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PURPOSE Adjuvant chemotherapy after D2 gastrectomy is standard for resectable locally advanced gastric cancer (LAGC) in Asia. Based on positive findings for perioperative chemotherapy in European phase III studies, the phase III PRODIGY study (ClinicalTrials.gov identifier: NCT01515748 ) investigated whether neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 could improve outcomes versus standard treatment in Korean patients with resectable LAGC. PATIENTS AND METHODS Patients 20-75 years of age, with Eastern Cooperative Oncology Group performance status 0-1, and with histologically confirmed primary gastric or gastroesophageal junction adenocarcinoma (clinical TNM staging: T2-3N+ or T4Nany) were randomly assigned to D2 surgery followed by adjuvant S-1 (40-60 mg orally twice a day, days 1-28 every 6 weeks for eight cycles; SC group) or neoadjuvant DOS (docetaxel 50 mg/m2, oxaliplatin 100 mg/m2 intravenously day 1, S-1 40 mg/m2 orally twice a day, days 1-14 every 3 weeks for three cycles) before D2 surgery, followed by adjuvant S-1 (CSC group). The primary objective was progression-free survival (PFS) with CSC versus SC. Two sensitivity analyses were performed: intent-to-treat and landmark PFS analysis. RESULTS Between January 18, 2012, and January 2, 2017, 266 patients were randomly assigned to CSC and 264 to SC at 18 Korean study sites; 238 and 246 patients, respectively, were treated (full analysis set). Follow-up was ongoing in 176 patients at data cutoff (January 21, 2019; median follow-up 38.6 months [interquartile range, 23.5-62.1]). CSC improved PFS versus SC (adjusted hazard ratio, 0.70; 95% CI, 0.52 to 0.95; stratified log-rank P = .023). Sensitivity analyses confirmed these findings. Treatments were well tolerated. Two grade 5 adverse events (febrile neutropenia and dyspnea) occurred during neoadjuvant treatment. CONCLUSION PRODIGY showed that neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, is effective and tolerable in Korean patients with LAGC.

The benefits of enhanced recovery after surgery (ERAS) in patients undergoing gastrectomy have been reported in several studies; however, there is limited evidence supporting the efficacy of ERAS in clinical settings. We aimed to identify the benefits of ERAS in the clinical setting by investigating short-term surgical outcomes before and after the implementation of ERAS in patients who underwent gastrectomy.We searched our gastric cancer database from 2008 to 2018 to identify patients who underwent gastrectomy before ERAS was implemented (2008-2009) and after the final version of ERAS was implemented (2016-2018). We enrolled 424 patients who were treated before ERAS was implemented and 565 patients who received our completed version of ERAS. After propensity score matching, each group included 219 patients, and short-term surgical outcomes were compared between the two groups.The length of hospital stay was significantly shorter in the ERAS group (8.8 vs. 11.5 days, p = 0.001), but the readmission rates were similar in the two groups, at 2.3%. There were no significant differences in morbidity, mortality, and complications of ≥ grade III between the groups. Of the complications, intra-abdominal bleeding (0% vs. 4.1%, p = 0.002) and intra-abdominal abscess (0% vs. 2.7%, p = 0.038) were significantly lower, whereas postoperative ileus was significantly higher in the ERAS group (8.6% vs. 0.5%, p 0.001). In subgroup analyses by age, operative approach, and the extent of gastric resection, the ERAS group experienced a shorter hospital stay without increased readmission in all subgroups.These results demonstrated that ERAS was associated with a 3-day reduction in hospital stay without increased readmission after gastrectomy. This study validated the benefits of ERAS in the clinical setting of gastrectomy.

Purpose The role of prophylactic abdominal drainage in total gastrectomy is not well-established. This study aimed to evaluate the efficacy of abdominal drainage in the prevention and management of major intra-abdominal complications after total gastrectomy for gastric carcinoma. Materials and methods We retrospectively reviewed the data of 499 patients who underwent total gastrectomy for gastric carcinoma in a high-volume institution. The patients were divided into drainage and non-drainage groups and compared for the development and management of major intra-abdominal complications, including anastomotic leak, abdominal bleeding, abdominal infection, and pancreatic fistulas. Results The drainage group included 388 patients and the non-drainage group included 111 patients. The 2 groups showed no significant differences in clinicopathological characteristics or operative procedures, except for more frequent D2 lymphadenectomies in the drainage group. After surgery, the overall morbidity (drainage group vs. non-drainage group: 24.7% vs. 28.8%, P=0.385) and incidence of major intra-abdominal complications (6.4% vs. 6.3%, P=0.959) did not significantly differ between the two groups. The non-drainage group showed no significant increase in the incidence rate of major intra-abdominal complications in the subgroups divided by age, sex, comorbidity, operative approach, body mass index, extent of lymphadenectomy, and pathological stage. Abdominal drainage had no significant impact on early diagnosis, secondary intervention or reoperation, or recovery from major intra-abdominal complications. Conclusions Prophylactic abdominal drainage showed little demonstrable benefit in the prevention and management of major intra-abdominal complications of total gastrectomy for gastric carcinoma.

PURPOSE To compare postoperative complications, long-term survival, and quality of life (QOL) after laparoscopic sentinel node navigation surgery (LSNNS) and laparoscopic standard gastrectomy (LSG). METHODS Five hundred eighty patients with preoperatively diagnosed stage IA gastric adenocarcinoma (≤ 3 cm) were assigned to undergo either LSG or LSNNS. Observers were not blinded to patient grouping. The primary outcome was 3-year disease-free survival (3y-DFS). Secondary outcomes included postoperative complications, QOL, 3-year disease-specific survival (3y-DSS), and 3-year overall survival (3y-OS). RESULTS In total, 527 patients were included in the modified intention-to-treat analysis population for the primary outcome (LSG, 269; LSNNS, 258). Stomach-preserving surgery was performed in 210 patients (81%) in the LSNNS group. During the median follow-up duration, the 3y-DFS rates in the LSG and LSNNS groups were 95.5% and 91.8%, respectively (difference: 3.7%; 95% CI, –0.6 to 8.1). Three patients with recurrence and five with metachronous gastric cancer in the LSNNS group underwent standard surgery. Two patients with distant metastasis in both groups were treated with palliative chemotherapy. The 3y-DSS and 3y-OS rates in the LSG and LSNNS groups were 99.5% and 99.1% ( P = .59) and 99.2% and 97.6% ( P = .17), respectively. Postoperative complications occurred in 19.0% of the LSG group and 15.5% of the LSNNS group ( P = .294). The LSNNS group showed better physical function ( P = .015), less symptoms ( P < .001), and improved nutrition than the LSG group. CONCLUSION LSNNS did not show noninferiority to LSG for 3y-DFS, with a 5% margin. However, the 3y-DSS and 3y-OS were not different after rescue surgery in cases of recurrence/metachronous gastric cancer, and LSNNS had better long-term QOL and nutrition than LSG.

