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The "bystander effect" is a transmission phenomenon mediating communication from target to non-target cells, as well as cell-to-cell interactions between neighboring and distantly located cells. In this narrative review, we describe the fundamental and clinical significance of the bystander effect with respect to cell-to-cell interactions in carcinogenesis, therapeutic response, and tissue regeneration. In carcinogenesis, the bystander effect mediates communications between tumor microenvironments and non-malignant epithelial cells and has been suggested to impact heterogeneous tumorigenic cells in tumors and cancerized fields. In therapeutic response, the bystander effect mediates communications between drug-sensitive and drug-resistant cells and may transmit both drug efficacy and resistance. Therefore, control of therapeutic response transmission via the bystander effect might offer a promising future cancer treatment. Finally, in tissue regeneration, circulating cells and stromal cells may differentiate into various cells for the purpose of tissue regeneration under direction of the bystander effect arising from surrounding cells in a defective space. We hope that the findings we present will promote the development of innovative cancer therapies and tissue regeneration methodologies from the viewpoint of cell-to-cell interactions through the bystander effect.

PDF - 52KB, Legends for Supplementary Figures 1 and 2.

PDF - 98KB, Supplementary Figure 2. FBXW7 expression in cell lines treated with MS-275.

PDF - 103KB, Supplementary Figure 1. Water-soluble tetrazolium (WST) assay in FBXW7 siRNA-treated cells. The proliferation rate of FBXW7 siRNA-treated cells was compared to that of control siRNA-treated and parent NSCLC cells.

Chronic inflammation by infiltrating immune cells promotes colitis-associated dysplasia/colitic cancer in ulcerative colitis (UC) via activating inflammatory cytokine signalling (IL-6/p-STAT3 and TNFα/NF-κB). Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is a cell adhesion molecule expressed on high endothelial venules that promote immune cell migration from the bloodstream to the gut. MAdCAM-1 targeting strategy is attracting attention as a novel therapeutic option for UC. However, the significance of MAdCAM-1-positive vessels in dysplasia/colitic cancers remains unclear. We conducted immunohistochemistry against MAdCAM-1, and immune cell markers in surgically resected samples from 11 UC patients with dysplasia/colitic cancer and 17 patients with sporadic colorectal cancer (SCRC). Moreover, we used a colitic cancer model, azoxymethane (AOM)/dextran sodium sulphate (DSS) mouse, to evaluate whether anti-MAdCAM-1 blocking antibody can suppress colitic cancer progression. MAdCAM-1-positive vessel number and infiltrating CD8-, CD68-, and CD163-positive immune cell numbers were significantly higher in dysplasia/colitic cancer than in normal mucosa, SCRC, and UC mucosa. In the AOM/DSS mouse model, MAdCAM-1 antibody reduced the tumour number, tumour diameter, number of CD8-, CD68-, and CD163-positive immune cells, and IL-6/p-STAT3 and TNFα/NF-κB expression levels. Targeting MAdCAM-1 could be promising for inflammatory carcinogenesis, and tumour progression by regulating inflammation/immune cell infiltration in patients with UC.Lay summary:MAdCAM-1 targeting strategy can control ulcerative colitis severity, carcinogenesis, and tumour progression by regulating inflammation/immune cell infiltration in patients with ulcerative colitis.

Alcohol consumption is a major risk factor for esophageal cancer. In Asia, heavy drinkers are considered to have a higher risk of esophageal cancer than nondrinkers and light drinkers. However, no study has shown an association between alcohol reduction and the morbidity of esophageal cancer in Asian heavy drinkers. Therefore, this study investigated the significance of reducing alcohol consumption to prevent esophageal cancer in Asian heavy drinkers by conducting a systematic review and meta-analysis. The MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases were searched from January 1995 to December 2020. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a random-effects model. I2 statistics were used to detect heterogeneity. This study included 21 articles in the qualitative synthesis. Light drinkers and heavy drinkers were categorized based on alcohol consumption amount as ≤ 25 ethanol g/day and ≥ 66 ethanol g/day, respectively, as described in many previous studies, and five cohort studies were eligible for this meta-analysis. The HR of esophageal cancer among heavy drinkers versus nondrinkers was 4.18 (95% CI 2.34–7.47, I2 = 74%). On the other hand, the HR of esophageal cancer among light drinkers was 1.82 compared with nondrinkers (95% CI 1.57–2.10, I2 = 0%). Heavy drinkers have a higher esophageal cancer incidence than light drinkers and nondrinker. It is possible that alcohol reduction may decrease the risk of esophageal cancer in Asian heavy drinkers.

