Incidence, clinicopathological characteristics, and therapeutic strategy for gastric cancer patients with metastasis to the central nervous system.

AIM: This study aimed to analyze the clinicopathologic features and treatment outcomes of central nervous system (CNS) metastasis from gastric cancer. METHODS: A total of 419 patients diagnosed with unresectable advanced or recurrent gastric cancer at Kochi Medical School between January 2007 and December 2021 were evaluated. Data of patients were reviewed, and clinicopathological information and survival outcomes of those with CNS metastases were compared to patients without CNS metastases. RESULTS: In total, 12/419 (2.9%) patients (median age: 66.5 years [range, 41-82 years]) were diagnosed with CNS metastasis from gastric cancer. Eleven had diffuse-type gastric cancer which was significantly more common than in those without CNS metastasis (91% vs. 61%, p = .034). Human epidermal growth factor receptor 2 status was positive in one of the 12 patients. The median survival time was significantly lower for patients with CNS metastasis than for those without CNS metastasis (1.8 months vs. 11.4 months, p < .001). The median survival time for patients who underwent surgical resection, radiation, or chemotherapy for CNS metastasis was significantly higher than those who received only best supportive care (3.5 months vs. .6 months; p = .007). CONCLUSIONS: CNS metastasis was found in 2.9% (12/419) of patients with unresectable advanced or recurrent gastric cancer. Diffuse-type histology was a risk factor for CNS metastasis. Multidisciplinary treatment, including surgical resection, radiation treatment, or chemotherapy, for CNS metastasis from gastric cancer may benefit selected patients.

Assessment of Systemic Inflammatory Response and Nutritional Markers in Patients With Trastuzumab-treated Unresectable Advanced Gastric Cancer.

AIM: To determine whether markers of systemic inflammatory response and nutrition are a predictor of treatment response in patients with trastuzumab-treated unresectable advanced gastric cancer. PATIENTS AND METHODS: Twenty-one patients who received chemotherapy for unresectable advanced gastric cancer at Kochi Medical School from 2013 to 2020 were enrolled. Clinicopathological information and systemic inflammatory response data were obtained retrospectively to investigate associations between baseline cancer-related prognostic variables and survival outcomes. RESULTS: The median overall survival (OS) and progression-free survival (PFS) for the whole cohort were 24.5 (range=1.9-88.4) months and 7.0 (range=2.0-23.4) months, respectively. The objective response rate and disease control rate were 52.4% and 81.0%, respectively. The median PFS for patients with a neutrophil to lymphocyte ratio (NLR) <2.8 was significantly longer than that for those with NLR ≥2.8 (8.9 vs. 6.0 months; p=0.048). Although the median OS also tended to be longer for patients with NLR <2.8, the difference was not statistically significant. No significant differences in median OS and PFS were observed between patients with a prognostic nutrition index (PNI) <41.6 and those with PNI ≥41.6. CONCLUSION: An NLR ≥2.8 is a predictor of poorer prognosis in patients receiving systemic treatment with trastuzumab and chemotherapy for unresectable advanced or recurrent gastric cancer.

Correlation between indocyanine green visualization time in the gastric tube and postoperative endoscopic assessment of the anastomosis after esophageal surgery.

PURPOSE: To evaluate the correlation between blood supply speed in the gastric tube (GT), assessed by the intraoperative indocyanine green (ICG) fluorescence method, and postoperative endoscopic assessment (PEA) of the anastomosis or anastomotic leakage (AL). METHODS: The subjects of this retrospective analysis were 66 consecutive patients who underwent GT reconstruction using ICG fluorescence during esophageal surgery. We measured the ICG visualization time, from ICG injection to visualization at the top of the GT. We performed PEA on 54 patients and classified ulcer formation as involving less than or more than half of the circumference. RESULTS: PEA revealed that nine patients (16.7%) had an anastomotic ulcer involving more than half of the circumference and ten (15.4%) had AL. The ICG visualization time in these patients was significantly delayed compared with that in those with less than half of the circumference involved by ulcer formation (37 s vs. 27 s; P = 0.015) and without AL (36 s vs. 28 s; P = 0.045). Multivariate analysis revealed that delay in the ICG visualization time (> 36 s) of the pulled-up GT (odds ratio, 6.098; 95% confidence interval, 1.125-33.024; P = 0.036) was an independent risk factor associated with AL. CONCLUSION: Delay in the ICG visualization time of pulled-up GT was associated with ulcer formation on the anastomosis and AL after esophageal surgery.

Assessment of the blood supply using the indocyanine green fluorescence method and postoperative endoscopic evaluation of anastomosis of the gastric tube during esophagectomy.

