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.

Twelve-Year Trajectory of Disease Burden and Mortality by Obesity Level in Korea: Analysis of the National Health Insurance Service Database.

INTRODUCTION: Despite increases in obesity prevalence, awareness of obesity as a disease requiring active treatment remains lacking in Korea. We investigated differences in medical problems and expenditures and mortality across obesity categories using 12-year data from the National Health Insurance Service. MATERIALS AND METHODS: Individuals aged 40-79 years who underwent medical examinations during 2003-2004 (n = 415,201) were divided based on Asian body mass index (kg/m2) criteria: normal weight (18.5 to < 23.0, 36.4%), overweight (23.0 to < 25.0, 28.3%), obesity (25.0 to < 30.0, 32.5%), and severe obesity (≥ 30.0, 2.8%). Medical problems and expenditures were fitted to linear mixed models. Mortality was analyzed via Cox proportional-hazards model. RESULTS: More severe obesity was associated with a higher rate of medical problems, relative to normal weight: coefficient = 0.31 (95% confidence interval [CI], 0.30-0.32) for overweight, 0.61 (0.60-0.61) for obesity, and 1.07 (1.04-1.09) for severe obesity. A similar association was observed for medical expenditure: coefficient = 8.85 (95%CI, 6.80-10.89) for overweight, 20.04 (18.07-22.01) for obesity, and 48.76 (43.66-53.86) for severe obesity. Relative to overweight participants, those with normal weight and severe obesity exhibited a higher mortality risk (hazard ratio [HR] 1.21 [95%CI, 1.18-1.25] for normal; 1.27 [1.19-1.36] for severe obesity). In age-specific analyses, mortality risk was the highest for participants with severe obesity, aged < 60 years (HR, 1.58 [95%CI, 1.41-1.77]). CONCLUSION: Disease burden including medical problems and expenditure, and mortality in middle-aged adults, increased proportionally to the degrees of obesity. Health policies and medical systems aimed at reducing the burden of obesity may help reduce the burden of disease on society.

Laparoscopic proximal gastrectomy with double tract reconstruction is superior to laparoscopic total gastrectomy for proximal early gastric cancer.

BACKGROUND: Laparoscopic proximal gastrectomy (LPG) with double tract reconstruction (DTR) is known to reduce reflux symptoms, which is a major concern after proximal gastrectomy. The aim of this study is to compare retrospectively the clinical outcomes of patients undergoing LPG with DTR with those treated by laparoscopic total gastrectomy (LTG). METHODS: Ninety-two and 156 patients undergoing LPG with DTR and LTG for proximal stage I gastric cancer were retrospectively analyzed for short- and long-term clinical outcomes. RESULTS: There were no significant differences in the demographics, T-stage, N-stage, and complications between the groups. The LPG with DTR group had a shorter operative time and lower estimated blood loss than the LTG group (198.3 vs. 225.4 min, p < 0.001; and 84.7 vs. 128.3 mL p = 0.001). The incidence of reflux symptoms ≥ Visick grade II did not significantly differ between the groups during a mean follow-up period of 37.2 months (1.1 vs. 1.9%, p = 0.999). The hemoglobin change was significantly lower in the LPG with DTR group compared to in the LTG group in the first and second postoperative years (5.03 vs. 9.18% p = 0.004; and 3.45 vs. 8.30%, p = 0.002, respectively), as was the mean amount of vitamin B12 supplements 2 years after operation (0.1 vs. 3.1 mg, p < 0.001). The overall survival rate was similar between the groups. CONCLUSIONS: LPG with DTR maintained comparable oncological safety and anastomosis-related late complications compared to LTG and is preferred over LTG in terms of preventing postoperative anemia and vitamin B12 deficiency.

Feasibility of hyperthermic pressurized intraperitoneal aerosol chemotherapy in a porcine model.

