Effect of Laparoscopic Proximal Gastrectomy With Double-Tract Reconstruction vs Total Gastrectomy on Hemoglobin Level and Vitamin B12 Supplementation in Upper-Third Early Gastric Cancer: A Randomized Clinical Trial.

Importance: Patients undergoing proximal gastrectomy (PG) with double-tract reconstruction (DTR) have been reported to have an incidence of reflux esophagitis that is as low as that observed after total gastrectomy (TG). It is unclear whether PG has an advantage over TG for the treatment of patients with upper early gastric cancer (GC). Objective: To evaluate the effect of laparoscopic PG with DTR (LPG-DTR) vs laparoscopic TG (LTG) on levels of hemoglobin and vitamin B12 supplementation required among patients with clinically early GC in the upper third of the stomach (upper-third early GC). Design, Setting, and Participants: This multicenter open-label superiority randomized clinical trial was conducted at 10 institutions in Korea. A total of 138 patients with upper-third cT1N0M0 GC were enrolled between October 27, 2016, and September 9, 2018. Follow-up ended on December 3, 2020. Interventions: Patients were randomized to undergo either LPG-DTR or LTG. Main Outcomes and Measures: The primary co-end points were change in hemoglobin level and cumulative amount of vitamin B12 supplementation at 2 years after LPG-DTR or LTG. The secondary end points included morbidity, postoperative reflux esophagitis, quality of life, overall survival, and disease-free survival. Quality of life outcomes were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) 30-item core questionnaire (C30) and the EORTC QLQ stomach cancer-specific questionnaire at 3 months, 12 months, and 24 months. Results: Among 138 patients (mean [SD] age, 60.0 [10.9] years; 87 men [63.0%]; all of Asian race and Korean ethnicity), 68 (mean [SD] age, 56.7 [10.4] years; 39 men [57.4%]) were randomized to receive LPG-DTR and 69 (mean [SD] age, 61.3 [11.3] years; 48 men [69.6%]) were randomized to receive LTG. The mean (SD) changes in hemoglobin levels from baseline to month 24 were -5.6% (7.4%) in the LPG-DTR group and -6.9% (8.3%) in the LTG group, for an estimated difference of -1.3% (95% CI, -4.0% to 1.4%; P = .35). The mean (SD) cumulative amount of vitamin B12 supplementation was 0.4 (1.3) mg in the LPG-DTR group and 2.5 (3.0) mg in the LTG group, for an estimated difference of 2.1 mg (95% CI, 1.3-2.9 mg; P < .001). The late complication rates in the LPG-DTR and LTG groups were 17.6% and 10.1%, respectively (P = .31). The incidence of reflux esophagitis was not different between the LPG-DTR and LTG groups (2.9% vs 2.9%; P = .99). Compared with the LTG group, the LPG-DTR group had better physical functioning scores (85.2 [15.6] vs 79.9 [19.3]; P = .03) and social functioning scores (89.5 [17.9] vs 82.4 [19.4]; P = .03) on the EORTC QLQ-C30. Two-year overall survival (98.5% vs 100%; P = .33) and disease-free survival (98.5% vs 97.1%; P = .54) did not significantly differ between the LPG-DTR vs LTG groups. Conclusions and Relevance: In this study, patients with upper-third early GC who received LPG-DTR required less vitamin B12 supplementation than those who received LTG, with no increase in complication rates and no difference in overall and disease-free survival rates. There was no difference in change in hemoglobin level between groups. In addition, the LPG-DTR group had better physical and social functioning than the LTG group. These findings suggest that LPG-DTR may be as safe as LTG and may be a function-preserving procedure for the treatment of patients with upper-third early GC. Trial Registration: ClinicalTrials.gov Identifier: NCT02892643.

Combined IgE neutralization and Bifidobacterium longum supplementation reduces the allergic response in models of food allergy.