Obesity can hinder laparoscopic procedures and impede oncological safety during laparoscopic cancer surgery. Deep neuromuscular block (NMB) reportedly improves laparoscopic surgical conditions, but its oncological benefits are unclear. We aimed to evaluate whether deep NMB improves the oncologic quality of laparoscopic cancer surgery in obese patients.We conducted a double-blinded, parallel-group, randomized, phase 3 trial at 9 institutions in Korea. Clinical stage I and II gastric cancer patients with a BMI at or above 25 kg m -2 were eligible and randomized 1:1 ratio to the deep or moderate NMB groups, with continuous infusion of rocuronium (0.5-1.0 and 0.1-0.5 mg kg -1 h -1, respectively). The primary endpoint was the number of retrieved lymph nodes (LNs). The secondary endpoints included the surgeon's surgical rating score (SRS) and interrupted events.Between August 2017 and July 2020, 196 patients were enrolled. Fifteen patients were excluded, and 181 patients were finally included in the study. There was no significant difference in the number of retrieved LNs between the deep (N = 88) and moderate NMB groups (N = 93; 44.6 ± 17.5 vs 41.5 ± 16.9, p = 0.239). However, deep NMB enabled retrieving more LNs in patients with a BMI at or above 28 kg/m2 than moderate NMB (49.2 ± 18.6 vs 39.2 ± 13.3, p = 0.026). Interrupted events during surgery were lower in the deep NMB group than in the moderate NMB group (21.6% vs 36.6%; p = 0.034). The SRS was not influenced by NMB depth.Deep NMB provides potential oncologic benefits by retrieving more LNs in patients with BMI at or above 28 kg/m2 during laparoscopic gastrectomy.

Background D2 lymph node dissection (LND) is a widely performed as a standard procedure for advanced gastric cancer (AGC). However, there is little evidence supporting D2 over D1+ LND for gastric cancer treatment. This study compared the long-term outcomes of D2 and D1+ LND for AGC. Methods We retrospectively reviewed data on 1121 patients who underwent curative distal gastrectomy and had pathologic stage of ≥ pT2 or pN+. The patients were categorized into the D1+ and D2 LND groups, and long-term survival was compared in the original and propensity score matching (PSM) cohorts. Results Overall, 909 and 212 patients underwent D2 and D1+ LND, respectively. The D2 group showed more advanced stage and more frequently underwent open surgery. Postoperative morbidity was significantly higher in the D2 group (19.5% vs. 13.2%, p = 0.034); however, mortality or ≥ grade III complications did not significantly differ between the groups. The 5-year overall survival (OS) and disease-free survival (DFS) did not significantly differ between D2 and D1+ groups at the same stage. Multivariate analysis of prognostic factors revealed that the extent of LND did not significantly affect survival, after adjusting for tumor stage and other clinicopathological factors. In the PSM cohort, the D2 and D1 groups showed no significant difference in OS (p = 0.488) and DFS (p = 0.705). Conclusions Long-term survival with D1+ LND was comparable to that with D2 LND for ≥ pT2 or pN + gastric carcinoma. A large randomized trial is warranted to validate the optimal extent of LND for gastric carcinoma.

Sentinel node navigation surgery reduces the extent of gastric and lymph node dissection, and may improve quality of life. The benefit and harm of laparoscopic sentinel node navigation surgery (LSNNS) for early gastric cancer is unknown. The SENORITA (SEntinel Node ORIented Tailored Approach) trial investigated the pathological and surgical outcomes of LSNNS compared with laparoscopic standard gastrectomy (LSG) with lymph node dissection.The SENORITA trial was an investigator-initiated, open-label, parallel-assigned, non-inferiority, multicentre RCT conducted in Korea. The primary endpoint was 3-year disease-free survival. The secondary endpoints, morbidity and mortality within 30 days of surgery, are reported in the present study.A total of 580 patients were randomized to LSG (292) or LSNNS (288). Surgery was undertaken in 527 patients (LSG 269, LSNNS 258). LSNNS could be performed according to the protocol in 245 of 258 patients, and a sentinel node basin was detected in 237 (96·7 per cent) Stomach-preserving surgery was carried out in 210 of 258 patients (81·4 per cent). Postoperative complications occurred in 51 patients in the LSG group (19·0 per cent) and 40 (15·5 per cent) in the LSNNS group (P = 0·294). Complications with a Clavien-Dindo grade of III or higher occurred in 16 (5·9 per cent) and 13 (5·0 per cent) patients in the LSG and LSNNS groups respectively (P = 0·647).The rate and severity of complications following LSNNS for early gastric cancer are comparable to those after LSG with lymph node dissection. Registration number: NCT01804998 ( http://www.clinicaltrials.gov).La cirugía de navegación del ganglio centinela (sentinel node navigation surgery, SNNS) reduce la extensión de la resección gástrica y ganglionar, y puede mejorar la calidad de vida. Se desconoce el beneficio y el daño de la cirugía de navegación del ganglio centinela por vía laparoscópica (laparoscopic sentinel node navigation surgery, LSNNS) para el cáncer gástrico precoz. El ensayo clínico SENORITA investigó los resultados patológicos y quirúrgicos de LSNNS en comparación con la gastrectomía laparoscópica estándar (laparoscopic gastrectomy, LSG) con disección ganglionar (lymph node dissection, LND). MÉTODOS: El ensayo SENORITA fue un ensayo multicéntrico aleatorizado y controlado, iniciado por investigadores, abierto, con asignación a grupos paralelos y de no inferioridad llevado a cabo en Corea. El resultado primario fue la supervivencia libre de enfermedad a los 3 años. En el presente estudio, se describen los resultados secundarios correspondientes a morbilidad y mortalidad a los 30 días del postoperatorio.Un total de 580 pacientes fueron aleatorizados a LG (n = 292) o LSNNS (n = 288). La cirugía se realizó en 527 pacientes (LG 269, LSNNS 258). LSNNS pudo ser realizada de acuerdo con el protocolo en 245 de 258 pacientes y en 237 de 245 pacientes (96,7%) se detectó un ganglio centinela. La cirugía con preservación del estómago se realizó en 210 de 258 pacientes (81,4%). Las complicaciones postoperatorias se presentaron en 51 pacientes del grupo LSG (19,0%) y en 40 pacientes (15,5%) del grupo LSNNS (P = 0,294). Las complicaciones grado III o mayor de Clavien-Dindo se detectaron en 16 (5,9%) y 13 pacientes (5,0%) de los grupos LSG y LSNNS, respectivamente (P = 0,647). CONCLUSIÓN: El porcentaje y la gravedad de las complicaciones tras LSNNS para cancer gástrico precoz son comparables a la LSG con LND.

