Remnant Gastric Cancer Patients Research Articles

Identification of prognostic signatures in remnant gastric cancer through an interpretable risk model based on machine learning: a multicenter cohort study

ObjectiveThe purpose of this study was to develop an individual survival prediction model based on multiple machine learning (ML) algorithms to predict survival probability for remnant gastric cancer (RGC).MethodsClinicopathologic data of 286 patients with RGC undergoing operation (radical resection and palliative resection) from a multi-institution database were enrolled and analyzed retrospectively. These individuals were split into training (80%) and test cohort (20%) by using random allocation. Nine commonly used ML methods were employed to construct survival prediction models. Algorithm performance was estimated by analyzing accuracy, precision, recall, F1-score, area under the receiver operating characteristic curve (AUC), confusion matrices, five-fold cross-validation, decision curve analysis (DCA), and calibration curve. The best model was selected through appropriate verification and validation and was suitably explained by the SHapley Additive exPlanations (SHAP) approach.ResultsCompared with the traditional methods, the RGC survival prediction models employing ML exhibited good performance. Except for the decision tree model, all other models performed well, with a mean ROC AUC above 0.7. The DCA findings suggest that the developed models have the potential to enhance clinical decision-making processes, thereby improving patient outcomes. The calibration curve reveals that all models except the decision tree model displayed commendable predictive performance. Through CatBoost-based modeling and SHAP analysis, the five-year survival probability is significantly influenced by several factors: the lymph node ratio (LNR), T stage, tumor size, resection margins, perineural invasion, and distant metastasis.ConclusionsThis study established predictive models for survival probability at five years in RGC patients based on ML algorithms which showed high accuracy and applicative value.

Clinical risk factors for splenic hilar nodal metastasis in remnant gastric cancer after distal gastrectomy.

270 Background: Splenectomy is usually considered to be required for complete dissection of splenic hilar lymph node (#10 LN) in gastric cancer (GC). Although spleen-preserving D2 was established for the advanced GC not invading the grater coverture based on the JCOG0110 clinical trial, D2 gastrectomy with splenectomy remains the standard procedure for the advanced GC involving grater coverture in Japan. However, the applicability of this treatment for remnant gastric cancer (RGC) is unclear because the lymphatic flow and lymphatic metastatic pattern may have been changed after initial gastrectomy. There are no guidelines for splenic hilar nodal dissection for RGC. In this study we evaluated risk factors for #10 nodal metastasis in RGC. Methods: This study retrospectively examined RGC patients who received gastrectomy with #10 nodal dissection after distal gastrectomy at two high-volume cancer centers in Japan between 1998 and 2015. Results: 99 patients were entered in this study. The #10 nodal metastatic rate was 12.1% (12/99). Initial gastrectomy was performed for benign in 42 patients and for malignant in 52 patients. The median duration from the initial gastrectomy was 20 (1-55) years. Main tumor location was lesser curvature in 46 patients, anterior wall in 11, greater curvature in 19, posterior wall in 11, and the whole in 12. Large type 3(≥8cm) and type 4 were found in 18 cases. The median tumor size was 50 (10-232) mm. The depth of invasion was cT1 in 31 patients, cT2 in 19, cT3 in 11, cT4a in 28, and cT4b in 10. Histology was differentiated type in 46 patients and undifferentiated type in 56. Completion gastrectomy was performed in 98 patients and partial gastrectomy in 1. 89 patients underwent splenectomy. The univariate analysis showed that tumor location (lesser curvature vs others, p=0.027) and depth of invasion (cT1-3 vs cT4, p=0.032) were significant risk factors for #10 nodal metastasis. By multivariate analysis, these two factors remained significant. Metastasis to #10 nodal metastasis was 0% (0/28) in patients without both risk factors, 11-12% in those with at least one risk factor, and 30% (6/20) in those with both risk factors. Conclusions: The tumors not confined to the lesser curvature and cT4 were significant risk factors for #10 nodal metastasis of RGC after distal gastrectomy. Splenectomy should be considered for complete splenic hilar nodal dissection when these risk factors are positive.