IgE is central to the development of allergic diseases, and its neutralization alleviates allergic symptoms. However, most of these antibodies are based on IgG1, which is associated with an increased risk of fragment crystallizable-mediated side effects. Moreover, omalizumab, an anti-IgE antibody approved for therapeutic use, has limited benefits for patients with high IgE levels. Here, we assess a fusion protein with extracellular domain of high affinity IgE receptor, FcεRIα, linked to a IgD/IgG4 hybrid Fc domain we term IgETRAP, to reduce the risk of IgG1 Fc-mediated side effects. IgETRAP shows enhanced IgE binding affinity compared to omalizumab. We also see an enhanced therapeutic effect of IgETRAP in food allergy models when combined with Bifidobacterium longum, which results in mast cell number and free IgE levels. The combination of IgETRAP and B. longum may therefore represent a potent treatment for allergic patients with high IgE levels.

Lymph-node ratio is an important clinical determinant for selecting the appropriate adjuvant chemotherapy regimen for curative D2-resected gastric cancer.

PURPOSE: Adjuvant chemotherapy for gastric cancer, particularly stage III, improves survival after curative D2 gastrectomy. We investigated the clinical value of the lymph-node ratio (LNR; number of metastatic lymph nodes/number of lymph nodes examined) for selecting the appropriate adjuvant chemotherapy regimen in patients with D2-resected stage II/III gastric cancer. METHODS: We reviewed the data of 819 patients who underwent curative D2 gastrectomy followed by adjuvant chemotherapy. Of them, 353 patients received platinum-based chemotherapy and 466 received TS-1. The patients were categorized into three groups according to their LNR (LNR 1, 0-0.1; LNR 2, > 0.1-0.25; and LNR 3, > 0.25), and their disease-free survival (DFS) was evaluated. RESULTS: The DFS curves of the patients were well separated according to stage and LNR. In multivariate analyses, an LNR > 0.1 was strongly associated with the 3-year DFS (hazard ratio 2.402, 95% confidence interval 1.607-3.590, P < 0.001). Platinum-based chemotherapy improved the 3-year DFS compared to TS-1 in patients with LNR 3 group in stage III gastric cancer (platinum vs. TS-1, median DFS 26.87 vs. 16.27 months, P = 0.028). An LNR > 0.1 was associated with benefiting from platinum-based adjuvant chemotherapy in stage III gastric cancer patients with lymphovascular invasion (platinum vs. TS-1, median DFS 47.57 vs. 21.77 months, P = 0.011). CONCLUSIONS: The LNR can be used to select the appropriate adjuvant chemotherapy regimen for patients with D2-resected gastric cancer, particularly in stage III.

The Korean Gastric Cancer Cohort Study: Study Protocol and Brief Results of a Large-Scale Prospective Cohort Study.

PURPOSE: This study aimed to establish a large-scale database of patients with gastric cancer to facilitate the development of a national-cancer management system and a comprehensive cancer control policy. MATERIALS AND METHODS: An observational prospective cohort study on gastric cancer was initiated in 2010. A total of 14 cancer centers throughout the country and 152 researchers were involved in this study. Patient enrollment began in January 2011, and data regarding clinicopathological characteristics, life style-related factors, quality of life, as well as diet diaries were collected. RESULTS: In total, 4,963 patients were enrolled until December 2014, and approximately 5% of all Korean patients with gastric cancer annually were included. The mean age was 58.2±11.5 years, and 68.2% were men. The number of patients in each stage was as follows: 3,394 patients (68.4%) were in stage IA/B; 514 patients (10.4%), in stage IIA/B; 469 patients (9.5%), in stage IIIA/B/C; and 127 patients (2.6%), in stage IV. Surgical treatment was performed in 3,958 patients (79.8%), endoscopic resection was performed in 700 patients (14.1%), and 167 patients (3.4%) received palliative chemotherapy. The response rate for the questionnaire on the quality of life was 95%; however, diet diaries were only collected for 27% of patients. CONCLUSIONS: To provide comprehensive information on gastric cancer for patients, physicians, and government officials, a large-scale database of Korean patients with gastric cancer was established. Based on the findings of this cohort study, an effective cancer management system and national cancer control policy could be developed.

