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.

Detrimental impact of late-onset pneumonia on long-term prognosis in oesophageal cancer survivors.

BACKGROUD: Oesophageal cancer patients are prone to early- and late-onset pneumonia after oesophagectomy. We aimed to investigate the incidence rate and impact on the long-term prognosis of late-onset pneumonia in oesophageal cancer survivors who survived for at least one year after oesophagectomy without cancer recurrence. METHODS: We retrospectively reviewed 233 patients with thoracic oesophageal cancer who underwent oesophagectomy with gastric conduit reconstruction between September 2009 and June 2019 at a tertiary referral hospital in Japan. Pneumonia that occurred ≥1 year after oesophagectomy was defined as late-onset pneumonia. RESULTS: Among the 185 oesophageal cancer survivors, 31 (17%) developed late-onset pneumonia. The cumulative incidence rates of late-onset pneumonia 24, 36, and 60 months after oesophagectomy were 6.4%, 10%, and 21%, respectively, whereas pneumonia recurred at 21%, 31%, and 52% within 6, 12, and 24 months, respectively, after the first pneumonia. Chronic obstructive pulmonary disease, postoperative anastomotic leakage, and loss of skeletal muscle mass were independently associated with late-onset pneumonia, and a combination of these factors further increased the risk. Late-onset pneumonia with hospitalisation had the greatest negative impact on the long-term prognosis as non-cancer deaths (HR, 21; p < 0.001), followed by recurrent late-onset pneumonia (HR, 18; p < 0.001). CONCLUSIONS: Late-onset pneumonia in oesophageal cancer survivors is significantly associated with an increased risk of recurrent infections and non-cancer deaths. Chronic obstructive pulmonary disease and postoperative muscle loss are risk factors for late-onset pneumonia, and more intensive pharmacological and nutritional interventions should be considered to improve long-term prognosis after oesophagectomy.

Reactive lymphoid hyperplasia of the liver after surgery for advanced sigmoid colon cancer: a case report.

We report a case of reactive lymphoid hyperplasia (RLH) mimicking colorectal liver metastases (CRLM) on preoperative workup that was clinically indistinguishable. A 78-year-old woman was found to have locally-advanced sigmoid cancer (T4), and then treated with radical sigmoidectomy. One year after the surgery, plain computed tomography (CT) revealed a low-density area in the right hepatic lobe. Metastatic liver tumors could not be ruled out with CT/ magnetic resonant imaging (MRI) and positron emission tomography-CT . Based on these findings, the patient was diagnosed with CRLM at S7 of the liver. The patient underwent right posterior sectionectomy. The tumor was adjacent to the right hepatic vein; however, no invasion was observed. The patient was pathologically diagnosed as having RLH. The patient showed no signs of recurrence 16 months after initial surgery. RLH is clinically indistinguishable from CRLM. Further evaluation is required to elucidate the effective strategies of detecting and treating hepatic RLH.

Combined thoracoscopic and laparoscopic surgery for epiphrenic diverticulum with associated gastroesophageal reflux disease: a case report.

BACKGROUND: Surgery is indicated for symptomatic epiphrenic esophageal diverticula. Based on the features of a case, thoracoscopic or laparoscopic approaches may be used. Epiphrenic diverticula are often associated with esophageal motility disorders, but cases of reflux esophagitis have rarely been reported. In this report, we describe a case of an epiphrenic esophageal diverticulum with reflux esophagitis, which was successfully treated by thoracoscopic diverticulectomy and laparoscopic fundoplication. CASE PRESENTATION: A 69-year-old man visited the hospital with a chief complaint of eructation and hiccup. Upper gastrointestinal endoscopy revealed a diverticulum in the left wall of the esophagus, which was 37-45 cm distal to the incisors. High-resolution manometry (HRM) showed no esophageal motility disorders. Due to the large size of the diverticulum, a thoracoscopic resection of the esophageal diverticulum was performed. Additionally, the patient had reflux esophagitis due to a hiatal hernia. The anti-reflux mechanism would be more impaired during the diverticulectomy; therefore, we decided that anti-reflux surgery should be performed simultaneously. Thoracoscopic esophageal diverticulectomy and laparoscopic Dor fundoplication were performed. The patient had an uncomplicated postoperative course and was discharged on the tenth operative day. He has been symptom-free without acid secretion inhibitors for 21 months after the surgery. CONCLUSIONS: We described a rare case of a large epiphrenic diverticulum with reflux esophagitis. A good surgical outcome was achieved by thoracoscopic resection of the diverticulum and laparoscopic Dor fundoplication.