With advances in surgical technique and instrumentation, intracorporeal anastomosis is increasingly being performed for laparoscopic total gastrectomy (LTG). However, the benefits of intracorporeal anastomosis in reducing postoperative complications have not been demonstrated, although its technical feasibility has been proven in many studies. In this study, we investigated the impact of intracorporeal anastomosis in reducing postoperative complications after LTG. We analyzed 410 consecutive gastric cancer patients who underwent LTG between 2008 and 2018. Of these, 118 underwent intracorporeal anastomosis using linear staplers (overlap method), while 292 underwent extracorporeal anastomosis using a circular stapler. Short-term surgical outcomes including postoperative complications were compared between the two groups. The two groups showed no significant differences in age, sex, comorbidity, and abdominal surgery history. D2 lymph node dissection was more frequently performed in the intracorporeal group because of the presence of more advanced cancer stages. The overall morbidity in the intracorporeal and extracorporeal group was 23.7% and 27.7%, respectively (p = 0.405). However, the intracorporeal group showed a significantly lower incidence of late complications (0.8% vs. 7.5%, p = 0.008). Concerning complications, the incidence of anastomotic bleeding (0% vs. 5.5%, p = 0.008) and anastomotic stenosis (0% vs. 4.5%, p = 0.024) was significantly lower in the intracorporeal group. In univariate and multivariate analyses, American Society of Anesthesiologists score and operative bleeding were independent predictive factors for postoperative complications in patients who underwent intracorporeal anastomosis. Intracorporeal anastomosis using linear staplers reduced anastomotic bleeding and stenosis compared to extracorporeal anastomosis after LTG. Future research will be required to determine the ideal method for intracorporeal anastomosis in LTG.

Purpose The numeric N stage has replaced the topographic N stage in the current tumor node metastasis (TNM) staging in gastric carcinoma. However, the usefulness of the topographic N stage in the current TNM staging system is uncertain. We aimed to investigate the prognostic value of the topographic N stage in the current TNM staging system. Materials and Methods We reviewed the data of 3350 patients with gastric cancer who underwent curative gastrectomy. The anatomic regions of the metastatic lymph nodes (MLNs) were classified into 2 groups: perigastric and extra-perigastric. The prognostic value of the anatomic region was analyzed using a multivariate prognostic model with adjustments for the TNM stage. Results In patients with lymph node metastasis, extra-perigastric metastasis demonstrated significantly worse survival than perigastric metastasis alone (5-year survival rate, 39.6% vs. 73.1%, respectively, P

Lymph nodes (LNs) at the splenic hilum (no. 10) are treated as regional LNs in proximal gastric carcinoma. However, patients with no.10 LN metastasis show a poor prognosis after curative surgery. This study aimed to investigate the prognostic impact of no.10 LN metastasis in proximal gastric carcinoma.We retrospective reviewed 665 proximal gastric carcinoma patients who underwent total gastrectomy and D2 LN dissection. Clinicopathological features were compared between patients with and without no.10 LN metastasis. The prognostic value of no.10 LN metastasis was examined using Cox prognostic model.There were 63 (9.5%) patients with no. 10 LN metastasis. No. 10 LN metastasis only existed in stage III/IV, and was significantly associated with greater curvature/circumferential tumor location, larger tumor size, B4 gross type, undifferentiated histology, lymphovascular invasion. The 5-year survival of no.10 LN metastasis group was 26%, which was significantly lower than those without no.10 LN metastasis (79%, p 0.001). Patients with no. 10 LN metastasis also showed a significantly worse survival than those without in each tumor stage (stage III = 45% vs. 66%, p = 0.044, stage IV = 13% vs. 33%, p = 0.024). In the multivariate cox model, no.10 LN metastasis was an independent poor prognostic factor when adjusting for TNM stage and other prognostic factors.The prognosis of no.10 LN metastasis is as poor as that of distant metastasis. This suggests that no. 10 LN should rather be considered as non-regional LNs in the treatment of proximal gastric carcinoma.

4050 Background: A phase III multicenter randomized controlled clinical trial (SEntinel Node ORIented Tailored Approach [SENORITA] trial) has been performed to confirm the oncologic safety of laparoscopic sentinel node navigation surgery (LSNNS) for early gastric cancer (EGC). The results did not show the non-inferiority of LSNNS relative to laparoscopic standard gastrectomy (LSG) in terms of 3-year disease-free survival (DFS), the primary endpoint of the SENORITA trial even though the improved quality of life (QOL) in the LSNNS group. However, the long-term oncologic outcomes of LSNNS have not been compared with conventional surgery. This study was planned to investigate the comparison of LSG and LSNNS for EGC in terms of 5 years survival. Methods: We collected 5-year follow-up data of 527 patients recruited in the SENORITA trial. The overall survival (OS), disease-free survival (DFS), and recurrence pattern were evaluated in full analysis sets of both LSG (n = 269) and LSNNS (n = 258). Results: The mean follow-up period was 58.5 and 57.7 months in LSNNS and LSG groups. There was no statistically significant difference in 5-year OS (p = 0.7403) and DFS (p = 0.0561) between LSG and LSNNS. In terms of DFS, additional five events in the LSG group and 7 in LSNNS occurred after a 3-year follow-up until 5-years. Primary site recurrence in 1 LSNNS, and metachronous gastric cancer occurred in one LSG and two in LSNNS were diagnosed from 3 to 5-year follow-up period. Other organ cancer developed in two vs. three and other deaths occurred in two v s. one in each group, respectively, from 3 to 5-year follow-up. Overall survival events were 6 in LSG and 7 in LSNNS, and disease-specific death events were two patients in both groups until five years. Conclusions: Although the SENORITA trial did not show non-inferiority of LSNNS in the primary endpoint, 3-year DFS relative to LSG, the 5-year DFS and OS did not reveal the statistical difference between the two groups. Considering the benefit of LSNNS regarding the postoperative QOL, LSNNS could be recommended as an alternative treatment option of LSG for EGC. Clinical trial information: NCT01804998.