The Effect of Surgical Approach on Clinical Outcomes in 535 Patients with Remnant Gastric Cancer.

Purpose: This study aimed to evaluate the effect of laparoscopic gastrectomy (LG) and open gastrectomy (OG) on clinical outcomes in patients with remnant gastric cancer (RGC). Materials and Methods: The databases of PubMed, EMBASE, and Cochrane Library were used to search for eligible studies from inception to April 1st, 2023. Hazard ratios (HRs), mean difference (MD), odds ratios (OR), and 95% confidence intervals (CIs) were pooled up to analyze. The Newcastle-Ottawa Scale (NOS) scores were used to evaluate the quality of the included studies. This study was performed with RevMan 5.3 (The Cochrane Collaboration, London, United Kingdom) software. Results: A total of 11 studies involving 535 RGC patients were included in this study. In terms of basic information, we found that the OG group had a higher American Society of Anesthesiologists (ASA) grade (≥2) (OR = 0.24, I2 = 54%, 95% CI = 0.08-0.71, P = .01) than the LG group. In terms of postoperative outcomes, we found that the LG group had longer operative time (MD = 33.95, I2 = 58%, 95% CI = 15.05-52.85, P < .01), shorter postoperative hospital stay (MD = 5.08, I2 = 84%, 95% CI = -9.74 to -0.42, P = .03), shorter length of incision (MD = -7.15, I2 = 94%, 95% CI = -10.99 to -3.31, P < .01), earlier food intake (MD = -3.09, I2 = 76%, 95% CI = -4.84 to -1.35, P < .01), and earlier time to first flatus (MD = -0.84, I2 = 0%, 95% CI = -1.09 to -0.59, P < .01). We found that there was no statistically significant difference in overall survival (HR = 0.96, I2 = 0%, 95% CI = 0.48-1.93, P = .92) between the LG group and the OG group. Conclusion: LG for RGC patients had longer surgical time, shorter postoperative hospital stay, shorter length of incision, earlier food intake, and earlier time to first flatus.

The value of lymph nodes ratios in the prognosis of resectable remnant gastric cancer through the retrospective propensity score matching analysis

PurposeCurrently, the characteristics and prognosis of remnant gastric cancer (RGC) are not fully understood yet. The present study aimed to describe the details of clinicopathological features of resectable RGC and investigated the factors affecting survival after the curative operation.MethodsFrom Jan. 2006 to Dec. 2015, a total of 118 resectable RGC patients (the RGC group) and 236 age-, sex- and TNM stages-matched resectable gastric cancer (GC) patients (the control group) were recruited retrospectively. Clinicopathological characteristics and overall survival were compared between the two groups.ResultsThe overall survival rate was 46.61% for RGC patients compared to 55.08% for control groups (P < 0.01), and the mean overall survival time of RGC patients was 40.23 ± 32.27 months, compared to 55.06 ± 34.29 months in the control group (P = 0.023 after matching). The overall survival (OS) of RGC patients with stage IIb was much worse than IIa (P < 0.001) and similar to IIIa (P = 0.463) and IIIb (P = 0.014). Multivariate Cox proportional hazards model analysis revealed that TNM stage (HR: 3.899, P < 0.001) and lymph nodes ratio (LNR) (HR: 2.405, P = 0.028) were independent prognostic significance to OS.ConclusionsThe OS of RGC was much worse than GC with similar TNM stages, and LNR might consider a highly reliable indicator to evaluate the prognostic in RGC.

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

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. 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. 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). 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 value of preoperative immune-nutritional scoring systems in remnant gastric cancer patients undergoing surgery.