Effective Postoperative Surveillance Protocol after Thoracoscopic Esophagectomy Focusing on Symptoms in Patients with Esophageal Cancer.

BACKGROUND: The optimal postoperative surveillance protocol after esophagectomy for patients with esophageal cancer has still not been established. We investigated the risk factors for recurrence of esophageal cancer to devise an appropriate surveillance protocol. We focused on the appearance and worsening of symptoms to determine if additional imaging examinations should be performed. STUDY DESIGN: We enrolled 416 patients with esophageal and esophagogastric junctional cancer who had undergone thoracoscopic esophagectomy at Tokai University Hospital. Outpatient visits for the patients are usually scheduled at least 4 times per year with CT imaging and blood biochemical examination. We evaluated the time to recurrence after esophagectomy, especially the correlation of this parameter with the appearance and worsening of symptoms during the postoperative outpatient follow-up. RESULTS: Of the 416 patients, recurrence occurred in 127 patients (30.5%). The median time to recurrence was 6 months after esophagectomy; recurrence occurred within 24 months in 112 patients (88%), and 51 of these patients (40%) developed some new symptom(s) (symptomatic group) before the diagnosis of recurrence. The number of patients who developed recurrence within 6 months was significantly higher in the symptomatic group compared with that in the asymptomatic group (66.7% vs 46.0%, p = 0.02). The overall survival in the symptomatic group was significantly shorter than that in the asymptomatic group (p < 0.001). CONCLUSIONS: We advocate an effective surveillance protocol depending on the appearance and worsening of symptoms to diagnose recurrence of esophageal cancer; we recommend routine imaging examinations every 6 months and clinical outpatient follow-up at even shorter intervals for the first 24 months after esophagectomy.

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 three-dimensional thoracoscope for prone position thoracoscopic esophagectomy improves mediastinal lymph node dissection and prognosis for esophageal cancer.

OBJECTIVES: This study aimed to assess the superiority of 3D flexible thoracoscope against 2D thoracoscope for lymph node dissection (LND) and prognosis for prone-position thoracoscopic esophagectomy (TE) in esophageal cancer. METHODS: Three hundred and sixty-seven esophageal cancer patients who underwent prone-position TE with 3-field LND between 2009 and 2018 were evaluated. 2D and 3D thoracoscope was used in 182 (2D group) and 185 cases (3D group), respectively. Short-term surgical outcomes, numbers of retrieved mediastinal lymph node (LN), and rates of LN recurrence were compared. Risk factors for mediastinal LN recurrence and long-time prognosis were also evaluated. RESULTS: No differences in postoperative complications were observed between the groups. The numbers of retrieved mediastinal LN were significantly higher, and the rates of LN recurrence were significantly lower in the 3D group compared to 2D group. Use of 2D thoracoscope was a significant independent factor of middle mediastinal LN recurrence by multivariable analysis. Survival was compared by cox regression analysis, and the 3D group had a significantly better prognosis than the 2D group. CONCLUSIONS: Prone position TE using 3D thoracoscope may improve the accuracy of mediastinal LND and prognosis without increasing postoperative complications for esophageal cancer.

MicroRNAs associated with postoperative outcomes in patients with limited stage neuroendocrine carcinoma of the esophagus.

