Prognostic Impact of Serum SCC Antigen in the 566 Upfront Surgery Group of Esophageal Squamous Cell Carcinoma: A Multi-Institutional Study of the Japan Esophageal Society.

PURPOSE: This study aimed to determine the clinicopathologic and prognostic significance of squamous cell carcinoma antigen (SCC-Ag) in patients with esophageal SCC who underwent radical surgery without neoadjuvant therapy. METHODS: This study included 566 patients with primary esophageal SCC who underwent radical resection without neoadjuvant therapy at 15 Japanese hospitals between 2008 and 2016. The cutoff value of SCC-Ag was 1.5 ng/mL based on the receiver operating characteristic curves. Preoperative SCC-Ag and postoperative SCC-Ag were analyzed to evaluate clinicopathological and prognostic significance. Survival curves were compared between the SCC-Ag-positive group and the SCC-Ag-negative group. The prognostic impact of SCC-Ag was evaluated using univariate and multivariate analyses. RESULTS: The preoperative SCC-Ag-positive rate was 23.5% (133/566). SCC-Ag-positive status was significantly associated with old age (p = 0.042), tumor depth (p <0.001), and tumor stages (p <0.001). The preoperative SCC-Ag-positive group had significantly poorer overall survival than the SCC-Ag-negative group (p = 0.030), but it was not an independent predictor of poor prognosis. Postoperative SCC-Ag-positive status was an independent risk factor for poor overall survival (p = 0.034). CONCLUSION: Both pre- and postoperative SCC-Ag-positive statuses were significantly associated with poor prognosis. Postoperative SCC-Ag-positive status was an independent risk factor for predicting overall survival.

Surgical outcomes of reconstruction using the gastric tube and free jejunum for cervical esophageal cancer: analysis using the National Clinical Database of Japan.

BACKGROUND: Cervical esophageal cancer accounts for a small proportion of all esophageal cancers. Therefore, studies examining this cancer include a small patient cohort. Most patients with cervical esophageal cancer undergo reconstruction using a gastric tube or free jejunum after esophagectomy. We examined the current status of postoperative morbidity and mortality of cervical esophageal cancer based on big data. METHODS: Based on the Japan National Clinical Database, 807 surgically treated patients with cervical esophageal cancer were enrolled between January 1, 2016, and December 31, 2019. Surgical outcomes were retrospectively reviewed for each reconstructed organ using gastric tubes and free jejunum. RESULTS: The incidence of postoperative complications related to reconstructed organs was higher in the gastric tube reconstruction (17.9%) than in the free jejunum (6.7%) for anastomotic leakage (p < 0.01), but not significantly different for reconstructed organ necrosis (0.4% and 0.3%, respectively). The incidence rates of overall morbidity, pneumonia, 30-day reoperation, tracheal necrosis, and 30-day mortality using these reconstruction methods were 64.7% and 59.7%, 16.7% and 11.1%, 9.3% and 11.4%, 2.2% and 1.6%, and 1.2% and 0.0%, respectively. Only pneumonia was more common in the gastric tube reconstruction group (p = 0.03), but was not significantly different for any other complication. CONCLUSIONS: The incidence of overall morbidities and reoperation, especially anastomotic leakage after gastric tube reconstruction, suggested a necessity for further improvement. However, the incidence of fatal complications, such as tracheal necrosis or reconstructed organ necrosis, was low for both reconstruction methods, and the mortality rate was acceptable as a means of radical treatment.

A survey of the clinical outcomes of cervical esophageal carcinoma surgery focusing on the presence or absence of laryngectomy using the National Clinical Database in Japan.

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

Prognostic impact of carcinoembryonic antigen in 1822 surgically treated esophageal squamous cell carcinoma: multi-institutional study of the Japan Esophageal Society.

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

Prognostic Impact of Pretreatment Serum CYFRA Status in 1047 Patients with Esophageal Squamous Cell Carcinoma Who Underwent Radical Resection: A Japan Esophageal Society Promotion Research.

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

Effect of adding magnifying BLI, magnifying NBI, and iodine staining to white light imaging in diagnosis of early esophageal cancer.

Background and study aims We investigated the effect of adding magnifying blue laser imaging (BLI), magnifying narrow-band imaging (NBI), and iodine staining to white light imaging in diagnosis of early esophageal squamous cell carcinoma (EESCC) in high-risk patients. Patients and methods Between May 2013 and March 2016, two parallel prospective cohorts of patients received either primary WLI followed by NBI-magnifying endoscopy (ME) or primary WLI followed by BLI-ME, were studied. At the end of screening, both groups underwent iodine staining. The percentage of patients with newly detected esophageal malignant lesions in each group and the diagnostic ability of image-enhanced endoscopy (IEE)-ME were evaluated. Results There are 258 patients assigned to the NBI-ME group and 254 patients assigned to the BLI-ME group. The percentage of patients with one or more malignant lesions detected in the WLI + NBI-ME examination was similar in the WLI + BLI-ME examination (15 of 258 patients or 5.81 % vs. 14 of 254 patients or 5.51 %). However, four of 19 lesions in the NBI-ME group and six of 21 lesions in the BLI-ME group were overlooked and were detected by iodine staining. NBI-ME and BLI-ME showed similar accuracy in differentiation of cancerous lesions from non-cancerous lesions in diagnosis of EESCC (NBI/BLI: sensitivity, 87.5/89.5; specificity, 78.9/76.6; accuracy, 80.8/79.5; positive predictive value, 53.8/53.1; negative predictive value, 95.7/96.1). Conclusions Both NBI and BLI were useful for detection of EESCC. However, because some lesions were overlooked by even NBI and BLI, high-risk patients may benefit from use of iodine staining during endoscopic screening of EESCC (UMIN000023596).

