A multi-center, prospective, clinical study to evaluate the anti-reflux efficacy of laparoscopic double-flap technique (lD-FLAP Study).

Background: Double-flap technique (DFT) is a reconstruction procedure after proximal gastrectomy (PG). We previously reported a multi-center, retrospective study in which the incidence of reflux esophagitis (RE) (Los Angeles Classification ≥Grade B [LA-B]) 1 year after surgery was 6.0%. There have been many reports, but all of them were retrospective. Thus, a multi-center, prospective study was conducted. Methods: Laparoscopic PG + DFT was performed for cT1N0 upper gastric cancer patients. The primary endpoint was the incidence of RE (≥LA-B) 1 year after surgery. The planned sample size was 40, based on an estimated incidence of 6.0% and an upper threshold of 20%. Results: Forty patients were recruited, and 39, excluding one with conversion to total gastrectomy, received protocol treatment. Anastomotic leakage (Clavien-Dindo ≥Grade III) was observed in one patient (2.6%). In 38 patients, excluding one case of postoperative mortality, RE (≥LA-B) was observed in two patients (5.3%) 1 year after surgery, and the upper limit of the 95% confidence interval was 17.3%, lower than the 20% threshold. Anastomotic stricture requiring dilatation was observed in two patients (5.3%). One year after surgery, body weight change was 88.9 ± 7.0%, and PNI <40 and CONUT ≥5, indicating malnutrition, were observed in only one patient (2.6%) each. In the quality of life survey using the PGSAS-45 questionnaire, the esophageal reflux subscale score was 1.4 ± 0.6, significantly better than the public data (2.0 ± 1.0; p = 0.001). Conclusion: Laparoscopic DFT showed anti-reflux efficacy. Taken together with the acceptable incidence of anastomotic stricture, DFT can be an option for reconstruction procedure after PG.

Prognostic nutritional index is a prognostic factor for patients with gastric cancer and esophagogastric junction cancer undergoing proximal gastrectomy with esophagogastrostomy by the double-flap technique: A secondary analysis of the rD-FLAP study.

PURPOSE: Although proximal gastrectomy (PG) is commonly used in patients with upper gastric cancer (GC) and esophagogastric junction (EGJ) cancer, long-term prognostic factors in these patients are poorly understood. The double-flap technique (DFT) is an esophagogastrostomy with anti-reflux mechanism after PG; we previously conducted a multicenter retrospective study (rD-FLAP) to evaluate the short-term outcomes of DFT reconstruction. Here, we evaluated the long-term prognostic factors in patients with upper GC and EGJ cancer. METHODS: The study was conducted as a secondary analysis of the rD-FLAP Study, which enrolled patients who underwent PG with DFT reconstruction, irrespective of disease type, between January 1996 and December 2015. RESULTS: A total of 509 GC and EGJ cancer patients were enrolled. Univariate and multivariate analyses of overall survival demonstrated that a preoperative prognostic nutritional index (PNI) < 45 (p < 0.001, hazard ratio [HR]: 3.59, 95% confidential interval [CI]: 1.93-6.67) was an independent poor prognostic factor alongside pathological T factor ([pT] ≥2) (p = 0.010, HR: 2.29, 95% CI: 1.22-4.30) and pathological N factor ([pN] ≥1) (p = 0.001, HR: 3.27, 95% CI: 1.66-6.46). In patients with preoperative PNI ≥45, PNI change (<90%) at 1-year follow-up (p = 0.019, HR: 2.54, 95%CI: 1.16-5.54) was an independent poor prognostic factor, for which operation time (≥300 min) and blood loss (≥200 mL) were independent risk factors. No independent prognostic factors were identified in patients with preoperative PNI <45. CONCLUSIONS: PNI is a prognostic factor in upper GC and EGJ cancer patients. Preoperative nutritional enhancement and postoperative nutritional maintenance are important for prognostic improvement in these patients.

Incidence of Metachronous Remnant Gastric Cancer after Proximal Gastrectomy with the Double-flap Technique (rD-FLAP-rGC Study): A Multicenter, Retrospective Study.

