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.

The Clinical Implication of Conversion Surgery in Patients with Stage IV Gastric Cancer Who Received Systemic Chemotherapy.

With the advances in chemotherapy and immunotherapy, a small subset of patients may be eligible for conversion surgery after achieving tumor regression with chemotherapy. This is a retrospective cohort study of 118 patients with stage IV gastric cancer who received palliative chemotherapy and conversion surgery with a negative resection margin at Samsung Medical Center. Baseline features included comorbidities, body mass index (BMI), carcinoembryonic antigen (CEA) level, primary tumor size, biopsy histology, distant metastatic sites, and molecular markers-HER2, MSI/MMR, PD-L1, and EBV. Post-chemotherapy features included BMI, CEA level, chemotherapy regimen, objective response to chemotherapy, and number of preoperative chemotherapy cycles. Post-operational features included tumor size, histologic differentiation and Lauren's classification, pathologic tumor and nodal stages, invasion of lymphatics/vessels/nerves, peritoneal cytology, and the receipt of postoperative chemotherapy. Of 118 patients, 60 patients received total gastrectomy and 58 patients received subtotal gastrectomy. In all, 21 patients achieved a pathologic complete response, and 97 patients achieved downstaging to yp stage I, II, or III. Before conversion surgery, patients received first-line capecitabine/oxaliplatin (62%), HER2 inhibitors combined with chemotherapy (18%), immune checkpoint inhibitors (15%), and inhibitors of MET or VEGFR2 (5%). In the multivariable analysis, BMI at the time of diagnosis, either HER2 positive, high MSI, or deficient MMR, and the use of targeted agents were significant prognostic factors. Conversion surgery could be considered in patients with stage IV gastric cancer regardless of the initial disease burden. BMI and molecular markers are important prognostic factors that can be used to select candidates.

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.

Associations of patient-generated subjective global assessment (PG-SGA) and NUTRISCORE with survival in gastric cancer patients: timing matters, a retrospective cohort study.

BACKGROUND: The timing of nutritional assessment may be important to treat cancer patients and predict their prognosis. This study examined whether Patient-Generated Subjective Global Assessment (PG-SGA) and NUTRISCORE scores were associated with survival among gastric cancer patients who underwent surgery and chemotherapy and whether the timing of the assessment after surgery mattered. METHODS: A total of 952 gastric cancer patients (622 men and 330 women) were included in this retrospective cohort study. The PG-SGA and NUTRISCORE scores were calculated at 1 month (n = 952), 2 months (n = 657), and 3 months (n = 294) after surgery. Cox proportional hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The PG-SGA scores assessed at 1 month after gastrectomy were not associated with survival. However, high PG-SGA scores at 2 months after gastrectomy (median = 65 days) were associated with an increased risk of mortality; the HR (95% CI) was 2.26 (1.22-4.21) for 9-11 vs. ≤ 5 of PG-SGA scores. When we included patients who received all three consecutive consultations, HR (95% CI) was 2.56 (1.02-6.42) for ≥ 9 (malnutrition) vs. ≤ 8 of PG-SGA scores assessed at 3 months after surgery (median days = 98 days). Likewise, high NUTRISCORE scores assessed at the 3-month follow-up were associated with higher mortality; the HR (95% CI) was 3.84 (1.18-12.55) for ≥ 7 vs. ≤ 4 of NUTRISCORE scores. CONCLUSION: Malnutrition assessed with the PG-SGA and NUTRISCORE at 2 to 3 months after gastrectomy was associated with poor survival among gastric cancer patients. Our findings suggest that the timing of the nutritional evaluation may be important in identifying and treating malnutrition related to gastric cancer prognosis.

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.

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.

Comparison of Long-Term Efficacy in S-1 and Capecitabine With Oxaliplatin as Adjuvant Chemotherapy for Patients With Gastric Cancer After Curative Surgery: A Retrospective, Single-Center Observational Study.

