RESUMO
BACKGROUND: This study evaluated the prognostic value of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) together with host-related factors in patients with unresectable advanced gastric cancer. METHODS: The study enrolled 262 patients who received chemotherapy for unresectable advanced gastric cancer at Kochi Medical School from 2007 to 2015. Clinicopathological information and systemic inflammatory response data were analyzed for associations between baseline cancer-related prognostic variables and survival outcomes. RESULTS: The median survival time was significantly lower for patients with high ALP, high LDH, high total bilirubin, high aspartate aminotransferase, high alanine transaminase, high gamma-glutamyltransferase, high creatinine, a Glasgow prognostic score (GPS) of 1 or 2 score compared to GPS 0, higher compared to lower neutrophil to lymphocyte ratio (NLR) 3.9, lower compared to higher prognostic nutrition index 36.1, T3-4 compared to T1-2 tumor and diffuse-type compared to intestinal-type histology. Multivariate survival analysis identified high ALP 322 (HR 1.808; 95% CI 1.015-3.220; P = 0.044), T2-3 (HR 2.622; 95% CI 1.224-5.618; P = 0.013), and diffuse-type gastric cancer (HR 2.325; 95% CI 1.341-4.032; P = 0.003) as significant independent predictors of worse prognosis in the studied group of cancer patients. CONCLUSIONS: High level of ALP is an independent, worse prognosis factor for patients receiving chemotherapy for unresectable and recurrent gastric cancer.
Assuntos
Adenocarcinoma/patologia , Fosfatase Alcalina/sangue , Biomarcadores Tumorais/sangue , Neoplasias Ósseas/secundário , Lactato Desidrogenases/sangue , Neoplasias Hepáticas/secundário , Neoplasias Gástricas/patologia , Adenocarcinoma/sangue , Adenocarcinoma/enzimologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/sangue , Neoplasias Ósseas/enzimologia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/enzimologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/enzimologia , Taxa de Sobrevida , Adulto JovemRESUMO
PURPOSE: We evaluated the diagnostic and prognostic value of three tumor markers: carcino-embryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 125 (CA125), in the pretreatment serum of patients with unresectable advanced or recurrent gastric cancer. METHODS: The subjects of this retrospective analysis were 245 patients with unresectable advanced or recurrent gastric cancer diagnosed at Kochi Medical School between 2007 and 2015. We ascertained the sensitivity of CEA, CA19-9, and CA125 to identify a certain survival time and then evaluated the relative prognosis of the patients. RESULTS: The overall positive rates for each tumor marker in the study group were as follows: 57.6% (141/245) for CEA, 38.4% (94/245) for CA19-9, and 34.3% (84/245) for CA125; the sensitivity of these three biomarkers in combination was 73.1% (179/245). The median survival time of the CA125-positive patients was 4.5 months, which was significantly shorter than that of a normal range group (18.3 months, P < 0.001). Multivariate survival analysis identified that high CA125 was independently associated with a worse prognosis (HR 3.941; 95% CI 2.544-6.106; P < 0.001). CONCLUSIONS: Pretreatment serum CA125 is a useful prognostic biomarker in patients with unresectable advanced or recurrent gastric cancer. Evaluating a panel of serum tumor biomarkers is a useful diagnostic tool as elevated values might be associated with poor survival.
Assuntos
Biomarcadores Tumorais/sangue , Antígeno Ca-125/sangue , Recidiva Local de Neoplasia , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida , Adulto JovemRESUMO
The natural amino acid 5-aminolevulinic acid (ALA) is a protoporphyrin IX (PpIX) precursor and a new-generation photosensitive substance that accumulates specifically in cancer cells. When indocyanine green (ICG) is irradiated with near-infrared (NIR) light, it shifts to a higher energy state and emits infrared light with a longer wavelength than the irradiated NIR light. Photodynamic diagnosis (PDD) using ALA and ICG-based NIR fluorescence imaging has emerged as a new diagnostic technique. Specifically, in laparoscopic examinations for serosa-invading advanced gastric cancer, peritoneal metastases could be detected by ALA-PDD, but not by conventional visible-light imaging. The HyperEye Medical System (HEMS) can visualize ICG fluorescence as color images simultaneously projected with visible light in real time. This ICG fluorescence method is widely applicable, including for intraoperative identification of sentinel lymph nodes, visualization of blood vessels in organ resection, and blood flow evaluation during surgery. Fluorescence navigation by ALA-PDD and NIR using ICG imaging provides good visualization and detection of the target lesions that is not possible with the naked eye. We propose that this technique should be used in fundamental research on the relationship among cellular dynamics, metabolic enzymes, and tumor tissues, and to evaluate clinical efficacy and safety in multicenter cooperative clinical trials.