BACKGROUND: Although proximal gastrectomy (PG) with the double-flap technique (DFT) is a function-preserving surgery that prevents esophagogastric reflux, there is a risk of developing metachronous remnant gastric cancer (MRGC). Moreover, details of MRGC and appropriate postoperative follow-up after PG with DFT are unclear. METHODS: We reviewed the medical records of 471 patients who underwent PG with DFT for cancer in a preceding, multicenter, retrospective study (rD-FLAP Study). We investigated the incidence of MRGC, frequency of follow-up endoscopy, and eradication of Helicobacter pylori (H. pylori) infection. RESULTS: MRGC was diagnosed in 42 (8.9%) of the 471 patients, and 56 lesions of MRGC were observed. The cumulative 5- and 10-year incidence rates were 5.7 and 11.4%, respectively. There was no clinicopathological difference at the time of primary PG between patients with and without MRGC. Curative resection for MRGC was performed for 49 (88%) lesions. All patients with a 1-year, follow-up, endoscopy interval were diagnosed with early-stage MRGC, and none of them died due to MRGC. Overall and disease-specific survival rates did not significantly differ between patients with and without MRGC. The incidence rate of MRGC in the eradicated group after PG was 10.8% and that in the uneradicated group was 19.6%, which was significantly higher than that in patients without H. pylori infection at primary PG (7.6%) (p = 0.049). CONCLUSIONS: The incidence rate of MRGC after PG with DFT was 8.9%. Early detection of MRGC with annual endoscopy provides survival benefits. Eradicating H. pylori infection can reduce the incidence of MRGC.

Accurate resection of nonpalpable, ultrasonography undetectable breast cancer tumor by preoperative indocyanine green injection using stereotactic mammography: A case report.

Introduction: and importance: Tumor localization is vital in the surgical management of nonpalpable breast cancer. Various localization methods exist, each with their own disadvantages. Therefore, we need to investigate the optimal method of diagnosis for this condition. Case presentation: A 66-year-old woman presented to our facility with a microcalcification detected on screening mammography (MMG). The lesion was neither palpable nor detectable on ultrasonography (US). Three-dimensional stereotactic biopsy using MMG revealed ductal carcinoma in situ. The precise tumor location was needed to perform breast-conserving surgery. Clinical discussion: Our hospital did not have radioisotope imaging; hence, wire placement would have been difficult for this lesion location. To aid in localization, indocyanine green (ICG) and fluorescence imaging were used. ICG was injected preoperatively using stereotactic MMG, which enabled clear visualization of the lesion. Then, an accurate resection was performed. The patient was discharged without any complications 2 days after surgery. Conclusion: The findings of this case report suggest that stereotactic MMG-guided ICG can be useful in localizing breast cancer tumors that are nonpalpable and undetectable by US.

Successful intragastric suture repair using endoscopy for refractory ischemic stomach perforation: A case report.

INTRODUCTION: Ischemic stomach perforation and bleeding are major complications after distal pancreatectomy with en bloc celiac axis resection (DP-CAR) for locally advanced pancreatic cancer. Although there are some treatment options for ischemic gastric events, we need to discuss the optimal treatment based on the patient's general condition and history. CASE PRESENTATION: A 76-year-old woman with advanced pancreatic cancer underwent DP-CAR with the reconstruction of the common hepatic artery-celiac artery. She presented with a high fever and melena at 13 days and twenty-nine days after the operation, respectively. Contrast-enhanced computed tomography (CECT) demonstrated ischemic stomach perforation, which was localized. Although nonsurgical treatments, including endoscopic clipping and proton-pump inhibitor administration, were attempted, her symptoms were not relieved. Therefore, we performed intragastric suture repair using oral endoscopy (ISE) for gastric perforation. Although she presented with surgical site infection and a catheter-related blood stream infection after ISE, she was discharged 140 days after the first operation. CLINICAL DISCUSSION: Ischemic gastric events following DP-CAR can be treated with non-surgical and surgical approaches. In this case, non-surgical management could not improve the patient's gastric complications, and she had to undergo surgery. Given the patient's condition, ISE was an indication for this complication and was, thus, performed among surgical procedures, resulting in the alleviation of the complication. Using ISE may provide safe and less invasive surgery. CONCLUSION: This is the first case of ISE for use in refractory ischemic stomach perforation following DP-CAR. ISE can be a useful and minimally invasive surgical procedure.

