Identification of maximal tumor size associated with negligible lymph node metastasis for endoscopic submucosal dissection of undifferentiated-type early gastric cancer.

BACKGROUND AND AIMS: When treating undifferentiated-type early gastric cancer (UD-EGC) that is limited to the mucosa (clinically T1a), endoscopic submucosal dissection (ESD) can be considered if the tumor is 2 cm or less and is not ulcerated. However, there is insufficient evidence to determine the relationships between tumor size and oncological safety of ESD in UD-EGC. METHODS: The pathology reports of Korean patients who were diagnosed with UD-EGC (n = 5286) were retrospectively reviewed. The cumulative incidence of lymph node metastasis (LNM) according to tumor size was evaluated in subgroups. The tumor-size cut-off was identified as the upper limit of the 95% confidence interval (CI) of cumulative LNM incidence that did not exceed 1.0%. RESULTS: We identified 1516 patients with non-ulcerated T1a tumors ≤2 cm in size. Among patients without lymphatic invasion, 1.5% (95% CI 0.91-2.16%) had LNM. In patients with poorly differentiated tubular adenocarcinoma (PD), LNM increased from 0 to 0.74% based on a tumor size of 1.0 cm. Regardless of tumor size, smaller percentages of undifferentiated-type (UD) and poorly cohesive carcinoma (PCC) patients experienced LNM than did those with PD. In non-ulcerated mucosal cancer without lymphatic invasion and tumor size ≤0.9 cm, no LNM was observed in patients with UD (95% CI 0-0.53%), PCC (95% CI 0-0.59%), or PD (95% CI 0-0.86%) histologic type. CONCLUSION: In patients diagnosed with non-ulcerated T1a UD-EGC, ESD can be performed if the tumor size is 0.9 cm or less, regardless of histologic type.

Meso-jejunal lymph node dissection has a survival benefit in patients with remnant gastric cancer.

BACKGROUND: Clinical benefits of the meso-jejunal lymph node (MJLN) dissection in remnant gastric cancer (RGC) patients have not been fully established. Hence, in this retrospective study, we evaluated the survival benefit of MJLN dissection and prognostic significance of MJLN metastasis in RGC patients who underwent gastrojejunostomy reconstruction after their initial gastrectomy. METHODS: We retrospectively reviewed 391 patients who underwent surgery for RGC at our institution between 1996 and 2019. Among them, 60 patients had MJLN dissection. The index value of the survival benefit gained by dissection of the MJLN was calculated by multiplying the frequency of metastasis at the MJLN station and the 5-year overall survival rate (5YOS) of patients with metastasis at that station. When the metastatic rate or 5YOS exceeded 10%, dissection was recommended. An index value of dissection greater than 1.0 was considered significant. RESULTS: Total metastatic rate of MJLN was 35% (n = 21/60). Patients with MJLN metastasis had advanced pathologic stage compared to patients in the no-metastasis group (p < 0.001). In T2-T4 RGC patients, the metastatic rate of MJLN was 48.6% (n = 17/35), and their 5YOS was 28.4%. The calculated index value was 13.8. Also, patients with MJLN metastasis had a poorer overall survival than those without metastasis. MJLN metastasis was an independent prognostic factor of overall survival in multivariate analysis (HR 6.77, 95%CI 2.21-20.79, p = 0.001). CONCLUSION: MJLN dissection should be considered for advanced RGC patients who underwent gastrojejunostomy after distal gastrectomy during their initial surgery according to the index value.

Prognostic Significance of Esophagogastric Junction Invasion in Patients with Adenocarcinoma of the Cardia or Subcardia.