Esophageal neuroendocrine carcinoma (E-NEC) is an aggressive disease with a poor prognosis. The present study aimed to assess the role of surgery in the treatment of patients with resectable E-NEC, and identify a microRNA (miRNA/miR) signature in association with positive postoperative outcomes. Between February 2017 and August 2019, 36 patients with E-NEC who underwent curative surgery at the Japan Neuroendocrine Tumor Society partner hospitals were enrolled in the study. A total of 16 (44.4%) patients achieved disease-free survival (non-relapse group), whereas 20 (55.6%) patients developed tumor relapse (relapse group) during the median follow-up time of 36.5 months (range, 1-242) after surgery with a 5-year overall survival rate of 100 and 10.8%, respectively (P<0.01). No clinicopathological parameters, such as histological type or TNM staging, were associated with tumor relapse. Microarray analysis of 2,630 miRNAs in 11 patients with sufficient quality RNA revealed 12 miRNAs (miR-1260a, -1260b, -1246, -4284, -612, -1249-3p, -296-5p, -575, -6805-3p, -12136, -6822-5p and -4454) that were differentially expressed between the relapse (n=6) and non-relapse (n=5) groups. Furthermore, the top three miRNAs (miR-1246, -1260a and -1260b) were associated with overall survival (P<0.01). These results demonstrated that surgery-based multidisciplinary treatment is effective in a distinct subpopulation of limited stage E-NEC. A specific miRNA gene set is suggested to be associated with treatment outcome.

Laparoscopic Heller myotomy and Dor fundoplication following an unsuccessful peroral endoscopic myotomy.

BACKGROUND: Achalasia is an esophageal motility disorder that presents as dysphagia and severely affects quality of life. An esophageal myotomy has been the golden standard for treatment. Peroral endoscopic myotomy (POEM) as a first-line therapy has an acceptable outcome. However, after the clinical failure of POEM, appropriate second-line therapy is rather controversial. Here, we present the first published case in English of a patient who was successfully treated using laparoscopic Heller myotomy (LHM) with Dor fundoplication following an unsuccessful POEM. CASE PRESENTATION: A 64-year-old man with type 1 achalasia who had been previously treated with POEM visited our hospital for further treatment. After undergoing LHM with Dor fundoplication, his Eckardt score improved from 3 to 0 points. On a timed barium esophagogram (TBE), the barium height improved from 119 mm/119 mm (1 min/5 min) to 50 mm/45 mm. No significant complications have occurred postoperatively for 1 year. CONCLUSION: Treating refractory achalasia is challenging, and treatment options are controversial. LHM with Dor fundoplication after POEM could be a safe and efficient option for the treatment of refractory achalasia.

Essential updates 2020/2021: Recent topics in surgery and perioperative therapy for esophageal cancer.

In this review, we focused on four topics, namely, minimally invasive esophagectomy (MIE), robot-assisted minimally invasive esophagectomy (RAMIE), conversion and salvage surgery, and neoadjuvant and adjuvant therapy, based on notable reports published in the years 2020 and 2021. It seems that while the short-term outcomes of minimally invasive Ivor Lewis esophagectomy (MIE-IL) were better than those of open Ivor Lewis esophagectomy (OE-IL), there were no significant differences in the long-term outcomes between MIE-IL and OE-IL. Similarly, the short-term outcomes of minimally invasive McKeown esophagectomy (MIE-MK) were better than those of open McKeown esophagectomy (OE-MK), while there were no significant differences in the long-term outcomes between MIE-MK and OE-MK. Furthermore, the short-term outcomes of robot-assisted minimally invasive Ivor Lewis esophagectomy (RAMIE-IL) were superior to those of completely minimally invasive Ivor Lewis esophagectomy (CMIE-IL). On the other hand, there were advantages and disadvantages in relation to the short-term outcomes of robot-assisted minimally invasive McKeown esophagectomy (RAMIE-MK) as compared with completely minimally invasive McKeown esophagectomy (CMIE-MK). However, there were no significant differences in the long-term outcomes between RAMIE-MK and CMIE-MK. Further research is needed to evaluate of short-term and long-term outcomes of transmediastinal esophagectomy with and without robotic assistance. Both induction chemotherapy and induction chemoradiotherapy appear to be promising to secure a higher rate of conversion surgery. Neoadjuvant chemoimmunotherapy and chemoimmunoradiotherapy have shown promising results and are expected as new powerful therapies.

