Laparoscopic repair of gastric conduit obstruction after robot-assisted minimally invasive esophagectomy: a case report.

BACKGROUND: Gastric conduit obstruction (GCO) is a known complication after esophagectomy. Laparoscopic revision surgery for GCO is relatively rare, with limited reports in the literature. Here, we report a case of GCO after robot-assisted subtotal esophagectomy and posterior mediastinal gastric conduit reconstruction, which was successfully repaired laparoscopically. CASE PRESENTATION: A 66-year-old man presented with a passage disorder that became noticeable 14 months after surgery. Fluid passage was difficult, and the patient opted for revision surgery. The conduit had entered and deflected into the mediastinum; it also twisted due to band formation. The revision surgery was performed laparoscopically through five ports. The bands were dissected, esophageal hiatus was sutured, and conduit re-fixed. The intraoperative endoscopy was used to confirm that the obstruction had been released. The lack of adhesion of the posterior half of the gastric conduit wall, combined with postoperative weight loss leading to a decrease in omental volume, as well as inadequate fixation during the initial surgery, are believed to have contributed to the ease of the conduit deviation into the intrathoracic cavity. In addition, the twisting of the conduit due to band formation exacerbated the obstruction. CONCLUSIONS: Laparoscopic revision surgery may become an effective treatment option as the number of minimally invasive esophagectomies is expected to increase in the future. Furthermore, the fixation method during initial surgery should be carefully considered and optimized to prevent gastric conduit obstruction. Additionally, the use of intraoperative endoscopy to evaluate the lumen of the conduit during surgery proved beneficial in this case, highlighting its potential value in identifying and addressing obstruction.

Perioperative gum-chewing training prevents a decrease in tongue pressure after esophagectomy in thoracic esophageal cancer patients: a nonrandomized trial.

Tongue pressure (TP) decreases significantly after esophagectomy in esophageal cancer patients (ECPs). Meanwhile, 2 weeks of gum-chewing training (GCT) significantly increased TP in healthy university students. We examined whether perioperative GCT would decrease the proportion of patients exhibiting a decline in TP at 2 weeks postoperatively, and prevent postoperative complications, in thoracic ECPs (TECPs). This was a single-center interventional study, and nonrandomized study with a historical control group (HCG). TECPs who underwent first-stage radical esophagectomy were recruited. Thirty-two patients of 40 in the gum-chewing group (GCG) were completed perioperative GCT in 3 times daily. Propensity score matching was performed with covariates related to TP including preoperative age, sex, body mass index, and the repetitive saliva swallowing test result, and yielded a matched cohort of 25 case pairs. Eleven GCG patients [44.0%] exhibited significantly lower TP at 2 weeks postoperatively than before esophagectomy was significantly fewer than that of 19 patients [76.0%] in the HCG. The median number of fever days (> 38 °C) in the 2 weeks after esophagectomy in the GCG was significantly fewer than those in the HCG. Perioperative GCT may prevent postoperative TP decline and postoperative dysphagia-related complications after esophagectomy.

A 72-Year-Old Diabetic Man with Carcinoma of the Ileocecal Region, Sepsis Due to Klebsiella pneumoniae, and Hepatic Portal Venous Gas.

BACKGROUND Gas in the portal venous system, or hepatic portal venous gas, is a rare occurrence associated with ischemic colitis, inflammatory bowel disease, or any cause of bowel perforation, including from a necrotic tumor. This report presents the case of a 72-year-old man with diabetes who had carcinoma of the ileocecal region, sepsis due to Klebsiella pneumoniae, and hepatic portal venous gas. CASE REPORT A 72-year-old man with ileocecal cancer was admitted to our hospital for preoperative diabetes control. He developed a fever and septic shock, without abdominal symptoms or signs of peritoneal irritation. Klebsiella pneumoniae was detected in blood cultures. Abdominal ultrasonography showed hepatic portal venous gas, and a simple computed tomography scan revealed gas in the vasculature and hepatic portal vein in the lateral segment, which led us to believe that the ileocecal mass was the source of infection, and emergency surgery was performed. The patient was discharged from the hospital on postoperative day 34 with good progress despite dehydration due to high-output syndrome. CONCLUSIONS Sepsis due to necrosis of ileocecal cancer is often difficult to diagnose because it is not accompanied by abdominal symptoms, as in our case. However, abdominal ultrasound is useful because it allows for a broad evaluation. This report has demonstrated and highlighted that the findings of hepatic portal venous gas on imaging should be regarded seriously, requiring urgent investigation to identify the cause and commence treatment in cases of infection or sepsis.