Prognostic significance of the concomitant existence of lymphovascular and perineural invasion in locally advanced gastric cancer patients who underwent curative gastrectomy and adjuvant chemotherapy.

OBJECTIVE: In this study, we evaluated the prognostic significance of the concomitant existence of lymphovascular invasion and perineural invasion in patients with advanced gastric cancer. METHODS: A total of 206 consecutive patients with Stage II or III gastric cancer who underwent curative D2 gastrectomy and adjuvant chemotherapy from April 2004 to December 2011 were analyzed. Patients were classified into four groups according to the presence (+) or absence (-) of lymphovascular invasion and perineural invasion: lymphovascular invasion-/perineural invasion- (n = 33), lymphovascular invasion+/perineural invasion- (n = 31), lymphovascular invasion-/perineural invasion+ (n = 54) and lymphovascular invasion+/perineural invasion+ (n = 88). RESULTS: A total of 136 patients (66.0%) received 5-fluorouracil plus cisplatin adjuvant chemotherapy and 70 patients (34.0%) received TS-1. During the median follow-up period of 35.18 months, the median disease-free survival times for lymphovascular invasion-/perineural invasion-, lymphovascular invasion+/perineural invasion- and lymphovascular invasion-/perineural invasion+ were not reached at the time of analysis; however, median disease-free survival for lymphovascular invasion+/perineural invasion+ was the worst (36.73 months, P = 0.001). The median overall survival in the four groups was also not reached at the time of analysis; however, median overall survival with lymphovascular invasion+/perineural invasion+ was the poorest (P = 0.002). In a multivariate analysis, lymphovascular invasion+/perineural invasion+ was an independent prognostic factor for both disease-free survival (hazard ratio = 1.940, 95% confidence interval 1.157-3.252, P = 0.012) and overall survival (hazard ratio = 2.973, 95% confidence interval 1.561-5.662, P = 0.001). CONCLUSIONS: The concomitant existence of lymphovascular and perineural invasion has a significant prognostic impact on disease-free survival and overall survival in patients with Stage II or III gastric cancer.

Colonoscopy procedural skills and training for new beginners.

The incidence of colorectal cancer has been increasing in the developed world including South Korea and China. Colonoscopy allows for greater diagnostic specificity and sensitivity compared with other types of examinations, such as the stool occult blood test, barium enema, and computed tomography colonography. Therefore, in recent years, the demand for colonoscopies has grown rapidly. New beginners including primary care physicians may help meet the increasing demand by performing colonoscopies. However, it is a challenge to learn the procedure due to the long learning-curve and the high rate of complications, such as perforation and bleeding, as compared to gastroscopy. Thus, considerable training and experience are required for optimal performance of colonoscopies. In order to perform a complete colonoscopic examination, there were a few important things to learn and remember, such as the position of examinee (e.g., left and right decubitus, supine, and prone) and examiner (two-man method vs one-man standing method vs one-man sitting method), basic skills (e.g., tip deflection , push forward and pull back, torque, air suction and insufflation), advanced skills (e.g., jiggling and shaking, right and left turn shortening, hooking, and slide-by technique), assisting skills (e.g., position change of examinee, abdominal compression, breathing-holding, and liquid-infusion technique), and intubation techniques along the lower gastrointestinal tract. In this article, we attempt to describe the methods of insertion and advancement of the colonoscope to the new beginners including primary care physician. We believe that this article may be helpful to the new beginners who wish to learn the procedure.

Effect of intravenous iron supplementation for acute postoperative anemia in patients undergoing gastrectomy for gastric carcinoma: a pilot study.

