. actinomycetemcomitans in saliva, as well as a drinking habit, were associated with a high risk of esophageal cancer, with a high odds ratio. Conclusions The current findings have potential implications for the early diagnosis of esophageal cancer.

Interest in minimally invasive surgery has increased in recent decades. Robotic‐assisted laparoscopic surgery (RALS) was introduced as the latest advance in minimally invasive surgery. RALS has the potential to provide better clinical outcomes in rectal cancer surgery, allowing for precise dissection in the narrow pelvic space. In addition, RALS represents an important advancement in surgical education with respect to use of the dual‐console robotic surgery system. Because the public health insurance systems in Japan have covered the cost of RALS for rectal cancer since April 2018, RALS has been attracting increasingly more attention. Although no overall robust evidence has yet shown that RALS is superior to laparoscopic or open surgery, the current evidence supports the notion that technically demanding subgroups (patients with obesity, male patients, and patients treated by extended procedures) may benefit from RALS. Technological innovation is a constantly evolving field. Several companies have been developing new robotic systems that incorporate new technology. This competition among companies in the development of such systems is anticipated to lead to further improvements in patient outcomes as well as drive down the cost of RALS, which is one main concern of this new technique.

Objective To assess the usefulness of modified esophagogastroduodenoscopy (EGD) for the detection of second primary malignancies of the esophagus or hypopharynx in patients with oral squamous cell carcinoma and determine the association between the oral lesion subsite and esophageal or hypopharyngeal lesion occurrence. Study Design Retrospective review. Methods In total, 166 patients with oral squamous cell carcinoma without any established symptoms of esophageal or hypopharyngeal squamous cell carcinoma underwent modified EGD based on the Valsalva maneuver and U-turn method, image-enhanced endoscopy, and chromoendoscopy using Lugol's iodine for diagnosis. All suspected lesions were biopsied to determine the clinical stages and duplication rates. Odds ratios for the occurrence of duplicate lesions according to the oral lesion subsite were determined. Results In total, 37 esophageal and 16 hypopharyngeal lesions were detected. According to the Union for International Cancer Control/American Joint Committee on Cancer classification (2009), 75.7% and 5.4% esophageal lesions were classified as stage IA and IB, respectively, and 50% and 18.8% hypopharyngeal lesions as stage II and stage I, respectively. Approximately 59.1% and 50% esophageal and hypopharyngeal lesions, respectively, were successfully treated by endoscopic resection. Oral lesions involving the floor of the mouth were more frequently accompanied by second primary malignancies of the esophagus or hypopharynx. Conclusions Modified EGD is an effective noninvasive technique for early diagnosis and treatment of second primary malignancies of the esophagus and hypopharynx in patients with oral squamous cell carcinoma. In particular, patients with floor of the mouth lesions need close monitoring for hypopharyngeal and esophageal lesions. Level of Evidence 3b.

Herein, we described the surgical technique of esophageal reconstruction using ileocolon with preserved ileocolic vessels. Although colon reconstruction is a difficult reconstruction method that includes all the essence of digestive surgery, it is a procedure that esophageal surgeons should fully understand and learn.

Mucosa-associated lymphoid tissue (MALT) lymphoma is a type of lymphoma that commonly originates in the gastrointestinal (GI) tract, and in rare instances may also occur in the head and neck region. In this report, we present a case of early stage, primary asymptomatic MALT lymphoma of the hypopharynx as detected by esophagogastroduodenoscopy (EGD). A 73-year-old man underwent EGD for an examination of the upper GI tract. At the left pyriform sinus, a swollen irregular mucosa was detected. Biopsy specimens confirmed histologically prominent proliferation of lymphocytes in the epithelium. Immunohistochemical analysis showed that the neoplastic lymphocytes were positive for CD20 and negative for CD3. Based on the other imaging studies, we diagnosed the lesion as a localized MALT lymphoma of the hypopharynx at Stage IA. In total, 46 Gy of radiotherapy was administered to the lesion. In the subsequent 5 years after the treatment, there have been no signs of recurrence.