Purpose To date, there are no promising treatments for gastric carcinoma with peritoneal metastasis. Some researchers have suggested a survival benefit of gastrectomy in select patients. This study investigated the survival of gastric carcinoma patients with stand-alone peritoneal metastasis according to the type of treatment modality. Materials and Methods We reviewed the data of 132 patients with gastric carcinoma and stand-alone peritoneal metastasis. We performed gastrectomy when the primary tumor was deemed resectable and systemic chemotherapy was administered. We analyzed patient survival according to the type of treatment, and the prognostic value of gastrectomy was evaluated in univariate and multivariate models. Results Among all patients, 70 underwent gastrectomy plus chemotherapy, 20 underwent gastrectomy alone, 36 underwent chemotherapy alone, and 6 received supportive care. The median patient survival was 13 months. Patients who underwent gastrectomy had significantly longer survival than those who did not undergo gastrectomy (14 vs. 8 months, P

Purpose With increasing life expectancy, the presence of comorbidities has become a major concern in elderly patients who require surgery. However, little is known about the impact of different comorbidities on the outcomes of laparoscopic total gastrectomy (LTG). In this study, we investigated the impact of comorbidities on postoperative complications in patients undergoing LTG for gastric carcinoma. Materials and methods We retrospectively reviewed the cases of 303 consecutive patients who underwent LTG for gastric carcinoma between 2005 and 2016. The associations between each comorbidity and postoperative complications were assessed using univariate and multivariate analyses. Results A total of 189 patients (62.4%) had one or more comorbidities. Hypertension was the most common comorbidity (37.0%), followed by diabetes mellitus (17.8%), chronic viral hepatitis (2.6%), liver cirrhosis (2.6%), and pulmonary (27.1%), ischemic heart (3.3%), and cerebrovascular diseases (2.3%). The overall postoperative morbidity and mortality rates were 20.1% and 1.0%, respectively. Patients with pulmonary disease significantly showed higher complication rates than those without comorbidities (32.9% vs. 14.9%, respectively, P=0.003); patient with other comorbidities showed no significant difference in the incidence of LTG-related complications. During univariate and multivariate analyses, pulmonary disease was found to be an independent predictive factor for postoperative complications (odds ratio, 2.14; 95% confidence interval, 1.03-4.64), along with old age and intraoperative bleeding. Conclusions Among the various comorbidities investigated, patients with pulmonary disease had a significantly higher risk of postoperative complications after LTG. Proper perioperative care for optimizing pulmonary function may be required for patients with pulmonary disease.

Enhanced recovery after surgery (ERAS) programs have gained widespread acceptance in different fields of major surgery. However, most elements of perioperative care in ERAS are based on practices that originated from colorectal surgery. This study investigated compliance with the main elements of ERAS for patients undergoing gastrectomy for gastric carcinoma. This phase 2 study enrolled 168 patients undergoing elective gastrectomy for gastric carcinoma. An ERAS program consisting of 18 main elements was implemented, and compliance with each element was evaluated (ClinicalTrials.gov, NCT01653496). Distal gastrectomy was performed for 142 patients (84.5%) and total gastrectomy for 26 patients (10.1%). Laparoscopic surgery was performed for 141 patients (86%). The postoperative morbidity rate was 9.5%, and the mortality rate was 0%. The rates of compliance with the 18 main elements of ERAS ranged from 88.1 to 100%. The lowest compliance rate was observed in the restriction of intravenous fluid element (88.1%). Overall, all ERAS elements were successfully applied for 122 patients (72.6%). In the multivariate analysis, the significant factors that adversely affected compliance with ERAS were surgery during the early study period [odds ratio (OR) 0.39; p = 0.038], open surgery (OR 0.15; p

Nutritional risk screening (NRS) score has been reported as a predictor of postoperative outcomes in patients undergoing abdominal surgery, although the correlation between NRS and anastomotic leakage (AL) after rectal cancer surgery is uncertain. This study aimed to evaluate the association between NRS score and AL following rectal cancer surgery. We retrospectively reviewed data of rectal cancer patients from a tertiary referral center in South Korea, and included 1063 patients with primary rectal cancer who underwent sphincter-preserving surgery between January 2011 and December 2015. We utilized the Chonnam National University Hwasun Hospital-Nutritional Risk Screening Tool (CNUHH-NRST), which was developed and cross-validated on the basis of the NRS 2002 and MST, as a screening tool of nutritional risk. Patients with NRS scores ≥4 were compared with those with NRS scores

Enhanced recovery after surgery (ERAS) aims at expediting postoperative recovery by implementing specific strategies in perioperative management. However, the tolerance to such fast-tracking protocols is under debate, especially in elderly patients. We aimed to investigate rate of compliance with the main ERAS guidelines in elderly gastrectomy patients. Using data for 168 gastric cancer patients who underwent ERAS after gastrectomy as part of Clinical Trial NCT01653496, we calculated the rates of compliance with nine main ERAS guidelines and compared the compliance rates of elderly (≥70 years) and non-elderly ( 90%) for every ERAS guideline. Notably, the overall compliance rates did not differ significantly between the groups. Postoperatively, the mean time to fulfillment of discharge criteria was slightly longer for elderly patients (4.7 vs. 4.2 days, p = 0.005), but there were no significant differences between the groups with respect to the incidence of postoperative complications, length of hospitalization, and readmission rate. Compliance of the medically and physically fit elderly patients with the main ERAS guidelines is comparable to that of non-elderly patients, and such protocols can be safely applied to elderly patients without significant modification.

