Doublet chemotherapy, triplet chemotherapy, or doublet chemotherapy combined with radiotherapy as neoadjuvant treatment for locally advanced oesophageal cancer (JCOG1109 NExT): a randomised, controlled, open-label, phase 3 trial.

BACKGROUND: Neoadjuvant therapy is the standard treatment for patients with locally advanced oesophageal squamous cell carcinoma (OSCC). However, the prognosis remains poor and more intensive neoadjuvant treatment might be needed to improve patient outcomes. We therefore aimed to compare the efficacy and safety of neoadjuvant doublet chemotherapy, triplet chemotherapy, and doublet chemotherapy plus radiotherapy in patients with previously untreated locally advanced OSCC. METHODS: In this randomised, open-label, phase 3 trial, patients aged 20-75 years with previously untreated locally advanced OSCC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were recruited from 44 centres across Japan. Patients were randomly assigned (1:1:1) centrally via a web-based system to receive neoadjuvant doublet chemotherapy (two courses of fluorouracil [800 mg/m2 per day intravenously on days 1-5] and cisplatin [80 mg/m2 per day on day 1] separated by an interval of 3 weeks [NeoCF]), triplet chemotherapy (three courses of fluorouracil [750 mg/m2 per day on days 1-5], cisplatin [70 mg/m2 per day on day 1], and docetaxel [70 mg/m2 per day on day 1] repeated every 3 weeks [NeoCF+D]), or doublet chemotherapy (two courses of fluorouracil [1000 mg/m2 per day on days 1-4] and cisplatin [75 mg/m2 per day on day 1] separated by an interval of 4 weeks) plus 41·4 Gy radiotherapy [NeoCF+RT]) followed by oesophagectomy with regional lymph node dissection. Randomisation was stratified by T stage and institution. Participants, investigators, and those assessing outcomes were not masked to group assignment. The primary endpoint was overall survival, analysed by intention to treat. Analysis of safety included all patients who received at least one course of chemotherapy, and analysis of surgical complications included those who also underwent surgery. This study is registered with the Japan Registry of Clinical Trials, jRCTs031180202, and the trial is complete. FINDINGS: A total of 601 patients (529 male individuals and 72 female individuals) were randomly assigned between Dec 5, 2012, and July 20, 2018, with 199 patients in the NeoCF group, 202 patients in the NeoCF+D group, and 200 patients in the NeoCF+RT group. Compared with the NeoCF group, during a median follow-up period of 50·7 months (IQR 23·8-70·7), the 3-year overall survival rate was significantly higher in the NeoCF+D group (72·1% [95% CI 65·4-77·8] vs 62·6% [55·5-68·9]; hazard ratio [HR] 0·68, 95% CI 0·50-0·92; p=0·006) but not in the NeoCF+RT group (68·3% [61·3-74·3]; HR 0·84, 0·63-1·12; p=0·12). Grade 3 or higher febrile neutropenia occurred in two (1%) of 193 patients in the NeoCF group, 32 (16%) of 196 patients in the NeoCF+D group, and nine (5%) of 191 patients in the NeoCF+RT group. Treatment-related adverse events leading to termination of neoadjuvant therapy were more common in the NeoCF+D group (18 [9%] of 202 participants) than in the NeoCF+RT group (12 [6%] of 200) and NeoCF group (eight [4%] of 199). There were three (2%) treatment-related deaths during neoadjuvant therapy in the NeoCF group, four (2%) deaths in the NeoCF+D group, and two (1%) deaths in the NeoCF+RT group. Grade 2 or higher postoperative pneumonia, anastomotic leak, and recurrent laryngeal nerve paralysis were reported in 19 (10%), 19 (10%), and 28 (15%) of 185 patients, respectively, in the NeoCF group; 18 (10%), 16 (9%), and 19 (10%) of 183 patients, respectively, in the NeoCF+D group; and 23 (13%), 23 (13%), and 17 (10%) of 178 patients, respectively, in the NeoCF+RT group. The in-hospital deaths following surgery included three deaths in the NeoCF group, two deaths in the NeoCF+D group, and one in the NeoCF+RT group. INTERPRETATION: Neoadjuvant triplet chemotherapy followed by oesophagectomy resulted in a statistically significant overall survival benefit compared with doublet chemotherapy and might be the new standard of care for locally advanced OSCC who are in good condition in Japan. Neoadjuvant doublet chemotherapy plus radiotherapy did not show significant improvement of survival compared with doublet chemotherapy. FUNDING: Japan Agency for Medical Research and Development and National Cancer Center Research and Development Fund.