Rapid recurrence of spindle cell type undifferentiated carcinoma early after radical surgery in a bile duct cancer patient - A case report.

INTRODUCTION: Spindle cell type undifferentiated carcinoma of the extrahepatic bile duct is extremely rare and has a poor prognosis. However, its pathology is not fully known, yet. CASE PRESENTATION: 76-year-old man with abdominal pain and dark-colored urine was referred to our department. Contrast-enhanced computed tomography showed an enhanced tumor at the junction of the cystic duct and direct invasion of the portal vein. He was diagnosed as having resectable biliary cancer and underwent a subtotal stomach-preserving pancreaticoduodenectomy with a reconstruction of the portal vein. Histopathological findings demonstrated undifferentiated spindle cell carcinoma. Forty-two days post-surgery, he presented with peritoneal dissemination and local recurrence with ascites, and died sixty-five days after his operation. CLINICAL DISCUSSION: Spindle cell type undifferentiated carcinoma has highly metastatic potentials and also easily invade adjacent organs. Therefore, the prognosis of an undifferentiated, spindle cell type cholangiocarcinoma was poor. Although only surgery ensures cure, multidisciplinary treatment, including chemotherapy and radiotherapy is required. CONCLUSION: Although surgery for spindle cell type undifferentiated carcinoma may provide a cure, we must consider the induction of multidisciplinary treatment.

Effectiveness of gallium scintigraphy in diagnosing a spontaneous giant chronic expanding hematoma of the adrenal gland: A case report.

INTRODUCTION: A chronic expanding hematoma in the retroperitoneal space is a rare disease with poorly understood pathology, and preoperative diagnosis of such hematomas using conventional methods is sometimes difficult. PRESENTATION OF CASE: A 68-year-old man with a history of slowly progressive abdominal distention was referred to our department for further evaluation. Contrast-enhanced CT revealed a large retroperitoneal tumor of the adrenal gland. MRI revealed that the tumor was iso-intense to hyperintense on T2-weighted imaging, with heterogeneous signal intensity on T1-weighted imaging without fat components. Angiography of the left adrenal artery confirmed many extravasations into the tumor. However, gallium scintigraphy showed no accumulation in the tumor. These findings were suggestive of a chronic expanding hematoma of left adrenal gland. This patient underwent complete tumor resection. Postoperative histopathological findings revealed a chronic expanding hematoma. DISCUSSION: Chronic expanding hematomas are slowly expanding, space-occupying masses as a result of trauma, surgery, or bleeding disorders. Chronic expanding hematomas mimic malignant tumors such as sarcomatous lesions. Although CT and MRI are used to obtain the diagnosis, the diagnosis is sometimes difficult. Gallium scintigraphs play a pivotal role in the differential diagnosis between them. CONCLUSION: Gallium scintigraphs, magnetic resonance imaging and computed tomography, are useful tools to differentiate chronic expanding hematomas from sarcomatous lesions.

Multicenter retrospective study to evaluate the efficacy and safety of the double-flap technique as antireflux esophagogastrostomy after proximal gastrectomy (rD-FLAP Study).

