Can prospective monitoring improve complication rates after gastrectomy? Experience of Billroth I reconstruction at a high-volume tertiary center.

INTRODUCTION: Prospective database is imperative in surgical outcome monitoring and has shown success in providing a comprehensive complication index to monitor surgical quality. This study aims to review whether prospective monitoring has an effect on postoperative complication rates, especially leakage after Billroth I (BI) anastomosis and to identify risk factors of anastomosis leakage after BI anastomosis. MATERIALS AND METHODS: Patients who underwent distal gastrectomy with BI reconstruction at Seoul National University Hospital between January 2018 and April 2021 were enrolled. Clinicopathological characteristics and perioperative variables were retrieved. The risk factor that was statistically significant in univariate analysis was further analyzed by binomial logistic regression analysis. RESULTS: BI leakage rate in three years has declined by half on a yearly basis from 5.7% to 1.8%. The leakage group patients were predominantly male (100%) when compared to the non-leakage group (67.6%) (p = 0.04). The BMI (25.00 ± 1.42 vs. 24.16 ± 3.15, p = 0.048) and CRP measured on POD#2 (16.47 ± 5.64 vs. 9.99 ± 5.42, p < 0.001) showed significant differences between the two groups. POD#2 CRP greater than 12.7 mg/dL was able to predict risk of anastomosis leak with sensitivity 73.3% and specificity 73.1%. CONCLUSION: Understanding variations in outcomes is important for improvements in surgical care, and through prospective monitoring and intra-departmental feedback, it is possible to reduce complication rates after gastrectomy. This study shows that age, gender and BMI are risk factors to BI leakage and POD#2 CRP greater than 12.7 mg/dL can be used to suspect leakage after BI anastomosis.

Impact of the Interval between Previous Endoscopic Exam and Diagnosis on the Mortality and Treatment Modality of Undifferentiated-Type Gastric Cancer.

PURPOSE: The impact of the interval between previous endoscopy and diagnosis on the treatment modality or mortality of undifferentiated (UD)-type gastric cancer is unclear. This study aimed to investigate the effect of endoscopic screening interval on the stage, cancer-related mortality, and treatment methods of UD-type gastric cancer. MATERIALS AND METHODS: We reviewed the medical records of newly diagnosed patients with UD gastric cancer in 2013, in whom the interval between previous endoscopy and diagnosis could be determined. The patients were classified into different groups according to the period from the previous endoscopy to diagnosis (<12 months, 12-23 months, 24-35 months, ≥36 months, and no history of endoscopy), and the outcomes were compared between the groups. In addition, patients who underwent endoscopic and surgical treatment were reclassified based on the final treatment results. RESULTS: The number of enrolled patients was 440, with males representing 64.1% of the study population; 11.8% of the participants reported that they had undergone endoscopy for the first time in their cancer diagnosis. The percentage of stage I cancer at diagnosis significantly decreased as the interval from the previous endoscopy to diagnosis increased (65.4%, 63.2%, 64.2%, 45.9%, and 35.2% for intervals of <12 months, 12-23 months, 24-35 months, ≥36 months, and no previous endoscopy, respectively, P<0.01). Cancer-related mortality was significantly lower for a 3-year interval of endoscopy (P<0.001). CONCLUSIONS: A 3-year interval of endoscopic screening reduces gastric-cancer-related mortality, particularly in cases of UD histology.

Prediction Model for Screening Patients at Risk of Malnutrition After Gastric Cancer Surgery.

BACKGROUND: Malnutrition after gastrectomy is associated with a poor prognosis; however, no accurate model for predicting post-gastrectomy malnutrition exists. Hence, we conducted a retrospective study to develop a prediction model identifying gastric cancer patients at high risk of malnutrition after gastrectomy. METHOD: Gastric cancer patients who underwent curative gastrectomy with more than one weight measurement during a 3-year follow-up period were included. Malnutrition was defined as body mass index (BMI) < 18.5 kg/m2 according to the European Society of Clinical Nutrition and Metabolism diagnostic criteria. BMI-loss pattern was analyzed using a group-based trajectory model. A prediction model for malnutrition 6 months after gastrectomy was developed based on significant risk factors, and then validated. RESULTS: Overall, 1421 patients were examined. The BMI-loss trajectory model showed significant BMI loss at 6 months after gastrectomy. Severe BMI loss (mean 21.5%; n = 109) was significantly associated with the elderly, female sex, higher preoperative BMI, advanced cancer stage, open surgery, total gastrectomy, Roux-en-Y reconstruction, chemotherapy, and postoperative complications (all p < 0.05). Malnutrition 6 months after gastrectomy was observed in 152 (11.9%) of 1281 patients. Preoperative BMI, sex, and type of operation were included in the final prediction model as predictive factors (p < 0.05). The C-index of the developmental set and bootstrap validation of the prediction model was 0.91 (95% confidence interval 0.89-0.94) and 0.91, respectively. CONCLUSION: The prediction model for the risk of malnutrition 6 months after gastrectomy was accurately developed, with three independent risk factors: low preoperative BMI, female sex, and total or proximal gastrectomy.