Effectiveness of computed tomography scoring for the early diagnosis of anastomotic leakage after esophagectomy.

PURPOSE: Anastomotic leakage after esophagectomy is associated with increased mortality; therefore, early diagnosis is highly important. This study aimed to identify the characteristic computed tomography (CT) findings of cervical anastomotic leakage after esophagectomy for esophageal cancer and evaluate the effectiveness of CT scoring in screening the anastomotic leakage. METHODS: Overall, 91 patients who underwent thoracoscopic esophagectomy with cervical esophago-gastric anastomosis were included. We investigated the correlation between anastomotic leakage and the presence of the microbubble sign, evident air retention, and fluid collection in the cervical and mediastinal regions. CT findings were scored, and the cutoff value was set to 2 points on the receiver operating characteristic curve. The patients were divided into two groups based on the CT score (≥ 2 points and ≤ 1 point). RESULTS: CT findings of the microbubble sign (p = 0.01; odds ratio [OR], 8.545; 95% confidence interval [CI], 1.596-45.73), cervical air retention (p < 0.01; OR, 12.43; 95% CI, 2.084-74.17), and cervical fluid collection (p < 0.01; OR, 9.359; 95% CI, 1.753-49.96) significantly correlated with anastomotic leakage. The ≥ 2-point CT score group showed a significantly higher incidence of anastomotic leakage than the ≤ 1-point group (p < 0.01; OR, 16.28; 95% CI [4.704-56.38]). A ≥ 2-point CT score had higher sensitivity (84.2%) than upper gastrointestinal series (36.8%). CONCLUSION: The presence of microbubble sign, air retention, and fluid collection in the cervical area correlated with anastomotic leakage after cervical anastomosis in thoracoscopic esophagectomy. CT scores are useful early anastomotic leakage detectors.

Usefulness of skeletal muscle measurement by computed tomography in patients with esophageal cancer: changes in skeletal muscle mass due to neoadjuvant therapy and the effect on the prognosis.

PURPOSE: This analysis was performed to clarify the usefulness of skeletal muscle measurements using computed tomography (CT) in patients with esophageal cancer and the effect of treatment-induced changes in the skeletal muscle mass on the prognosis. METHODS: Ninety-seven male patients who underwent thoracoscopic esophagectomy for esophageal squamous cell carcinoma were included in the study. The preoperative CT images were analyzed retrospectively. RESULTS: In a survival analysis performed according to the preoperative data of skeletal muscle, the low-skeletal muscle index (l-SMI) group had a poorer outcome than the normal skeletal muscle index (n-SMI) group in terms of both the overall survival (OS) and the relapse-free survival (RFS) (OS: P < 0.01, RFS: P = 0.01). In the multivariate analysis for the OS, preoperative l-SMI was an independent predictor (hazard ratio: 3.68, 95% confidence interval 1.32-10.2, P = 0.01). In patients who underwent neoadjuvant therapy (NAT), the SMI was significantly reduced after NAT (P < 0.01). The preoperative skeletal muscle area on CT was strongly correlated with the results of a bioelectrical impedance analysis (BIA) (ρ = 0.77, P < 0.01). CONCLUSIONS: A decreased preoperative skeletal muscle mass was associated with a poor outcome. In patients who underwent NAT, the SMI was significantly reduced after NAT. An analysis of the skeletal muscle mass using CT images was found to be useful for providing data that corresponded with BIA data.

Predictive impact of the thoracic inlet space on ICG fluorescence blood flow speed in the gastric conduit wall and anastomotic leakage after esophagectomy.