Gastric Emphysema Related to Percutaneous Endoscopic Gastrostomy After Two-Stage Esophagectomy: A Report of Two Cases.

Patients with esophageal cancer who have severe complications such as diabetes sometimes require two-stage surgery. Herein, we describe two cases of gastric emphysema that were treated at our facility after the patients had previously undergone minimally invasive esophagectomy as the first-stage surgical treatment of esophageal cancer. Case 1: A 72-year-old man with a history of diabetes mellitus (DM) was diagnosed with esophageal cancer and an esophageal obstruction and subsequently underwent percutaneous endoscopic gastrostomy (PEG) placement followed by neoadjuvant chemoradiotherapy. The treatment efficacy was good; once the tumor was deemed resectable, the patient underwent robot-assisted minimally invasive esophagectomy and cervical esophagostomy placement as the first stage of surgical treatment. The patient had a good postoperative course and was discharged on postoperative day (POD) 10. However, on POD 16, he returned to the hospital with abdominal distension. Computed tomography (CT) revealed gastric emphysema and hepatic portal vein gas. Conservative treatment was initiated as there were no signs of peritoneal irritation. An upper gastrointestinal (GI) series revealed delayed gastric emptying (DGE); therefore, replacement of the PEG with a percutaneous endoscopic gastrojejunostomy (PEG-J) was necessary. On POD 42, the patient underwent reconstructive surgery as the second-stage surgical treatment of esophageal cancer. Case 2: A 74-year-old man had a history of DM, chronic renal failure, and PEG placement for dysphagia caused by left recurrent nerve palsy after thoracic aortic aneurysm surgery. The patient underwent a thoracoscopic esophagectomy with cervical esophagostomy placement as the first-stage surgical treatment of esophageal cancer. On POD 6, the patient developed abdominal distension, his CT showed gastric emphysema. An upper GI series was performed, which showed DGE. After conservative treatment and improvement in his general condition, the patient underwent a jejunostomy placement on POD 30. Both patients developed gastric emphysema related to PEG placement after undergoing esophagectomy as the first-stage surgical treatment of esophageal cancer. Additionally, both patients had a history of DM. Gastric emphysema, which is thought to be caused by increased intragastric pressure due to postoperative DGE, developed within 30 days of undergoing minimally invasive esophagectomy in both patients. Therefore, the rate of nutrient administration and symptoms should be carefully monitored during the postoperative management of patients with these characteristics.

Subtotal esophagectomy and concurrent reconstruction with free jejunal flap for primary esophageal cancer after pancreatoduodenectomy.

BACKGROUND: Pancreatoduodenectomy and subtotal esophagectomy are widely considered the most invasive and difficult surgical procedures in gastrointestinal surgery. Subtotal esophagectomy after pancreatoduodenectomy is expected to be extremely difficult due to complicated anatomical changes, and selecting an appropriate intestinal reconstruction method will also be a difficult task. Therefore, perhaps because the method is considered impossible, there have been few reports of subtotal esophagectomy after pancreatoduodenectomy. CASE PRESENTATION: A 73-year-old man with a history of pancreatoduodenectomy was diagnosed with superficial thoracic esophageal squamous cell carcinoma. Definitive chemoradiation therapy was recommended at another hospital; however, he visited our department to undergo surgery. We performed the robot-assisted thoracoscopic subtotal esophagectomy. There were some difficulties with the reconstruction: the gastric tube could not be used, the reconstruction was long, and the organs reconstructed in the previous surgery had to be preserved. However, the concurrent reconstruction was achieved with the help of a free jejunal flap and vascular reconstruction. All reconstructions from the previous surgery, including the remnant stomach, were preserved via regional abdominal lymph node dissection. After reconstruction, intravenous indocyanine green showed that circulation in the reconstructed intestines was preserved. On postoperative day 1, no recurrent nerve paralysis was observed during laryngoscopy. The patient could start oral intake smoothly 2 weeks after surgery and did not exhibit any postoperative complications related to the reconstruction. The patient was transferred to another hospital on postoperative day 21. CONCLUSIONS: Owing to the free jejunal flap interposition method, we safely performed one stage subtotal esophagectomy and concurrent reconstruction, preservation of the remnant stomach, and pancreaticobiliary reconstruction in patients with a history of pancreatoduodenectomy. We believe that this method is acceptable and useful for patients undergoing complicated reconstruction.