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.

Clinical significance of sarcopenic dysphagia for patients with esophageal cancer undergoing esophagectomy: A review.

The relationships among esophagectomy for esophageal cancer, dysphagia, and sarcopenia are still unclear. We considered appropriate interventions for patients with resectable esophageal cancer for the purpose of reducing postoperative dysphagia and aspiration pneumonia. Dysphagia in patients with esophageal cancer is caused by patient characteristics, such as pathophysiology and age, or complications after esophagectomy. Recently, sarcopenic dysphagia, defined as dysphagia associated with whole-body sarcopenia, has attracted attention in various fields, and a large proportion of patients with esophageal cancer are expected to have sarcopenic dysphagia. Our systematic review and meta-analysis suggested that preoperative sarcopenia in patients with esophageal cancer is related to pulmonary complications after esophagectomy, and some reports also suggested that sarcopenia in swallowing-related muscles, such as the geniohyoid muscle and tongue, might be associated with postoperative pneumonia or dysphagia after esophagectomy. However, clinical studies on sarcopenic dysphagia in patients with esophageal cancer have been limited. To prevent sarcopenic dysphagia after esophagectomy, perioperative interventions involving not only swallowing rehabilitation, but also physical exercise and nutritional support are important. Moreover, several reports have suggested that the chin-down maneuver might be effective for preventing aspiration after an esophagectomy. To inhibit the progression of sarcopenic dysphagia after esophagectomy, evaluations and interventions by multidisciplinary staff are likely to be necessary.

Successful treatment with laparoscopic surgery and sequential multikinase inhibitor therapy for hepatocellular carcinoma: A case report.

BACKGROUND: Hepatocellular carcinoma (HCC) with massive portal vein tumor thrombosis (PVTT) and distant metastasis is considered unresectable. However, due to recent developments in systemic chemotherapy, successful cases of conversion therapy for unresectable diseases have been reported. Herein, we report a successful multidisciplinary approach for treatment of multi-visceral recurrence with sequential multikinase inhibitor and laparoscopic surgery. CASE SUMMARY: A 63-year-old woman with chronic hepatitis B virus infection was diagnosed with HCC. Subsequently, she underwent two rounds of laparoscopic partial hepatectomy, laparoscopic left adrenalectomy, and transcatheter arterial chemoembolization plus sorafenib for recurrence. Four years after initial hepatectomy, she presented with a 43-mm mass in the spleen and tumor thrombus involving the main portal vein trunk with ascites. Her liver function was Child-Pugh B (8), and protein induced by vitamin K absence or antagonist II (PIVKA II) levels were elevated up to 46.291 mAU/mL. Since initial treatment with regorafenib for three months was unsuccessful, the patient was administered lenvatinib. Ten months post-treatment, there was no contrast enhancement of PVTT or splenic metastasis. Chemotherapy was discontinued due to severe diarrhea. Afterward, splenic metastasis became viable, and PIVKA II increased. Therefore, hand-assisted laparoscopic splenectomy was performed. She experienced no clinical recurrence 14 mo after resection. CONCLUSION: Conversion surgery after successful multikinase inhibitor treatment might be considered an effective treatment option for advanced HCC.

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.

Clinicopathological features of PD-L1 protein expression, EBV positivity, and MSI status in patients with advanced gastric and esophagogastric junction adenocarcinoma in Japan.