Surgical treatment is usually required for Boerhaave’s syndrome (post-emetic esophageal perforation), and the technique should be chosen based on the local infection status and patient’s general condition. This study was performed to examine the current status of surgical treatment of Boerhaave’s syndrome in Japan. Ninety-five patients with Boerhaave’s syndrome who underwent surgical treatment from January 2010 to December 2015, obtained from a national survey were retrospectively analyzed. The details of each surgical treatment and the type of treatment performed according to the patients’ characteristics were examined. Primary closure was performed in 75 (78.9%) patients, T-tube insertion in 15 (15.8%), and esophagectomy in 5 (5.3%). The length of the postoperative stay was significantly shorter in patients who underwent primary closure (p = 0.0011). Esophagectomy tended to be performed more often in patients with a long perforation and was performed significantly more often in patients with a high C-reactive protein concentration (p = 0.0118). The postoperative hospital stay was significantly longer in patients with leakage of the primary closure site (p

Ulcerative colitis (UC) is a DNA damage-associated chronic inflammatory disease; the DNA double-strand break (DSB) repair pathway participates in UC-associated dysplasia/colitic cancer carcinogenesis. The DSB/interferon regulatory factor-1 (IRF-1) pathway can induce PD-L1 expression transcriptionally. However, the association of PD-L1/DSB/IRF-1 with sporadic colorectal cancer (SCRC), and UC-associated dysplasia/colitic cancer, remains elusive. Therefore, we investigated the significance of the PD-L1/DSB repair pathway using samples from 17 SCRC and 12 UC patients with rare UC-associated dysplasia/colitic cancer cases by immunohistochemical analysis. We compared PD-L1 expression between patients with SCRC and UC-associated dysplasia/colitic cancer and determined the association between PD-L1 and the CD8+ T-cell/DSB/IRF-1 axis in UC-associated dysplasia/colitic cancer. PD-L1 expression in UC and UC-associated dysplasia/colitic cancer was higher than in normal mucosa or SCRC, and in CD8-positive T lymphocytes in UC-associated dysplasia/colitic cancer than in SCRC. Moreover, PD-L1 upregulation was associated with γH2AX (DSB marker) and IRF-1 upregulation in UC-associated dysplasia/colitic cancer. IRF-1 upregulation was associated with γH2AX upregulation in UC-associated dysplasia/colitic cancer but not in SCRC. Multicolour immunofluorescence staining validated γH2AX/IRF-1/PD-L1 co-expression in colitic cancer tissue sections. Thus, immune cell-induced inflammation might activate the DSB/IRF-1 axis, potentially serving as the primary regulatory mechanism of PD-L1 expression in UC-associated carcinogenesis.

The impact of preoperative albuminuria on the prognosis after transcatheter aortic valve implantation (TAVI) has not been studied. A total of 228 patients who underwent TAVI for severe aortic stenosis (AS) and for whom preoperative urinary data was available were retrospectively investigated. Patients were divided into two groups according to the urinary albumin-to-creatinine ratio (ACR): high (ACR≥ 30 mg/g) and low (ACR30 mg/g). The urinary total protein-to-creatinine ratio (PCR) and dipstick proteinuria were also evaluated. The primary outcome was the composite outcome of all-cause death and readmission for heart failure. In total, 117 patients had a high ACR and 111 patients had a low ACR. During the median follow-up period of 467 days, patients with a high ACR had a higher incidence of the primary outcome than those with a low ACR (p0.001). Patients with a high PCR or positive dipstick proteinuria were also at a higher risk for the primary outcome (p0.001 and p=0.008, respectively). Multivariable Cox proportional hazards analysis showed a high ACR was independently associated with a primary outcome (hazard ratio, 4.98; 95% confidence interval, 1.84-13.49; p=0.002). In conclusion, preoperative albuminuria is an independent predictor of cardiac events in patients with severe AS undergoing TAVI.

