Purpose: Intracorporeal esophagojejunostomy during reduced-port gastrectomy for proximal gastric cancer is a technically challenging technique. No study has yet reported a robotic technique for anastomosis. Therefore, to address this gap, we describe our reduced-port technique and the short-term outcomes of intracorporeal esophagojejunostomy. Materials and Methods: We conducted a retrospective review of patients who underwent a totally robotic reduced-port total or proximal gastrectomy between August 2016 and March 2020. We used an infra-umbilical Single-Site® port with two additional ports on both sides of the abdomen. To transect the esophagus, a 45-mm endolinear stapler was inserted via the right abdominal port. The common channel of the esophagojejunostomy was created between the apertures in the esophagus and proximal jejunum using a 45-mm linear stapler. The entry hole was closed with a 45-mm linear stapler or robot-sewn continuous suture. All anastomoses were performed without the aid of an assistant or placement of stay sutures. Results: Among the 40 patients, there were no conversions to open, laparoscopic, or conventional 5-port robotic surgery. The median operation time and blood loss were 254 min and 50 mL, respectively. The median number of retrieved lymph nodes was 40.5. The median time to first flatus, soft diet intake, and length of hospital stay were 3, 5, and 7 days, respectively. Three (7.5%) major complications, including two anastomosis-related complications and a case of small bowel obstruction, were treated with an endoscopic procedure and re-operation, respectively. No mortality occurred during the study period. Conclusions Intracorporeal esophagojejunostomy during reduced-port gastrectomy can be safely performed and is feasible with acceptable surgical outcomes.

Purpose: No consensus exists on whether to preserve or ligate an aberrant left hepatic artery (ALHA), which is the most commonly encountered hepatic arterial variation during gastric surgery. Therefore, we aimed to evaluate the clinical effects of ALHA ligation by analyzing the perioperative outcomes. Materials and Methods: We retrospectively reviewed the data of 5,310 patients who underwent subtotal/total gastrectomy for gastric cancer. Patients in whom the ALHA was ligated (n=486) were categorized into 2 groups according to peak aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels: moderate-to-severe (MS) elevation (≥5 times the upper limit of normal [ULN]; MS group, n=42) and no-to-mild (NM) elevation (<5 times the ULN; NM group, n=444). The groups were matched 1:3 using propensity score-matching analysis to minimize confounding factors that can affect the perioperative outcomes. Results: The mean operation time (P=0.646) and blood loss amount (P=0.937) were similar between the 2 groups. The length of hospital stay was longer in the MS group (13.0 vs.7.8 days, P=0.022). No postoperative mortality occurred. The incidence of grade ≥ IIIa postoperative complications (19.0% vs. 5.1%, P=0.001), especially pulmonary complications (11.9% vs. 2.5%, P=0.003), was significantly higher in the MS group. This group also showed a higher Comprehensive Complication Index (29.0 vs. 13.9, P<0.001). Conclusions Among patients with a ligated ALHA, those with peak AST/ALT ≥5 times the ULN showed worse perioperative outcomes in terms of hospital stay and severity of complications. More precise perioperative decision-making tools are needed to better determine whether to preserve or ligate an ALHA.

Purpose: Various studies have indicated that reduced-port robotic gastrectomies are safe and feasible for treating patients with early gastric cancer. However, there have not been any comparative studies conducted that have evaluated patients with clinically advanced gastric cancer. Therefore, we aimed to compare the perioperative outcomes of D2 lymph node dissections during reduced-port robotic distal subtotal gastrectomies (RRDGs) and conventional 5-port laparoscopic distal subtotal gastrectomies (CLDGs). Materials and Methods: We retrospectively evaluated 118 patients with clinically advanced gastric cancer who underwent minimally invasive distal subtotal gastrectomies with D2 lymph node dissections between February 2016 and November 2019. To evaluate the patient data, we performed a 1:1 propensity score matching (PSM) according to age, sex, body mass index, American Society of Anesthesiologists physical status classification score, and clinical T status. The short-term surgical outcomes were also compared between the two groups. Results: The PSM identified 40 pairs of patients who underwent RRDG or CLDG. The RRDG group experienced a significantly longer operation time than the CLDG group (P<0.001), although the RRDG group had significantly less estimated blood loss (P=0.034). The number of retrieved extraperigastric lymph nodes in the RRDG group was significantly higher than that of the CLDG group (P=0.008). The rate of postoperative complications was not significantly different between the two groups (P=0.115). Conclusions D2 lymph node dissections can be safely performed during RRDGs and the perioperative outcomes appear to be comparable to those of conventional laparoscopic surgeries. Further studies are needed to compare long-term survival outcomes.