Proposal of a New TNM Classification for Gastric Cancer: Focusing on pN3b and Cytology-Positive (CY1) Disease.

PURPOSE: Gastric cancer with lymph node metastasis (LNM) more than 15 (N3b) was defined as stage IV until the 6th AJCC system. However, it has been reclassified as a localized disease (stage IIb or III) since the 7th system. The aim of this study is to demonstrate that the survival of N3b is comparable to cytology-only positive (CY1-only) stage IV and to propose a new TNM system interpreting N3b as an eligibility criterion for receiving more intensive chemotherapy regimens. MATERIALS AND METHODS: 1,430 patients who underwent gastric cancer surgery at Seoul National University Hospital from 2007 to 2012 were retrospectively analyzed. The 5-year survival rate (5YSR) and 3-year recurrence-free survival (RFS) were evaluated according to the 7th and 8th systems, as well as a new categorization based on N-classification; N0-2 (LNM<7), N3a (LNM 7-15), or N3b (LNM>15). RESULTS: The survival of N3b is comparable to that of CY1-only stage IV (log rank test, P=0.671) and is distinct from that of grossly stage IV (log rank test, P<0.001). The survival of the remaining stage IIIc (T4bN3a) was comparable to those of N3b and CY1-only stage IV. Most N3b patients had significantly shorter 3-year RFS and mean RFS than those with IIb-IIIc, as if N3b itself was a higher TNM stage. CONCLUSIONS: In terms of survival, T4bN3a, N3b, and CY1-only stage IV were unified as stage IVa, while grossly stage IV was defined as stage IVb. N3b can be regarded as an eligibility criterion for undergoing more intensive chemotherapy regimens.

Pylorus-preserving gastrectomy for early cancer involving the upper third: can we go higher?

BACKGROUND: Pylorus-preserving gastrectomy (PPG) is commonly performed for early gastric cancer (EGC) located in middle third of the stomach. We investigated the surgical, oncological, and functional outcomes of PPG involving the upper third of stomach. METHODS: We included all patients of the period 2013-2016 who underwent PPG, distal subtotal gastrectomy (DSG), and total gastrectomy (TG) for EGC involving the upper third by carefully defining the localization. Surgical, oncological, and functional outcome analyses included postoperative morbidity, lymph-node metastasis, tumor recurrence, postoperative body weight, body mass index, hemoglobin, total protein, albumin, quantification of intraabdominal fat, and gallstone development. RESULTS: Overall, 288 cases were analyzed: 145 PPG, 61 DSG, and 82 TG. In the study period, patients potentially underwent PPG for EGC involving the upper third, if enough proximal remnant stomach was found whilst achieving a sufficient proximal margin. PPG resulted in less operation time (p < 0.001), less blood loss (p = 0.002) and lower postoperative morbidity compared to TG. For lymph-node (LN) stations being resected in all groups, no difference was found in number of resected LN. Recurrence-free survival was similar for all groups. PPG showed advantages regarding postoperative body weight, hemoglobin, total protein, albumin in postoperative 6 and 12 month follow-up. Lowest decrease of abdominal fat area after 12 months was seen for PPG. Gallstone incidence was significantly lower after PPG compared to TG (p < 0.001). CONCLUSIONS: For EGC involving the upper third, PPG can be another good option with lower postoperative morbidity, better functional outcomes, and same oncological safety.

Methylation Levels of LINE-1 As a Useful Marker for Venous Invasion in Both FFPE and Frozen Tumor Tissues of Gastric Cancer.

Long interspersed nuclear element-1 (LINE-1) is a retrotransposon that contains a CpG island in its 5'-untranslated region. The CpG island of LINE-1 is often heavily methylated in normal somatic cells, which is associated with poor prognosis in various cancers. DNA methylation can differ between formalin-fixed paraffin-embedded (FFPE) and frozen tissues. Therefore, this study aimed to compare the LINE-1 methylation status between the two tissue-storage conditions in gastric cancer (GC) clinical samples and to evaluate whether LINE-1 can be used as an independent prognostic marker for each tissue-storage type. We analyzed four CpG sites of LINE-1 and examined the methylation levels at these sites in 25 FFPE and 41 frozen GC tissues by quantitative bisulfite pyrosequencing. The LINE-1 methylation status was significantly different between the FFPE and frozen GC tissues (p < 0.001). We further analyzed the clinicopathological features in the two groups separately. In the frozen GC tissues, LINE-1 was significantly hypomethylated in GC tissues compared to their corresponding normal gastric mucosa tissues (p < 0.001), and its methylation status was associated with gender, differentiation state, and lymphatic and venous invasion of GC. In the FFPE GC tissues, the methylation levels of LINE-1 differed according to tumor location and venous invasion of GC. In conclusion, LINE-1 can be used as a useful methylation marker for venous invasion in both FFPE and frozen tumor tissues of GC.