PURPOSE: The thoracic inlet space might influence the blood vessel perfusion in the gastric conduit. The purpose of this study was to clarify the impacts of the thoracic inlet space on blood vessel perfusion in the gastric conduit and anastomotic leakage after esophagectomy. METHODS: One hundred and forty-two esophageal cancer patients underwent esophagectomy followed by gastric conduit reconstruction via the retrosternal route. The blood flow speed in the gastric conduit was measured using indocyanine green fluorescence before and after reconstruction. Parameters at the thoracic inlet space were measured using CT. We then investigated the correlation between these two parameters and whether they could predict anastomotic leakage after esophagectomy. RESULTS: Blood flow speed in the gastric conduit was slower after reconstruction than before reconstruction (P < 0.001). The incidence of anastomotic leakage (n = 23) was higher among patients with a delayed blood flow speed before reconstruction (n = 27) than among those with a non-delayed blood flow speed before reconstruction (n = 115) (P < 0.001). Among the patients with a non-delayed blood flow speed before reconstruction, the thoracic inlet area (TIA, sternum-tracheal distance × clavicle head distance) was positively correlated with the blood flow speed after reconstruction (P = 0.023) and was identified as an independent predictor of anastomotic leakage (P < 0.001). CONCLUSION: A narrow TIA was associated with a delayed blood flow speed in the gastric conduit after reconstruction and was capable of predicting anastomotic leakage in the patients with a non-delayed blood flow speed before reconstruction.

Detecting lymph node metastasis of esophageal cancer on dual-energy computed tomography.

BACKGROUND: Using conventional computed tomography (CT), the accurate diagnosis of lymph node (LN) metastasis of esophageal cancer is difficult. PURPOSE: To examine dual-energy CT parameters to predict LN metastasis preoperatively in patients with esophageal cancer. MATERIAL AND METHODS: Twenty-six consecutive patients who underwent dual-energy CT before an esophageal cancer surgery (19 patients with LN metastases) were analyzed. The included LNs had a short-axis diameter of ≥4 mm and were confirmed to be resected on postoperative CT. Their short-axis diameter, CT value, iodine concentration (IC), and fat fraction were measured on early- and late-phase contrast-enhanced dual-energy CT images and compared between pathologically confirmed metastatic and non-metastatic LNs. RESULTS: In total, 51 LNs (34 metastatic and 17 non-metastatic) were included. In the early phase, IC and fat fraction were significantly lower in the metastatic than in the non-metastatic LNs (IC = 1.6 mg/mL vs. 2.2 mg/mL; fat fraction = 20.3% vs. 32.5%; both P < 0.05). Furthermore, in the late phase, IC and fat fraction were significantly lower in the metastatic than in the non-metastatic LNs (IC = 2.0 mg/mL vs. 3.0 mg/mL; fat fraction = 20.4% vs. 33.0%; both P < 0.05). Fat fraction exhibited accuracies of 82.4% and 78.4% on early- and late-phase images, respectively. Conversely, short-axis diameter and CT value on both early- and late-phase images were not significantly different between the metastatic and non-metastatic LNs (P > 0.05). CONCLUSION: Using dual-energy CT images, IC and fat fraction are useful for diagnosing LN metastasis in patients with esophageal cancer.

Clinicopathological Role of Vasohibin in Gastroenterological Cancers: A Meta-Analysis.

Vasohibin-1 (VASH1) is an angiogenesis inhibitor, while vasohibin-2 (VASH2) is a proangiogenic factor. The roles of VASH1 and VASH2 expression in gastroenterological cancers remain unclear. We searched for relevant literature, specifically studies on gastroenterological cancer, and evaluated the relationship between VASH expression and clinical outcomes. Nine studies on VASH1 involving 1,574 patients were included. VASH1 expression was associated with the TNM stage [OR (odds ratio) 2.05, 95% CI (confidence interval) 1.24-3.40], lymph node metastasis (OR 1.79, 95% CI 1.24-2.58), lymphatic invasion (OR 1.95, 95% CI 1.41-2.68), and venous invasion (OR 2.49, 95% CI 1.60-3.88); poor clinical outcomes were associated with high VASH1 expression. High VASH1 expression was associated with a significantly shorter overall survival (OS) [HR (hazard ratio) 1.69, 95% CI 1.25-2.29] and disease-free survival (DFS) (HR 2.01, 95% CI 1.28-3.15). Three studies on VASH2 involving 469 patients were analyzed. VASH2 expression was associated with the TNM stage (OR 4.21, 95% CI 1.89-9.51) and venous invasion (OR 2.10, 95% CI 1.15-3.84); poor clinical outcomes were associated with high VASH2 expression. High VASH2 expression was associated with a significantly lower OS (HR 1.61, 95% CI 1.09-2.37). In conclusion, high VASH1 and VASH2 expression levels were associated with poor clinical outcomes and prognosis in patients with gastroenterological cancers.