Remnant gastric cancer (GC) is defined as GC that occurs five years or more after gastrectomy. Systematically evaluating the preoperative immune and nutritional status of patients and analyzing its prognostic impact on postoperative remnant gastric cancer (RGC) patients are crucial. A simple scoring system that combines multiple immune or nutritional indicators to identify nutritional or immune status before surgery is necessary. To evaluate the value of preoperative immune-nutritional scoring systems in predicting the prognosis of patients with RGC. The clinical data of 54 patients with RGC were collected and analyzed retrospectively. Prognostic nutritional index (PNI), controlled nutritional status (CONUT), and Naples prognostic score (NPS) were calculated by preoperative blood indicators, including absolute lymphocyte count, lymphocyte to monocyte ratio, neutrophil to lymphocyte ratio, serum albumin, and serum total cholesterol. Patients with RGC were divided into groups according to the immune-nutritional risk. The relationship between the three preoperative immune-nutritional scores and clinical characteristics was analyzed. Cox regression and Kaplan-Meier analysis was performed to analyze the difference in overall survival (OS) rate between various immune-nutritional score groups. The median age of this cohort was 70.5 years (ranging from 39 to 87 years). No significant correlation was found between most pathological features and immune-nutritional status (P > 0.05). Patients with a PNI score < 45, CONUT score or NPS score ≥ 3 were considered to be at high immune-nutritional risk. The areas under the receiver operating characteristic curves of PNI, CONUT, and NPS systems for predicting postoperative survival were 0.611 [95% confidence interval (CI): 0.460-0.763; P = 0.161], 0.635 (95%CI: 0.485-0.784; P = 0.090), and 0.707 (95%CI: 0.566-0.848; P = 0.009), respectively. Cox regression analysis showed that the three immune-nutritional scoring systems were significantly correlated with OS (PNI: P = 0.002; CONUT: P = 0.039; NPS: P < 0.001). Survival analysis revealed a significant difference in OS between different immune-nutritional groups (PNI: 75 mo vs 42 mo, P = 0.001; CONUT: 69 mo vs 48 mo, P = 0.033; NPS: 77 mo vs 40 mo, P < 0.001). These preoperative immune-nutritional scores are reliable multidimensional prognostic scoring systems for predicting the prognosis of patients with RGC, in which the NPS system has relatively effective predictive performance.

Fluorescent Lymphography-Guided Lymphadenectomy during Minimally Invasive Completion Total Gastrectomy for Remnant Gastric Cancer Patients.

Simple SummaryThe altered lymphatic anatomy around the remnant stomach after initial surgery causes technical difficulties in systematic lymphadenectomy during the completion total gastrectomy. A fluorescent lymphography with indocyanine green under near-infrared imaging is a reliable intraoperative technique for lymphatic identification in minimally invasive gastric cancer surgery. This study aimed to assess the clinical application of fluorescent lymphography in minimally invasive completion total gastrectomy for remnant gastric cancer. More lymph node retrieval was demonstrated in minimally invasive completion total gastrectomy with fluorescent lymphography than without fluorescent lymphography. Fluorescent lymphography is an effective tool for the intraoperative assessment of lymphatics around the remnant stomach and systemic lymphadenectomy during minimally invasive completion total gastrectomy.No study has evaluated fluorescent lymphography for lymphadenectomy in remnant gastric cancer (RGC). This study aimed to assess the clinical application of fluorescent lymphography in minimally invasive completion total gastrectomy for RGC. Patients who had undergone minimally invasive completion total gastrectomy for RGC from 2013 to 2020 were retrospectively reviewed. The perioperative outcomes and long-term prognosis were compared between patients who had undergone minimally invasive completion total gastrectomy with fluorescent lymphography (the FL group) and those without fluorescent lymphography (the non-FL group). The FL group comprised 32 patients, and the non-FL group comprised 36 patients. FL visualized lymphatics in all 32 patients without complications related to the fluorescent injection. The median number [the interquartile range] of LN retrieval was significantly higher in the FL group (17 [9.3–23.5]) than in the non-FL group (12.5 [4–17.8]); p = 0.016). The sensitivity of fluorescent lymphography in detecting metastatic LN stations was 75%, and the negative predictive value was 96.9% in the FL group. The overall relapse-free survivals were comparable between the groups (p = 0.833 and p = 0.524, respectively). FL is an effective tool to perform a more thorough lymphadenectomy during minimally invasive completion total gastrectomy for RGC. Using FL in RGC surgery may improve surgical quality and proper staging.

Clinicopathological Features of Remnant Gastric Cancer After Gastrectomy.