The registration committee for esophageal cancer in the Japan Esophageal Society (JES) has collected the patients' characteristics, treatment, and outcomes of patients who underwent any treatment during 2015 in Japan.We analyzed patients' data who had visited the participating hospitals in 2015. We collected the data using the National Clinical Database with a web-based data collection system. We used the Japanese Classification of Esophageal Cancer 10A total of 9368 cases were registered from 355 institutions in Japan. Squamous cell carcinoma and adenocarcinoma accounted for 86.7% and 7.4%, respectively. The 5-year survival rates of patients treated by endoscopic resection, concurrent chemoradiotherapy, radiotherapy alone, and esophagectomy were 87.2%, 33.5%, 24.2%, and 59.9%, respectively. Esophagectomy was performed in 5172 cases. Minimally invasive approaches were selected for 60.6%, and 54.4% underwent thoracoscopic esophagectomy. The operative mortality (within 30 days after surgery) was 0.79% and the hospital mortality was 2.3%. The survival curves showed an excellent discriminatory ability both in the clinical and pathologic stages by the JES system. The survival of pStage IV was better than IIIC in the UICC system because pStage IV included the patients with supraclavicular lymph node metastasis (M1 LYM).We hope this report improves all aspects of diagnosing and treating esophageal cancer in Japan.

n our previous nationwide survey report on esophageal perforation, we proposed the existence of cases with idiopathic esophageal perforation at a certain rate. To elucidate the clinical characteristics of idiopathic esophageal perforation, we performed a comparative analysis between cases with idiopathic type and post-emetic type esophageal perforation. This study enrolled 139 patients with esophageal perforation (post-emetic type: idiopathic type = 115:24) as the subjects of nationwide survey on esophageal perforation. We conducted detailed studies on chief complaints, inflammatory responses, initial diagnosis, location and situation of the perforation site, time to therapeutic intervention, and prognosis between the two groups. Compared with post-emetic type, cases of idiopathic type tended to exhibit rear-side perforation (p = 0.052) and significantly less presented chest pain (p = 0.002). Consequently, cases of idiopathic type significantly missed to diagnose as esophageal perforation compared with post-emetic type (p = 0.042). With regard to inflammatory response, cases of post-emetic type experienced hyperthermia compared with idiopathic type (p = 0.033). On the other hand, cases of idiopathic type exhibited significantly higher level of C-reactive protein than post-emetic type (p = 0.004). In addition, it took longer time until starting treatment in the cases of idiopathic type (p

Background : Anastomotic leakage after esophagectomy is significantly associated with more severe complications, such as sepsis and mortality. Early prediction for anastomotic leakage is usually difficult and needs to be treated rapidly. In the current study, we investigated the correlation between hemodynamic and several complications after esophagectomy in patients with esophageal cancer, using the FloTrac system. Materials and Methods : Between April 2013 and December 2014, 39 patients with a mean age of 66.6 ± 8.9 years underwent postoperative supervision using the FloTrac sensor / Vigileo monitoring system after curative surgery for esophageal cancer. We retrospectively evaluated the association between the number of aberrant cardiac index (CI) along with stroke volume variability (SVV) values and clinicopathological parameters of postoperative complications in this report. Results : There were significant positive correlations between the number of aberrant values of CI along with SVV and depth of invasion during pathological stage. Concerning major postoperative complications, there was a significant positive correlation between the number of aberrant values of CI and anastomotic leakage. Discussion: The hemodynamic change by employing the FloTrac system could predicts the complication of anastomotic leakage after esophagectomy. Adequate management of hemodynamic stability by utilizing it will reduce the complications of anastomotic leakage. J. Med. Invest. 67 : 240-245, August, 2020.