BACKGROUND: There has been no comparison of the prognoses of Korean patients who underwent curative surgery for cancer located at the cardia or subcardia of the stomach. We performed this comparison and further investigated the prognostic significance of esophagogastric junction (EGJ) invasion in patients. METHODS: The medical records of patients (n = 511) who were diagnosed with cardia or subcardia cancer and underwent surgery between January 2010 and May 2019 were retrospectively reviewed. Patients were further categorized into four groups for analysis: subcardia gastric cancer (sGC; subcardia cancer without EGJ invasion; n = 97), AEG (adenocarcinoma of the esophagogastric junction) type III (subcardia cancer with EGJ invasion, n = 54), AEG type II without EGJ invasion (n = 158), and AEG type II with EGJ invasion (n = 202). We compared the overall survival of the four groups using a gastric cancer staging system and evaluated the prognostic significance of EGJ invasion with multivariate analysis. RESULTS: The median follow-up of patients was 46.0 months (range: 0-124 months). There was significant difference in overall survival curves among the four groups (p < 0.001). Subgroup analysis showed a significant difference in overall survival between the groups with and without EGJ invasion (p < 0.001). Cancers with EGJ invasion were more frequently in the cardia (p < 0.001), had a larger size (p < 0.001), and showed a more advanced pathologic stage (stages II and III; 67.6% versus 33.7%, p < 0.001) than those without EGJ invasion. EGJ invasion and the pathologic stage were significant independent prognostic factors of overall survival in cardia and subcardia cancer patients (hazard ratio 2.24, 95% confidence interval 1.32-3.81, p = 0.003). CONCLUSION: The overall survival between patients with cardia or subcardia cancer was significantly different according to EGJ invasion. EGJ invasion was an independent prognostic factor and should be considered for staging. Additional research is needed to apply this feature to gastric and esophageal cancer classification.

Trends in vitamin D level and risk of vitamin D deficiency after gastrectomy for gastric cancer: A retrospective study of a single high-volume center experience.

BACKGROUND & AIMS: Post-gastrectomy vitamin D deficiency can result in osteoporosis and fractures, which can decrease patient quality of life and increase their socioeconomic burden. However, because there is no consensus around preoperative measurement and regular postoperative monitoring of serum vitamin D [25(OH)vitD] level for gastric cancer patients, we performed a retrospective study with a single high-volume center experience. METHODS: We reviewed a database of 614 gastric cancer patients who underwent curative gastrectomy between December 2015 and December 2019. Multivariate analyses were performed to identify risk factors for 25(OH)vitD deficiency after one year postoperative (n = 546). A linear mixed model was used to evaluate changes between preoperative (n = 585) and postoperative (6 [n = 504] and 12 months [n = 572]) 25(OH)vitD values. RESULTS: Preoperative 25(OH)vitD deficiency occurred in 67.7% of patients with gastric cancer. Patients who underwent postoperative chemotherapy for advanced pathologic disease were more likely to be 25(OH)vitD deficient at postoperative year one than those who did not receive chemotherapy (P = 0.005). Postoperative chemotherapy was an independent risk factor along with preoperative 25(OH)vitD level for one year postoperative 25(OH)vitD deficiency (P = 0.002). Meanwhile, there was significant change in 25(OH)vitD level after surgery according to reconstruction (increased in Billroth I group compared to gastrojejunostomy group, P = 0.016), pathologic stage (increased in stage I group, decreased in stage II and III group, P = 0.005), postoperative chemotherapy (increased in non-chemotherapy group, decreased in chemotherapy group, P = 0.001), and season of surgery (increased when the blood tests were performed at summer, decreased when tested in non-summer season, P = 0.009). CONCLUSION: More than half of gastric cancer patients had preoperative 25(OH)vitD deficiency, and those who had postoperative chemotherapy were at risk for 25(OH)vitD deficiency one year after surgery. There was a significant change in 25(OH)vitD level after surgery according to reconstruction method and postoperative chemotherapy. Preoperative measurement and regular postoperative monitoring should be considered for high-risk patients.

Clinical Significance of Preoperative Hematological Parameters in Patients with D2-Resected, Node-Positive Stomach Cancer.

The purpose of the present study was to investigate the clinical significance of preoperative hematological parameters in patients with advanced stomach cancer, and to explore who might benefit from adjuvant concurrent chemoradiotherapy (CCRT) compared to chemotherapy alone. Among 1032 patients with node-positive stomach cancer who had a confirmed diagnosis after complete D2 resection, and who received adjuvant chemotherapy alone or CCRT, a total of 692 patients was selected using propensity score matching. Among absolute neutrophil count, absolute lymphocyte count (ALC), absolute monocyte count (AMC), platelet count, neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio, AMC was the most relevant prognostic factor for overall survival and recurrence-free survival (hazard ratio (HR) 1.674, 95% confidence interval (CI) 1.180-2.376; HR 1.908, 95% CI 1.650-2.695, respectively). In a subgroup with a high ALC, patients treated with adjuvant CCRT had a favorable recurrence-free survival (HR 0.620, 95% CI 0.393-0.980) compared to those treated with chemotherapy alone. Further study is needed to confirm our findings and to develop tailored adjuvant treatment.