PURPOSE: Clinical implications of single patient classifier (SPC) and microsatellite instability (MSI) in stage II/III gastric cancer have been reported. We investigated SPC and the status of MSI and Epstein-Barr virus (EBV) as combinatory biomarkers to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer. MATERIALS AND METHODS: Tumor specimens and clinical information were collected from patients enrolled in CLASSIC trial, a randomized controlled study of capecitabine plus oxaliplatin-based adjuvant chemotherapy. The results of nine-gene based SPC assay were classified as prognostication (SPC-prognosis) and prediction of chemotherapy benefit (SPC-prediction). Five quasimonomorphic mononucleotide markers were used to assess tumor MSI status. EBV-encoded small RNA in situ hybridization was performed to define EBV status. RESULTS: There were positive associations among SPC, MSI, and EBV statuses among 586 patients. In multivariate analysis of disease-free survival, SPC-prognosis [hazard ratio (HR): 1.879 (1.101–3.205), 2.399 (1.415–4.067), p=0.003] and MSI status (HR: 0.363, 95% confidence interval: 0.161–0.820, p=0.015) were independent prognostic factors along with age, Lauren classification, TNM stage, and chemotherapy. Patient survival of SPC-prognosis was well stratified regardless of EBV status and in microsatellite stable (MSS) group, but not in MSI-high group. Significant survival benefit from adjuvant chemotherapy was observed by SPC-Prediction in MSS and EBV-negative gastric cancer. CONCLUSION: SPC, MSI, and EBV statuses could be used in combination to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer.
Biomarkers ; Capecitabine ; Chemotherapy, Adjuvant ; Classification ; Disease-Free Survival ; Drug Therapy ; Herpesvirus 4, Human ; Humans ; In Situ Hybridization ; Microsatellite Instability ; Microsatellite Repeats ; Multivariate Analysis ; Prognosis ; RNA ; Stomach Neoplasms

As radical gastrectomy with lymph node dissection is currently the best strategy to cure gastric cancer, the role of the surgeon remains quite important in conquering it. Dr. Sung Hoon Noh, a surgeon and surgical oncologist specializing in gastric cancer, has treated gastric cancer for 30 years and has conducted over 10000 cases of gastrectomy for gastric cancer. He first adapted an electrocautery device into gastric cancer surgery and has led standardization of surgical procedures, including spleen preserving gastrectomy. His procedures based on patient-oriented insights have become the basis of the concept of enhanced recovery after surgery. He has also contributed to improving patient's survival through adoption of a multidisciplinary approach: he proved the benefit of adjuvant chemotherapy after radical D2 gastrectomy for stage II/III gastric cancer in clinical trials, updating treatment guidelines throughout the world. Dr. Noh also opened the era of precision medicine for treating gastric cancer, as he developed and validated a mRNA expression based algorithm to predict prognosis and response to chemotherapy. This article reviews his contribution and long history of service in the field of gastric cancer. The perspectives of this master surgeon, based on his profound experience and insights, will outline directions for integrative multidisciplinary health care and how can surgeons prepare for the future.
Chemotherapy, Adjuvant ; Delivery of Health Care ; Drug Therapy ; Electrocoagulation ; Gastrectomy ; Lymph Node Excision ; Precision Medicine ; Prognosis ; RNA, Messenger ; Spleen ; Stomach Neoplasms ; Surgeons