4054 Background: Laparoscopic sentinel node navigation surgery (LSNNS) has been suggested as an alternative to laparoscopic standard gastrectomy (LSG) in early gastric cancer patients to improve long-term quality of life (QOL) and nutritional outcomes. Here, we present 3-year results of patient-reported quality of life (QOL) and nutrition, secondary endpoints of SENORITA trial. Methods: SENORITA is a prospective multicenter randomized phase 3 trial. Patients diagnosed with early gastric cancer of 3 cm or less were randomly allocated (1:1) to LSNNS for stomach preservation or LSG. The primary endpoint was 3-year disease-free survival. In this study, we analyzed QOL assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EORTC stomach module (STO22) and nutritional parameters at 3, 12, 24, and 36 months after surgery. Linear mixed model analyses was used to evaluate differences between the two groups. This trial is registered with ClinicalTrials.gov, NCT01804998. Results: From March 2013 to March 2017, a total of 580 patients were randomly assigned and 527 patients were included in the modified intention-to-treat analysis population (258 in LSNNS and 269 in LSG group). QOL questionnaires were available for 99.4% of patients at baseline and then for 92.2%, 83.2%, 72.8%, and 66.9% at 3, 12, 24, and 36 months after surgery, respectively. The LSNNS group had higher physical function score than the LSG group at all time points (p = 0.002). However, there were no significant differences in other scales of EORTC QLQ-C30. Regarding EORTC QLQ-STO22, pain, eating restriction, anxiety, and taste scores were lower (better QOL) at all time points in the LSNNS group than in the LSG group (p = 0.002, < 0.001, < 0.001, and < 0.001, respectively). The summary score of EORTC QLQ-STO22 was also higher in the LSNNS group representing better QOL (p < 0.001). Body mass index, hemoglobin and total protein were significantly higher in the LSNNS group compared with the LSG group. Conclusions: The LSNNS group had better physical function and less symptoms, including pain, eating restriction, anxiety, and taste change compared with the LSG group. Moreover, the nutritional parameters were better maintained in the LSNNS group than in the LSG group. These findings showed benefits of stomach preserving surgery in LSNNS and can be used to help decision making about treatment for patients with early gastric cancer. Clinical trial information: NCT01804998.

Background Enhanced recovery after surgery (ERAS) aims at expediting postoperative recovery by implementing specific strategies in perioperative management. However, the tolerance to such fast-tracking protocols is under debate, especially in elderly patients. We aimed to investigate rate of compliance with the main ERAS guidelines in elderly gastrectomy patients.

Since the eighth American Joint Committee on Cancer (AJCC) classification recently introduced the clinical classification for preoperative staging of gastric cancer, the new clinical classification has not been extensively validated yet. Therefore, in this study, we compared the prognostic performance of the new clinical classification and the pathologic classification for preoperative staging of gastric cancer. We reviewed 3027 patients with gastric cancer who were surgically treated between 2009 and 2013. Patient survival was analyzed according to the preoperative stage by the clinical classification and the pathologic classification in the eighth AJCC classification. The prognostic performance was examined using the Akaike information criterion (AIC) value and Harrell c-index. Patient survival was significantly different across the different stages when both classifications were used. However, individual pairwise comparisons showed that survival differences between each stage were more distinctive and homogeneous in the pathologic classification. In the multivariate model adjusted for the final pathologic stage, preoperative staging by the pathologic classification was an independent prognostic factor, whereas the clinical classification was not. The pathologic classification showed a lower AIC value compared with the clinical classification (5100.64 vs. 5114.14). The Harrell c-index was higher in the pathologic classification than in the clinical classification (0.741 vs. 0.739). The new clinical classification in the eighth AJCC classification discriminates patient survival well. However, it does not appear to have a better prognostic performance compared with the pathologic classification for preoperative staging of gastric cancer.

Background: Risks and benefits of laparoscopic sentinel node navigation surgery (LSNNS) compared with laparoscopic standard gastrectomy (LSG) with lymph node dissection (LND) for early gastric cancer (EGC) are unknown. The SENORITA trial investigated the clinical impact of LSNNS for EGC regarding short-term surgical outcomes, long-term survival, and quality of life (QOL). Methods: Patients with preoperatively diagnosed T1N0 gastric adenocarcinoma with a diameter of 3 cm or smaller regardless of histology (except absolute indication for endoscopic resection) were eligible. Patients were randomized to LSG with LND or LSNNS. The primary endpoint was 3-year disease-free survival. Morbidity and mortality within 30 postoperative days were evaluated as secondary endpoints and graded by the Clavien-Dindo classification. Findings: From March 2013 to December 2016, 580 patients were randomized (LSG, 292; LSNNS, 288). Fifty-three patients dropped out before surgery due to various reasons. Surgery was performed for 527 patients (LSG, 269; LSNNS, 258) representing the full analysis set. LSNNS was not performed in 13 patients due to intraoperative findings. LSNNS was performed according to protocol for 245 patients, and detection of sentinel basin was possible for 237 patients (96.7%, 237/245). Stomach-preserving surgery was performed in 210 patients (81.4%. 210/258). Postoperative complications occurred in 51 LSG patients (19.0%) and 40 LSNNS patients (15.5%) (P=0.294). Clavien-Dindo grade III or higher complications occurred in 16 LSG patients (5.9%) and 13 LSNNS patients (5.0%) (P=0.647). Postoperative mortality occurred in one LSG patient. LSNNS was not a risk factor for postoperative morbidity in multivariate analysis except sex. Interpretation: LSNNS for EGC is a safe procedure in terms of postoperative morbidity and mortality when compared with LSG with LND. Results: From March 2013 to December 2016, 580 patients were randomized (LSG, 292; LSNNS, 288). Surgery was performed for 527 patients (LSG, 269; LSNNS, 258) representing the full analysis set. LSNNS was not performed in 13 patients due to intraoperative findings. LSNNS was performed according to protocol for 245 patients, and detection of sentinel basin was possible for 237 patients (96.7%, 237/245). Stomach-preserving surgery was performed in 210 patients (81.4%. 210/258). Postoperative complications occurred in 51 LSG patients (19.0%) and 40 LSNNS patients (15.5%) (P=0.294). Clavien-Dindo grade III or higher complications occurred in 16 LSG patients (5.9%) and 13 LSNNS patients (5.0%) (P=0.647). Postoperative mortality occurred in one LSG patient. LSNNS was not a risk factor for postoperative morbidity in multivariate analysis except sex. Conclusions: LSNNS for EGC is a safe procedure in terms of postoperative morbidity and mortality when compared with LSG with LND. Trial Registration Number: NCT01804998. Funding: National Cancer Center, Republic of Korea (grant number: 1710160-2). Declaration of Interest: The authors declare that they have no conflicts of interest or financial ties to disclose. Ethical Approval: All patients provided written informed consent before the surgery. This study was reviewed and approved by the local institutional review boards of all participating institutions.