Feasibility of Gastric Tumor Xenograft (GTX)-derived Cell Lines for Individualized Anti-cancer Drug Screening.

BACKGROUND/AIM: Because there are ongoing efforts to identify and develop novel drugs in the treatment of refractory gastric cancer, it is necessary to develop effective preclinical studies. Here, the preclinical efficacy of gastric tumor xenograft (GTX)-derived cell line models for the personalized treatment of gastric cancer was investigated. MATERIALS AND METHODS: Anti-cancer drugs were scanned with high-throughput screening (HTS) using pre-established GTX-derived cell lines. The efficacy of a selected drug (afatinib) was re-confirmed in vivo and intracellular signaling pathways were investigated in xenograft tumor cell lysates using western blotting. Validation studies, such as cell proliferation and caspase activity assays, were also conducted in vitro with GTX-derived cell lines. RESULTS: HTS indicated that afatinib was effective in one of the five GTX-derived cell lines (GTX-087). A xenograft mouse model was established from GTX-087, and administration of afatinib at 1 mg/20 g body weight/day per oral resulted in tumor-suppressive activity in vivo. The RAS-ERK pathway was inactivated by an increase in Bax and cleaved caspase-3 in this xenograft model. In vitro cell proliferation assay also revealed that afatinib was able to suppress the growth of the GTX-087 cell line. Caspase activity assay confirmed that afatinib had an apoptotic role on GTX-087 and showed that caspase-3/7 activity increased in a time dependent manner. CONCLUSION: The GTX-derived cell line model might be useful for estimating novel drug responses and could be an alternative to patient-derived xenograft animal models.

A preoperative risk prediction model for high malignancy potential gastrointestinal stromal tumors of the stomach.

BACKGROUND: Gastric gastrointestinal stromal tumors (GISTs) exhibit various degrees of aggression and malignant potential. However, no systematic preoperative evaluation strategy to predict the malignancy potential of gastric GISTs has yet been developed. This study aimed to develop a reliable and easy-to-use preoperative risk-scoring model for predicting high malignancy potential (HMP) gastric GISTs. METHODS: The data of 542 patients with pathologically confirmed gastric GISTs who underwent resection were reviewed. Multivariate logistic regression analysis was used to identify significant predictors of HMP. The risk-scoring system (RSS) was based on the predictive factors for HMP, and its performance was validated using a split-sample approach. RESULTS: A total of 239 of 542 (44.1%) surgically resected gastric GISTs had HMP. Multivariate analysis demonstrated that tumor size, location, and surface changes were independent risk factors for HMP. Based on the accordant regression coefficients, the presence of surface ulceration was assigned 1 point. Tumor sizes of 4-6 cm and > 6 cm were assigned 2 and 5 points, respectively. Two points were assigned to cardia or fundus locations. A score of 3 points was the optimal cut-off value for HMP prediction. HMP were found in 19.8% and 82.7% of the low and high-risk groups of the RSS, respectively. The area under the receiver-operating characteristic curve for predicting HMP was 0.81 (95% confidence interval (CI) 0.75-0.86). Discrimination was good after validation (0.75, 95% CI 0.69-0.81). CONCLUSION: This simple RSS could be useful for predicting the malignancy potential of gastric GISTs and may aid preoperative clinical decision making to ensure optimal treatment.

Comparison of transabdominal and transthoracic surgical approaches in the treatment of Siewert type II esophagogastric junction cancers: A propensity score-matching analysis.