Japanese Classification of Esophageal Cancer, 12th Edition: Part I.

This is the first half of English edition of Japanese Classification of Esophageal Cancer, 12th Edition that was published by the Japan Esophageal Society in 2022.

Near-infrared Photoimmunotherapy Targeting Cancer-Associated Fibroblasts in Patient-Derived Xenografts Using a Humanized Anti-Fibroblast Activation Protein Antibody.

Esophageal cancer remains a highly aggressive malignancy with a poor prognosis, despite ongoing advancements in treatments such as immunotherapy. The tumor microenvironment, particularly cancer-associated fibroblasts (CAF), plays a crucial role in driving the aggressiveness of esophageal cancer. In a previous study utilizing human-derived xenograft models, we successfully developed a novel cancer treatment that targeted CAFs with near-infrared photoimmunotherapy (NIR-PIT), as an adjuvant therapy. In this study, we sought to translate our findings toward clinical practice by employing patient-derived xenograft (PDX) models and utilizing humanized mAbs, specifically sibrotuzumab, which is an antihuman fibroblast activation protein (FAP) Ab and already being investigated in clinical trials as monotherapy. PDX models derived from patients with esophageal cancer were effectively established, preserving the expression of key biomarkers such as EGFR and FAP, as observed in primary tumors. The application of FAP-targeted NIR-PIT using sibrotuzumab, conjugated with the photosensitizer IR700DX, exhibited precise binding and selective elimination of FAP-expressing fibroblasts in vitro. Notably, in our in vivo investigations using both cell line-derived xenograft and PDX models, FAP-targeted NIR-PIT led to significant inhibition of tumor progression compared with control groups, all without inducing adverse events such as weight loss. Immunohistologic assessments revealed a substantial reduction in CAFs exclusively within the tumor microenvironment of both models, further supporting the efficacy of our approach. Thus, our study demonstrates the potential of CAF-targeted NIR-PIT employing sibrotuzumab as a promising therapeutic avenue for the clinical treatment of patients with esophageal cancer.

Japanese Classification of Esophageal Cancer, 12th Edition: Part II.

This is the second half of English edition of Japanese Classification of Esophageal Cancer, 12th Edition that was published by the Japan Esophageal Society in 2022.

PD-L1-expressing cancer-associated fibroblasts induce tumor immunosuppression and contribute to poor clinical outcome in esophageal cancer.

The programmed cell death 1 protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays a crucial role in tumor immunosuppression, while the cancer-associated fibroblasts (CAFs) have various tumor-promoting functions. To determine the advantage of immunotherapy, the relationship between the cancer cells and the CAFs was evaluated in terms of the PD-1/PD-L1 axis. Overall, 140 cases of esophageal cancer underwent an immunohistochemical analysis of the PD-L1 expression and its association with the expression of the α smooth muscle actin, fibroblast activation protein, CD8, and forkhead box P3 (FoxP3) positive cells. The relationship between the cancer cells and the CAFs was evaluated in vitro, and the effect of the anti-PD-L1 antibody was evaluated using a syngeneic mouse model. A survival analysis showed that the PD-L1+ CAF group had worse survival than the PD-L1- group. In vitro and in vivo, direct interaction between the cancer cells and the CAFs showed a mutually upregulated PD-L1 expression. In vivo, the anti-PD-L1 antibody increased the number of dead CAFs and cancer cells, resulting in increased CD8+ T cells and decreased FoxP3+ regulatory T cells. We demonstrated that the PD-L1-expressing CAFs lead to poor outcomes in patients with esophageal cancer. The cancer cells and the CAFs mutually enhanced the PD-L1 expression and induced tumor immunosuppression. Therefore, the PD-L1-expressing CAFs may be good targets for cancer therapy, inhibiting tumor progression and improving host tumor immunity.

Stroke volume variation and dynamic arterial elastance predict fluid responsiveness even in thoracoscopic esophagectomy: a prospective observational study.