Indocyanine green fluorescence imaging for evaluating blood flow in the reconstructed conduit after esophageal cancer surgery.

We investigated the effectiveness of indocyanine green (ICG) fluorescence blood flow imaging of the gastric conduit to evaluate anastomotic leakage after esophagectomy. We identified 19 articles using the PRISMA standard for systematic reviews. The more recent studies reported attempts at objective quantification of ICG fluorescence imaging, rather than qualitative assessment. Anastomotic leakage after esophagectomy occurred in 0-33% of the patients who underwent ICG fluorescence imaging. According to the six studies that compared the incidence of anastomotic leakage in the ICG group and the control group, it ranged from 0 to 18.3% in the ICG group and from 0 to 25.2% in the control group, respectively. Overall, the incidence of anastomotic leakage in the ICG group (8.4%) was lower than that in the control group (18.5%). Although the incidence of anastomotic leakage was as high as 43.1% in patients who did not undergo any intraoperative intervention for poor blood flow, it was only 24% in patients who underwent intraoperative intervention. This systematic review revealed that ICG fluorescence imaging may be a crucial adjunctive tool for reducing anastomotic leakage after esophagectomy, suggesting that it should be performed during esophageal reconstruction.

A study on safe forceps grip force for the intestinal tract using haptic technology.

PURPOSE: The present study used haptic technology to determine the safe forceps grip force for preventing organ damage when handling the intestinal tract. MATERIAL AND METHODS: The small intestines of ten male beagle dogs (weighing 9.5-10 kg) were grasped with the entire forceps for one minute; the small intestines were then pulled out of the forceps and evaluated for damage. The force at which the shaft inside the forceps was pulled to close the tip of the forceps was defined as the grip force. Small intestine damage was classified into macroscopic (serosal defects, hemorrhage, hematomas, grip marks) and microscopic (damage layer to the mucosa, submucosa/muscularis mucosa, inner orbicularis muscle, external longitudinal muscle, serosa/subserosa). Grip marks and damage layer to the serosa/subserosa have been considered as acceptable safety margins when grasping the small intestines of beagle dogs. RESULTS: The macroscopic findings showed that the maximum grip force that produced a 0% incidence of hemorrhage and hematoma was 15 N. At the microscopic level, the maximum grip force that produced a 0% incidence of external longitudinal muscle injury was 15 N, respectively. CONCLUSIONS: A grip force of 15 N does not damage the small intestines of beagle dogs.

Comprehensive registry of esophageal cancer in Japan, 2014.

BACKGROUND: The registration committee for esophageal cancer in the Japan Esophageal Society (JES) has collected the patients' characteristics, treatment, and outcomes annually. METHODS: We analyzed the data of patients who had visited the participating hospitals in 2014. We collected the data with a web-based data collection system using the National Clinical Database. We used the Japanese Classification of Esophageal Cancer 10th edition by JES and the TNM classification 7th edition by the Union of International Cancer Control (UICC) for cancer staging. RESULTS: A total of 9026 cases were registered from 344 institutions in Japan. Squamous cell carcinoma and adenocarcinoma accounted for 87.9% and 7.1%, respectively. The 5-year survival rates of patients treated using endoscopic resection, concurrent chemoradiotherapy, radiotherapy alone, and esophagectomy were 87.1%, 33.7%, 25.3%, and 59.3%, respectively. Esophagectomy was performed in 5204 cases. Concerning the approach used for esophagectomy, 48.1% of the cases were treated thoracoscopically. The operative mortality (within 30 days after surgery) was 0.75%, and the hospital mortality was 2.0%. 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). CONCLUSION: We hope that this report contributes to improving all aspects of diagnosing and treating esophageal cancer in Japan.

Combined primary hepatic neuroendocrine carcinoma and hepatocellular carcinoma: case report and literature review.