PURPOSE: Identification of biomarkers to predict recurrence risk is essential to improve adjuvant treatment strategies in stage II/III gastric cancer patients. This study evaluated biomarkers for predicting survival after surgical resection. MATERIALS AND METHODS: This post-hoc analysis evaluated patients from the CLASSIC trial who underwent D2 gastrectomywith orwithout adjuvant chemotherapy (capecitabine plus oxaliplatin) at the Yonsei Cancer Center. Tumor expressions of thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), and programmed death-ligand 1 (PD-L1) were evaluated by immunohistochemical (IHC) staining to determine their predictive values. RESULTS: Among 139 patients, IHC analysis revealed high tumor expression of TS (n=22, 15.8%), ERCC1 (n=23, 16.5%), and PD-L1 (n=42, 30.2%) in the subset of patients. Among all patients, high TS expression tended to predict poor disease-free survival (DFS; hazard ratio [HR], 1.80; p=0.053), whereas PD-L1 positivity was associated with favorable DFS (HR, 0.33; p=0.001) and overall survival (OS; HR, 0.38; p=0.009) in multivariate Cox analysis. In the subgroup analysis, poor DFS was independently predicted by high TS expression (HR, 2.51; p=0.022) in the adjuvant chemotherapy subgroup (n=66). High PD-L1 expression was associated with favorable DFS (HR, 0.25; p=0.011) and OS (HR, 0.22; p=0.015) only in the surgery-alone subgroup (n=73). The prognostic impact of high ERCC1 expression was not significant in the multivariate Cox analysis. CONCLUSION: This study shows that high TS expression is a predictive factor for worse outcomes on capecitabine plus oxaliplatin adjuvant chemotherapy, whereas PD-L1 expression is a favorable prognostic factor in locally advanced gastric cancer patients.
Biomarkers ; Capecitabine ; Chemotherapy, Adjuvant ; Disease-Free Survival ; DNA Repair ; Humans ; Immunohistochemistry ; Prognosis ; Prospective Studies ; Recurrence ; Stomach Neoplasms ; Thymidylate Synthase

PURPOSE: Splenic hilar lymph node dissection (LND) during total gastrectomy is regarded as the standard treatment for proximal advanced gastric cancer (AGC). This study aimed to investigate whether splenic hilar LND or D2 LND is essential for proximal AGC of pT2-4aN0M0 stage. MATERIALS AND METHODS: Data of curative total gastrectomies (n=370) performed from 2000 to 2010 for proximal AGC of pT2-4aN0 stage were retrospectively reviewed. Clinicopathological characteristics and long-term outcomes were compared using propensity score matching between patients who underwent splenectomy (n=43) and those who did not (n=327) and between patients who underwent D2 LND (n=122) and those who underwent D1+ LND (n=248). RESULTS: Tumors of larger size and a more advanced T stage and significantly lower overall and relapse-free survival (P<0.001) were observed in the splenectomy group than in the 2 spleen-preserving groups. Before propensity score matching, worse overall and relapse-free survival (P<0.001) was observed in the splenectomy group than in the non-splenectomy group. After matching, although the overall survival became similar (P=0.123), relapse-free survival was worse in the splenectomy group (P=0.021). Compared with D1+ LND, D2 LND had no positive impact on the overall (P=0.619) and relapse-free survival (P=0.112) after propensity score matching. CONCLUSIONS: Splenic hilar LND with or without splenectomy may not have an oncological benefit for patients with pathological AGC with no LN metastasis.
Gastrectomy ; Humans ; Lymph Node Excision ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis ; Propensity Score ; Retrospective Studies ; Splenectomy ; Stomach Neoplasms

PURPOSE: The robotic system for surgery was introduced to gastric cancer surgery in the early 2000s to overcome the shortcomings of laparoscopic surgery. The more recently introduced da Vinci Xi® system offers benefits allowing four-quadrant access, greater range of motion, and easier docking through an overhead boom rotation with laser targeting. We aimed to identify whether the Xi® system provides actual advantages over the Si® system in gastrectomy for gastric cancer by comparing the operative outcomes. MATERIALS AND METHODS: We retrospectively reviewed all patients who underwent robotic gastrectomy as treatment for gastric cancer from March 2016 to March 2017. Patients' demographic data, perioperative information, and operative and pathological outcomes were collected and analyzed. RESULTS: A total of 109 patients were included in the Xi® group and 179 in the Si® group. Demographic characteristics were similar in both groups. The mean operative time was 229.9 minutes in the Xi® group and 223.7 minutes in the Si® group. The mean estimated blood loss was 72.7 mL in the Xi® group and 62.1 mL in the Si® group. No patient in the Xi® group was converted to open or laparoscopy, while 3 patients in the Si® group were converted, 2 to open surgery and 1 to laparoscopy, this difference was not statistically significant. Bowel function was resumed 3 days after surgery, while soft diet was initiated 4 days after surgery. CONCLUSIONS: We found no difference in surgical outcomes after robotic gastrectomy for gastric cancer between the da Vinci Xi® and da Vinci Si® procedures.
Diet ; Gastrectomy ; Humans ; Laparoscopy ; Operative Time ; Range of Motion, Articular ; Retrospective Studies ; Stomach Neoplasms