PURPOSE: It remains unknown whether stroke volume variation (SVV), pulse pressure variation (PPV), and dynamic arterial elastance (Eadyn) are suitable for monitoring fluid management during thoracoscopic esophagectomy (TE) in the prone position with one-lung ventilation and artificial pneumothorax. Our study aimed to evaluate the accuracy of SVV, PVV, and Eadyn in predicting the fluid responsiveness in these patients. METHODS: We recruited 24 patients who had undergone TE. Patients with a mean arterial blood pressure ≤ 65 mmHg received a 200-ml bolus of 6% hydroxyethyl starch over 10 min. Fluid responders showed the stroke volume index ≥ 15% 5 min after the fluid bolus. Receiver operating characteristic (ROC) curves were generated and area under the ROC curve (AUROC) was calculated. RESULTS: We obtained 61 fluid bolus data points, of which 20 were responders and 41 were non-responders. The median SVV before the fluid bolus in responders was significantly higher than that in non-responders (18% [interquartile range (IQR) 13-21] vs. 12% [IQR 8-15], P = 0.001). Eadyn was significantly lower in responders than in non-responders (0.55 [IQR 0.45-0.78] vs. 0.91 [IQR 0.67-1.00], P < 0.001). There was no difference in the PPV between the groups. The AUROC was 0.76 for SVV (95% confidence interval [CI] 0.62-0.89, P = 0.001), 0.56 for PPV (95% CI 0.41-0.71, P = 0.44), and 0.82 for Eadyn (95% CI 0.69-0.95, P < 0.001). CONCLUSIONS: SVV and Eadyn are reliable parameters for predicting fluid responsiveness in patients undergoing TE.

Adenocarcinoma arising from widespread heterotopic gastric mucosa in the cervicothoracic esophagus: a case report.

BACKGROUND: In Japan, about 6% of esophageal cancers are adenocarcinomas, although most of them arise from Barrett's epithelium. Adenocarcinoma arising from heterotopic gastric mucosa (HGM) is very rare. Due to its rarity, there is no unified view on its treatment strategy and prognosis. CASE PRESENTATION: A 57-year-old man presented with a protruding lesion in the cervicothoracic esophagus that was detected by an upper gastrointestinal series at a medical checkup. Esophagoscopy revealed a 30 mm Type 1 tumor circumferentially surrounded by widespread HGM. Computed tomography (CT) and fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT showed no metastasis or invasion of the surrounding organs. We diagnosed the lesion as cT2N0M0 cStageIIB [Union for International Cancer Control (UICC) 8th Ed] cancer and performed subtotal esophagectomy with three-field lymph node dissection. The tumor was determined to be a well-differentiated adenocarcinoma arising from HGM, with deep invasion of the submucosa. The patient underwent no adjuvant therapy and has currently survived without any evidence of recurrence for 15 months. CONCLUSIONS: Although the treatment for adenocarcinoma arising from HGM is basically the same as that for squamous cell carcinoma (SCC) of the esophagus, it is important to determine the treatment strategy based on the characteristics of the adenocarcinoma arising from HGM.

Safe and curative modified two-stage operation for T4 esophageal cancer after definitive chemoradiotherapy: a case report.

BACKGROUND: The prognosis of esophageal cancer (EC) with organ invasion is extremely poor. In these cases, definitive chemoradiotherapy (CRT) followed by salvage surgery can be planned; however, the issue of high morbidity and mortality rates persists. Herein, we report the long-term survival of a patient with EC and T4 invasion who underwent a modified two-stage operation after definitive CRT. CASE PRESENTATION: A 60-year-old male presented with type 2 upper thoracic EC with tracheal invasion. First, definitive CRT was performed, which resulted in tumor shrinkage and improvement in the tracheal invasion. However, an esophagotracheal fistula subsequently developed, and the patient was treated with fasting and antibiotics. Although the fistula recovered, severe esophageal stenoses made oral intake impossible. To improve quality of life and cure the EC, a modified two-stage operation was planned. In the first surgery, an esophageal bypass was performed using a gastric tube with cervical and abdominal lymph node dissections. After confirming improved nutritional status and absence of distant metastasis, the second surgery was performed with subtotal esophagectomy, mediastinal lymph node dissection, and tracheobronchial coverage of the fistula. The patient discharged without major complications after radical resection and has been recurrence-free for 5 years since the start of treatment. CONCLUSION: A standard curative strategy could be difficult for EC with T4 invasion due to differences in the invaded organs, presence of complications, and patient condition. Therefore, patient-tailored treatment plans are needed, including a modified two-stage operation.

Assessing the Role of Perioperative Nutritional Education in Improving Oral Intake after Oesophagectomy: A Retrospective Study.