BACKGROUND: Hepatocellular carcinoma (HCC) can grow in a mosaic pattern, often combined with various non-hepatocellular cells. However, HCC combined with a neuroendocrine carcinoma (NEC) component is rarely reported, and its clinical features, origin, diagnosis, and behavior have not been established. In the literature, mixed HCC-NEC tumors are categorized as either collision type or combined type, depending on their microscopic features. Here, we report a patient with a combined-type HCC-NEC tumor. CASE PRESENTATION: An asymptomatic 84-year-old woman was found to have a solid mass in the right lobe of the liver. Laboratory and radiologic examinations showed typical findings of HCC, including arterial-phase enhancement, and portal- and delay-phase washout. She was treated by partial laparoscopic hepatectomy of segment 5. Pathological examination showed that the tumor was predominantly HCC, partly admixed with an NEC component. A transitional zone between the HCC and NEC tissues was also observed. The tumor was finally diagnosed as a combined-type primary mixed NEC-HCC tumor. After the preoperative diagnosis, the patient underwent somatostatin receptor scintigraphy to detect the primary NEC lesion, but no accumulation was found in any other part of her body. She has been free of recurrence for 9 months since the surgery. CONCLUSION: Mixed HCC-NEC tumors are extremely rare, and correct diagnosis requires multidisciplinary collaboration. The accumulation of further cases is needed to help understand the exact pathology, diagnosis, and treatment of this disease.

Significance of pulmonary resection in patients with metachronous pulmonary metastasis from pancreatic ductal adenocarcinoma: a retrospective cohort study.

BACKGROUND: Pulmonary metastases from pancreatic ductal adenocarcinoma (PDAC) are relatively rare. Systemic chemotherapy is the first choice of treatment in patients with distant metastases, and the role of metastasectomy is controversial. The aim of the present study was to evaluate the outcome of patients with pulmonary metastases after resection of PDAC and the indications for metastasectomy. METHODS: We retrospectively analysed patients with pulmonary metastases as the first recurrence after resection of primary PDAC between January 2006 and December 2018. Clinical data were obtained from the patients' medical records. Relapse-free survival (RFS) and overall survival (OS) were analysed using the Kaplan-Meier method, and statistical significance was evaluated by the log-rank test. RESULTS: Of the 417 patients with resected PDACs, 24 (7.9%) had pulmonary metastases. Six patients (25.0%) underwent pulmonary resection and 18 (75.0%) received systemic chemotherapy and best supportive care. There were no major complications requiring therapeutic intervention after pulmonary resection. The median RFS was 24.0 months (95% CI 10.8-37.2), and the 1-, 3-, and 5-year RFS rates were 66.7%, 33.3%, and 4.2%, respectively. The median OS was 50.0 months (95% CI 15.9-84.1), and the 1-, 3-, and 5-year OS rates were 95.8%, 70.3%, and 46.4%, respectively. All patients with resected pulmonary metastases were alive at the end of the study, whereas the median OS of the patients who did not undergo resection was 37.0 months (95% CI 34.4-39.6). Therefore, patients with resected pulmonary metastases had a significantly better prognosis (p = 0.008). CONCLUSIONS: Pulmonary resection may improve the prognosis in selected patients with pulmonary metastases from PDAC. However, the present study is based on a small number of patients and may include a selection bias; therefore, a multi-institutional prospective study is needed to clarify the indications for pulmonary resection.

Association between indocyanine green fluorescence blood flow speed in the gastric conduit wall and superior mesenteric artery calcification: predictive significance for anastomotic leakage after esophagectomy.

BACKGROUND: Near-infrared fluorescence using indocyanine green (ICG) has been applied as a real-time navigation tool to observe blood flow in gastric conduit wall after esophagectomy. Atherosclerosis might impair the blood flow of the systemic organs. The aim of the study was to investigate the significances of ICG blood flow speed in the gastric conduit wall and atherosclerotic calcification for the prediction of anastomotic leakage after esophagectomy. METHODS: The 109 esophageal cancer patients were prospectively enrolled. ICG fluorescence blood flow speed in the gastric conduit wall and abdominal aortic calcification index (ACI), celiac artery (CA) calcification, and superior mesenteric artery (SMA) calcification were determined. Then, the correlation between ICG fluorescence blood flow speed and anastomotic leakage as well as ACI, CA, and SMA calcification were evaluated. RESULTS: Anastomotic leakage occurred in 15 patients. ACI ranged from 0 to 65. CA calcification and SMA calcification were present in 25 and 12 patients. Multivariate analysis demonstrated that ICG fluorescence blood flow speed in the gastric conduit wall of 2.07 cm/s or less (P < 0.001) and SMA calcification (P = 0.026) were the significant independent predictors of anastomotic leakage. Only SMA calcification was significantly associated with ICG fluorescence blood flow speed in the gastric conduit wall (P = 0.026). CONCLUSIONS: This study demonstrated that ICG fluorescence blood flow speed in the gastric conduit wall can predict anastomotic leakage after esophagectomy and microvascular perfusion of capillary vessels of the gastric conduit might be impaired by systemic atherosclerosis.