AIM: As a result of the difficulty in effective prevention of gastroesophageal reflux, no standard reconstruction procedure after proximal gastrectomy (PG) has yet been established. The double-flap technique (DFT), or Kamikawa procedure, is an antireflux reconstruction procedure in esophagogastrostomy. The efficacy of DFT has recently been reported in several studies. However, these were all single-center studies with a limited number of cases. METHODS: We conducted a multicenter retrospective study in which patients who underwent DFT, irrespective of disease type and reconstruction approach, at each participating institution between 1996 and 2015 were registered. Primary endpoint was incidence of reflux esophagitis at 1-year after surgery, and secondary endpoint was incidence of anastomosis-related complications. RESULTS: Of 546 patients who were eligible for this study, 464 patients who had endoscopic examination at 1-year follow up were evaluated for reflux esophagitis. Incidence of reflux esophagitis of all grades was 10.6% and that of grade B or higher was 6.0%. Male gender and anastomosis located in the mediastinum/intra-thorax were independent risk factors for grade B or higher reflux esophagitis (odds ratio [OR]: 4.21, 95% confidence interval [CI]: 1.44-10.9, P = 0.0109). Total incidence of anastomosis-related complications was 7.2%, including leakage in 1.5%, strictures in 5.5% and bleeding in 0.6% of cases. Laparoscopic reconstruction was the only independent risk factor for anastomosis-related complications (OR: 3.93, 95% CI: 1.93-7.80, P = 0.0003). CONCLUSION: Double-flap technique might be a feasible option after PG for effective prevention of reflux, although anastomotic stricture is a complication that must be well-prepared for.

Composite neuroendocrine carcinoma and squamous cell carcinoma with regional lymph node metastasis: a case report.

BACKGROUND: Neuroendocrine cell carcinoma is a rare variant of esophageal carcinoma. The characteristic clinical features and diagnosis of superficial neuroendocrine cell carcinoma remain to be established. We report a rare case of superficial coexistence of neuroendocrine cell carcinoma with squamous cell carcinoma treated by endoscopic submucosal dissection, and regional lymph node metastasis was detected after additional surgical treatment. CASE PRESENTATION: A 77-year-old Japanese man with esophageal squamous cell carcinoma received endoscopic submucosal dissection in en-bloc resection. Histopathological findings showed that lymphovascular invasion by the neuroendocrine cell carcinoma component occurred in the deep part of the muscularis mucosa. Regional lymph node metastasis was identified after additional surgical treatment. After surgical treatment, our patient received chemotherapy consisting of etoposide and carboplatin for 3 months. He is alive and shows no sign of disease recurrence 12 months after surgery. CONCLUSIONS: This case report highlights the fact that even if neuroendocrine cell carcinoma is small and limited to superficial, the tumor has the potential for metastasis if lymphovascular invasion by the neuroendocrine cell carcinoma component occurs. In addition, this case indicates the necessity of close follow-up of small neuroendocrine cell carcinoma after treatment.

A multi-institution phase II study of docetaxel and S-1 in combination with trastuzumab for HER2-positive advanced gastric cancer (DASH study).

BACKGROUND: Trastuzumab when combined with fluoropyrimidine and cisplatin was proven to improve survival in patients with human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) in the ToGA study. The safety and efficacy of trastuzumab in combination with docetaxel and S-1 have not yet been evaluated. METHODS: This study was a multicenter, phase II study. Patients with chemotherapy-naïve HER2-positive advanced or metastatic GC were eligible. Trastuzumab was administered intravenously on day 1 of the first cycle at 8 and 6 mg/kg in subsequent cycles. Docetaxel was administered intravenously at 40 mg/m2 on day 1 of each cycle. S-1 was administered at a dosage based on body surface area for 14 days in a 3-weekly cycle. The primary endpoint was progression-free survival (PFS). RESULTS: A total of 23 patients were enrolled. Median PFS was 6.7 months (95% CI 4.1-10.1). The response rate (RR) was 39.1%. Median overall survival (OS) and time to treatment failure (TTF) were 17.5 and 4.4 months, respectively. Major grade 3-4 adverse events were neutropenia (39.1%), leukopenia (30.4%), and febrile neutropenia (8.7%). CONCLUSION: Trastuzumab in combination with docetaxel and S-1 showed effective antitumor activity and manageable toxicities as first-line treatment for patients with HER2-positive GC.

Laparoscopy-Assisted Proximal Gastrectomy with the Hinged Double Flap Method.