BACKGROUND: This study aimed to determine whether nutritional education, from the preoperative to postoperative period, and nutritional management designed to improve nutritional status alone, could improve patients' health-related self-management and nutritional management skills during the postoperative period. METHODS: We evaluated 101 hospitalised patients with oesophageal cancer who underwent surgery between 2015 and 2016 and received perioperative nutritional education (PERIO-N). The control group included 52 patients who underwent surgery between 2014 and 2015 and were supported only by normal interventions according to the Enhanced Recovery After Surgery protocol. The PERIO-N group paid specific attention to nutrition risk screening, nutrition assessment, nutrition monitoring, and lifestyle education. RESULTS: The patients in the PERIO-N group were 1.8 times more likely to be able to consume food orally than the control group (p=0.010). In the PERIO-N group, 50.5% of the patients could orally consume food, 42.6% received a combination of oral and enteral nutrition, and 6.9% only underwent enteral nutrition. In comparison, in the control group, 28.8% of the patients could orally consume food, 53.8% received a combination of oral and enteral nutrition, and 17.3% were only administered enteral nutrition (p=0.004). In addition, patients in the PERIO-N group were discharged at a 1.5 times higher rate than those in the control group (p=0.027). The readmission rate for malnutrition within 3 months was 4% in the PERIO group (5.4% for home discharge only) and 5.8% in the control group (10.5% for home discharge only) (p=0.61). CONCLUSION: This study found that perioperative nutrition education in patients who underwent oesophageal cancer surgery led to increase in the amount of oral intake at discharge. Moreover, the group that received nutrition education did not have an increased probability of hospitalisation due to the risk of malnutrition within 3 months after discharge.

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.

Cadaver surgical training and research using donated cadavers in the field of surgery in Japan: an overview of reports from 2012 to 2021.

PURPOSE: Subsequent to the publication of "Guidelines for cadaver dissection in education and research of clinical medicine" in 2012, cadaver surgical training (CST) was implemented in various surgical fields across Japan. This article summarizes the recent progress made in the implementation of CST using donated cadavers, and its associated research, focusing on the field of surgery, and discusses its future direction. METHODS: All reports from 2012 to 2021 registered with the CST Promotion Committee of the Japan Surgical Society were analyzed. There were 292 (24.9%) programs in the field of surgery, including acute care surgery, out of a total of 1173 programs overall. Data were classified by the purpose of implementations and fields of surgery, with subclassification by organ, costs and participation fees. RESULTS: CST and its research were introduced in 27 (33.3%) of a total 81 universities. The total number of participants was 5564 and the major (80%) purpose of the program was to advance surgical techniques. When classified by objectives, 65, 59 and 11% were for mastering operations for malignant disease, minimally invasive surgery, and transplantation surgery, respectively. CONCLUSION: CST in the field of surgery is increasing progressively in Japan, but still with disproportionate dissemination. Further efforts are needed to achieve full adoption.

Overcoming cancer-associated fibroblast-induced immunosuppression by anti-interleukin-6 receptor antibody.

Cancer-associated fibroblasts (CAFs) are a critical component of the tumor microenvironment and play a central role in tumor progression. Previously, we reported that CAFs might induce tumor immunosuppression via interleukin-6 (IL-6) and promote tumor progression by blocking local IL-6 in the tumor microenvironment with neutralizing antibody. Here, we explore whether an anti-IL-6 receptor antibody could be used as systemic therapy to treat cancer, and further investigate the mechanisms by which IL-6 induces tumor immunosuppression. In clinical samples, IL-6 expression was significantly correlated with α-smooth muscle actin expression, and high IL-6 cases showed tumor immunosuppression. Multivariate analysis showed that IL-6 expression was an independent prognostic factor. In vitro, IL-6 contributed to cell proliferation and differentiation into CAFs. Moreover, IL-6 increased hypoxia-inducible factor 1α (HIF1α) expression and induced tumor immunosuppression by enhancing glucose uptake by cancer cells and competing for glucose with immune cells. MR16-1, a rodent analog of anti-IL-6 receptor antibody, overcame CAF-induced immunosuppression and suppressed tumor progression in immunocompetent murine cancer models by regulating HIF1α activation in vivo. The anti-IL-6 receptor antibody could be systemically employed to overcome tumor immunosuppression and improve patient survival with various cancers. Furthermore, the tumor immunosuppression was suggested to be induced by IL-6 via HIF1α activation.

Incidence of Metachronous Remnant Gastric Cancer after Proximal Gastrectomy with the Double-flap Technique (rD-FLAP-rGC Study): A Multicenter, Retrospective Study.