BACKGROUND: The appropriate surgical approach for Siewert type II esophagogastric junction (EGJ) cancer remains under discussion. We compared surgical outcomes between transabdominal (TA) and transthoracic (TT) approaches for treating type II EGJ cancers. MATERIALS AND METHODS: This retrospective study reviewed 397 type II EGJ cancer patients who underwent surgery from January 2001 to May 2019. We used a 1:3 propensity score-matching method for the analysis. The matching factors were age, sex, American Society of Anesthesiologists score, period of operation, and pathologic stage. Matching was performed using the MatchIt package of R 4.0.2. RESULTS: A total of 46 patients in the TT group was matched to 126 patients in the TA group. R0 resection was achieved in both groups and was not statistically different between groups (p = 0.455). In the TA group, the operation time and in-hospital stay length were significantly shorter (p < 0.001) and the intraoperative estimated blood loss (EBL) was significantly lower than in the TT group (p = 0.011). The postoperative complication rate between the two groups was significantly different (p = 0.003). There was marginal difference in the five-year OS rate (p = 0.049) and significant difference in the five-year DFS (p = 0.039). However, surgical approach was not a significant prognostic factor in multivariate analysis of OS or DFS. CONCLUSIONS: There was no clear survival benefit of one approach over the other. However, less intraoperative bleeding, lower postoperative complication rate, shorter operation time, and reduced in-hospital stay length were correlated with the TA approach.

Prospective multicentre randomised clinical trial comparing survival rates, quality of life and nutritional status between advanced gastric cancer patients with different follow-up intensities: study protocol for the STOFOLUP trial.

INTRODUCTION: Patients who underwent curative gastrectomy for gastric cancer are regularly followed-up for the early detection of recurrence and postoperative symptom management. However, there is a lack of evidence with regard to proper surveillance intervals and diagnostic tools. This study aims to evaluate whether frequent surveillance tests have a survival benefit or improve the quality of life in patients who underwent curative resection for advanced gastric cancer. METHODS AND ANALYSIS: The STOFOLUP trial is an investigator-initiated, parallel-assigned, multicentre randomised controlled trial involving 16 hospitals in the Republic of Korea. Patients (n=886) diagnosed with pathological stage II or III gastric adenocarcinoma will be randomised to either the 3-month or the 6-month group at a 1:1 ratio, stratified by trial site and tumour stage. Patients allocated to the 3-month group will undergo an abdominal CT scan every 3 months postoperatively and those allocated to the 6-month group will undergo CT every 6 months. The primary endpoint is 3-year overall survival and the secondary endpoints are quality of life, as assessed using KOrean QUality of life in Stomach cancer patients Study group-40, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and the stomach cancer-specific module (STO22), and nutritional outcomes. Other survival data including data concerning 3-year disease-free survival, recurrence-free survival, gastric cancer-specific survival and postrecurrence survival will also be estimated. The first patient was enrolled on July 2021 and active patient enrolment is currently underway. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board of eight of the participating hospitals (NCC 2021-0085, KBSMC2021-01-059, SMC 2021-01-140, KC21OEDE0082, 4-2021-0281, AJIRB-MED-INT-20-608, 2021-0515 and H-2102-093-1198). This study will be disseminated through peer-reviewed publications, national or international conferences. TRIAL REGISTRATION NUMBER: NCT04740346.

Prognostic Value of Highly Expressed Type VII Collagen (COL7A1) in Patients With Gastric Cancer.

Collagen is a major component in the tumor microenvironment. This study reveals a novel biomarker candidate, type VII collagen (COL7A1), in patients with gastric cancer. To identify genes differentially expressed in gastric cancer tissue, we analyzed cancerous (n = 20) and noncancerous tissues (n = 13) using a DNA microarray. To perform immunohistochemistry and validate the upregulation of COL7A1 expression, we collected 200 more gastric cancer tissues and 100 normal gastric tissues from 200 randomly selected patients who underwent gastrectomy for gastric cancer between January 2010 and December 2013. The correlations between COL7A1 expression and clinicopathological parameters and patients' overall survival (OS) were analyzed. In the microarray, COL7A1 was upregulated in gastric cancer tissue compared with normal tissue. In the immunohistochemistry study, COL7A1 was more highly expressed in cancer tissue than in normal tissue (p = 0.001). Patients with intracellular COL7A1 expression had significantly poorer five-year OS than those with only extracellular expression (41.5 versus 69.7%, p = 0.001), and the site of expression was an independent prognostic factor of OS (hazard ratio 2.00, 95% CI 1.26-3.16, p = 0.003). Also, we found a significant association between the COL7A1 immunohistochemistry score and distant metastasis (high versus low, odds ratio 4.45, 95% CI 1.40-14.16, p = 0.011). The site and total immunohistochemistry score of COL7A1 expression in gastric cancer showed prognostic significance for OS and distant metastasis, respectively. COL7A1 could be a novel biomarker with diagnostic and therapeutic value.