To get a clear view of the current state of treatment for esophageal perforation in Japan. Esophagus perforations are the most serious gastrointestinal tract perforations and are associated with high morbidity and mortality. The optimal treatment choice remains unknown. We conducted a retrospective clinical review of 182 esophageal perforation cases at 108 hospitals accredited by the Japanese Esophageal Society between January 2010 and December 2015. We found that 20.9% of patients were incorrectly diagnosed initially. We observed mediastinum emphysema in 83.5% of patients, and serious abscess formations of the mediastinum and intrathoracic cavity in 38.6% and 29.6%, respectively. The lower esophagus was the most commonly perforated site (77.7%). Management of esophageal perforations included nonoperative treatment in 20 patients (11%) and operative treatment in 162 patients (89%). The overall mortality rate was 6.9%. The survivors had significantly shorter times from symptom appearance to visit (p = 0.0016), and from time to visit to diagnosis confirmation (p = 0.0011). Moreover, patients older than 65 years, white blood cells less than 3000/mm3, C-reactive protein > 10 mg/L, or abscesses in the thoracic cavity showed significantly higher mortality than others. Shortening the time from onset to the start of treatment contributes to reduce mortality in patients with esophageal perforation. Moreover, strict medical treatment is necessary to lower the mortality rate of elderly patients with strong inflammation and abscesses in the thoracic cavity.

This study aims to clarify the influence of the COVID-19 pandemic on cancer surgery in Gunma Prefecture.A total of 9839 cases (1406 gastric cancer, 3569 colorectal cancer, 1614 lung cancer, and 3250 breast cancer) from 17 hospitals in Gunma Prefecture were investigated. We compared the number of surgical cases, proportion of cases found by screening, and cStage at the time of the first visit by month in 2020 and 2021 with those in 2019.The rate of decline in cancer surgery was 8.9% in 2020 compared with 2019 (p = 0.0052). Compared with the same month of 2019, in some months of 2020 and 2021, significant decreases were observed in the number of surgeries for gastric and colorectal cancer, the percentage of surgical cases detected by screening in all four cancers, and the proportion of cancers with a relatively early cStage in gastric and breast cancer.The number of surgical cases of the four cancer types detected by cancer screening decreased in Gunma Prefecture owing to the influence of the COVID-19 pandemic. Furthermore, for some cancer types, the number of operations performed in patients with early-stage cancer is also decreased.

Endoscopic diagnosis of the invasion depth of superficial esophageal squamous cell carcinoma (ESCC) is an important determinant of the treatment strategy. The three endoscopic imaging modalities commonly used to predict the invasion depth of superficial ESCC in Japan are non-magnifying endoscopy (non-ME), magnifying endoscopy (ME), and endoscopic ultrasonography (EUS). However, which of these three modalities is most effective remains unclear. We performed a systematic review of the literature to compare the diagnostic accuracy of the three modalities for prediction of the invasion depth of superficial ESCC. We used Medical Subject Heading terms and free keywords to search the PubMed, Cochrane Central, and Ichushi databases to identify direct comparison studies published from January 2000 to August 2020. The results of direct comparison studies were used to compare the diagnostic accuracy of each modality. The primary outcome was defined as the proportion of overdiagnosis of pT1b-SM2/3 cancers, and the main secondary outcome was the proportion of underdiagnosis of pT1b-SM2/3 cancers. Other secondary outcomes were the sensitivity and specificity values of the modalities. Four articles were finally selected for qualitative evaluation. Although ME showed no significant advantages over non-ME in terms of sensitivity and specificity, it had a slightly lower proportion of overdiagnosis. EUS had sensitivity and specificity similar to those of non-ME and ME, but EUS had a higher proportion of overdiagnosis. Non-ME and ME are useful for the diagnosis of cancer invasion depth. EUS may increase overdiagnosis, and caution is required in determining its indications.