Plasma expression of the intestinal metaplasia markers CDH17 and TFF3 in patients with gastric cancer.

BACKGROUND: Few reliable blood markers are available for detecting gastric cancer, mainly owing to the heterogeneity of the cancer. OBJECTIVE: To establish gastric cancer diagnostic markers, we evaluated the levels of plasma cadherin 17 (CDH17) and trefoil factor 3 (TFF3), which are secretory proteins and known markers for intestinal metaplasia (IM), in patients with gastric cancer. METHOD: The protein expression level was analyzed in blood plasma samples from 111 gastric cancer patients and 44 healthy individuals, using a sandwich ELISA kit, followed by statistical analyses. RESULT: Overall, the plasma levels of CDH17 and TFF3 were not significantly different between groups (p= 0.160 and p= 0.113, respectively). However, CDH17 expression was significantly elevated in patients with stage II and III gastric cancers compared to that in healthy controls (p= 0.023 and p= 0.037, respectively). In contrast, TFF3 levels were significantly elevated in patients with stage I (p= 0.001) and T1 gastric cancer (p= 0.013). The sensitivity and specificity of CDH17 were 66.7 and 61.4%, respectively (cutoff point: 0.189 ng/mL); for TFF3, these values were 62.2 and 56.8%, respectively (cutoff point: 5.215 ng/mL). CONCLUSIONS: These findings indicate that secretory protein markers for metaplastic lineages can be used as blood markers for gastric cancer.

Ultrasonically Activated Shears Reduce Blood Loss without Increasing Inflammatory Reactions in Open Distal Gastrectomy for Cancer: A Randomized Controlled Study.

BACKGROUND: Previous studies regarding ultrasonically activated shears (UAS) were performed without controlled surgical procedures or consideration of potential thermal injury due to high temperature of active blade of UAS. The purpose of this study was to evaluate the efficacy and safety of UAS through a comparison with conventional monopolar electrocautery (CME) in open distal gastrectomy for gastric cancer. METHODS: From October 2011 to November 2012, 56 gastric cancer patients eligible for open distal gastrectomy were randomized into UAS or CME groups. Primary endpoints were estimated blood loss (EBL) during surgery and amount of drainage through the fifth postoperative day. Secondary endpoints were operation time, length of hospital stay, postoperative morbidity, changes in cytokine levels in serum, peritoneal irrigation saline, and peritoneal drainage, and inflammatory markers of serum. (Registration-number of ClinicalTrials.gov: NCT01971775). RESULTS: EBL was lower in the UAS group than that in the CME group (339.8 ± 201.2 vs. 428.6 ± 165.8 mL, p = 0.021). However, the amount of postoperative drainage was not significantly different between the two groups. Although the complication rate was not different between the two groups, there were three cases of intra-abdominal bleeding requiring transfusion only in the CME group. Inflammatory markers from the cytokine assays and serum laboratory tests showed no significant differences between the two groups. CONCLUSIONS: UAS reduced EBL without increasing inflammatory reactions.

Outcomes of minimally invasive surgery for early gastric cancer are comparable with those for open surgery: analysis of 1,013 minimally invasive surgeries at a single institution.

BACKGROUND: This study aimed to compare the short- and long-term results of minimally invasive surgery (MIS) and open surgery for primary early gastric cancer (EGC) at a single high-volume institution. METHODS: The clinicopathologic and survival data of primary gastric cancer patients who underwent a minimally invasive radical gastrectomy at Seoul National University Hospital from December 2003 to January 2012 were retrospectively analyzed. For comparison of short-term outcomes, the data for 1,112 patients who underwent a radical open gastrectomy from 2007 to 2011 were collected. For long-term outcome analysis, the data for 962 patients who underwent a radical open gastrectomy from 2004 to 2006 were collected. Because the application of MIS was limited to suspected EGC, the control groups were similarly limited to patients deemed to have EGC as shown by preoperative endoscopy, endoscopic ultrasound, or both. RESULTS: The review of our database identified 1,013 patients who had undergone MIS for gastric cancer. In the short-term outcome analysis, the MIS group showed statistically better results than the open surgery group in terms of postoperative hospital stay (8.7 vs. 11.3 days; p < 0.001), estimated blood loss (75.4 vs. 142.3 ml; p < 0.001), and overall complication rate (17.5 vs. 24.4 %; p < 0.001). In the subset analysis of total gastrectomy, the local complication rate was much higher in the MIS group than in the open surgery group. Both uni- and multivariate analyses showed that not only the surgical approach but also age, chronic liver disease, chronic renal disease, and additional organ resection had significant effects on complications. In the long-term outcome analysis, the two groups showed comparable disease-free survival rates. CONCLUSIONS: The use of MIS for EGC showed a shorter operation time, a shorter postoperative hospital stay, and a lower overall complication rate than open surgery but a comparable disease-free survival rate. Total gastrectomy in the MIS group was associated with a higher complication rate than in the open group. Therefore, a new stable surgical technique needs to be established.