Remnant gastric cancer (RGC) encompasses all cancers arising from the remnant stomach. Various studies have reported on RGC and its prognosis, but no consensus on its surgical treatment and postoperative management has been reached. Moreover, the correlation between the clinicopathological characteristics and long-term outcomes of RGC remains unclear. This study investigated the clinicopathological factors associated with the long-term survival of RGC patients. The medical records (March 1993-September 2020) of 104 RGC patients from Tokyo Medical University Hospital database were analyzed. Of these 104 patients, the medical records of 63 patients who underwent surgical curative resection were analyzed using R. Kaplan-Meier plots of cumulative incidence of RGC were made. Differences in survival rates were compared using the log-rank test. Prognostic factors were analyzed using multivariate Cox regression analysis (P < .05). Of the 104 RGC patients, 63 underwent total remnant stomach excision. The median time from the first surgery to the total excision was 10 years. The 5-year survival rate of the 63 RGC patients was .55 ((95% CI); .417-.671). The clinicopathological factors that were significantly associated with the long-term outcome of the RGC patients were tumor diameter (≥3.5cm), presence or absence of combined resection of multiple organs, tumor invasion (deeper than T2), TNM stage, and postoperative morbidity. The multivariate Cox regression analysis showed that tumor invasion depth was the only independent prognostic factor for RGC patients [HR (95% CI): 5.49 (2.629-11.5), P ≤ .005]. Among prognostic factors, tumor invasion depth was the only independent factor affecting RGC's long-term outcome.

Expression profiles of gastric cancer molecular subtypes in remnant tumors.

BACKGROUNDRemnant gastric cancer (RGC) is a carcinoma arising in the stomach remnant after previous gastric resection. It is frequently reported as a tumor with a poor prognosis and distinct biological features from primary gastric cancer (PGC). However, as it is less frequent, its profile regarding the current molecular classifications of gastric cancer has not been evaluated.AIMTo evaluate a cohort of RGC according to molecular subtypes of GC using a panel of immunohistochemistry and in situ hybridization to determine whether the expression profile is different between PGC and RGC.METHODSConsecutive RGC patients who underwent gastrectomy between 2009 and 2019 were assessed using seven GC panels: Epstein-Barr virus in situ hybridization, immunohistochemistry for mismatch repair proteins (MutL homolog 1, MutS homolog 2, MutS homolog 6, and PMS1 homolog 2), p53 protein, and E-cadherin expression. Clinicopathological characteristics and survival of these patients were compared to 284 PGC patients.RESULTSA total of 40 RGC patients were enrolled in this study. Compared to PGC, older age (P < 0.001), male (P < 0.001), lower body mass index (P = 0.010), and lower hemoglobin level (P < 0.001) were associated with RGC patients. No difference was observed regarding Lauren’s type and pathologic Tumor Node Metastasis stage between the groups. Regarding the profiles evaluated, EBV-positive tumors were higher in RGC compared to PGC (P = 0.039). The frequency of microsatellite instability, aberrant p53 immunostaining, and loss of E-cadherin expression were similar between RGC and PGC. Higher rates of simultaneous alterations in two or more profiles were observed in RGC compared to PGC (P < 0.001). According to the molecular classification, the subtypes were defined as EBV in nine (22.5%) cases, microsatellite instability in nine (22.5%) cases, genomically stable in one (2.5%) case, and chromosomal instability in 21 (52.5%) cases. There was no significant difference in survival between molecular subtypes in RGC patients.CONCLUSIONRGC was associated with EBV positivity and higher rates of co-altered expression profiles compared to PGC. According to the molecular classification, there was no significant difference in survival between the subtypes of RGC.