Stator coils of automobiles in operation generate heat and are cooled by coolant poured from above. The flow characteristic of the coolant depends on the coil structure, flow condition, solid–fluid interaction, and fluid property, which has not been clarified due to its complexities. Since straight coils are aligned and layered with an angle at the coolant-touchdown region, the coil structure is simplified to a horizontal square rod array referring to an actual coil size. To obtain the flow and wetting characteristics, two-phase fluid flow simulations are conducted by using the phase-field lattice Boltzmann method. First, the flow onto the single-layered rod array is discussed. The wetting area is affected both by the rod gap and the wettability, which is normalized by the gap and the averaged boundary layer thickness. Then, the flow onto the multi-layered rod arrays is investigated with different rod gaps. The top layer wetting becomes longitudinal due to the reduction of the flow advection by the second layer. The wetting area jumps up at the second layer and increases proportionally to the below layers. These become remarkable at the narrow rod gap case, and finally, the dimensionless wetting area is discussed at each layer.

Background & Aims Mixed neuroendocrine–non‐neuroendocrine neoplasm (MiNEN) is a rare neuroendocrine neoplasm (NEN) comprising dual neuroendocrine and non‐neuroendocrine components. Although the coexistence pattern of neuroendocrine and non‐neuroendocrine components in definitive MiNEN is thought to overlap, there may be a coexistent pattern of both components, such as superficial carcinoma adjacent to NEN. The present study evaluated the histopathological findings of the coexistence pattern of superficial carcinomas adjacent to NENs in the esophagogastrointestinal tract. Methods From 2000 to 2019, 35 serial NEN resections of the esophagus (n = 9), stomach (n = 3), and large intestine (n = 23), respectively, were performed at Gunma University Hospital. Borderline areas between NEN and resident superficial epithelium were observed in the 35 serial NEN cases as well as two additional cases from affiliated hospitals. Results Among the 35 serial NEN samples, squamous cell carcinomatous/dysplastic components were identified 77.8% (7/9 cases) of esophageal NENs, and adenocarcinomatous areas were seen in 66.7% (2/3 cases) of gastric NENs and 26% (6/23 cases) of colorectal NENs. Thus, all superficial carcinomatous components adjacent to NENs were observed as squamous cell carcinoma/dysplasia in esophagus and adenocarcinoma in stomach and large intestine, which showed histological characteristics as the resident epithelial pattern in each organ. Conclusions These findings suggested a potential “paratransformation” or “bystander effect” in resident epithelium by NENs. Thus, “bystander carcinogenesis” could be a pathogenic mechanism of resident epithelium transformation adjacent to NENs in the esophagogastrointestinal tract.

The consumption of fruit and vegetables was reported to be associated with a reduced risk of esophageal cancer (EC) in many studies of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) from different regions worldwide. Therefore, to provide precise information to reduce the risk of EC in Asia, we performed a systematic review and meta-analysis of studies conducted in the Asian region about fruit and vegetable consumption and the risk of EC. We searched the MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases from January 2010 to December 2020. The summary relative risk (SRR) and 95% CI were calculated using a random-effects model. In addition, I