This real-world study examined the prevalence of programmed death ligand-1 (PD-L1) expression and assessed the frequency of microsatellite instability-high (MSI-H) status and Epstein-Barr virus (EBV) positivity in Japanese patients with advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma. This multicenter (5 sites), retrospective, observational study (November 2018-March 2019) evaluated Japanese patients with advanced gastric and GEJ adenocarcinoma after surgical resection (Stage II/III at initial diagnosis) or unresectable advanced cancer (Stage IV). The primary objectives were prevalence of PD-L1 expression (combined positive score [CPS] ≥1), MSI status, and EBV positivity. Tumor specimens of 389/391 patients were analyzed (male, 67.1%; mean age, 67.6 ± 12.2 years); 241/389 (62%) were PD-L1 positive, 24/379 (6.3%) had MSI-H tumors, and 13/389 (3.3%) were EBV positive. PD-L1 expression was higher in tumor-infiltrating immune cells than in tumor cells for lower CPS cutoffs. Among patients with MSI-H tumors and EBV-positive tumors, 19/24 (79.2%) and 9/13 (69.2%), respectively, were PD-L1 positive. A greater proportion of patients with MSI-H tumors (83.3% [20/24]) were PD-L1 positive than those with MSI-low/stable tumors (60.8% [216/355]; p = .0297); similarly, an association was observed between history of H pylori infection and PD-L1 expression. A higher proportion of patients with MSI-H tumors demonstrated PD-L1 expression with a CPS ≥10 (66.7% [16/24]) vs those with MSI-low/stable tumors (24.8% [88/355]; p < .0001). The prevalence of PD-L1 positivity among Japanese patients was comparable to that in previous pembrolizumab clinical trials and studies in gastric cancer. Particularly, higher PD-L1 expression was observed in MSI-H tumors.

Impact of Reconstruction Route on Postoperative Morbidity After Esophagectomy: Analysis of Esophagectomies in the Japanese National Clinical Database.

BACKGROUND: Esophagectomy followed by gastric conduit reconstruction is a standard surgical procedure for esophageal cancer. However, there is no evidence of the superiority or inferiority of the posterior mediastinal (PM) versus the retrosternal (RS) reconstruction route with regard to short-term outcomes after esophagectomy. We aimed to elucidate whether the reconstruction route can affect the short-term outcomes after esophagectomy followed by gastric conduit reconstruction. METHODS: We reviewed the clinical data of patients who underwent esophagectomy between 2016 and 2018 from the Japanese National Clinical Database. This study included 9786 patients who underwent gastric conduit reconstruction through the PM or RS route with cervical anastomosis. RESULTS: Of the 9786 patients analyzed, 3478 and 6308 underwent gastric conduit reconstruction thorough the PM and RS routes, respectively. The incidence of anastomotic leak and surgical site infection (SSI) was significantly lower in the PM group than in the RS group (11.7% vs 13.8%, P = .005 and 8.4% vs 14.9%, P < .001, respectively), while the incidence of pneumonia was higher in the PM group (13.7% vs 12.2%, P = .040). Generalized estimating equation logistic regression analysis revealed a higher risk of anastomotic leak and SSI (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.15-1.51; P < .001 and OR, 2.06; 95% CI, 1.78-2.38; P < .001, respectively) and a lower risk of pneumonia (OR, 0.86; 95% CI, 0.75-0.98; P = .028) in the RS group than in the PM group. CONCLUSION: The findings of this study will help surgeons to design the reconstruction route following esophagectomy.

Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2021.

In Japan, with the increasing prevalence of gastroesophageal reflux disease (GERD) and growing public interest, the Japanese Society of Gastroenterology issued Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009 and a revised 2nd edition in 2015. A number of studies on GERD were subsequently conducted in Japan and abroad, and vonoprazan, a potassium-competitive acid blocker (P-CAB), became available for the first time in Japan in February 2015. The revised 3rd edition (Japanese edition), which incorporates new findings and information, was published in April 2021. These guidelines are summarized herein, particularly sections related to the treatment of GERD. The important clinical issues addressed in the present revision are (i) the introduction of treatment algorithms that classify GERD into reflux esophagitis and non-erosive reflux disease, (ii) the clarification of treatment algorithms based on to the severity of reflux esophagitis, and (iii) the positioning of vonoprazan in the treatment for GERD. The present guidelines propose vonoprazan as the initial/maintenance treatment for severe reflux esophagitis. They also recommend vonoprazan or PPI as an initial treatment for mild reflux esophagitis and recommended PPI and proposed vonoprazan as maintenance treatment. These updated guidelines offer the best clinical strategies for GERD patients in Japan and hope that they will be of global use for the diagnosis and treatment for GERD.

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.

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.