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1.
Ann Surg Oncol ; 30(4): 2307-2316, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36692611

RESUMEN

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.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Neoplasias Primarias Secundarias , Neoplasias Gástricas , Humanos , Incidencia , Estudios Retrospectivos , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/cirugía , Neoplasias Primarias Secundarias/patología , Gastrectomía/efectos adversos , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/diagnóstico , Estudios Multicéntricos como Asunto
3.
World J Surg ; 40(10): 2419-24, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27094564

RESUMEN

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.


Asunto(s)
Gastrectomía/métodos , Laparoscopía/métodos , Neoplasias Gástricas/cirugía , Colgajos Quirúrgicos , Anciano , Anciano de 80 o más Años , Fuga Anastomótica/etiología , Femenino , Gastrectomía/efectos adversos , Humanos , Laparoscopía/efectos adversos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología
4.
Front Endocrinol (Lausanne) ; 15: 1301352, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38966210

RESUMEN

Introduction: Incretin-based drugs are extensively utilized in the treatment of type 2 diabetes (T2D), with remarkable clinical efficacy. These drugs were developed based on findings that the incretin effect is reduced in T2D. The incretin effect in East Asians, whose pancreatic ß-cell function is more vulnerable than that in Caucasians, however, has not been fully examined. In this study, we investigated the effects of incretin in Japanese subjects. Methods: A total of 28 Japanese subjects (14 with normal glucose tolerance [NGT], 6 with impaired glucose tolerance, and 8 with T2D) were enrolled. Isoglycemic oral (75 g glucose tolerance test) and intravenous glucose were administered. The numerical incretin effect and gastrointestinally-mediated glucose disposal (GIGD) were calculated by measuring the plasma glucose and entero-pancreatic hormone concentrations. Results and discussion: The difference in the numerical incretin effect among the groups was relatively small. The numerical incretin effect significantly negatively correlated with the body mass index (BMI). GIGD was significantly lower in participants with T2D than in those with NGT, and significantly negatively correlated with the area under the curve (AUC)-glucose, BMI, and AUC-glucagon. Incretin concentrations did not differ significantly among the groups. We demonstrate that in Japanese subjects, obesity has a greater effect than glucose tolerance on the numerical incretin effect, whereas GIGD is diminished in individuals with both glucose intolerance and obesity. These findings indicate variances as well as commonalities between East Asians and Caucasians in the manifestation of incretin effects on pancreatic ß-cell function and the integrated capacity to handle glucose.


Asunto(s)
Glucemia , Diabetes Mellitus Tipo 2 , Intolerancia a la Glucosa , Prueba de Tolerancia a la Glucosa , Incretinas , Obesidad , Humanos , Incretinas/sangre , Intolerancia a la Glucosa/sangre , Masculino , Femenino , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Obesidad/sangre , Persona de Mediana Edad , Glucemia/metabolismo , Japón/epidemiología , Adulto , Anciano , Pueblo Asiatico , Índice de Masa Corporal , Pueblos del Este de Asia
5.
Ann Gastroenterol Surg ; 8(3): 374-382, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38707222

RESUMEN

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.

6.
Surg Oncol ; 50: 101990, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37717376

RESUMEN

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.


Asunto(s)
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Evaluación Nutricional , Pronóstico , Estudios Retrospectivos , Gastrectomía , Unión Esofagogástrica/cirugía
7.
Gan To Kagaku Ryoho ; 39(11): 1715-8, 2012 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-23152026

RESUMEN

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.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Terapia Neoadyuvante , Anciano , Cisplatino/administración & dosificación , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Femenino , Fluorouracilo/administración & dosificación , Humanos , Inducción de Remisión , Tomografía Computarizada por Rayos X
8.
Gan To Kagaku Ryoho ; 39(5): 829-32, 2012 May.
Artículo en Japonés | MEDLINE | ID: mdl-22584342

RESUMEN

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.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Tumor Rabdoide/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Anciano , Cisplatino/administración & dosificación , Terapia Combinada , Combinación de Medicamentos , Resultado Fatal , Humanos , Masculino , Estadificación de Neoplasias , Ácido Oxónico/administración & dosificación , Tumor Rabdoide/patología , Neoplasias Gástricas/patología , Tegafur/administración & dosificación
9.
Ann Med Surg (Lond) ; 79: 103965, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35860109

RESUMEN

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.

10.
Ann Med Surg (Lond) ; 64: 102212, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33747503

RESUMEN

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.

11.
Int J Surg Case Rep ; 81: 105800, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33756162

RESUMEN

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.

12.
Int J Surg Case Rep ; 76: 270-273, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33053488

RESUMEN

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.

13.
Ann Gastroenterol Surg ; 3(1): 96-103, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30697614

RESUMEN

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.