BACKGROUND: No standard proximal gastrectomy method for gastric cancer of the upper third of the stomach (UGC) has been established because few of the current methods prevent gastro-esophageal reflux and allow easy postoperative endoscopic surveillance. In the present study, we describe laparoscopic proximal gastrectomy with the hinged double flap method (Kamikawa's method) in detail and examine the short- to medium-term outcomes of this approach, which resulted in excellent postoperative function. METHODS: Between 2011 and 2015, 24 patients with early-stage primary UGC underwent laparoscopic proximal gastrectomy with the above-mentioned method. The celiac and hepatic nerves were preserved without pyloroplasty. A hand-sewn esophagogastric anastomosis was produced intracorporeally. RESULTS: There were no in-hospital deaths, and none of the patients were converted to open surgery. Complications occurred in two patients in the early part of this study (minor anastomotic leakage in one case and an abdominal abscess in the other). None of the patients exhibited symptoms of reflux. Regarding the patients' postoperative endoscopic classifications, 17, 2, and 1 patient were considered to have grade N or M, grade A, and grade B esophagitis, respectively. All of the patients remain alive, and no cases of postoperative bowel obstruction or recurrent cancer have been observed. CONCLUSIONS: This method can be performed safely and achieves excellent outcomes in terms of preventing gastro-esophageal reflux. It deserves further evaluation in a multi-center clinical study.

Enteral supplementation with glutamine, fiber, and oligosaccharide modulates incretin and glucagon-like peptide-2 secretion.

AIMS/INTRODUCTION: A dietary supplementation product enriched with glutamine, dietary fiber and oligosaccharide (GFO) is widely applied for enteral nutrition support in Japan. The aim of the present study was to evaluate the effects of GFO ingestion on secretion of incretins, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), and glucagon-like peptide-2 (GLP-2). MATERIALS AND METHODS: We carried out a cross-over study involving 20 healthy Japanese volunteers. The participants received GFO or 17 g of glucose, the equivalent carbohydrate in GFO as the control. Plasma glucose, serum insulin, and plasma total GIP, total GLP-1 and total GLP-2 levels during GFO or glucose loading were determined. RESULTS: GFO loading produced significantly higher plasma GLP-1 levels at 30 min and 60 min, area under the curve-GLP-1 value, and area under the curve-GLP-2 value after administration compared with those by glucose loading. In contrast, plasma GIP levels at both 30 and 60 min, and area under the curve-GIP value after glucose loading were significantly higher than those after GFO loading. CONCLUSIONS: These results show that GFO ingestion stimulates GLP-1 and GLP-2 secretion, and reduces GIP secretion compared with glucose ingestion. Therefore, GFO could have an intestinotrophic effect as well as an ameliorating effect on metabolic disorders through modification of release of gut hormones.

A hospital-based cross-sectional study to develop an estimation formula for 2-h post-challenge plasma glucose for screening impaired glucose tolerance.

AIMS: To create and validate an estimation formula for 2-h post-challenge plasma glucose (2-hPG) as an alternative to oral glucose tolerance test (OGTT) for impaired glucose tolerance (IGT) screening. METHODS: 380 Japanese subjects (57.6% males, aged 58.5 (14.0); mean (SD) years) undergoing OGTT were included in this hospital-based cross-sectional study mainly at Kyoto University Hospital between 2000 and 2011. We determined the main predictive variables of 2-hPG from clinical variables and separated the subjects randomly into two groups: a derivation group to construct an estimation formula of 2-hPG on the basis of predictive variables and a validation group to evaluate the accuracy of the formula. RESULTS: Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) were highly correlated with 2-hPG measured by OGTT. Multiple linear regression analysis showed that estimated 2-hPG (e2-hPG) was calculated by the formula: e2-hPG = 1.66 × FPG (mmol/l) + 1.63 × HbA1c (%)-10.11 (R(2), coefficient of determination=60.2%). When the cut-off value was set to the diagnostic criteria of IGT, 7.8 mmol/l of e2-hPG, sensitivity, specificity, and negative predictive value (NPV) were 83.3%, 44.1%, and 74.3%, respectively. When the cut-off value was set lower (7.2 mmol/l), these values were 94.4%, 30.5%, and 85.7%, respectively. The area under the receiver operating characteristic (ROC) curve was 0.68. CONCLUSIONS: This high-sensitive estimation formula may be a useful alternative to OGTT for IGT screening. For the levels ≤ 7.2 mmol/l, this formula may also be useful in cross-sectional study to identify people whose glucose tolerance is normal.