PURPOSE: We aimed to evaluate the clinical characteristics of microsatellite instability in early gastric cancer.MATERIALS AND METHODS: The microsatellite instability status of resected early gastric tumors was evaluated using two mononucleotide repeat markers (BAT25 and BAT26) and three dinucleotide repeat markers (D5S346, D2S123, and D17S250). Tumors with instability in two or more markers were defined as microsatellite instability-high (MSI-H) and others were classified as microsatellite stable (MSS).RESULTS: Overall, 1,156 tumors were included in the analysis, with 85 (7.4%) classified as MSI-H compared with MSS tumors. For MSI-H tumors, there was a significant correlation with the female sex, older age, tumor location in the lower gastric body, intestinal histology, lymphovascular invasion (LVI), and submucosal invasion (P<0.05). There was also a trend toward an association with lymph node (LN) metastasis (P=0.056). In mucosal gastric cancer, there was no significant difference in MSI status in tumors with LN metastasis or tumors with LVI. In submucosal gastric cancer, LVI was more frequently observed in MSI-H than in MSS tumors (38.9% vs. 25.0%, P=0.027), but there was no difference in the presence of LN metastases. The prognosis of MSI-H tumors was similar to that of MSS tumors (log-rank test, P=0.797, the hazard ratio for MSI-H was adjusted by age, sex, pT stage, and the number of metastatic LNs, 0.932; 95% confidence interval, 0.423–2.054; P=0.861).CONCLUSIONS: MSI status was not useful in predicting prognosis in early gastric cancer. However, the frequent presence of LVI in early MSI-H gastric cancer may help guide the appropriate treatment for patients, such as endoscopic treatment or limited LN surgical dissection.
Dinucleotide Repeats ; Female ; Humans ; Lymph Nodes ; Microsatellite Instability ; Microsatellite Repeats ; Neoplasm Metastasis ; Prognosis ; Stomach Neoplasms

PURPOSE: The modification of the cancer classification system aimed to improve the classical anatomy-based tumor, node, metastasis (TNM) staging by considering tumor biology, which is associated with patient prognosis, because such information provides additional precision and flexibility. MATERIALS AND METHODS: We previously developed an mRNA expression-based single patient classifier (SPC) algorithm that could predict the prognosis of patients with stage II/III gastric cancer. We also validated its utilization in clinical settings. The prognostic single patient classifier (pSPC) differentiates based on 3 prognostic groups (low-, intermediate-, and high-risk), and these groups were considered as independent prognostic factors along with TNM stages. We evaluated whether the modified TNM staging system based on the pSPC has a better prognostic performance than the TNM 8th edition staging system. The data of 652 patients who underwent gastrectomy with curative intent for gastric cancer between 2000 and 2004 were evaluated. Furthermore, 2 other cohorts (n=307 and 625) from a previous study were assessed. Thus, 1,584 patients were included in the analysis. To modify the TNM staging system, one-grade down-staging was applied to low-risk patients according to the pSPC in the TNM 8th edition staging system; for intermediate- and high-risk groups, the modified TNM and TNM 8th edition staging systems were identical. RESULTS: Among the 1,584 patients, 187 (11.8%), 664 (41.9%), and 733 (46.3%) were classified into the low-, intermediate-, and high-risk groups, respectively, according to the pSPC. pSPC prognoses and survival curves of the overall population were well stratified, and the TNM stage-adjusted hazard ratios of the intermediate- and high-risk groups were 1.96 (95% confidence interval [CI], 1.41–2.72; P < 0.001) and 2.54 (95% CI, 1.84–3.50; P < 0.001), respectively. Using Harrell's C-index, the prognostic performance of the modified TNM system was evaluated, and the results showed that its prognostic performance was better than that of the TNM 8th edition staging system in terms of overall survival (0.635 vs. 0.620, P < 0.001). CONCLUSIONS: The pSPC-modified TNM staging is an alternative staging system for stage II/III gastric cancer.
Biology ; Classification ; Cohort Studies ; Gastrectomy ; Humans ; Neoplasm Metastasis ; Neoplasm Staging* ; Pliability ; Prognosis ; RNA, Messenger ; Stomach Neoplasms*