BACKGROUND: Several previous studies have concluded that iron supplementation is not beneficial for correcting acute postoperative anemia. However, little data are available about the effect of intravenous (i.v.) iron supplementation for acute postoperative anemia in patients undergoing gastrectomy. METHODS: Between February 2009 and May 2012, 527 patients underwent gastrectomy for gastric carcinoma. From February 2011, we began i.v. iron supplementation for patients with acute postoperative anemia (hemoglobin (Hb) ≤10 g/dL) at our institute. This study compared the changes of serum Hb up to postoperative 6 months between the patients treated before and after the introduction of i.v. iron supplementation. RESULTS: A total of 142 patients had acute postoperative anemia (Hb ≤10 g/dL). Of these, 68 patients (47.9%) received i.v. iron supplementation. There were no significant differences in age, gender, operation type, tumor stage, and the presence of postoperative chemotherapy between the i.v. iron supplementation and no-supplementation group. Postoperatively, the serum Hb increase over time was significantly better in the i.v. iron supplementation group (repeated measures ANOVA, p = .009). The mean increase of Hb at postoperative 6 months was 3.2 g/dL in the i.v. supplementation group and 2.5 g/dL in the no-supplementation group (p = .029). Multivariate analysis revealed that i.v. iron supplementation was an independent factor of increased serum Hb at postoperative 6 months. CONCLUSIONS: Unlike non-gastrointestinal surgery, i.v. iron significantly increased serum Hb in patients developing acute postoperative anemia after gastrectomy. A prospective randomized trial is warranted to confirm the role of i.v. iron supplementation in patients with gastrectomy.

Prevalence, severity, and evolution of postsurgical anemia after gastrectomy, and clinicopathological factors affecting its recovery.

PURPOSE: Postsurgical anemia is one of the common unpleasant postoperative sequels during the early postoperative period after gastrectomy, for which no standard care has been established. To facilitate proper management, we investigated the clinical features of postsurgical anemia and sought to identify the factors affecting its subsequent recovery. METHODS: A retrospective review of 406 consecutive gastric cancer patients who underwent gastrectomy without systemic chemotherapy between August 2008 and September 2009. Clinical courses of postsurgical anemia were monitored at 3, 6, and 12 months post-surgery. Clinicopathological factors affecting recovery of postsurgical anemia were analyzed using a multivariate logistic regression model. RESULTS: The study subjects consisted of 265 males and 141 females (mean age, 61.8 years). After operation, 318 (78.3%) presented with postsurgical anemia, and 217 (66.7%) and 47 (11.6%) had mild or moderate anemia, respectively, at the time of discharge. During the follow-up, 173 (54.4%) of the 318 with postsurgical anemia showed a spontaneous recovery at 3 months post-surgery, but no significant changes were observed in postsurgical anemia at 6 or 12 months post-surgery. Univariate and multivariate analysis revealed that old age (≥60 years), preoperative anemia, anemia severity (moderate anemia), and total gastrectomy were independent factors that adversely affect the spontaneous recovery of post-surgical anemia after gastrectomy. CONCLUSION: Proper intervention may be required for postsurgical anemia that does not achieve a spontaneous recovery until postoperative 3 months. However, proper management, such as the use of iron or the best route for iron supplementation, needs to be evaluated in future clinical trials.

Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial.

BACKGROUND: D2 gastrectomy is recommended in US and European guidelines, and is preferred in east Asia, for patients with resectable gastric cancer. Adjuvant chemotherapy improves patient outcomes after surgery, but the benefits after a D2 resection have not been extensively investigated in large-scale trials. We investigated the effect on disease-free survival of adjuvant chemotherapy with capecitabine plus oxaliplatin after D2 gastrectomy compared with D2 gastrectomy only in patients with stage II-IIIB gastric cancer. METHODS: The capecitabine and oxaliplatin adjuvant study in stomach cancer (CLASSIC) study was an open-label, parallel-group, phase 3, randomised controlled trial undertaken in 37 centres in South Korea, China, and Taiwan. Patients with stage II-IIIB gastric cancer who had had curative D2 gastrectomy were randomly assigned to receive adjuvant chemotherapy of eight 3-week cycles of oral capecitabine (1000 mg/m(2) twice daily on days 1 to 14 of each cycle) plus intravenous oxaliplatin (130 mg/m(2) on day 1 of each cycle) for 6 months or surgery only. Block randomisation was done by a central interactive computerised system, stratified by country and disease stage. Patients, and investigators giving interventions, assessing outcomes, and analysing data were not masked. The primary endpoint was 3 year disease-free survival, analysed by intention to treat. This study reports a prespecified interim efficacy analysis, after which the trial was stopped after a recommendation by the data monitoring committee. The trial is registered at ClinicalTrials.gov (NCT00411229). FINDINGS: 1035 patients were randomised (520 to receive chemotherapy and surgery, 515 surgery only). Median follow-up was 34·2 months (25·4-41·7) in the chemotherapy and surgery group and 34·3 months (25·6-41·9) in the surgery only group. 3 year disease-free survival was 74% (95% CI 69-79) in the chemotherapy and surgery group and 59% (53-64) in the surgery only group (hazard ratio 0·56, 95% CI 0·44-0·72; p<0·0001). Grade 3 or 4 adverse events were reported in 279 of 496 patients (56%) in the chemotherapy and surgery group and in 30 of 478 patients (6%) in the surgery only group. The most common adverse events in the intervention group were nausea (n=326), neutropenia (n=300), and decreased appetite (n=294). INTERPRETATION: Adjuvant capecitabine plus oxaliplatin treatment after curative D2 gastrectomy should be considered as a treatment option for patients with operable gastric cancer. FUNDING: F Hoffmann-La Roche and Sanofi-Aventis.