Clinical impacts of magnetic resonance thoracic ductography on preventing postoperative chylothorax after thoracoscopic esophagectomy for esophageal cancer.

PURPOSE: The study aimed to determine whether magnetic resonance thoracic ductography (MRTD) is useful for preventing injury to the thoracic duct (TD) during thoracoscopic esophagectomy and for reducing the incidence of postoperative chylothorax. MATERIALS AND METHOD: A total of 389 patients underwent thoracoscopic esophagectomy between September 2009 and February 2019 in Tokai University Hospital. Of them, we evaluated 228 patients who underwent preoperative MRTD (MRTD group) using Adachi's classification and our novel classification (Tokai classification). Then, the clinicopathological factors of the MRTD group (n = 228) were compared with those of the non-MRTD group (n = 161), and comparative analyses were conducted after propensity score matching (PSM). RESULTS: The TD could be visualized by MRTD in 228 patients. The MRTD findings were divided into 9 classifications including normal findings and abnormal TD findings (Adachi classification vs Tokai classification; 5.3% vs 16.2%). After PSM, both groups consisted of 128 patients. The rate of postoperative chylothorax after thoracoscopic esophagectomy was significantly lower in the MRTD group (0.8%) than in the non-MRTD group (6.3%) (p = 0.036). In the multivariate analysis for risk factors for chylothorax, the independent prognostic factors were preoperative therapy and the presence of MRTD. CONCLUSIONS: This study revealed that MRTD was useful for preventing of chylothorax after thoracoscopic esophagectomy for esophageal cancer.

Usefulness of prone-position computed tomography as preoperative simulation prior to thoracoscopic esophagectomy for thoracic esophageal cancer.

PURPOSE: The study aimed to evaluate the usefulness of prone-position computed tomography (CT) for predicting relevant thoracic procedure outcomes in minimally invasive esophagectomy (MIE) for thoracic esophageal cancer. MATERIALS AND METHODS: A total of 59 patients underwent esophagectomy between May 2019 and December 2020 in Tokai University Hospital. Preoperative CT imaging was conducted with the patient in both the supine and prone positions, and the magnitude of change in the intramediastinal space was calculated. In the 56 patients (94.9%) who had undergone MIE, the effects of such a difference on the surgical outcomes were analyzed. RESULTS: A significant correlation of the magnitude of change in VE (distance between ventral aspect of the vertebral body and the midpoint of the esophagus) with the surgical outcome was revealed in the 17 patients (30.4%) in whom the magnitude of change in VE was over the 75th percentile. That is, in this subgroup, the magnitude of change in VE showed a negative correlation with the thoracic operation time (rs = - 0.57, p = 0.01) and blood loss during the thoracic procedure (rs = - 0.46, p = 0.01). Multivariate analysis identified a magnitude of change in VE ≥ 9 mm (OR = 0.14, p = 0.03) as an independent risk factor for postoperative pneumonia. CONCLUSIONS: This study indicates that preoperative prone-position CT imaging is useful for predicting the level of ease or difficulty of securing an adequate operative field, surgical outcomes, and the risk of postoperative pneumonia in MIE.

Comprehensive registry of esophageal cancer in Japan, 2013.