BACKGROUND: Although proximal gastrectomy (PG) with the double-flap technique (DFT) is a function-preserving surgery that prevents esophagogastric reflux, there is a risk of developing metachronous remnant gastric cancer (MRGC). Moreover, details of MRGC and appropriate postoperative follow-up after PG with DFT are unclear. METHODS: We reviewed the medical records of 471 patients who underwent PG with DFT for cancer in a preceding, multicenter, retrospective study (rD-FLAP Study). We investigated the incidence of MRGC, frequency of follow-up endoscopy, and eradication of Helicobacter pylori (H. pylori) infection. RESULTS: MRGC was diagnosed in 42 (8.9%) of the 471 patients, and 56 lesions of MRGC were observed. The cumulative 5- and 10-year incidence rates were 5.7 and 11.4%, respectively. There was no clinicopathological difference at the time of primary PG between patients with and without MRGC. Curative resection for MRGC was performed for 49 (88%) lesions. All patients with a 1-year, follow-up, endoscopy interval were diagnosed with early-stage MRGC, and none of them died due to MRGC. Overall and disease-specific survival rates did not significantly differ between patients with and without MRGC. The incidence rate of MRGC in the eradicated group after PG was 10.8% and that in the uneradicated group was 19.6%, which was significantly higher than that in patients without H. pylori infection at primary PG (7.6%) (p = 0.049). CONCLUSIONS: The incidence rate of MRGC after PG with DFT was 8.9%. Early detection of MRGC with annual endoscopy provides survival benefits. Eradicating H. pylori infection can reduce the incidence of MRGC.

Case of robot-assisted salvage surgery for esophageal cancer with a mediastinal fistula after definitive chemoradiotherapy.

Salvage surgery for esophageal cancer after definitive chemoradiotherapy (dCRT) is effective, but it is associated with a high rate of perioperative complications. The indications for robot-assisted minimally invasive esophagectomy (RAMIE) are expanding. However, there are few reports of salvage RAMIE. A 73-year-old man was referred to our hospital for residual esophageal cancer with a mediastinal fistula after dCRT. The perioperative diagnosis was T3N1M0-Stage III, and the salvage RAMIE was performed. Although the dissection was difficult due to fibrosis caused by dCRT and the esophageal mediastinal fistula, RAMIE was performed safely with no complications. Multiple features of RAMIE contributed to stable surgery. The monopolar dissection is effective for hard scar tissue caused by CRT and inflammation.

First-line nivolumab plus ipilimumab or chemotherapy versus chemotherapy alone in advanced esophageal squamous cell carcinoma: a Japanese subgroup analysis of open-label, phase 3 trial (CheckMate 648/ONO-4538-50).

BACKGROUND: Programmed cell death 1 (PD-1)-based treatments are approved for several cancers. CheckMate 648, a global, phase 3 trial, showed that first-line nivolumab (anti-PD-1 antibody) plus ipilimumab (NIVO + IPI) or nivolumab plus chemotherapy (NIVO + Chemo) significantly increased survival in advanced esophageal squamous cell carcinoma (ESCC) without new safety signals versus chemotherapy alone (Chemo). METHODS: We evaluated the Japanese subpopulation of CheckMate 648 (n = 394/970), randomized to receive first-line NIVO + IPI, NIVO + Chemo, or Chemo. Efficacy endpoints included overall survival (OS) and progression-free survival assessed by blinded independent central review in Japanese patients with tumor-cell programmed death-ligand 1 (PD-L1) expression ≥ 1% and in all randomized Japanese patients. RESULTS: In the Japanese population, 131, 126, and 137 patients were treated with NIVO + IPI, NIVO + Chemo, and Chemo, and 66, 62, and 65 patients had tumor-cell PD-L1 ≥ 1%, respectively. In patients with tumor-cell PD-L1 ≥ 1%, median OS was numerically longer with NIVO + IPI (20.2 months; hazard ratio [95% CI], 0.46 [0.30-0.71]) and NIVO + Chemo (17.3 months; 0.53 [0.35-0.82]) versus Chemo (9.0 months). In all randomized patients, median OS was numerically longer with NIVO + IPI (17.6 months; 0.68 [0.51-0.92]) and NIVO + Chemo (15.5 months; 0.73 [0.54-0.99]) versus Chemo (11.0 months). Grade 3-4 treatment-related adverse events were reported in 37%, 49%, and 36% of all patients in the NIVO + IPI, NIVO + Chemo, and Chemo arms, respectively. CONCLUSION: Survival benefits with acceptable tolerability observed for NIVO + IPI and NIVO + Chemo treatments strongly support their use as a new standard first-line treatment in Japanese patients with advanced ESCC. GOV ID: NCT03143153.