Enteral supplement enriched with glutamine, fiber, and oligosaccharide attenuates experimental colitis in mice.

OBJECTIVE: Ulcerative colitis is a chronic recurrent disease characterized by acute inflammation of the colonic mucosa. In Japan, a dietary supplementation product enriched with glutamine, dietary fiber, and oligosaccharide (GFO) is widely applied for enteral nutrition support. These three components have been suggested to improve intestinal health. In this study, we investigated whether GFO has suppressive effects on mucosal damage in ulcerative colitis in an experimental mouse model. METHODS: C57BL/6 mice received 2.5% dextran sulfate sodium in drinking water for 5 d to induce colitis. Then, they were given 0.25 mL of GFO or a 20% glucose solution twice daily for 10 d. Another set of mice receiving unaltered drinking water was used as the normal control group. RESULTS: The body weight loss and disease activity index were significantly lower in the GFO-treated mice compared with the glucose-treated mice (P < 0.05). The decrease in colon length induced by dextran sulfate sodium was significantly alleviated in GFO-treated mice compared with glucose-treated mice (P < 0.01). In addition, the histologic findings showed that intestinal inflammation was significantly attenuated in mice treated with GFO. Furthermore, treatment with GFO significantly inhibited the dextran sulfate sodium-induced increase in the mRNA expression of interleukin-1ß. CONCLUSION: These results suggest that GFO has potential therapeutic value as an adjunct therapy for ulcerative colitis.

[A case of pathologically complete response of esophageal carcinoma treated with low-dose 5-FU/CDDP as neoadjuvant chemotherapy].

The patient was a 75-year-old woman with advanced esophageal cancer and lymph-node swelling in the mediastinum(cStage RR). We administered preoperative chemotherapy(5-FU 500mg/body×10, CDDP 10mg/body×10). She received the two courses without showing any serious side effects. The primary tumor revealed remarkable improvement, but the rigidity of the esophagus wall and swelling of the lymph nodes were not resolved, and images showed that the patient exhibited a partial response to the treatment. Radical resection of the esophageal carcinoma was performed. Pathological examination of the resected specimens revealed no malignant cells in the esophagus, no metastasis of the lymph node, and the response evaluation was grade 3. The patient showed no recurrence 4 years and eleven months after the operation. In lonclusion, this rare case of esophageal carcinoma showed a pathologically complete response when treated with low-dose 5-FU/CDDP as neoadjuvant chemotherapy.

[A case of gastric cancer with rhabdoid features showing better prognosis through S-1/CDDP chemotherapy].

Although gastric cancers(GCs)with rhabdoid features are rare, they are known to show a poorer prognosis compared with conventional GCs. Indeed, more than half of reported GCs with rhabdoid features died within 6 months after receiving any kind of initial treatment. Obviously, no effective chemotherapy has been reported. In this study, we present a case of GC with rhabdoid features which showed a better response to a chemotherapy, S-1/CDDP, and lived for over 12 months after the initial chemotherapy. A 75-year-old man was seen in our hospital for epigastralgia. Detailed examinations revealed that he had GC at Stage IV. Consequently, he underwent S-1/CDDP treatment. This treatment produced a good response for 6 months, minimizing the size of the primary tumor and eradicating distant metastases. Re-growth of the primary tumor without uprising distant metastasis was confirmed 8 months after the initialS -1/CDDP treatment, and the patient went through a gastrectomy for curative care. After surgery, a precise pathological examination revealed that the primary tumor possessed a poorly differentiated adenocarcinoma that contained tumor cells with typical rhabdoid features. In the end, the patient died of liver metastasis 13 months after the initial S-1/CDDP chemotherapy.

Effects of glucose and meal ingestion on incretin secretion in Japanese subjects with normal glucose tolerance.