Long-term effect of simplified dietary education on the nutritional status of patients after a gastrectomy.

Dietary education is regarded as an important and useful tool for influencing nutritional status. Since long, dietary education has been performed to improve the nutritional status of patients after a gastrectomy. This study aimed to investigate the effect of simplified dietary education on the nutritional status of patients after a gastrectomy. A total of 1,150 patients with gastric cancer underwent surgery between March 2014 and October 2015 at the Samsung Medical Center (SMC). Of these, we used the case-control matching method (1:1 match) by stratifying the factors of age and sex and included 100 patients in each group. The clinicopathologic data of the patients for two years after the gastrectomy were prospectively collected and retrospectively analyzed. The educated group (ED, N = 100) was provided with a simplified, ordinary dietary education at regular outpatient clinic visits that occurred at 1, 3, 6, and 12 months after gastrectomy and at 1-year intervals thereafter. The clinicopathologic characteristics and nutritional parameters of the educated group (ED) (N = 100) and the non-educated group (NED) (n = 100) were compared. There were no significant differences between the two groups in terms of clinical characteristics and serological parameters. Nutritional parameters, which included body weight loss, body mass index (BMI) change, and prognostic nutritional index (PNI), were also not significantly different between the two groups. Simplified dietary education at regular outpatient clinic visits was ineffective in reducing weight loss after a subtotal gastrectomy. Further research or other methods may be needed to reduce weight loss after a gastrectomy.

Long-Term Oncological Outcomes of Reduced Three-Port Laparoscopic Gastrectomy for Early-Stage Gastric Carcinoma: a Retrospective Large-Scale Multi-Institutional Study.

PURPOSE: With advances in surgical techniques, reduced-port laparoscopic surgery is increasingly being performed for the treatment of gastric carcinoma. Many studies have reported satisfactory short-term outcomes after reduced 3-port laparoscopic gastrectomy (LG). The aim of this study was to investigate the long-term oncological outcomes of 3-port LG in patients with gastric carcinoma. MATERIALS AND METHODS: We reviewed the medical records of 1,117 patients who underwent LG for gastric carcinoma in three major institutions between 2012 and 2015. The data showed that 460 patients underwent 3-port LG without assistance, and 657 underwent conventional 5-port LG. We compared the overall and disease-free survival rates between the 2 groups. RESULTS: There were 642 male and 475 female patients with a mean age of 56.1 years. Among them, 1,028 (92.0%) underwent distal gastrectomy and 89 (8.0%) underwent total gastrectomy. In the final pathologic examination, 1,027 patients (91.9%) were stage I, 73 (6.5%) were stage II, and 17 (1.5%) were stage III, and there were no significant difference in the pathologic stage between groups. The 3- and 5-port LG groups showed no significant differences in the 5-year overall survival (94.3% vs. 96.7%, P=0.138) or disease-free survival (94.3% vs. 95.9%, P=0.231). Stratified analyses according to pT and pN stages also showed no significant differences in overall or disease-free survival between the two groups. CONCLUSIONS: Long-term survival after 3- and 5-port LG was comparable in patients with early-stage gastric carcinoma. The 3-port technique requiring limited surgical assistance may be an appropriate surgical option for this patient population.

Compliance with D2 lymph node dissection in reduced-port totally laparoscopic distal gastrectomy in patients with gastric cancer.