BACKGROUND: Peritoneal carcinomatosis is an unmet therapeutic need. Several types of intraperitoneal chemotherapy have been introduced. However, hyperthermic intraperitoneal chemotherapy has limited drug distribution and poor peritoneal penetration. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) does not have the benefits of hyperthermia. We developed a device to apply hyperthermic PIPAC (H-PAC) and evaluated its feasibility in a porcine model. METHODS: The device for H-PAC consisted of a laparoscopic aerosol spray and a heater to create hyperthermic capnoperitoneum. We operated on five pigs for the development of the new device and on another five pigs as a survival model. After a pilot experiment of the survival model (Pig A), a hyperthermic pressurized intraperitoneal aerosol of indocyanine green was administered after insertion of three trocars (Pig B) and laparoscopy-assisted distal gastrectomy (LADG) (Pig C) without chemotherapeutic agents. After that, H-PAC with cisplatin was administered after insertion of three trocars (Pig D) and LADG (Pig E). Autopsies were performed on postoperative day 7. RESULTS: Median operation time was 85 min (80-110 min). Intraperitoneal temperature was constant for 1 h of H-PAC (38.8-40.2 °C). All five pigs were healthy and survived for 7 days. Median weight loss was 0.2 kg. Autopsy tissues of stomach, peritoneum, and jejunum were intact in all five pigs. CONCLUSIONS: H-PAC was feasible and safe in a porcine model.

Early gastric cancer: feasibility of CT lymphography with ethiodized oil for sentinel node mapping.

PURPOSE: To evaluate the feasibility of CT lymphography with ethiodized oil for sentinel node mapping in porcine stomachs and in patients with early gastric cancer. MATERIALS AND METHODS: Approval for the animal study was obtained from the authors' institutional animal use and care administrative advisory committee, the clinical study was approved by the institutional review board, and informed consent was obtained from each participant. Five pigs underwent CT lymphography 1 hour after gastric subserosal injection of 1 mL ethiodized oil and sentinel node mapping with injection of 1 mL methylene blue. Ethiodized oil retention nodes were identified on the radiographic images of the gastric specimen and removed for histopathologic examination. In addition, 10 patients with early gastric cancer underwent CT lymphography with peritumoral injection of 1 mL ethiodized oil, followed by sentinel basin extirpation with CT and routine nodal dissection. The removed sentinel basins were examined by radiography. Histopathologic examination was performed for dissected nodes, including sentinel nodes. RESULTS: In each of the five pigs, CT showed one perigastric ethiodized oil retention node. After harvesting the ethiodized oil retention node, blue-stained areas were identified in the five removed nodes and intranodal ethiodized oil was detected on histopathologic examination. In all 10 patients, CT lymphography with ethiodized oil successfully defined the sentinel basin with ethiodized oil retention nodes. CT lymphography revealed 20 ethiodized oil retention nodes. After basin extirpation, 28 and 46 nodes were detected on radiographic and histopathologic examinations. Histopathologic examination revealed that one patient had micrometastases at two sentinel nodes and another patient had isolated tumor cells at one sentinel node. No patient had metastasis in nonsentinel nodes. CONCLUSION: CT lymphography with ethiodized oil may be a feasible method for sentinel node mapping in patients with early gastric cancer.

Clinical implementations of preoperative computed tomography lymphography in gastric cancer: a comparison with dual tracer methods in sentinel node navigation surgery.

BACKGROUND: Current sentinel node (SN) detection techniques require a learning period and tracers have many disadvantages for practical use. The purpose of this study was to evaluate the feasibility of preoperative computed tomography (CT) lymphography using lipiodol for detecting SNs in gastric cancer. METHODS: A total of 24 patients who underwent laparoscopic surgery for early gastric cancer were enrolled in this study. Noncontrast CT images were obtained 1-2 h after endoscopic submucosal peritumoral injection of 1 mL of lipiodol the day before surgery. The final sentinel basins (SBs) were decided by the dual tracer method (indocyanine green plus (99m)Tc-antimony sulfur colloid) during laparoscopic gastrectomy. SN detection rate by preoperative CT lymphography using lipiodol and agreement between CT lymphography versus dual tracer method were evaluated. The agreement was confirmed with soft X-ray radiography of detected SBs. RESULTS: Technical failure of endoscopic lipiodol injection occurred in one patient. SNs were successfully detected in the remaining 23 patients (95.8 %), whereas the intraoperative SB detection rate using the dual method was 100 %. The agreement rate, defined as the concordance between two methods or inclusion of SNs detected by CT lymphography in SBs by the dual tracer method, was 87 %. CONCLUSIONS: Our initial experience of CT lymphography using lipiodol shows good potential in predicting SBs of gastric cancer preoperatively. However, SN detection by CT lymphography and the dual method should be applied complementarily in gastric cancer because discrepancies between these methods occur.