UNLABELLED: Aims/Introduction: Gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the major incretins; their secretion after various nutrient loads are well-evaluated in Caucasians. However, little is known of the relationship between incretin secretion and differing nutritional loading in Japanese subjects. In the present study, we evaluated GIP and GLP-1 secretion in Japanese subjects with normal glucose tolerance (NGT) after glucose loading (75 g glucose and 17 g glucose) and meal ingestion. MATERIALS AND METHODS: A total of 10 Japanese NGT subjects participated in 75 g oral glucose tolerance test (OGTT), 17 g OGTT and meal tolerance test (MTT). Plasma glucose (PG), serum insulin (IRI), serum C-peptide (CPR), plasma total GIP, and plasma total GLP-1 levels during OGTT and MTT were determined. RESULTS: Area under the curve (AUC)-GIP was increased in proportion to the amount of glucose, and was highest in MTT, showing that GIP secretion is also stimulated by nutrients other than glucose, such as lipid. In contrast, although the larger glucose load tended to induce a larger GLP-1 release, AUC-GLP-1 was not significantly different among the three loading tests (75 g OGTT, 17 g OGTT, MTT) irrespective of the kind or amount of nutrition load. CONCLUSIONS: Our results suggest that nutritional composition might have a greater effect on GIP secretion than that on GLP-1 secretion in Japanese NGT subjects. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00143.x, 2012).

Plasma gastric inhibitory polypeptide and glucagon-like peptide-1 levels after glucose loading are associated with different factors in Japanese subjects.

UNLABELLED: Aims/Introduction: Gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are major incretins that potentiate insulin secretion from pancreatic ß-cells. The factors responsible for incretin secretion have been reported in Caucasian subjects, but have not been thoroughly evaluated in Japanese subjects. We evaluated the factors associated with incretin secretion during oral glucose tolerance test (OGTT) in Japanese subjects with normal glucose tolerance (NGT). MATERIALS AND METHODS: We measured plasma GIP and GLP-1 levels during OGTT in 17 Japanese NGT subjects and evaluated the factors associated with GIP and GLP-1 secretion using simple and multiple regression analyses. RESULTS: GIP secretion (AUC-GIP) was positively associated with body mass index (P < 0.05), and area under the curve (AUC) of C-peptide (P < 0.05) and glucagon (P < 0.01), whereas GLP-1 secretion (AUC-GLP-1) was negatively associated with AUC of plasma glucose (P < 0.05). The insulinogenic index was most strongly associated with GIP secretion (P < 0.05); homeostasis model assessment ß-cell was the most the strongly associated factor in GLP-1 secretion (P < 0.05) among the four indices of insulin secretion and insulin sensitivity. CONCLUSIONS: Several distinct factors might be associated with GIP and GLP-1 secretion during OGTT in Japanese subjects. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00078.x, 2011).

Improvement of oral bioavailability of flurbiprofen from flurbiprofen/beta-cyclodextrin inclusion complex by action of cinnarizine.

Improvement of the oral bioavailability of flurbiprofen (Flu) after oral administration of flurbiprofen/beta-cyclodextrin inclusion complex (Flu/beta-CD) by the action of cinnarizine (CN) was investigated. Flu and Flu/beta-CD were administered orally to fasted rats at a dose of 20mg/kg as Flu. Thirty minutes after drug administration, CN dissolved in pH 4.0 buffer solution or pH 4.0 buffer solution alone was administered to the rats. The dose of CN was 0.17 mg/kg. Blood samples were taken from rats and Flu concentrations in plasma samples were determined by HPLC. It was found from the comparison of Flu and Flu with CN (Flu+CN) that CN had no effect on plasma concentrations of Flu after oral administration of Flu. The mean plasma levels after oral administration of Flu/beta-CD with CN (Flu/beta-CD+CN) were larger not only than those of Flu and Flu+CN but also than those of Flu/beta-CD. The value of C(max) in Flu/beta-CD+CN was significantly larger than that of Flu/beta-CD. This is considered to be caused by the action of CN as a competing agent. This mechanism was supported by the result of solubility study in which Flu solubility in beta-CD solution decreased with the addition of CN. It was found from these results that CN had strong ability as a competing agent in vivo.