Boerhaave’s syndrome, involving esophagus rupture, is considered a pathological response to vomiting that may occur just before perforation. However, the mechanism of vomiting and occurrence of this disease have not been clearly demonstrated. We identified patients with esophageal perforation between 1995 and 2017 and reviewed endoscopic findings at retching during upper gastrointestinal endoscopy. Finally, we proposed a theory for the underlying pathological mechanism. We retrospectively investigated 10 patients with esophageal perforation between 1995 and 2017. All patients presented after vomiting associated with large volumes of food and alcohol intake. Nine were treated by primary closure of the perforation and drainage of the thoracic cavity, and one was conservatively treated. In all cases, the perforations were longitudinal tears (1–4 cm) and located in the left of the esophagus, just above the gastric cardia. We hypothesize that vomiting occurred by retrograde propagation of gastrointestinal motor contraction from the jejunum to the gastric antrum, followed by prolapse of the gastric fornix mucosal into the esophagus. Subsequent esophageal perforation probably resulted from excessive prolapse due to strong contraction and destruction of the muscularis mucosa of the left side of abdominal esophagus, with longitudinal stretching of the whole left esophageal wall due to traction. We also propose that Boerhaave’s syndrome is defined as “post-emetic esophageal perforation” to ensure broader recognition and more expedient diagnosis and treatment. Remaining conditions without any definite causes may be labeled “idiopathic” or “spontaneous” rupture of the esophagus.

Background/aim Unresectable oesophageal cancer with surrounding invasion carries a particularly poor prognosis. The chemoradiotherapy treatment for locally-unresectable oesophageal cancer aims to initially control local invasion before proceeding to the next treatment, and is ideally used with curative intent. The aim of this study was to investigate patient treatment course and survival to determine the best treatment and evaluate surgical intervention for these advanced cancers. Patients and methods A total of 147 patients who were diagnosed with clinical T4b oesophageal cancer were included in this study. Results Forty-three patients had undergone curative resection of the tumour and surrounding invasion at midterm evaluation, 104 patients continued with definitive chemoradiotherapy, and salvage surgery was performed in 21 patients. Multivariate analysis of disease-specific survival showed that response at the midterm evaluation and surgical intervention (conversion surgery + salvage surgery) were significant prognostic factors. Conclusion Surgical intervention was an independent prognostic factor, and operation should be performed in eligible patients after considering the risks and proper timing.

To evaluate the efficacy of docetaxel, cisplatin, and 5-fluorouracil as combination chemoradiotherapy (DCF-RT) for cervical esophageal cancer (CEC), we performed a retrospective analysis of CEC patients treated by DCF-RT at a single institution. We conducted a single-center retrospective study. Twenty-one patients with CEC who underwent DCF-RT between 1999 and 2017 at our institute were included in this study. Chemotherapy consisted of intravenous docetaxel at 50 mg/m2 on day 1, intravenous CDDP at 60 mg/m2 on day 1, and intravenous 5-FU at 600 mg/m2 on days 1–4, repeated every 4 weeks for two cycles. Among the 21 patients, six were irradiated using three-dimensional conformal RT (3D- conformal RT) and 15 were treated using intensity-modulated RT (IMRT) consisting of 60 Gy in 30 fractions. The median follow-up period was 49.6 months (range 4.6–97.6). The overall complete response (CR) and local CR rates were 61.9% and 81.0% for all patients, and 76.9% and 84.6% for patients without hypopharyngeal and/or thoracic esophageal invasion, respectively. The 3-year overall survival (OS), progression-free survival (PFS), and local failure-free survival (LFFS) rates were 79.6, 52.4, and 74.7%, respectively. Grade 3–4 leucopenia developed in 12 patients (70.6%), neutropenia developed in 13 patients (81.2%), and mucositis developed in 2 patients (9.5%). There were no treatment-related deaths. The 3-year OS and LFFS of patients who underwent DCF-RT were higher than those in the previous studies. Although the high rate of myelosuppression requires careful management, DCF-RT is a safe and effective modality for CEC.