A 65-year-old man was admitted to our hospital following 6 months of dysphagia. At first, conventional endoscopy showed a reddish and depressed lesion in the stomach and an elevated lesion in the posterior wall of the hypopharynx. An endoscopic biopsy showed adenocarcinoma in the stomach, and squamous cell carcinoma in the hypopharynx. On the further examination, trans-nasal endoscopy with narrow band imaging (NBI) was performed. During the trumpet maneuver, a huge protruded lesion was observed and it reached to the orifice of the esophagus. Other superficial lesion located at left pyriform sinus was detected by NBI system as brownish area with brown dots. Furthermore, superficial esophageal cancer in the cervical esophagus was detected. Finally, 4 carcinomas in upper gastrointestinal tract were detected. Among them, the hypopharyngeal cancer was the most advanced (T3N0). The patient hoped to preserve his voice and swallowing function, endoscopic laryngo-pharyngeal surgery (ELPS) was performed for the hypopharyngeal cancer. Endoscopic mucosal resection (EMR) was performed for the esophageal cancer, and Endoscopic submucosal dissection (ESD) was performed for the gastric cancer. Under collaboration between a head and neck surgeon and an endoscopist, the tumor was resected en-bloc. The histopathological findings of hypopharyngeal cancer were squamous cell carcinoma, subeipthelial invasion, 29 × 28 × 4.2 mm. The others were diagnosed as mucosal cancers. The patient is currently alive with no recurrence at 28 months after the surgery; there is no stricture at the cervical esophagus. Endoscopic laryngopharyngeal surgery for the tumor of pharyngo-esophageal junction can provide a less invasive treatment.

NF-E2–related factor 2 (NRF2) is a master transcriptional regulator that integrates cellular stress responses and is negatively regulated by Kelch-like ECH-associated protein 1 (KEAP1) at the post-translational level. In human cancers, aberrantly stabilized NRF2, by the mutation of either NRF2 or KEAP1 or by the potential inhibition of autophagy, plays a vital role in tumor growth and chemoresistance through the activation of target genes. MicroRNAs (miRNA) are endogenous small noncoding RNAs that can negatively regulate gene expression by interfering with translation and/or stability of target transcripts. However, miRNA-mediated regulation of the NRF2–KEAP1 pathway under physiological conditions is poorly understood. Here, miR-432-3p positively regulates NRF2 activity through the downregulation of KEAP1 by a direct-binding mechanism to the coding region of KEAP1. Overexpression of miR-432-3p resulted in a decreased sensitivity of esophageal squamous cell carcinoma (ESCC) cells to chemotherapy drugs including cisplatin (CDDP). Conversely, the inhibition of miR-432-3p expression by the CRISPR/Cas9 system resulted in an increased sensitivity of ESCC cells to CDDP. Furthermore, miR-432-3p was overexpressed in primary ESCC tumors (55 of 84, 65.5%) and a negative correlation between the expression level of KEAP1 and miR-432-3p in primary ESCC tumors was observed. Implications: These findings provide novel insights into the mechanism of NRF2 stabilization in human cancers. Mol Cancer Res; 15(11); 1570–8. ©2017 AACR.

We previously reported the performance of “mediastinoscopic esophagectomy with lymph node dissection” (MELD) under pneumomediastinum using a transcervical and transhiatal approach, as a method of radical esophagectomy. The procedure included the dissection of the left tracheobronchial lymph nodes (106tbL). We described our technique for dissecting the upper mediastinal lymph nodes. We revealed that the 106tbL lymph nodes were almost completely retrieved but that the upper thoracic paraesophageal lymph nodes (105) and the right recurrent nerve lymph nodes (106recR) were not completely retrieved. We are therefore of the opinion that a right cervical pneumomediastinal approach is necessary to achieve total dissection. We herein describe a case that was surgically treated using a bilateral cervicopneumomediastinal approach. A 68-year-old male patient was referred to our institution to undergo treatment for lower thoracic esophageal squamous cell carcinoma. The right recurrent nerve was first identified using an open approach. Pneumomediastinum was then initiated to allow for the 105 and 106recR lymph nodes to be completely dissected along the right mediastinal pleura, the right vagus nerve, the proximal portion of the azygos vein, and the right bronchial artery. The left recurrent nerve lymph nodes (106recL) and 106tbL lymph nodes were dissected as described previously. In order to perform bilateral upper mediastinal lymph node dissection and esophagectomy, a bilateral cervicopneumomediastinal approach is needed.