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Background: The aim of the present study was to investigate the age-specific prognostic factors in patients who underwent gastrectomy for gastric cancer., Methods: The medical records of 366 patients with gastric cancer who underwent surgical resection at our hospital between January 2007 and December 2014 were retrospectively reviewed. Of the 366 patients, 117 were aged 75 years or older and 249 were aged 74 years or younger. All factors that were identified as significant using univariate analysis were included in the multivariate analysis., Results: The median follow-up duration was 52.9 months (range, 1.0-117.5 months). We found that in patients aged 75 years or older, postoperative complications and the extent of cancer were independent prognostic factors of overall survival and disease-free survival. In contrast, in patients aged 74 years or younger, only the lymph node status and postoperative chemotherapy were independent prognostic factors for overall survival and disease-free survival, respectively., Conclusions: Pathological outcomes and postoperative complications are important prognostic factors for survival in patients aged 75 years or older with gastric cancer, whereas pathological outcomes and postoperative chemotherapy are important prognostic factors for survival in patients aged 74 years or younger. Because the prevention of postoperative complications may contribute to improvements in the prognosis of elderly patients with gastric cancer, we suggest that it is necessary to consider limited surgery instead of radical surgery, depending on the patient's general condition and co-morbidities.

Background/aims: Carnitine plays an important role in the metabolism of fatty acids. It has also been reported that the administration of anticancer drugs may lead to reductions in serum carnitine levels due to decreased activity of organic cation transporter novel 2, which plays a role in the reabsorption of carnitine in the tubules of the kidney. We therefore studied the change in carnitine levels when chemotherapy was administered repeatedly to patients with gastric cancer., Methods: Ten patients with upper gastrointestinal cancer were enrolled in this study between December 2014 and August 2015. All patients were administered chemotherapy consisting of TS-1 and cisplatin every 3 weeks: 3 received it as adjuvant therapy post resection, the remaining 7 received it as treatment for unresectable tumors. Before the start of each chemotherapy cycle, serum was collected., Results: The mean total carnitine level was 54.5 ± 13.7 μmol/L prior to commencing chemotherapy; it was 46.7 ± 13.5 and 41.4 ± 14.8 μmol/L at the second and third cycles respectively. The total carnitine level was decreased in a statistically significant manner (p = 0.0039). The serum level of total protein and cholinesterase was also decreased significantly (p = 0.0218 and p = 0.0418)., Conclusion: Carnitine levels decreased during repeated chemotherapy in patients with gastric cancer, and they are associated with the nutritional status., (© 2017 S. Karger AG, Basel.)

Background: No definitive operative method has been established for the treatment of early subcardial gastric cancer. Our newly developed technique involves local resection of the subcardia while preserving the lower esophageal sphincter and vagus nerve. A new fornix is constructed to accept the transposed esophagus., Methods: Thirty patients underwent this procedure between July 2003 and December 2010. Continuous gastric pH monitoring was performed immediately after surgery, and esophageal manometry was undertaken 1 month later. Serum total protein, albumin, total cholesterol, cholinesterase, and body mass index (BMI) were recorded every 3 months. Pre- and postoperative oral intake were compared, reflux symptoms were recorded, and reflux esophagitis was assessed by endoscopy after 1 year., Results: Twenty-five patients (86 %) reported no symptoms of reflux, and 27 (92.8 %) patients could eat 70 % or more of what they had eaten before surgery. Lower esophageal pressures were found to be >10 mmHg in 66.7 % of patients, and the fraction of time that pH <4 was <5 % of the 24-h monitoring period in 70 %. Serum parameters and BMI were unchanged., Conclusions: This surgical technique is a useful means of preserving postoperative quality of life after local gastrectomy by preventing reflux and maintaining nutritional status.

Background/aims: To investigate whether imatinib dosage correlated with effective plasma levels and clinical characteristics for Japanese patients undergoing long-term (≥2 years) imatinib therapy for GISTs., Methodology: Twenty-five patients who received imatinib for a metastatic pathologically diagnosed GISTs at our hospital were enrolled. Imatinib response was assessed according to Choi’s criteria. Blood samples were collected 22–26 h after the previous imatinib dose before the next scheduled dose. Results: Fourteen patients were male and the median age was 65 years. The median duration of imatinib therapy was 3.8 years (range, 2.0–11.5 years). The median plasma level of imatinib was 1098 ng/ml and the minimal plasma level after ≥5 years of therapy was 789 ng/ml. Imatinib dosage was significantly correlated with history of gastrectomy. The minimum body surface area of patients who received 400-mg/day imatinib dosage was 1.560 m2., Conclusions: The minimum level in all patients showing response for ≥5 years of treatment was 789 ng/ml, suggesting an effective plasma imatinib level of ≥800 ng/ml. Our results suggest that imatinib dosage of 400 mg/day is recommended for a patient with a large BSA (≥1.56 m2) and that of 300 mg/day might be sufficient for patients who have undergone a gastrectomy.