Positive lymph node ratio is an index in predicting prognosis for remnant gastric cancer with insufficient retrieved lymph node in R0 resection

The staging system of remnant gastric cancer (RGC) has not yet been established, with the current staging being based on the guidelines for primary gastric cancer. Often, surgeries for RGC fail to achieve the > 15 lymph nodes needed for TNM staging. Compared with the pN staging system, lymph node ratio (NR) may be more accurate for RGC staging and prognosis prediction. We retrospectively analyzed the data of 208 patients who underwent R0 gastrectomy with curative intent and who have ≤ 15 retrieved lymph nodes (RLNs) for RGC between 2000 and 2014. The patients were divided into four groups on the basis of the NR cutoffs: rN0: 0; rN1: > 0 and ≤ 1/6; rN2: > 1/6 and ≤ 1/2; and rN3: > 1/2. The 5-year overall survival (OS) rates for rN0, rN1, rN2, and rN3 were 84.3%, 64.7%, 31.5%, and 12.7%, respectively. Multivariable analyses revealed that tumor size (p = 0.005), lymphovascular invasion (p = 0.023), and NR (p < 0.001), but not pN stage (p = 0.682), were independent factors for OS. When the RLN count is ≤ 15, the NR is superior to pN as an important and independent prognostic index of RGC, thus predicting the prognosis of RGC patients more accurately.

Evaluation of Lymph Node Staging Systems as Independent Prognosticators in Remnant Gastric Cancer Patients with an Insufficient Number of Harvested Lymph Nodes.

The lymph node (LN) ratio (LNR) and the log odds of positive LNs (LODDS) have been proposed as sensitive prognosticators in patients with primary gastric cancer, especially in patients with an insufficient number of harvested LNs. We investigated the association of LNR and LODDS with survival in patients with remnant gastric cancer (RGC) and explored whether these staging methods are prognostic factors in patients with an insufficient number of harvested LNs. The present study retrospectively examined 95 patients with RGC who received gastrectomy between January 2000 and December 2018. The patients were classified according to the adjusted X-tile cutoff for LNR and LODDS. The association between survival rates and clinicopathological features was investigated. The predictive accuracy of the LNR and LODDS was compared with that of the Union for International Cancer Control pathological N factor. Multivariate analysis revealed that the LNR and LODDS were independent risk factors for recurrence-free survival (RFS) [hazard ratio (HR) 2.623, p = 0.020; HR 3.404, p = 0.004, respectively] and overall survival (OS) (HR 3.694, p = 0.003; HR 2.895, p = 0.022, respectively) in patients with RGC. Moreover, even in patients with 15 or fewer harvested LNs, only the LNR was a significant independent risk factor for RFS (HR 21.890, p < 0.001) and OS (HR 6.597, p = 0.002). The receiver operating characteristic curves revealed that the prognostic accuracy of the three methods was comparable (p > 0.05). LNR has significant prognostic value for patients with RGC, including those with an insufficient number of harvested LNs.

Remnant gastric cancer: a neglected group with high potential for immunotherapy.

The importance of targeted therapy and interest in the study of predictive markers in gastric cancer (GC) have increased in recent years with the use of anti-HER2 therapy and immunotherapy with anti-PD1/PD-L1 for microsatellite instability (MSI) and PD-L1 + tumors. However, the behavior of remnant GC (RGC) in this scenario is poorly reported. Thus, this study aims to evaluate the clinicopathological characteristics and prognosis of RGC and its association with the expression of current markers for targeted therapy. All RGC resections performed in a single center from 2009 to 2019 were retrospectively reviewed. As a comparison group, 53 primary proximal GC (PGC) who underwent total D2-gastrectomy were selected. HER2, MSI status and PD-L1 expression were analyzed by immunohistochemistry. Combined Positive Score (CPS) was used to determine PD-L1 positivity. A total of 40 RGC were included. RGC patients were older (p = 0.001), had lower BMI (p = 0.001) and number of resected lymph nodes (p < 0.001) compared to the PGC. Regarding markers expression, MSI was higher in RGC than PGC (27.5% vs 9.4%, p = 0.022). The frequency of CPS-positive was 32.5% and 26.4% in RGC and PGC, respectively (p = 0.522). HER2 positivity was 17.5% and 22.6% for RGC and PGC, respectively (p = 0.543). In survival analysis, DFS was better for RGC CPS-positive than RGC CPS-negative (p = 0.039) patients. There was no difference in survival considering MSI status. RGC had higher incidence of MSI than PGC, and CPS-positive RGC was associated with better survival. The immunological profile of RGC patients suggests that they would be good candidates for immunotherapy.