Surgical treatment is usually required for Boerhaave's syndrome (post-emetic esophageal perforation), and the technique should be chosen based on the local infection status and patient's general condition. This study was performed to examine the current status of surgical treatment of Boerhaave's syndrome in Japan.Ninety-five patients with Boerhaave's syndrome who underwent surgical treatment from January 2010 to December 2015, obtained from a national survey were retrospectively analyzed. The details of each surgical treatment and the type of treatment performed according to the patients' characteristics were examined.Primary closure was performed in 75 (78.9%) patients, T-tube insertion in 15 (15.8%), and esophagectomy in 5 (5.3%). The length of the postoperative stay was significantly shorter in patients who underwent primary closure (p = 0.0011). Esophagectomy tended to be performed more often in patients with a long perforation and was performed significantly more often in patients with a high C-reactive protein concentration (p = 0.0118). The postoperative hospital stay was significantly longer in patients with leakage of the primary closure site (p 0.0001). As a result, leakage of the primary closure site was significantly correlated with a long duration from symptom onset to patient presentation (p = 0.042), diagnostic imaging of the intrathoracic perforation (p = 0.013), and abscess formation in the mediastinal cavity (p = 0.006).Selection of an appropriate surgical procedure may contribute to reduced mortality rates in patients with esophageal rupture. With regard to primary closure, it is necessary to understand that leaks are likely to occur in patients with a long duration from symptom onset to presentation or with severe intrathoracic/mediastinal inflammation, and to select an appropriate surgical procedure in consideration of the degree of invasiveness and QOL.

As esophageal gastrointestinal stromal tumors (GISTs) are very rare, their clinicopathological features remain obscure. We conducted a nationwide survey to clarify the characteristics of these tumors and to establish a consensus on their diagnosis and treatment. The clinicopathological information of patients with esophageal GISTs who underwent treatment between January 2010 and June 2016 at the accredited institutions by the Japan Esophageal Society was collected via a questionnaire method and analyzed statistically. Fifty-one patients (29 men and 22 women; median age, 68 years) were recruited from 31 institutions. Diagnosis was triggered most frequently during screening and other disease scrutiny. Symptoms were seen only in 17 patients: highest in 11 patients with dysphagia. Thirty-five patients underwent surgery alone; 15 patients, surgery with imatinib therapy; and one patient, endoscopic resection. The tumors preferentially occurred in the lower and middle parts of the thoracic esophagus, with a median size of 36.5 mm. Neoadjuvant and adjuvant imatinib therapies were performed in seven and eight patients, respectively. Administration of imatinib 400 mg/day was the standard regimen. Postoperative follow-up observations were conducted mostly via computed tomography (CT) scans every 3 or 6 months until 5 years after surgery. The tumors recurred in ten patients within 5 years postoperatively (high risk, 38.5%; intermediate risk, 20%; low risk, 0%; very low risk, 0%; three cases of relapse with an unknown risk assessment). A patient with a high-risk GIST died from the tumor 54 months after surgery. This nationwide survey revealed the current status of esophageal GISTs in Japan and provided important information for making a consensus on the treatment and follow-up method.

Esophageal neuroendocrine carcinoma (ENEC) has a poor prognosis, and predicting the prognosis by examining various markers may contribute to the determination of treatment strategies. Therefore, a multiple-institution retrospective study was performed to identify biomarkers using diagnostic immunohistochemistry and serum tumor markers that predict the prognosis of patients with ENEC. The results of immunohistochemical examination and serum tumor markers were extracted from the data of 141 ENEC patients at 39 institutions certified by the Japan Esophageal Society. The study then examined correlations between these data and prognosis or treatment effects. The ENEC patients with positively for all expression of synaptophysin (Syn), chromogranin A (CgA), and CD56 had a significantly worse prognosis than the patients with other expression patterns. Additionally, surgery and chemoradiotherapy were significantly more effective treatments than chemotherapy for the patients who were not positive for all expressions of Syn, CgA, and CD56. In terms of serum tumor markers, the patients with a high neuron-specific enolase (NSE) value had a significantly worse prognosis than the patients with a normal NSE value, and complete response (CR) cases treated with chemotherapy were significantly fewer in the high-NSE group. The results of multivariate analysis demonstrated that high NSE levels were an independent poor prognostic factor for esophageal endocrine cell carcinoma. This study showed that positivity for all expressions of Syn, CgA, and CD56, and a high NSE value were significantly worse prognostic factors for ENEC patients than other expression patterns and may be important prognostic biomarkers of ENEC.