Background/aim: The objective of this study was to investigate the influence of digestive gastrointestinal absorption function on the pharmacokinetics of the orally-administered anticancer drug, Tegafur-gimestat-otastat potassium (TS-1), by measuring the plasma 5-fluorouracil (5-FU) concentration using stable isotope breath tests., Patients and Methods: Twenty-nine patients with progressive/recurrent digestive organ cancer were enrolled for this pharmacokinetic study, and blood samples were obtained from each patient. The area under-the-time-concentration curve between 0 and 480 min (AUC0-480 min), time-of-drug concentration peak (T(max)), maximum drug concentration (C(max)) and the half-life period (t(1/2)) of 5-FU were investigated. Simultaneously, a continuous (13)C-acetate breath test was performed for each patient. The parameters measured with the breath test were the area under the (13)CO(2) excretion rate curve between 0-4 h (AUC(0-4h)), peak (13)CO(2) value and elimination rate constant (K(el)) value., Results: The AUC(0-8h) and C(max) of 5-FU were significantly correlated with K(el) (p=0.012 and p=0.024, respectively), and the 5-FU C(max) value was significantly correlated with the peak value of (13)CO(2) (p=0.037). Multivariate regression analysis also found the C(max) of 5-FU to be associated with K(el) (p=0.0118). The C(max) and AUC(0-8h) of 5-FU were also significantly correlated (p<0.0001)., Conclusion: The results of this study suggest that gastrointestinal absorption is closely-related to plasma 5-FU concentration after oral administration of TS-1.

Conventional gas chromatography-mass spectrometry (GC-MS) was compared with a new immunoassay method for measuring plasma (5-FU) concentrations in adjuvant chemotherapy with TS-1 for patients with gastric cancer. TS-1 was administered orally to patients after gastrectomy. Blood samples for pharmacokinetic analysis were collected on the seventh day of treatment. The mean area under the time concentration curve (AUC)(0-8), half-life (t(1/2)), and maximum drug concentration (C(max)) obtained by the two methods were as follows: GC-MS, 847.9 μg/ml/hr, 2.76 h, and 186.6 ng/ml; and immunoassay, 1311.2 μg/ml/hr, 3.5 h, and 259.8 ng/ml. Significant correlations were observed for AUC(0-8) (p=0.0001), C(max) (p=0.0007), and changes in the 5-FU concentration in blood over time (p=0.018) for the two methods. Compared with the conventional GC-MS method, the new immunoassay method provides similar results, but is simpler and results can be obtained earlier. This method will be useful for monitoring the 5-FU concentration in serum from patients with gastric cancer receiving TS-1.

In the current era of endoscopic submucosal dissection (ESD) for early gastric cancer, which carries a negligible risk of lymph node metastasis, local resection of the stomach remains an option for these lesions. This is particularly so for a large intramucosal lesion or a lesion with a strong ulcer scar, for which ESD becomes a difficult option. Here, we describe a case of lateral-spreading intramucosal gastric cancer of 6-cm diameter located at the fornix of the stomach, which was successfully treated by laparoscopic and endoscopic cooperative surgery (LECS) because of the expected risk of complications during ESD. In the LECS procedure, the resection margin was appropriately determined by the endoscopic evaluation in detail and by the ESD technique. If early gastric cancer fits the criteria for endoscopic resection but would present difficulty if performing ESD, this is a good indication for the LECS procedure.