Purpose: Many studies have demonstrated the advantage of maintaining intraoperative deep neuromuscular block (NMB) with sugammadex. This trial is designed to evaluate the impact of muscle relaxation during laparoscopic subtotal gastrectomy on the oncological benefits, particularly in obese patients with gastric cancer. Materials and methods: This is a double-blind, randomized controlled multicenter prospective trial. Patients with clinical stage I–II gastric cancer with a body mass index of 25 and over, who undergo laparoscopic subtotal gastrectomy will be eligible for trial inclusion. The patients will be randomized into a deep NMB group or a moderate NMB group with a 1:1 ratio. A total of 196 patients (98 per group) are required. The primary endpoint is the number of harvested lymph nodes, which is a critical index of the quality of surgery in gastric cancer treatment. The secondary endpoints are surgeon's surgical condition score, patient's sedation score, and surgical outcomes including peak inspiratory pressure, operation time, postoperative pain, and morbidity. Discussion: This is the first study that compares deep NMB with moderate NMB during laparoscopic gastrectomy in obese patients with gastric cancer. We hope to show the oncologic benefits of deep NMB compared with moderate NMB during subtotal gastrectomy. Trial registration number: ClinicalTrials.gov (NCT03196791), date of registration: October 10, 2017.

HOX (homeobox) genes encode a family of transcriptional regulators, which have an important role in morphogenesis and differentiation during embryonic development. Their deregulated expression is involved in the carcinogenesis of many human solid tumours. In the present study, we show that HOXB5 mRNA was significantly overexpressed in gastric cancer tissues compared with adjacent normal tissues. HOXB5-up-regulated cancer cells showed increased invasion and migration activity, but no change in proliferation activity, whereas HOXB5-down-regulated cells showed decreased invasion and migration activity. Up-regulation of HOXB5 resulted in up-regulation of β-catenin, whereas inhibition of HOXB5 expression by siRNA led to the down-regulation of β-catenin. Moreover, a significant correlation between HOXB5 and CTNNB1 (β-catenin) mRNA expression was detected in gastric cancer tissues. Furthermore, we found that HOXB5 binds directly to the CTNNB1 promoter region and activates the transcriptional expression of β-catenin, as well as its downstream target genes, encoding cyclin D1 and c-Myc, leading to an increase in the invasion and migration activity of human gastric cancer cells. Thus HOXB5 may be an important regulator of the Wnt/β-catenin signalling pathway, thereby contributing to gastric cancer progression and metastasis.

4510 Background: The benefits and hazards of laparoscopic sentinel node navigation surgery (LSNNS), compared with laparoscopic standard gastrectomy (LSG) with lymph node dissection in early gastric cancer (EGC), are unknown. The SENORITA trial investigated the clinical impact of LSNNS in EGC in terms of short-term surgical outcomes, long-term survival and quality of life. Methods: This study is a prospective, multicenter, randomized controlled, non-inferiority trial. Patients with preoperatively diagnosed gastric adenocarcinoma with T1N0 of 3 cm or less in diameter, regardless of histology, except absolute indication for endoscopic resection were eligible. Patients were randomized to LSG or LSNNS using dual tracers. The primary endpoint is 3-year disease-free survival (3yDFS). Planned sample size per arm is 290 patients with the non-inferiority margin of 2.737 in hazard ratio (HR) assuming that LSG achieve 97% 3yDFS, 5% of type 1 error and 80% of power. Three-year recurrence-free survival (3yRFS), overall survival (3yOS) and disease specific death rate (3yDSDR) were evaluated as secondary endpoints. Results: From March 2013 to December 2016, 580 patients were randomized (LSG arm 292 vs. LSNNS arm 288). After 53 patients dropped out before surgery, operation was performed in 527 patients (269 vs. 258), representing the full analysis set. LSG was performed in 266 according to the protocol excluding 3 open conversion. After exclusion of 13 without LSNNS due to various reasons, LSNNS was performed in 245 patients according to the protocol. After median follow up of 47.5 months, 3yDFS were 95.5% and 91.8% (HR 1.901, CI 0.911 – 3.967), respectively. The 3yRFS was 98.9% and 95.2% (p=0.019), and 3yOS was 99.2% and 97.6% (p=0.166), and 3yDSDR was 99.5% and 99.1% (p=0.591), respectively. Conclusion: LSNNS in EGC did not show non-inferiority compared with LSG in terms of 3yDFS. However, 3yOS and 3yDSDR of LSNNS were comparable to LSG by the rescue surgery of recurrence. LSNNS might be an alternative surgical option instead of LSG in selected EGC patients. Clinical trial information: NCT01804998 .