This phase II clinical trial was performed to determine whether reduced-port laparoscopic surgery with complete D2 lymph node (LN) dissection for gastric cancer is a safe and feasible surgical technique. The prospectively enrolled 65 gastric cancer patients underwent reduced-port surgery (i.e., triple-incision totally laparoscopic distal gastrectomy [Duet TLDG] with D2 lymphadenectomy). Compliance rate was the primary outcome, which was defined as cases in which there was no more than one missing LN station during D2 LN dissection. The secondary outcomes were the numbers of dissected and retrieved LNs in each station and other short-term surgical outcomes and postoperative course. The compliance rate was 58.5%. The total number of retrieved LNs was 41 (range: 14-83 LNs). The most common station missing from LN retrieval was station no. 5 (35/65; 53.8%), followed by station no. 1 (24/65; 36.9%). The overall postoperative complication rate was 20.0% (13/65). One patient underwent surgical treatment for postoperative complications. There was no instances of mortality. Duet TLDG is an oncologically and technically safe surgical method of gastrectomy and D2 lymphadenectomy.

Prognostic significance of splenectomy during completion total gastrectomy in patients with remnant gastric cancer: propensity score matching analysis.

Purpose: Splenectomy for patients with remnant gastric cancer has been controversial. The purpose of this study is to identify the impact of splenectomy in the treatment of remnant gastric cancer. Methods: We retrospectively analyzed 285 patients with remnant gastric cancer who underwent completion total gastrectomy with or without splenectomy in Samsung Medical Center, between September 1996 and December 2017. We used a 1:1 propensity score matching method for the analysis. The matching factors were age, sex, and pathologic stage. After the matching process, we compared the 5-year overall survival (OS) and the disease-free survival (DFS) between patients with and without splenectomy during completion total gastrectomy. Results: The median duration of follow-up was 58.0 months (range, 0-132 months). After propensity score matching, there were no statistically significant differences between the splenectomy group (n=77) and no splenectomy group (n=77) in terms of clinicopathological features. The 5-year OS rate between the no splenectomy and splenectomy group were not significantly different. There was no significant difference between 5-year DFS of the matched groups. Multivariate analysis revealed that splenectomy is not a significant prognostic factor in terms of 5-year OS (no splenectomy vs. splenectomy; 61.5% vs. 60.2%, P=0.884) or DFS (74.9% vs. 69.8%, P=0.880). Conclusion: Splenectomy has no impact on the OS and DFS in patients with remnant gastric cancer. Splenectomy during completion total gastrectomy may not be necessary.

Adjuvant Chemotherapy vs. Surgery Alone for pT3N0M0 Gastric Cancer.

BACKGROUND: As both the role and clinical application of adjuvant chemotherapy (CTx) for pT3N0M0 gastric cancer after curative gastrectomy have fluctuated chronologically, the oncological benefit of adjuvant CTx in patients should be elucidated. METHODS: Between 2000 and 2018, 1083 patients underwent radical gastrectomy for pT3N0M0 gastric cancer and were subsequently divided into two groups: the surgery-alone group (n = 471) and the adjuvant CTx group (n = 612). Chronological changes in adjuvant CTx and various chemotherapeutic regimens were evaluated and disease-free survival was compared between the two groups. Risk factors for tumor recurrence were also analyzed. RESULTS: The proportion of patients in the surgery-alone group was more than 60% until 2001, whereas in the CTx group this increased to over 80%, especially after publication of the American Joint Committee on Cancer (AJCC) 7th edition staging manual. The main chemotherapeutic agents were tegafur-uracil (UFT) and 5-fluorouracil with leucovorin until 2008, whereas tegafur/gimeracil/oteracil (TS-1) has been the main agent since 2009. The 5-year disease-free survival was 89.2% in the surgery-alone group and 89.9% in the CTx group, which was not significantly different (p = 0.694). In multivariate analysis, larger tumor size (≥ 4.5 cm) and venous invasion were significant risk factors for tumor recurrence. In addition, adjuvant CTx did not improve the oncological outcome, even in the large tumor size group (p = 0.760) and the venous invasion group (p = 0.753). CONCLUSIONS: As adjuvant CTx did not show any oncological benefit in pT3N0M0 gastric cancer in this large-scale study, it might be unnecessary for these patients after curative gastrectomy.

Impact of Radiotherapy on Kidney Function among Patients Who Received Adjuvant Treatment for Gastric Cancer: Logistic and Linear Regression Analyses.