BACKGROUND: Esophageal cancer is the eighth most common cause of cancer mortality in Japan. More than 11,000 people had died from esophageal cancer in 2018. The Japan Esophageal Society has collected the data on patients' characteristics, performed treatment, and outcomes annually. METHODS: We analyzed the data of patients who had first visited the participating hospitals in 2013. In 2019, the data collection method was changed from an electronic submission to a web-based data collection using the National Clinical Database (NCD). Japanese Classification of Esophageal Cancer 10th by the Japan Esophageal Society (JES) and UICC TNM Classification 7th were used for cancer staging RESULTS: A total of 8019 cases were registered from 334 institutions in Japan. Squamous cell carcinoma and adenocarcinoma accounted for 87.8% and 6.3%, respectively. The 5-year survival rates of patients treated using endoscopic resection, concurrent chemoradiotherapy, radiotherapy alone, or esophagectomy were 88.3%, 32.4%, 24.4%, and 59.3%, respectively. Esophagectomy was performed in 4910 cases. The operative and the hospital mortality rates were 0.77% and 1.98%, respectively. The survival curves showed a good discriminatory ability both in the clinical and pathologic stages by the JES system. The 5-year survival rate of patients with pStage IV in the UICC classification that included patients with supraclavicular node metastasis was better than that of patients with pStage IVb in JES classification. CONCLUSION: We hope this report contributes to improving all aspects of the diagnosis and treatment of esophageal cancer in Japan.

Visibility of bronchial arteries using virtual and advanced virtual monoenergetic imaging.

BACKGROUND: The utility of virtual monoenergetic imaging (VMI) for fine arteries has not been well clarified. PURPOSE: To assess bronchial artery visualization using VMI and noise-optimized advanced VMI (VMI+). MATERIAL AND METHODS: Eighty-seven patients with esophageal cancer underwent computed tomography (CT) using a third-generation dual-source system before surgery. Tube voltages were set to 90 kVp and 150 kVp, respectively. Images were reconstructed using VMI and VMI+ with energy levels of 40-120 keV (in 10-keV increments); composite images equivalent to CT images at 105 kVp were also generated. The CT attenuation value and contrast-to-noise ratio (CNR) of bronchial arteries using VMI and VMI+ were compared with those obtained using composite imaging. Two radiologists subjectively analyzed bronchial artery visualization with reference to the composite image. RESULTS: CT attenuation values for bronchial arteries using VMI at 40-60 keV and VMI+ at 40 keV and 50 keV were significantly higher than those obtained using composite imaging (P < 0.05). CNR using VMI at 40-60 keV was significantly higher than that obtained using composite imaging (P < 0.05), whereas no differences were noted for values obtained using composite imaging between VMI+ at 40 keV and 50 keV. In the subjective analysis, VMI at 40 keV and 50 keV yielded significantly better visibility of bronchial arteries than VMI+ (P < 0.05). CONCLUSION: VMI and VMI+ at low voltages (40-50 keV) may be useful for bronchial artery visualization. VMI+ may be less effective for fine vessels as bronchial artery visualization.

Prognostic significance of vasohibin-1 and vasohibin-2 immunohistochemical expression in gastric cancer.

PURPOSE: It was recently identified that the vasohibin family may regulate angiogenesis through suppression by the vasohibin-1 gene and promotion by the vasohibin-2 gene. We assessed vasohibin expression in gastric cancer patients and its effect on their prognosis. METHODS: We evaluated vasohibin immunohistochemical expression in 210 patients with gastric cancer, who underwent radical surgery. The patients were divided first into a vasohibin-1-positive group and a vasohibin-1-negative group, and then into groups with high or low vasohibin-2 expression, to allow us to investigate the clinicopathological factors of prognosis retrospectively. RESULTS: There were 139 patients in the vasohibin-1-positive group and 71 patients in the vasohibin-1-negative group, among which there were and 108 with high vasohibin-2 expression and 102 with low vasohibin-2 expression. Vasohibin-1 was associated with Ly (P = 0.003) and pT (P = 0.037), whereas vasohibin-2 was associated with Ly (P < 0.001), V (P < 0.001) and pStage (P < 0.001). Overall, cancer-specific and relapse-free survival rates were lower in the vasohibin-1-positive (P = 0.034, P < 0.001, P = 0.002, respectively) and high vasohibin-2 expression (P = 0.004, P = 0.003, P < 0.001, respectively) groups. Multivariate analysis revealed that vasohibin-1 expression was associated with cancer-specific (P = 0.014, hazard ratio [HR] 4.454) and relapse-free (P = 0.035, HR 2.557) survival and vasohibin-2 expression tended to influence relapse-free survival (P = 0.051, HR 2.061). Grouping patients by vasohibin expression status combinations showed correlation among their expressions (P = 0.005). Overall, cancer-specific and relapse-free survival rates were lowest in the vasohibin-1-positive and high vasohibin-2 expression group. CONCLUSION: Our findings demonstrate that vasohibin-1 and vasohibin-2 could be novel biomarkers for predicting gastric cancer prognosis.