Background/aims: The relationship between gastroesophageal junction adenocarcinoma (GEJA) and Helicobacter pylori infection is not well defined; thus, we retrospectively investigated this relationship., Methods: We examined 852 cases (646 men) of gastric cancer. GEJA was defined as type II according to the classification system of Siewert and Stein. We compared the prevalence of H. pylori infection and corporal gastritis in GEJA patients with distal gastric cancer., Results: GEJA was observed in 80 (including 6 cases of Barrett's esophageal cancer) of the 852 cases of gastric cancer examined (9.4%). The rate of H. pylori infection was significantly lower in patients with GEJA than in patients with distal gastric cancer (73.8 vs. 94.1%, p < 0.05). The prevalence of corporal gastritis was also significantly lower in patients with GEJA than in patients with distal gastric cancer (80.7 vs. 94.6%, p < 0.05). Concurrent H. pylori infection and corporal gastritis were not observed in patients with Barrett's esophageal cancer., Conclusion: Our study demonstrated that GEJA has 2 etiologic types; one of these types is associated with H. pylori infection and resembles distal gastric cancer, and the other one is not associated with H. pylori infection or Barrett's esophageal cancer., (Copyright © 2012 S. Karger AG, Basel.)

We studied the pharmacokinetics of 5-FU after S-1 oral administration at the usual dose (80 mg/m2) for adjuvant chemotherapy in 13 advanced gastric cancer patients (Stage II, III), and at a decreased dose (60 mg/m2) for adjuvant or combined chemotherapy in 13 advanced gastric cancer patients. Pharmacokinetic parameters of 5-FU in the serum were as follows: Cmax, 159 .9 2+/-45.2 ng/mL, Tmax, 2.17+/-0.58 h;T1/2, 3.13+/-2.88 h; and AUC(0-8), 768.0+/-260.8 ng h/mL in the patients with the usual dose, and Cmax, 117.3+/-55.1 ng/mL; Tmax, 2.62+/-0.9 6 h; T1/2, 3.09+/-1.9 5 h and AUC(0-8), 565.9+/-216.8 ng h/mL in the patients with the decreased dose. No difference in AUC was observed between operative methods. Adverse events of more than grade 3 were recognized in 7 patients, and AUC of 6 patients were more than 800 ng h/mL. The plasma concentration of 5-FU was quite different between patients. The difference of Cmax and AUC was 3-4 times. It was concluded that we must pay attention to individual differences in the plasma concentration of 5-FU in postoperative gastric cancer patients when S-1 would be administered.

Purpose: Proximal gastrectomy and lymph node dissection are often performed for T1 cancer of the gastric cardia; however, direct esophagogastrostomy is frequently complicated by reflux esophagitis. We describe a simple technique for preventing esophageal reflux and discuss its results., Methods: This technique is indicated for T1 cancer of the gastric cardia without lymphadenopathy. Partial resection, including the lesion, is performed, preserving the vagus nerve and lower esophageal sphincter (LES). Lymph node dissection is done around the left gastric, celiac, and splenic arteries. The esophagus is then anastomosed to the anterior wall in the center of the remnant stomach., Results: We evaluated the results of this procedure in eight patients. X-ray films showed no esophageal reflux in either the supine or the right decubitus position. None of the patients complained of reflux or other dyscrasic symptoms, and none had any feeling of microgastria. One patient had some localized erosion near the anastomosis., Conclusions: This simple and safe technique does not result in post-gastrectomy syndrome or microgastria, and the risk of leaving cancer cells is minimal.

Background: Peritoneal dissemination is the most frequent cause of recurrence in gastric cancer patients after gastrectomy. We have previously demonstrated the prognostic factors in gastric cancer including growth factors and their receptors and intra-peritoneal CEA (1,2)., Materials and Methods: In the present study, to elucidate whether CEA mRNA in peritoneal lavage is a good marker for the prediction of peritoneal recurrence of gastric cancer patients, quantitative real-time RT-PCR with primers specific for CEA was performed by peritoneal lavage of 124 gastric cancer patients collected at the time of operation., Results: CEA crossing-point values (CEA-CP) were significantly correlated with the depth of tumor invasion and the values were cut-off at 27.11, which was the minimum value of mucosal cancer patients. The CEA-CP was significantly correlated with lymph node metastasis, lymphatic invasion, venous invasion, stages and overall survivals. In prediction of peritoneal recurrence by CEA-CP, sensitivity and specificity were 76.9% and 67.7%, respectively. Cytology predicted peritoneal recurrence with 23.1% sensitivity and 98.1% specificity., Conclusion: Quantitative RT-PCR of CEA mRNA of peritoneal lavage is a useful factor for prognosis and predicting peritoneal recurrence.