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

BackgroundBecause 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. MethodA 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. ResultsAll 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. ConclusionThe 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.

Surveillance Endoscopy Guidelines for Postgastrectomy Patients Based on Risk of Developing Remnant Gastric Cancer

Remnant gastric cancer (RGC) has a major impact on the long-term survival of postgastrectomy patients. In this study, we established surveillance endoscopy guidelines for postgastrectomy patients based on the risk of RGC. A total of 6365 patients who underwent gastrectomy at Seoul St. Mary's Hospital from September 2005 to June 2018 were retrospectively reviewed; 85 patients were identified as having RGC. We divided the RGC patients into subgroups according to the interval between primary and secondary gastrectomy. The curative resection rate was significantly lower in patients with an interval of ≤ 5years versus > 5years (p = 0.017). RGC developed more frequently after Billroth II reconstruction, and at the anastomotic site, in patients with a > 10- versus ≤ 10-year interval (p = 0.006 and p = 0.014, respectively). Similar results were observed based on the 15-year interval cutoff (p = 0.001 and 0.018, respectively). The 5-year overall survival rate of patients with a ≤ 5-year interval was significantly lower than that of patients with a > 5-year interval (60.0% versus 85.7%, p = 0.015), while overall survival did not differ between the ≤ 10- and > 10-year, or ≤ 15- and 15-year interval groups. RGC incidence showed a decrease after around 20years postoperatively. Thorough endoscopic examination should be conducted for up to 5years postgastrectomy. Routine annual endoscopic follow-up should be performed for up to 20years after the primary operation for gastric cancer, to allow for early detection of RGC.

Conditional survival and recurrence of remnant gastric cancer after surgical resection: A multi-institutional study.

The present study was designed to evaluate the dynamic survival and recurrence of remnant gastric cancer (RGC) after radical resection and to provide a reference for the development of personalized follow‐up strategies. A total of 298 patients were analyzed for their 3‐year conditional overall survival (COS3), 3‐year conditional disease‐specific survival (CDSS3), corresponding recurrence and pattern changes, and associated risk factors. The 5‐year overall survival (OS) and the 5‐year disease‐specific survival (DSS) of the entire cohort were 41.2% and 45.8%, respectively. The COS3 and CDDS3 of RGC patients who survived for 5 years were 84.0% and 89.8%, respectively. The conditional survival in patients with unfavorable prognostic characteristics showed greater growth over time than in those with favorable prognostic characteristics (eg, COS3, ≥T3: 46.4%‐83.0%, Δ36.6% vs ≤T2: 82.4%‐85.7%, Δ3.3%; P < 0.001). Most recurrences (93.5%) occurred in the first 3 years after surgery. The American Joint Committee on Cancer (AJCC) stage was the only factor that affected recurrence. Time‐dependent Cox regression showed that for both OS and DSS, after 4 years of survival, the common prognostic factors that were initially judged lost their ability to predict survival (P > 0.05). Time‐dependent logistic regression analysis showed that the AJCC stage independently affected recurrence within 2 years after surgery (P < 0.05). A postoperative follow‐up model was developed for RGC patients. In conclusion, patients with RGC usually have a high likelihood of death or recurrence within 3 years after radical surgery. We developed a postoperative follow‐up model for RGC patients of different stages, which may affect the design of future clinical trials.