We investigated the incidence of renal function impairment after adjuvant treatment for gastric cancer and analyzed the impact of radiotherapy on estimated glomerular filtration rate (eGFR) five years after gastric surgery. We reviewed the medical records of 1490 patients with stomach cancer who underwent curative surgery and adjuvant treatment for gastric cancer. Finally, we included 663 patients who were followed up for ≥5 years without disease recurrence and whose baseline eGFR was ≥60 mL/min/1.73 m2. Logistic and linear regression analyses were performed to determine independent factors associated with the five-year eGFR. A total of 13 (2.0%) patients developed renal function impairment (five-year eGFR <60 mL/min/1.73 m2). In logistic regression analysis, the baseline eGFR was identified as a prognostic factor for renal function impairment (odds ratio (OR), 0.878; 95% confidence interval (CI), 0.831-0.927; p < 0.001), but radiotherapy was not (OR, 1.130; 95% CI, 0.366-3.491; p = 0.832). In linear regression analysis, age (B = -0.350, p < 0.001), baseline eGFR (B = 0.576, p < 0.001), cisplatin (B = -2.056, p = 0.010), and radiotherapy (B = -2.628, p < 0.001) were predictive variables for the five-year eGFR. Among patients who received adjuvant radiotherapy, age (B = -0.277, p < 0.001), hypertension (B = -4.986, p = 0.004), baseline eGFR (B = 0.665, p < 0.001), and volume of the kidneys receiving ≥20 Gy (B = -0.209, p = 0.012) were predictive variables for the five-year eGFR. Development of renal function impairment after adjuvant treatment for gastric cancer was rare among patients with normal baseline kidney function. While radiotherapy was negatively associated with the five-year eGFR, its impact would have been minimal if the kidneys were properly shielded. Further studies are needed to confirm the impact of radiotherapy in patients with poor kidney function.

Long-term oncological outcomes of laparoscopic gastrectomy for grossly early gastric cancer-mimicking advanced gastric cancer: Propensity score matching analysis.

Laparoscopic gastrectomy became an option in the treatment of early gastric cancer (EGC) in clinical practice. However, whether laparoscopic surgery for grossly EGC-mimicking advanced gastric cancer (AGC) patients is oncologically safe long-term is still controversial.We retrospectively analyzed 472 patients with AGC who were diagnosed as clinical EGC. Patients received laparoscopic or open gastrectomy with standard lymph node (LN) dissection from January 2007 to February 2015. We used a 1:3 propensity score matching method for the analysis. The matching factors were age, sex, body mass index, American Society of Anesthesiologists score and pathologic stage. After the matching process, we evaluated the 5-year overall survival and the cumulative incidence curve of recurrence.All of the analyzed patients were pathologically diagnosed with AGC after surgery (grossly EGC-mimicking AGC). The median (range) duration of follow-up was 58.0 (0-132) months. After propensity score matching, 31.5% of patients in the laparoscopy group had D1+ LN dissection and 99.2% of patients in the open group had D2 LN dissection. The 5-year overall survival rate between the laparoscopy (n = 92) and open groups (n = 244) were not significantly different (95.3% versus 91.4%, P = .224). There was no significant difference between the cumulative recurrence incidence curves of the matched groups (P = .319).Laparoscopic surgery for grossly EGC-mimicking AGC might be safe in terms of long-term survival outcome. After confirming grossly EGC-mimicking AGC in the final pathology report, no additional surgery might be required.

Effect of baseline sarcopenia on adjuvant treatment for D2 dissected gastric cancer: Analysis of the ARTIST phase III trial.