BACKGROUND: Postoperative anastomotic leakage is a severe complication after gastric tube reconstruction during esophagectomy. The aim of this study was to evaluate the usefulness of postoperative endoscopic assessment of anastomosis and its correlation with intraoperative indocyanine green (ICG) fluorescence assessment of the gastric tube. METHODS: We retrospectively reviewed 72 consecutive patients who underwent gastric tube reconstruction using the ICG fluorescence method during esophagectomy. Forty-six patients underwent the ICG line-marking method (LMM group; ICG before gastric tube creation). The other 26 underwent the conventional procedure and comprised the control group (ICG after gastric tube creation). Postoperative endoscopic assessment (PEA) of anastomosis was performed 7 days after surgery and results were classified as follows: grade 1 (normal or partial white coat), grade 2 (ulcer comprising less than half the circumference), and grade 3 (ulcer comprising more than half the circumference). RESULTS: Anastomotic leakage occurred in 7 of 72 patients (9.7%). The incidence of anastomotic leakage in the LMM group was tended to be lower than those in the control group (6.5% vs. 15.4%; P = 0.244). Of the 40 patients who underwent PEA, 3 (7.5%) had leakage. PEA grading was significantly associated with anastomotic leakage (P < 0.001). Better intraoperative ICG assessment was significantly associated with better endoscopic assessment grade (P = 0.041). CONCLUSION: Intraoperative ICG assessment of the gastric tube was associated with PEA grading on anastomosis during esophagectomy.

Energy expenditure measured using indirect calorimeter after minimally invasive esophagectomy in ventilated postoperative patients.

Minimally invasive esophagectomy has recently become popular after the laparoscopic technique was developed. However, the postoperative energy expenditure in patients undergoing this procedure has not been evaluated. Therefore, we hypothesized that postoperative resting energy expenditure (REE) following minimally invasive esophagectomy is lower than that estimated using the Harris-Benedict equation. Fifteen patients who underwent esophagectomy by thoracoscopy in the prone position were analyzed. After esophagectomy, an indirect calorimeter measured the energy expenditure during ventilation in the ICU. These values and the estimated basal energy expenditure values were compared using the paired t test. The mean age was 66 ± 10 years and mean duration of ventilator use in the ICU was 697 ± 70 mins. The acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) scores at the time of ICU admission were 13 ± 4 and 2 ± 1, respectively. The average temperature, heart rate, and respiratory rate during ventilation were 36.2 ± 0.6°C, 67 ± 9 beats/min, and 12 ± 2/min, respectively. The average REE during ventilation was 985 ± 167 kcal/day (18.1 ± 3.4 kcal/kg/day). The estimated REE was 1191 ± 159 kcal/day. The average REE measured using the indirect calorimeter during ventilation was significantly lower than the estimated REE (83 ± 10% of the estimated REE, p<0.001). In conclusion, the REE measured by an indirect calorimeter after minimally invasive esophagectomy at early postoperative stage under sedation was significantly lower than the REE estimated using the Harris-Benedict equation.

Population pharmacokinetic analysis of daikenchuto, a traditional Japanese medicine (Kampo) in Japanese and US health volunteers.

We constructed population pharmacokinetic (PK) models for the five constituents of daikenchuto (DKT), a traditional Japanese herbal medicine. Data were collected from two randomized PK studies conducted in Japan and the United States. Participants received single oral doses of 2.5 g, 5 g, and 10 g of DKT. The plasma concentrations of five DKT constituents--hydroxy-α-sanshool (HAS), hydroxyl-ß-sanshool (HBS), 6-shogaol (6S), 10-shogaol (10S), and ginsenoside Rb1 (GRB1)--were determined by liquid chromatography-tandem mass spectrometry. A total of 1859 samples from 55 participants (US, n = 36; Japanese, n = 19) were included in the analysis. Population PK models of HAS, HBS, 6S, and 10S were best described by a one or two-compartment model with a bolus input. On the other hand, the model of GRB1 was best described by a one-compartment model with nonlinear extravascular input. Among the covariates evaluated, body mass index (BMI) and age were found to influence oral clearance (CL/F) and volume of distribution (Vd/F) for HAS and HBS, respectively. The influence of body weight on CL/F and Vd/F for 6S was demonstrated. Marked differences were observed in mean plasma concentrations of HAS and HBS between Japanese and US participants. However, the simulation results indicated that the difference in plasma concentrations may be attributed to the difference in demographic factors such as BMI, body weight, and age, whereas ethnic difference between the Japanese and US participants was considered minimal.