Successful laparoscopic surgery combined with selective arterial embolization for bleeding due to jejunal angiodysplasia: a case report.

BACKGROUND: Angiodysplasia of the gastrointestinal tract is a rare vascular pathology that sometimes causes massive hemorrhage. Angiodysplasias are particularly difficult to find in the small intestine for anatomical reasons, often impeding their diagnosis and treatment. Lesion localization is a major challenge in cases of small bowel bleeding requiring surgical intervention. CASE PRESENTATION: The present case was a 52-year-old woman who was urgently hospitalized with repeated tarry stools. Surgical intervention was chosen after conservative treatment failed to improve her condition. The source of bleeding was suspected to be a vascular lesion discovered in the small intestine during a past double-balloon endoscopy. Abdominal contrast computed tomography revealed a jejunal hemorrhage. We chose selective arterial embolization to stabilize her hemodynamics followed by surgical intervention as her treatment plan. Several embolic and contrast agents (cyanoacrylate, indigo carmine, and Lipiodol) were combined to help identify the location of the lesion during surgery. This multi-pronged approach allowed us to localize the lesion under laparoscopic guidance with high confidence and accuracy, and to excise a 6-cm segment of the small intestine. The lesion was histologically diagnosed as angiodysplasia. No re-bleeding has been observed since the operation. CONCLUSION: We report our experience with a case of jejunal angiodysplasia, which was localized with selective arterial embolization using an array of embolic and contrast agents, and then excised laparoscopically. Selective arterial embolization with indigo carmine dye to treat small bowel bleeding preoperatively not only makes the surgery safer by stabilizing the patient's hemodynamics, but is also very useful for localizing the lesion intraoperatively.

[Radical Resection of a Locally Advanced Unresectable Pancreatic Adenosquamous Carcinoma after Treatment with Systemic Chemotherapy].

A 64-year-old man visited our hospital because of weight loss and after being detected with a tumor in the pancreatic body and tail on abdominal ultrasonography at a nearby hospital. Abdominal contrast-enhanced CT revealed a 45 mm tumor with celiac artery invasion in the pancreatic body and tail. This case was diagnosed as unresectable pancreatic cancer. After 2 regimens of systemic chemotherapy(5 courses of gemcitabine plus nab-paclitaxel and 2 courses of S-1), CT revealed a partial response(ie, reduction in the tumor size). Therefore, distal pancreatectomy was performed with en bloc celiac axis resection, portal vein resection, and left adrenalectomy, as well as lymph node dissection. The pathological diagnosis was adenosquamous carcinoma, and R0 resection was achieved. The histological response was Grade 1b. However, the patient developed lung metastasis 16 months after surgery and liver metastasis 18 months after surgery; he died 33 months after starting treatment.

[Multidisciplinary Therapy for Unresectable Pancreatic Cancer].

The treatment outcomes of unresectable pancreatic cancer(URPC)have improved due to the advent of gemcitabine with nab-paclitaxel(GnP)and FOLFIRINOX as first-line therapy. There have been increasing reports of URPC responding to chemotherapy or chemoradiation and that conversion surgery(CS)can help to achieve long-term survival. This study aims to assess the treatment outcomes of URPC in our department and consider CS adaptation. Thirty-six patients with URPC who were treated with GnP or FOLFIRINOX between 2015 and 2018 were included in this retrospective analysis. Thirty-five patients had GnP, while 1 patient had FOLFIRINOX. The median age of the patients was 68.0 years and included 17 males and 19 females. Twenty-eight of the tumors were located in the pancreas head and 8 in the body-tail. Twenty-one cases were locally advanced(UR-LA), and 15 cases had distant metastases(UR-M). CS was performed in 9 cases(25.0%). The 2-year survival rate for patients that underwent CS was 53.3%, and 34.1% for patients that did not undergo CS. The prognosis of patients who underwent CS tended to be better, but there was no significant difference(p=0.141). In the patients that underwent CS, there were cases of early recurrence in which the period of preoperative chemotherapy was short, and the tumor markers were not normalized. Therefore, it is thought that prolonging preoperative treatment could help to select more suitable patients for CS.