Clinicopathologic features of remnant gastric cancer after curative distal gastrectomy according to previous reconstruction method: a retrospective cohort study

BackgroundSurvival rate of patients treated for gastric cancer has increased due to early detection and improvements of surgical technique and chemotherapy. Increase in survival rate has led to an increase in the risk for remnant gastric cancer (RGC). The purpose of this study was to investigate clinicopathologic features of RGC according to previous reconstruction method and factors affecting the interval from previous curative distal gastrectomy for gastric cancer to RGC occurrence.MethodsMedical records of patients diagnosed with RGC at Yeungnam University Medical Center from January 2000 to December 2017 who had a history of distal gastrectomy with D2 LN dissection due to gastric cancer were reviewed retrospectively.ResultsForty-eight patients were enrolled in this study. The mean interval of 48 RGC patients was 105.6 months (8.8 years). RGC after Billroth II reconstruction recurred more often at anastomosis site than RGC after Billroth I reconstruction (p = 0.001). The mean interval of RGC after Billroth I reconstruction was 67 months, shorter than 119 months of RGC after Billroth II reconstruction (p = 0.003). On the contrary, interval showed no difference according to stage of previous gastric cancer, remnant gastric cancer, or sex (p = 0.810, 0.145, and 0.372, respectively).ConclusionsRGC after Billroth I reconstruction tends to arise earlier at non-anastomosis site than RGC after Billroth II. Therefore, we should examine non-anastomosis site carefully from the beginning of surveillance after gastric cancer surgery with Billroth I reconstruction for better outcome.

A novel prognosis prediction model after completion gastrectomy for remnant gastric cancer: Development and validation using international multicenter databases

BackgroundExamined lymph node counts of remnant gastric cancer patients are often insufficient, and the prognostic ability of tumor-node-metastasis staging is therefore limited. This study aimed to create a simple and universally applicable prediction model for RGC patients after completion of gastrectomy. MethodsA 5-year overall survival prediction model for remnant gastric cancer patients was developed using a test dataset of 148 consecutive patients. Model coefficients were obtained based on the Cox analysis of clinicopathological factors. Prognostic performance was assessed with the concordance index (C-index) and decision curve analysis. For internal validation, the bootstrap method and calibration assessment were used. The model was validated using 2 external cohorts from China (First Affiliated Hospital of Fujian Medical University, n = 46) and the United States (Mayo Clinic, n = 20). ResultsDepth of tumor invasion, number of metastatic lymph nodes, distant metastasis, and operative time were independent prognostic factors. Our model’s C-index (0.761) showed better discriminatory power than that of the eighth tumor-node-metastasis staging system (0.714, P = .001). The model calibration was accurate at predicting 5-year survival. Decision curve analysis showed that the model had a greater benefit, and the results were also confirmed by bootstrap internal validation. In external validation, the C-index and decision curve analysis showed good prognostic performances in patient datasets from 2 participating institutions. Moreover, we verified the reliability of the model in an analysis of patients with different examined lymph node counts (>15 or ≤15). ConclusionUtilizing clinically practical information, we developed a universally applicable prediction model for accurately determining the 5-year overall survival of remnant gastric cancer patients after completion of gastrectomy. Our predictive model outperformed tumor-node-metastasis staging in diverse international datasets regardless of examined lymph node counts.

Development and External Validation of Web-Based Models to Predict the Prognosis of Remnant Gastric Cancer after Surgery: A Multicenter Study.

Background Remnant gastric cancer (RGC) is a rare malignant tumor with poor prognosis. There is no universally accepted prognostic model for RGC. Methods We analyzed data for 253 RGC patients who underwent radical gastrectomy from 6 centers. The prognosis prediction performances of the AJCC7th and AJCC8th TNM staging systems and the TRM staging system for RGC patients were evaluated. Web-based prediction models based on independent prognostic factors were developed to predict the survival of the RGC patients. External validation was performed using a cohort of 49 Chinese patients. Results The predictive abilities of the AJCC8th and TRM staging systems were no better than those of the AJCC7th staging system (c-index: AJCC7th vs. AJCC8th vs. TRM, 0.743 vs. 0.732 vs. 0.744; P>0.05). Within each staging system, the survival of the two adjacent stages was not well discriminated (P>0.05). Multivariate analysis showed that age, tumor size, T stage, and N stage were independent prognostic factors. Based on the above variables, we developed 3 web-based prediction models, which were superior to the AJCC7th staging system in their discriminatory ability (c-index), predictive homogeneity (likelihood ratio chi-square), predictive accuracy (AIC, BIC), and model stability (time-dependent ROC curves). External validation showed predictable accuracies of 0.780, 0.822, and 0.700, respectively, in predicting overall survival, disease-specific survival, and disease-free survival. Conclusions The AJCC TNM staging system and the TRM staging system did not enable good distinction among the RGC patients. We have developed and validated visual web-based prediction models that are superior to these staging systems.