Purpose: Various adjuvant chemotherapies have been introduced for gastric cancer patients after gastrectomy with D2 lymph node dissection. Although the mainstream regimen of adjuvant chemotherapy in Korea includes S-1 monotherapy (TS-1) and capecitabine with oxaliplatin (XELOX), few studies have compared the long-term efficacies of these 2 regimens. Methods: Between January 2010 and June 2017, 2021 patients were diagnosed with gastric cancer and underwent curative resection with adjuvant chemotherapy at our institution. Of 1461 patients with stage IB-III gastric cancer, 825 received TS-1 and 636 received XELOX as adjuvant chemotherapy. We retrospectively reviewed their medical records and analyzed the postoperative 5-year overall survival (OS) and disease-free survival (DFS) of these 2 groups. Results: The patients in the XELOX group had more advanced stage of cancer than the TS-1 group (stages III and II: 56.6% and 43.1%, respectively, in XELOX and 35.3% and 57.0% in TS-1; P < .001). The DFS did not differ significantly between the 2 study groups at any pathologic stage. The OS differed significantly only at pathologic stages IIA (P = .024) and IIB (P = .015). In a multivariate analysis of stage II patients, type of regimen was an independent prognostic factor of OS (XELOX vs TS-1; hazard ratio: 0.47, 95% confidence interval: 0.25-0.89, P = .021). Conclusion: There were similar long-term efficacies between these 2 regimens in advanced gastric cancer patients who underwent curative surgery. However, the XELOX regimen might be favorable for OS of stage II patients.

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.

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.

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.

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.

A Multi-cohort Study of the Prognostic Significance of Microsatellite Instability or Mismatch Repair Status after Recurrence of Resectable Gastric Cancer.

PURPOSE: High microsatellite instability (MSI) is related to good prognosis in gastric cancer. We aimed to identify the prognostic factors of patients with recurrent gastric cancer and investigate the role of MSI as a prognostic and predictive biomarker of survival after tumor recurrence. MATERIALS AND METHODS: This retrospective cohort study enrolled patients treated for stage II/III gastric cancer who developed tumor recurrence and in whom the MSI status or mismatch repair (MMR) status of the tumor was known. MSI status and the expression of MMR proteins were evaluated using polymerase chain reaction and immunohistochemical analysis, respectively. RESULTS: Of the 790 patients included, 64 (8.1%) had high MSI status or MMR deficiency. The tumor-node-metastasis stage, type of recurrence, Lauren classification, chemotherapy after recurrence, and interval to recurrence were independently associated with survival after tumor recurrence. The MSI/MMR status and receiving adjuvant chemotherapy were not associated with survival after recurrence. In a subgroup analysis of patients with high MSI or MMR-deficient gastric cancer, those who did not receive adjuvant chemotherapy had better treatment response to chemotherapy after recurrence than those who received adjuvant chemotherapy. CONCLUSION: Patients with high MSI/MMR-deficient gastric cancer should be spared from adjuvant chemotherapy after surgery, but aggressive chemotherapy after recurrence should be considered. Higher tumor-node-metastasis stage, Lauren classification, interval to recurrence, and type of recurrence are associated with survival after tumor recurrence and should thus be considered when establishing a treatment plan and designing clinical trials targeting recurrent gastric cancer.

Efficacy and Safety of Ursodeoxycholic Acid for the Prevention of Gallstone Formation After Gastrectomy in Patients With Gastric Cancer: The PEGASUS-D Randomized Clinical Trial.