Backgrounds Patients with proximal gastric carcinoma undergo total gastrectomy with concomitant splenectomy to ensure the complete removal of splenic hilar lymph nodes. However, the impact of splenectomy on survival remains uncertain. This study aimed to investigate the impact of splenectomy on survival among patients with gastric carcinoma. Methods Of 1074 patients who underwent total gastrectomy for proximal gastric carcinoma between 2006 and 2014, 229 patients underwent concomitant splenectomy or pancreaticosplenectomy during surgery. We investigated the prognostic impact of splenectomy using a regression and propensity score matched model. Results The splenectomy and non-splenectomy groups differed in many baseline characteristics, including tumor stage, and had respective crude 5-year survival rates of 55% and 81% (p

Background Malnutrition is associated with many adverse clinical outcomes. The present study aimed to identify the prevalence of malnutrition in hospitalized patients in Korea, evaluate the association between malnutrition and clinical outcomes, and ascertain the risk factors of malnutrition. Methods A multicenter cross-sectional study was performed with 300 patients recruited from among the patients admitted in 25 hospitals on January 6, 2014. Nutritional status was assessed by using the Subjective Global Assessment (SGA). Demographic characteristics and underlying diseases were compared according to nutritional status. Logistic regression analysis was performed to identify the risk factors of malnutrition. Clinical outcomes such as rate of admission in intensive care units, length of hospital stay, and survival rate were evaluated. Results The prevalence of malnutrition in the hospitalized patients was 22.0%. Old age (≥ 70 years), admission for medical treatment or diagnostic work-up, and underlying pulmonary or oncological disease were associated with malnutrition. Old age and admission for medical treatment or diagnostic work-up were identified to be risk factors of malnutrition in the multivariate analysis. Patients with malnutrition had longer hospital stay (SGA A = 7.63 ± 6.03 days, B = 9.02 ± 9.96 days, and C = 12.18 ± 7.24 days, P = 0.018) and lower 90-day survival rate (SGA A = 97.9%, B = 90.7%, and C = 58.3%, P < 0.001). Conclusion Malnutrition was common in hospitalized patients, and resulted in longer hospitalization and associated lower survival rate. The rate of malnutrition tended to be higher when the patient was older than 70 years old or hospitalized for medical treatment or diagnostic work-up compared to elective surgery., Graphical Abstract

Background. Recent studies have shown a lower risk of surgical site infections (SSI) after laparoscopic distal gastrectomy compared to open surgery. This is a phase 2 study aiming to determine the incidence of SSI after laparoscopic distal gastrectomy without using antimicrobial prophylaxis (AMP). Methods. cT1N0 gastric cancers that were subject to laparoscopic distal gastrectomy were enrolled. Based on the unacceptable SSI incidence of ≥12.5% and the target SSI incidence of ≤5%, 105 patients were enrolled with an α of 0.05 and a power of 80% (ClinicalTrials.gov, NCT02200315). Results. In intention-to-treat analysis, patients did not reach the target SSI rate (12.4%, 95% confidence interval=6.8%–19.8%). Of patients, 44 patients had a protocol violation, such as extended lymph node dissection (LND) or inappropriate nonpharmacological SSI prevention measures. Per-protocol analysis excluding these patients (n=61) showed a SSI rate of 4.9%, which was within the target SSI range. Multivariate analysis revealed that extracorporeal anastomosis and extended LND were independent risk factors for SSI. Conclusions. This study failed to reach the target SSI rate without using AMP. However, per-protocol analysis suggests that no AMP might be feasible when limited LND and adequate SSI prevention measures were performed.

Background. We investigated the results of quality control study prior to phase III trial of sentinel lymph node navigation surgery (SNNS). Methods. Data were reviewed from 108 patients enrolled in the feasibility study of laparoscopic sentinel basin dissection (SBD) in gastric cancer. Seven steps contain tracer injection at submucosa (step 1) and at four sites (step 2) by intraoperative esophagogastroduodenoscopy (EGD), leakage of tracer (step 3), injection within 3 minutes (step 4), identification of at least one sentinel basin (SB) (step 5), evaluation of sentinel basin nodes (SBNs) by frozen biopsy (step 6), and identification of at least five SBNs at back table and frozen sections (step 7). Results. Failure in step 7 (n=23) was the most common followed by step 3 (n=15) and step 6 (n=13). We did not find any differences of clinicopathological factors between success and failure group in steps 1~6. In step 7, body mass index (BMI) was only the significant factor. The success rate was 97.1% in patients with BMI 2 and 80.3% in those with BMI ≥ 23 kg/m2 (P=0.028). Conclusions. Lower BMI group showed higher success rate in step 7. Surgeons doing SNNS should be cautious when evaluating sufficient number of SBN in obese patients.

Thymosin β4 (Tβ4) is a 43-amino-acid peptide involved in many biological processes. However, the precise molecular signaling mechanism(s) of Tβ4 in cell invasion and migration remain unclear. In this study, we show that Tβ4 was significantly overexpressed in colorectal cancer tissues compared to adjacent normal tissues and high levels of Tβ4 were correlated with stage of colorectal cancer, and that Tβ4 expression was associated with morphogenesis and EMT. Tβ4-upregulated cancer cells showed increased adhesion, invasion and migration activity, whereas Tβ4-downregulated cells showed decreased activities. We also demonstrated that Tβ4 interacts with ILK, which promoted the phosphorylation and activation of AKT, the phosphorylation and inactivation of GSK3β, the expression and nuclear localization of β-catenin, and integrin receptor activation. These results suggest that Tβ4 is an important regulator of the ILK/AKT/β-catenin/Integrin signaling cascade to induce cell invasion and migration in colorectal cancer cells, and is a potential target for cancer treatment.

Purpose: Information regarding antimicrobial prophylaxis (AMP) for gastric cancer surgery is limited. The present study investigated the efficacy of single-dose AMP for the prevention of surgical site infection (SSI) in patients undergoing gastrectomy for gastric carcinoma. Materials and Methods: Between 2011 and 2013, 1,330 gastric carcinoma surgery patients were divided into two AMP administration groups depending on the duration of treatment. Postoperative outcomes including morbidity and SSI were compared between the two groups overall and in matched patients. Risk factors for SSI were analyzed. Results: The extended group (n=1,129) received AMP until postoperative day 1 and the single-dose group (n=201) received singledose AMP only during an operation. Postoperatively, there were no significant differences between the two groups with respect to overall morbidity, mortality, or length of hospital stay. The SSI rate of the single-dose group was not significantly different from that of the extended group overall (4.5% vs. 5.5%, respectively, P=0.556) or in matched patients (4.5% vs. 4.0%, respectively, P=0.801). There was no increase in the SSI rate of the single-dose group compared to the extended group in subgroups based on different clinicopathological and operative factors. Univariate and multivariate analyses revealed male gender, open surgery, and operating time (≥180 minutes) as independent risk factors for SSI. Conclusions: Single-dose AMP showed no increase in the postoperative SSI rate compared to postoperative extended use in patients undergoing gastrectomy for gastric carcinoma. The efficacy of single-dose AMP requires further investigation in randomized clinical trials specific to gastric cancer surgery.