Identification of PDHX as a metabolic target for esophageal squamous cell carcinoma.

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

The evaluation of the gastric tube blood flow by indocyanine green fluorescence angiography during esophagectomy: a multicenter prospective study.

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

Histological study of the thin membranous dense connective tissue around the middle and lower thoracic esophagus, caudal to the bifurcation of the trachea.

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

Histological changes in the human esophagus following triamcinolone injection to prevent esophageal stricture after endoscopic submucosal dissection.

BACKGROUND: Locoregional steroid injection prevents post-endoscopic submucosal dissection (ESD) esophageal stricture, but histological changes that occur following steroid injection in the human esophagus are unclear. This study investigated the histopathological characteristics caused by locoregional triamcinolone acetonide (TA) injection using human esophagectomy specimens. METHODS: From January 2014 to December 2019, among 297 patients (373 lesions) who underwent esophageal ESD, 13 patients who underwent additional esophagectomy after ESD were examined. Seven patients (TA group) with wide excisions were injected with TA after ESD and another six patients (Non-TA group) with smaller tumors were not injected with TA. The clinical background of these patients and histopathological features of ESD ulcer scar obtained from esophagectomy specimens were retrospectively investigated. RESULTS: The circumferential rate of ESD excision was more than three-quarters in all cases in the TA group, whereas it was less than three-quarters in the Non-TA group. No other statistical difference in the clinical background was found between the two groups. The subepithelial fibrous tissue of the ESD ulcer scar in the TA group was significantly thinner than that in the Non-TA group (P < 0.05). There was no significant difference in the thickness of the regenerated epithelium and muscularis propria layer of the ESD ulcer scar. CONCLUSIONS: Histological finding of thinning of the subepithelial fibrous tissue of ESD ulcer scar in the human esophagus after TA injection was obtained. This suggests that TA suppresses the proliferation of the fibrous tissue of the subepithelial layer to help prevent esophageal stricture after widespread ESD in the human esophagus.

New Assay System Elecsys Anti-p53 to Detect Serum Anti-p53 Antibodies in Esophageal Cancer Patients and Colorectal Cancer Patients: Multi-institutional Study.

BACKGROUND: Several recent studies suggest that serum anti-p53 antibodies (s-p53-Abs) may be combined with other markers to detect esophageal and colorectal cancer. In this study, we assessed the sensitivity and specificity of s-p53-Abs detection of a new electrochemiluminescence immunoassay (ECLIA; Elecsys anti-p53). METHODS: Elecsys anti-p53 assay was used to analyze the level of s-p53-Abs in blood sera from patients with esophageal or colorectal cancer taken before treatment. Control blood sera from healthy volunteers, patients with benign diseases, and patients with autoimmune diseases served as a reference. In addition, squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragments (CYFRA21-1) were assessed in patients with esophageal cancer, and carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 were assessed in patients with colorectal cancer. RESULTS: Samples from 281 patients with esophageal cancer, 232 patients with colorectal cancer, and 532 controls were included in the study. The median value of s-p53-Abs in control samples was < 0.02 µg/mL (range < 0.02-29.2 µg/mL). Assuming 98% specificity, the cut-off value was determined as 0.05 µg/mL. s-p53-Abs were detected in 20% (57/281) of patients with esophageal cancer and 18% (42/232) of patients with colorectal cancer. In combination with SCC-Ag and CEA, respectively, s-p53-Abs detected 51% (144/281) of patients with esophageal and 53% (124/232) of patients with colorectal cancer. CONCLUSIONS: The new s-p53-Abs assay Elecsys anti-p53 was useful in detecting esophageal and colorectal cancers with high specificity. Adding s-p53-Abs to conventional markers significantly improved the overall detection rates.

Oral infectious bacteria in dental plaque and saliva as risk factors in patients with esophageal cancer.

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

Molecular motion in the nanospace of MOFs upon gas adsorption investigated by in situ Raman spectroscopy.

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

The Impact of Hybrid Minimally Invasive Esophagectomy with Neck-Abdominal First Approach on the Short- and Long-Term Outcomes for Esophageal Squamous Cell Carcinoma.

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

The evaluation of the hemodynamics of a gastric tube in esophagectomy using a new noninvasive blood flow evaluation device utilizing near-infrared spectroscopy.

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

Flexible Gastric Tube: A Novel Gastric Tube Formation Method to Prevent Anastomotic Leakage.

Gastric tube reconstruction is now the method most frequently used for digestive tract reconstruction after the resection of esophageal carcinoma. In our institute, a "flexible" gastric tube designed to supply a sufficient amount of blood to the tip of the gastric tube (the same as a subtotal gastric tube) and simultaneously provide sufficient length for tension-free anastomosis in the cervical surgical field (the same as a narrow gastric tube) was introduced. This gastric tube formation method has contributed to reducing the rate of anastomotic leakage.

Correction to: Perioperative chemotherapy for locally advanced gastric cancer in Japan: current and future perspectives.

The article Perioperative chemotherapy for locally advanced gastric cancer in Japan: current and future perspectives, written by Masanori Tokunaga, Yuya Sato, Masatoshi Nakagawa, Tomoki Aburatani, Takatoshi Matsuyama, Yasuaki Nakajima and Yusuke Kinugasa was originally published Online First without Open Access.

Perioperative chemotherapy for locally advanced gastric cancer in Japan: current and future perspectives.

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

Feasibility and Safety of Early Oral Intake and Discharge After Total or Proximal Gastrectomy: An Analysis of Consecutive Cases Without Exclusion Criteria.

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