BACKGROUND AND PURPOSE: This study evaluated the clinical significance of preoperative sarcopenia according to adjuvant concurrent chemo-radiotherapy (XP-RT) or chemotherapy alone (XP) in the D2 dissected gastric cancer patient cohort of the ARTIST trial. MATERIALS AND METHODS: Skeletal muscles at the L3 vertebra level from preoperative computed tomography images among the ARTIST trial participants were measured using validated in-house software. Skeletal muscle index (SMI) was defined as the measured skeletal muscle area divided by the square of the height, and sarcopenia was defined according to the Korean-specific cutoff, i.e. L3 SMI ≤ 49 cm2/m2 for men and ≤31 cm2/m2 for women. RESULTS: Among the 440 patients in whom we were able to evaluate L3 SMI, 75 (17.0%) met the definition for preoperative sarcopenia. No differences in treatment-related toxicities or treatment compliance were observed according to the presence of preoperative sarcopenia in either treatment arm. In the subgroup of patients without preoperative sarcopenia, recurrence was significantly lower in the XP-RT arm than that in the XP arm (p = 0.02). Recurrence-free survival (RFS) was also significantly higher in the XP-RT arm (p = 0.02, hazard ratio 0.633, 95% confidence interval 0.433-0.926) in this subgroup. In the multivariate analysis, and after adjusting for significant prognostic factors, the superior outcome of XP-RT arm regarding RFS was maintained in the subgroup of the patients without preoperative sarcopenia. CONCLUSIONS: Superior clinical outcomes of adjuvant XP-RT over XP were only observed in patients without preoperative sarcopenia.

Comparisons of remnant primary, residual, and recurrent gastric cancer and applicability of the 8th AJCC TNM classification for remnant gastric cancer staging.

BACKGROUND: Because there is no well-established postoperative staging system for patients with remnant gastric cancer (RGC), we compared the overall survival of patients categorized with the 8th AJCC TNM staging system. METHOD: A total of 391 patients underwent surgery for RGC at our institution between 1996 and 2019. Among them, 201 patients received their first surgery at our institution and 190 received primary surgery elsewhere. We retrospectively reviewed their medical records and classified each according to Kaminishi's classification and the 8th AJCC TNM staging system for comparison and analysis. RESULTS: All 201 patients who underwent their first operation at our institution for malignancy were classified as primary (n = 41, 20.4%), residual (n = 103, 51.2%), and recurrent (n = 57, 28.4%) RGC. The 5-year overall survival (OS) rates for the primary, residual, and recurrent RGC groups were 78.1%, 73.8% and 56.0%, respectively (p = 0.004). In a multivariate analysis, RGC classification was an independent prognostic factor along with the TNM staging system (p = 0.001). However, there was no significant difference in OS between the three groups of the same TNM stage. In addition, the OS of each stage related to primary cancer was not significantly different from the OS of RGC patients classified in TNM staging. CONCLUSION: The RGC classification system we used may reflect the comprehensive aspects of previous disease states and predict the prognosis of patients with gastric cancer. In addition, the 8th AJCC TNM classification is a practical and applicable staging system for RGC.

Outcomes of Radiotherapy for Mesenchymal and Non-Mesenchymal Subtypes of Gastric Cancer.

Background: The purpose of this study was to evaluate the clinical outcomes following postoperative chemotherapy (XP) versus chemoradiotherapy (XP-RT) according to mesenchymal subtype based on RNA sequencing in gastric cancer (GC) in a cohort of the Adjuvant chemoRadioTherapy In Stomach Tumor (ARTIST) trial. Methods: Of the 458 patients enrolled in the ARTIST trial, formalin-fixed, paraffin-embedded (FFPE) specimens were available from 106 (23.1%) patients for RNA analysis. The mesenchymal subtype was classified according to a previously reported 71-gene MSS/EMT signature using the NanoString assay. Results: Of the 106 patients analyzed (50 in XP arm, 56 in XP-RT arm), 36 (34.0%) patients were categorized as mesenchymal subtype by NanoString assay. Recurrence-free survival (RFS, p = 0.009, hazard ratio (HR) = 2.11, 95% confidence interval (CI): 1.21-3.70) and overall survival (OS, p = 0.003, HR = 2.28, 95% CI: 1.31-3.96) were significantly lower in the mesenchymal subtype than in the non-mesenchymal subtype. In terms of post-operative radiotherapy (RT), mesenchymal subtype was not an independent variable to predict RFS or OS regardless to the assigned arm (XP with or without RT) in this patient cohort. However, there was a trend in the adjuvant XP arm, which showed higher OS than the XP-RT arm for the mesenchymal subtype and lower OS than the XP-RT arm for the non-mesenchymal subtype. Conclusions: We could not determine any significant differences between the mesenchymal and non-mesenchymal subtypes with respect to the effects of adjuvant XP with or without RT in gastric cancer following curative surgery.