Enhancing the charge transfer rate in dye sensitized solar cells (DSSCs) is one of the most important criteria determining the cell efficiency. This paper reports a novel strategy for enhancing charge transfer between squaraine dyes and TiO 2 by increasing the anchoring number. Symmetrical (SSQ) and unsymmetrical squaraine (USQ) sensitizers with different numbers of anchoring groups in their chromophores are synthesized. SSQ dye containing a bis-anchoring group shows better electronic coupling with TiO 2 than the USQ dye with a mono-bridge. This enhanced electronic coupling leads SSQ to exhibit better photovoltaic performance, though smaller amounts of SSQ dye is loaded on the TiO 2 than the USQ dye. Under standard global AM 1.5 solar conditions, the optimized SSQ-sensitized solar cells show 7.76 mA cm −2 of short-circuit photocurrent density, 0.62 V of open-circuit voltage, and 0.65 of fill factor (FF), to give overall conversion efficiency of 3.20%, which is approximately 25% higher than the USQ-sensitized solar cells.

Enhanced recovery after surgery (ERAS) aims at expediting postoperative recovery by implementing specific strategies in perioperative management. However, the tolerance to such fast-tracking protocols is under debate, especially in elderly patients. We aimed to investigate rate of compliance with the main ERAS guidelines in elderly gastrectomy patients.Using data for 168 gastric cancer patients who underwent ERAS after gastrectomy as part of Clinical Trial NCT01653496, we calculated the rates of compliance with nine main ERAS guidelines and compared the compliance rates of elderly (≥70 years) and non-elderly (70 years) patients. Surgical outcomes and fulfillment of criteria for postoperative discharge were also compared.The study included 55 elderly and 113 non-elderly patients. There were no significant differences between these groups of patients with respect to operative techniques and tumor stage. Except for restricted intravenous fluid administration, the patients in both groups showed very high compliance rates (90%) for every ERAS guideline. Notably, the overall compliance rates did not differ significantly between the groups. Postoperatively, the mean time to fulfillment of discharge criteria was slightly longer for elderly patients (4.7 vs. 4.2 days, p = 0.005), but there were no significant differences between the groups with respect to the incidence of postoperative complications, length of hospitalization, and readmission rate.Compliance of the medically and physically fit elderly patients with the main ERAS guidelines is comparable to that of non-elderly patients, and such protocols can be safely applied to elderly patients without significant modification.

Purpose Laparoscopic surgery is associated with lower surgical site infection (SSI) rates due to minimal skin incision and non-exposure of visceral organs. Most previous studies have analyzed the efficacy of prophylactic antibiotic use in open surgery. Here, we investigated the feasibility of total laparoscopic distal gastrectomy (TLDG) for gastric carcinoma without prophylactic antibiotic use. Materials and methods Seventy-one patients who underwent TLDG without prophylactic antibiotic use were 1:1 propensity score matched with 393 patients who underwent TLDG with antibiotic prophylaxis. The short-term surgical outcomes, including SSI rates, were compared between the groups. Results After matching, 65 patients were selected in each group. The baseline clinicopathological characteristics were well balanced in the matched sample. In the matched group, there was no significant increase in postoperative morbidity in the non-prophylactic group compared with the prophylactic group (18.5% vs. 15.4%, P=0.640), and there were no grade 3≤ complications (1.4% vs. 0%, respectively; P=1.000). The SSI rates in the non-prophylactic and prophylactic groups were 3.1% and 1.5%, respectively (P=0.559). The time to gas passage, diet initiation, and mean hospital stay were not significantly different between the 2 groups. The SSI rate did not increase in the non-prophylactic group in the different subgroups based on different clinicopathological characteristics. Conclusions Postoperative morbidity, including SSI rates, did not significantly increase in patients undergoing TLDG without prophylactic antibiotic use. A large prospective randomized trial is warranted to reappraise the efficacy of prophylactic antibiotic use in patients undergoing TLDG.

Purpose Although standard radical gastrectomy is recommended after noncurative resection of endoscopic submucosal dissection (ESD) for early gastric cancer in most cases, residual tumor and lymph node metastasis have not been identified after surgery. The aim of this study is to evaluate the feasibility of sentinel node navigation surgery after noncurative ESD. Materials and methods This trial is an investigator-initiated, multicenter prospective phase II trial. Patients who underwent ESD for clinical stage T1N0M0 gastric cancer with noncurative resections were eligible. Qualified investigators who completed the prior phase III trial (SENORITA 1) are exclusively allowed to participate. In this study, 2 detection methods will be used: 1) intraoperative endoscopic submucosal injection of dual tracer, including radioisotope and indocyanine green (ICG) with sentinel basins detected using gamma-probe; 2) endoscopic injection of ICG, with sentinel basins detected using a fluorescence imaging system. Standard laparoscopic gastrectomy with lymphadenectomy will be performed. Sample size is calculated based on the inferior confidence interval of the detection rate of 95%, and the calculated accrual is 237 patients. The primary endpoint is detection rate, and the secondary endpoints are sensitivity and postoperative complications. Conclusions This study is expected to clarify the feasibility of laparoscopic sentinel basin dissection after noncurative ESD. If the feasibility is demonstrated, a multicenter phase III trial will be initiated to compare laparoscopic sentinel node navigation surgery versus laparoscopic standard gastrectomy in early gastric cancer after endoscopic resection. Trial registration ClinicalTrials.gov Identifier: NCT03123042.

We prepared the ionic dyes and investigated their electrochemical properties and photosensitizing performances in the quasi-solid state dye-sensitized solar cells (QS-DSSCs). The LUMO energy level of ionic dye with carbazole moiety is higher than that of the dyes with phenothiazine and triphenylamine chromophore, resulting in highest power conversion efficiency (PCE) in the QD-DSSC. Compared with Ru-complex sensitizer, the ionic dyes showed relatively low photovoltaic performance in the QS-DSSCs, originating in lower LUMO energy level. The effect of Li+ion in the quasi-solid state electrolyte on the photovoltaic characteristics of QS-DSSCs was investigated in order to confirm the correlation between the conduction band of TiO2electrode and LUMO energy level of photosensitizers. The conduction band of TiO2electrode could be reduced by adding the Li+ion in the electrolyte, attributing for the enlargement of PCE value in the QS-DSSC.