14.
Yakugaku Zasshi ; 128(1): 89-95, 2008 Jan.
Artículo en Japonés | MEDLINE | ID: mdl-18176059

RESUMEN

The use of competing agents is considered a powerful tool for the development of a drug-delivery system with drug/cyclodextrin inclusion complexes. However, there are very few studies examining this issue. To explain this phenomenon, it was thought that a competing agent with a sufficiently high stability constant had not yet been reported. In this study, cinnarizine (CN), which has a high stability constant with beta-cyclodextrin (beta-CD) and unique solubility characteristics, was selected, and its ability as a competing agent was examined in a membrane permeability study. The permeability study showed that the permeation rates of the drugs flurbiprofen, progesterone, and spironolactone decreased with their stability constants with the addition of beta-CD. In one of the drugs, progesterone (Pro), the decrease was restored by the addition of CN. The amount of CN added was a 1:1 molar ratio to the amount of Pro. However, no similar action was induced with the addition of DL-phenylalanine (Phe) in the permeation study at the 1:5 (Pro:Phe) molar ratio. These finding indicate that CN acts as a competing agent, and its action is much stronger than that of Phe.


Asunto(s)
Cinarizina/farmacología , Sistemas de Liberación de Medicamentos , Progesterona/metabolismo , beta-Ciclodextrinas , Unión Competitiva , Membranas Artificiales , Permeabilidad
15.
J Med Case Rep ; 12(1): 227, 2018 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-30139375

RESUMEN

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.


Asunto(s)
Carcinoma Neuroendocrino/patología , Carcinoma de Células Escamosas/patología , Mucosa Esofágica/cirugía , Neoplasias Esofágicas/patología , Ganglios Linfáticos/patología , Anciano , Carcinoma Neuroendocrino/cirugía , Carcinoma de Células Escamosas/cirugía , Disección , Mucosa Esofágica/patología , Neoplasias Esofágicas/cirugía , Esofagoscopía , Humanos , Japón , Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Metástasis Linfática , Masculino
16.
Cancer Chemother Pharmacol ; 81(2): 387-392, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29290024

RESUMEN

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.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Receptor ErbB-2/genética , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Antineoplásicos Fitogénicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Docetaxel/administración & dosificación , Combinación de Medicamentos , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Ácido Oxónico/administración & dosificación , Supervivencia sin Progresión , Estudios Prospectivos , Tegafur/administración & dosificación , Trastuzumab/uso terapéutico
17.
J Diabetes Investig ; 6(3): 302-8, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25969715

RESUMEN

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.

18.
Eur J Pharm Biopharm ; 58(3): 667-71, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15451543

RESUMEN

The dissolution profiles of flurbiprofen (Flu) and its beta-cyclodextrin inclusion complex (Flu/beta-CD) in buffer solutions at various pH values were examined. The percent dissolved at 15 min for Flu and Flu/beta-CD was almost 100% at pH 6.8 and 8.0 but the dissolution rate of Flu was extremely reduced at pH 1.2 and 4.0. In these lower pH conditions, Flu/beta-CD improved the dissolution rate of Flu. The percent dissolved at 1 h for Flu/beta-CD at pH 1.2 and 4.0 were 33.4 and 41.3%, respectively, and about 10 times larger than those for Flu. The oral bioavailability of Flu from Flu or Flu/beta-CD at doses of 1, 3, 10, and 30 mg/kg (as Flu) was examined in rats. An apparent linear relationship between doses and C(max) and AUC was observed after administration of Flu and Flu/beta-CD. The Flu C(max) and AUC values at 30 mg/kg, however, were much lower than would have been predicted from doses of 1-10 mg/kg. Those of Flu/beta-CD were also lower than the predicted values, but the gap was quite small. The results suggest that the absorption of Flu in rats was saturated at 10 mg/kg, and that the enhanced dissolution rate of Flu/beta-CD increased the saturation dose to 30 mg/kg.


Asunto(s)
Flurbiprofeno/administración & dosificación , Flurbiprofeno/farmacocinética , beta-Ciclodextrinas/administración & dosificación , beta-Ciclodextrinas/farmacología , Administración Oral , Animales , Disponibilidad Biológica , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos/métodos , Flurbiprofeno/química , Masculino , Ratas , Ratas Sprague-Dawley , beta-Ciclodextrinas/química
19.
Nutrition ; 29(3): 549-55, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23274091

RESUMEN

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.


Asunto(s)
Colitis Ulcerosa/terapia , Fibras de la Dieta/administración & dosificación , Glutamina/administración & dosificación , Oligosacáridos/administración & dosificación , Animales , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/patología , Colon/química , Citocinas/genética , Sulfato de Dextran , Suplementos Dietéticos , Modelos Animales de Enfermedad , Nutrición Enteral , Interleucina-1beta/genética , Mucosa Intestinal/química , Mucosa Intestinal/patología , Masculino , Ratones , Ratones Endogámicos C57BL , ARN Mensajero/análisis
20.
Diabetes Res Clin Pract ; 101(2): 218-25, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23806480

RESUMEN

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.


Asunto(s)
Glucemia/análisis , Intolerancia a la Glucosa/diagnóstico , Adulto , Anciano , Estudios Transversales , Ayuno/sangre , Femenino , Intolerancia a la Glucosa/sangre , Prueba de Tolerancia a la Glucosa , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo
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