Novel technique for intraoperative tumor localization during totally laparoscopic distal gastrectomy: endoscopic autologous blood tattooing.

BACKGROUND: Knowledge of the intraoperative location of lesions is a prerequisite for deciding the proper extent of gastric resection or the choice of anastomosis technique during totally laparoscopic distal gastrectomy (TLDG) for early gastric cancer (EGC). In this study we introduce a novel tumor localization method for TLDG: endoscopic blood tattooing. METHODS: Twenty-three consecutive patients scheduled for TLDG for EGC were enrolled in this prospective study. The day before surgery, 2-3 ml of autologous blood was injected into the gastric muscle layer at 3-4 cm proximal to the lesion during endoscopy. RESULTS: The study subjects consisted of 15 males and 8 females with a mean age of 61 ± 10.4 years. During surgery, the endoscopic blood tattooed sites were successfully identified in all 23 patients. No complications associated with the procedure occurred, and no patient had microscopic residual tumor cells at the proximal resection margin, with a mean proximal margin length of 3.3 ± 2.7 cm. Eighteen patients underwent TLDG with Billroth II anastomosis, four patients with Roux-en-Y gastrojejunostomy, and one patient with laparoscopic total gastrectomy. At final pathologic examinations, 20 patients were of stage IA and 3 were of stage IB according to the UICC TNM classification (6th ed.). CONCLUSIONS: Endoscopic blood tattooing provides a simple and useful means of localizing lesions during TLDG for EGC. Although the superiority of this technique over other localization methods needs to be evaluated further, the authors recommend endoscopic blood tattooing as an alternative to other intraoperative localization methods for laparoscopic surgery for EGC.

A genome-wide scan for the Sasang constitution in a Korean family suggests significant linkage at chromosomes 8q11.22-23 and 11q22.1-3.

OBJECTIVES: We aim to identify the genetic loci responsible for Sasang constitution type, which is important for effective personalized treatments in traditional Korean medicine. SUBJECTS: Forty (40) individuals in a Korean family were recruited for linkage analysis and 310 unrelated individuals for association analysis to confirm the linkage result. OUTCOME MEASURES: Genome-wide linkage analysis was performed for the Korean family using the Affymetrix 500K arrays. MERLIN software was used for multipoint nonparametric linkage (NPL) analysis. The significant candidate regions in linkage analysis were also investigated with association analysis of independent 310 individuals. RESULTS: Linkage analysis showed four significant peaks, 3q27.3, 8p11.21, 8q11.22-23, and 11q22.1-3, whose NPL Z scores are greater than 5.0. Among the significant loci, the 8q11.22-23 and 11q22.1-3 regions were supported by independent association analysis at the level of p < 0.05. CONCLUSIONS: The 8q11.22-23 and 11q22.1-3 regions were suggested as the candidate region for significant linkage to Sasang constitution.