Prediction of onset of remnant gastric cancer by promoter DNA methylation of CDO1/HOPX/Reprimo/E-cadherin.

BackgroundEarly detection of remnant gastric cancer (RGC) is required to reduce the risk of death, but long-term endoscopic surveillance is difficult after gastrectomy. In this study, data for the methylation status of 4 methylation genes (CDO1, HOPX, Reprimo, and E-cadherin) to predict the onset of RGC are presented.ResultsThe 4 genes showed hypermethylation in RGC tumors in contrast to the corresponding non-cancerous mucosa tissues. The methylation level in the non-cancerous mucosa tissues of the initial surgery was obviously high in initial malignant disease for CDO1 (P = 0.0001), while in initial benign one for E-cadherin (P = 0.003). Promoter DNA methylation status in the remnant non-cancerous mucosa tissues together with the basic clinical data in turn predicted either initial malignant disease or initial benign disease with a high AUC score of 0.94, suggesting that methylation events are differentially recognized between the initial malignant and benign disease. We then finally confirmed that 4 genes hypermethylation of the non-cancerous tissues by biopsy prior to onset of RGC could predict terms until RGC occurred (P < 0.0001).MethodsA total of 58 RGC patients were used to establish the model. The 4 genes promoter methylation were analyzed for DNA obtained from the patient’s specimens using quantitative methylation specific polymerase chain reaction.ConclusionsThis risk model would help provide guidance for endoscopic surveillance plan of RGC after gastrectomy.

Risk factor analysis and prediction model establishment of lymph node metastasis in remnant gastric cancer

To explore the risk factors and establish an effective model to predict lymph node metastasis (LNM) for remnant gastric cancer (RGC). Clinicopathological characteristics of 91 RGC patients undergoing radical gastrectomy at Sun Yat-sen University Cancer Center from January 2000 to December 2017 were retrospectively analyzed. RGC was defined as cancer detected in the remnant stomach >5 years for primary benign diseases or >10 years for malignant diseases following distal gastrectomy. Risk factors of LNM in RGC were identified using logistic regression (P<0.1). Covariates were then scored according to the β regression coefficient in the multivariate analysis, and a score model was established, in which higher score indicated higher risk of LNM. Finally, receiver operating characteristic(ROC) curve was used to evaluate the diagnostic efficacy of risk factors and the score model. Among the 91 RGC patients, 84 were male and 7 were female with the age ranging from 47 to 82 years (63.7±8.5) years. Mean harvested lymph node (LN) was 16.0±11.8, including ≥15 LNs in 42(46.2%) patients and <15 LNs in 49(53.8%) patients. Forty-six (50.5%) patients were identified as LNM. Univariate analysis showed that tumor size ≥4 cm (χ2=8.106, P=0.004), Borrmann III(-IIII( gross type (χ2=6.129, P=0.013), increased CEA level (χ2=4.041, P=0.044) and T3-4 stage (χ2=17.321, P=0.000) were associated with LNM in RGC. In Logistic multivariate analysis, tumor size ≥4 cm (OR: 2.362, 95%CI: 0.829-6.730, P=0.100, β regression coefficient: 0.859) and T3-4 stage (OR: 7.914, 95%CI: 1.956-32.017, P=0.004, β regression coefficient: 2.069) remained as the independent risk factors for LNM, and were scored as 1 and 2 point in the final prediction model. In the final score model, LNM of patients with 0, 1, 2, 3 point were 11.1%(2/18), 1/5, 51.6%(16/31) and 73.0%(27/37), respectively. The AUC of the prediction model was 0.756 (P=0.000). Increased CEA level, tumor size ≥4 cm, Borrmann III(-IIII( gross type, and deeper T stage are associated with LNM in RGC. Moreover, the score model combining with tumor size and T stage can effectively predict the LNM in RGC.