Importance: The incidence of gallstones has been reported to increase after gastrectomy. However, few studies have been conducted on the prevention of gallstone formation in patients who have undergone gastrectomy. Objective: To evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) in preventing gallstone formation after gastrectomy in patients with gastric cancer. Design, Setting, and Participants: The PEGASUS-D study (Efficacy and Safety of DWJ1319 in the Prevention of Gallstone Formation after Gastrectomy in Patient with Gastric Cancer: A Multicenter, Randomized, Double-blind, Placebo-controlled Study) was a randomized, double-blind, placebo-controlled clinical trial conducted at 12 institutions in the Republic of Korea. Adults (aged ≥19 years) with a diagnosis of gastric cancer who underwent total, distal, or proximal gastrectomy were enrolled between May 26, 2015, and January 9, 2017; follow-up ended January 8, 2018. Efficacy was evaluated by both the full analysis set, based on the intention-to-treat principle, and the per-protocol set; full analysis set findings were interpreted as the main results. Interventions: Eligible participants were randomly assigned to receive 300 mg of UDCA, 600 mg of UDCA, or placebo at a ratio of 1:1:1. Ursodeoxycholic acid and placebo were administered daily for 52 weeks. Main Outcomes and Measures: Gallstone formation was assessed with abdominal ultrasonography every 3 months for 12 months. Randomization and allocation to trial groups were carried out by an interactive web-response system. The primary end point was the proportion of patients developing gallstones within 12 months after gastrectomy. Results: A total of 521 patients (175 received 300 mg of UDCA, 178 received 600 mg of UDCA, and 168 received placebo) were randomized. The full analysis set included 465 patients (311 men; median age, 56.0 years [interquartile range, 48.0-64.0 years]), with 151 patients in the 300-mg group, 164 patients in the 600-mg group, and 150 patients in the placebo group. The proportion of patients developing gallstones within 12 months after gastrectomy was 8 of 151 (5.3%) in the 300-mg group, 7 of 164 (4.3%) in the 600-mg group, and 25 of 150 (16.7%) in the placebo group. Compared with the placebo group, odds ratios for gallstone formation were 0.27 (95% CI, 0.12-0.62; P = .002) in the 300-mg group and 0.20 (95% CI, 0.08-0.50; P < .001) in the 600-mg group. No significant adverse drug reactions were detected among the enrolled patients. Conclusions and Relevance: Administration of UDCA for 12 months significantly reduced the incidence of gallstones after gastrectomy for gastric cancer. These findings suggest that UDCA administration prevents gallstone formation after gastrectomy in patients with gastric cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02490111.

Long term oncological outcome of patients with grossly early gastric cancer-mimicking advanced gastric cancer.

BACKGROUND: The survival of grossly early gastric cancer-mimicking advanced gastric cancer (EGC-mimicking AGC) patients had not been investigated. We evaluated the prognosis of patients who were diagnosed as early gastric cancer before surgery and advanced gastric cancer after surgery. METHODS: This retrospective study reviewed 3592 gastric cancer patients who had radical surgery from January 2007 to February 2015. We used a 1:2 propensity score matching method for the analysis. The matching factors were age, sex, body mass index and the depth of cancer invasion. The 5-year overall survival (OS) and disease-free survival (DFS) of the two study groups were analyzed. RESULTS: The 475 grossly EGC-mimicking AGC patients were matched to 910 Borrmann type advanced gastric cancer (AGC) patients. The 5-year OS and DFS of the EGC-mimicking AGC patients were significantly higher than the Borrmann type AGC patients, (89.2% versus 83.4%, p = 0.025; 93.0% versus 85.6%, p < 0.001, respectively). The proportion of patients with lymph node (LN) metastasis was 45.5% in the EGC-mimicking AGC group and 57.1% in the Borrmann type AGC patients (p < 0.001). The ratio of metastatic LNs of N1 and N2 station was 5.2% and 3.1%, respectively, in EGC-mimicking AGC patients; this was lower than in Borrmann type AGC patients (N1: 8.9%, p < 0.001; N2: 3.7%, p = 0.308). CONCLUSIONS: Patients with grossly EGC-mimicking AGC had better prognosis than patients with the Borrmann type AGC due to fewer LN metastases. This suggests that limited LN dissection of EGC-mimicking AGC patients may be feasible.

Comprehensive pharmacogenomic characterization of gastric cancer.

BACKGROUND: Gastric cancer is among the most lethal human malignancies. Previous studies have identified molecular aberrations that constitute dynamic biological networks and genomic complexities of gastric tumors. However, the clinical translation of molecular-guided targeted therapy is hampered by challenges. Notably, solid tumors often harbor multiple genetic alterations, complicating the development of effective treatments. METHODS: To address such challenges, we established a comprehensive dataset of molecularly annotated patient derivatives coupled with pharmacological profiles for 60 targeted agents to explore dynamic pharmacogenomic interactions in gastric cancers. RESULTS: We identified lineage-specific drug sensitivities based on histopathological and molecular subclassification, including substantial sensitivities toward VEGFR and EGFR inhibition therapies in diffuse- and signet ring-type gastric tumors, respectively. We identified potential therapeutic opportunities for WNT pathway inhibitors in ALK-mutant tumors, a significant association between PIK3CA-E542K mutation and AZD5363 response, and transcriptome expression of RNF11 as a potential predictor of response to gefitinib. CONCLUSIONS: Collectively, our results demonstrate the feasibility of drug screening combined with tumor molecular characterization to facilitate personalized therapeutic regimens for gastric tumors.