Assuntos
Neoplasias Peritoneais/tratamento farmacológico , Fotoquimioterapia , Neoplasias Gástricas/tratamento farmacológico , Fluorescência , Humanos , Verde de Indocianina/química , Laparoscopia , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologiaRESUMO
A 50-year-old man was referred to our hospital with gastric cancer. Esophagogastroduodenoscopy(EGD)revealed an irregular nodular lesion with an ulcer in the esophagogastric junction, the biopsy specimens of which showed moderately differentiated adenocarcinoma. Abdominal computed tomography(CT)showed a lymph node measuring 1.2 cm in the perigastric area. A clinical diagnosis of advanced gastric cancer was made, and the patient underwent total gastrectomy with D2 lymphadenectomy followed by Roux-en-Y reconstruction. Microscopic examination confirmed that the moderately differentiated adenocarcinoma invaded the muscularis propria with 1 lymph node metastasis and lymphovascular invasion. The final diagnosis according to the Japanese classification of gastric carcinoma was UE, Less, Type 2, 3.8×1.7 cm, T2(MP), M0, H0, P0, N1(1/15), tub2, ly1, v2, Stageâ ¡. The postoperative course was uneventful, and he received postoperative adjuvant chemotherapy with S-1. The patient underwent periodic follow-up physical examinations, and 1 year after the surgery, CT showed a well-defined mass measuring 1.0 cm in diameter located in the middle lobe of the right lung. Because there was no evidence of further metastatic lesions in any other organs, he underwent surgical resection of the solitary pulmonary lesion by video-assisted thoracic surgery. Pathological examination confirmed the presence of moderately differentiated adenocarcinoma, and the proliferating tumor cells were positive for cytokeratin(CK)7 and CK20, and negative for thyroid transcription factor 1, which confirmed metastasis from gastric cancer. After the surgery, the patient received combination chemotherapy with S-1 plus cisplatin, followed by S-1 monotherapy. Five years after pulmonary metastasectomy, we discontinued chemotherapy because of no evidence of recurrence and the patient's wishes. The patient has remained in good health without evidence of recurrence for 7 years following the second surgery. Resection of the metastatic lesion might be a promising treatment for solitary pulmonary metastasis of gastric cancer; however, further investigations involving the accumulation of a large number of cases and prospective cohort studies are required to verify the above issue, and future development of multidisciplinary therapy is expected.
Assuntos
Adenocarcinoma , Gastrectomia , Neoplasias Gástricas , Adenocarcinoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Prospectivos , Neoplasias Gástricas/cirurgiaRESUMO
BACKGROUND: The metastasis of malignant tumors to the spleen is rare, and only a small percentage of cases can be treated surgically, as splenic metastases generally occur in the context of multivisceral metastatic cancer at a terminal stage. We report a rare case of metachronous solitary splenic metastasis arising from early gastric cancer. CASE PRESENTATION: A 75-year-old man was initially referred to our hospital for examination of gastric cancer, diagnosed at a medical check-up. Esophagogastroduodenoscopy showed a slightly elevated lesion with a central irregular depression in the upper-third of the stomach. Biopsy specimens of the lesion showed a moderately-differentiated adenocarcinoma, and abdominal computed tomography showed no evidence of distant metastases. Endoscopic submucosal dissection was performed, with histological confirmation of a moderately-differentiated adenocarcinoma invading the submucosal layer. The patient subsequently underwent laparoscopic total gastrectomy with regional lymph node dissection, resulting in no residual carcinoma and no lymph node metastasis. Computed tomography, 28 months later, showed a well-defined mass measuring 4.2 cm in diameter in the spleen, and the patient underwent a splenectomy, since there was no evidence of further metastatic lesions in any other organs. Histological examination confirmed the diagnosis of a poorly-differentiated adenocarcinoma originating from the previous gastric cancer. The patient was alive 2 months after surgical resection of the splenic metastasis without any recurrence. CONCLUSION: To the best of our knowledge, this is only the second case of a solitary splenic metastasis from early gastric cancer to be reported in the English literature. The present case suggests surgical resection may be the preferred treatment of choice for patients with a solitary splenic metastasis from gastric cancer.
Assuntos
Adenocarcinoma/secundário , Neoplasias Esplênicas/secundário , Neoplasias Gástricas/patologia , Adenocarcinoma/cirurgia , Idoso , Detecção Precoce de Câncer , Endoscopia do Sistema Digestório , Gastrectomia/métodos , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Esplenectomia/métodos , Neoplasias Gástricas/cirurgia , Tomografia Computadorizada por Raios XRESUMO
A 76-year-old man was referred to our hospital with gastric cancer.Esophagogastroduodenoscopy (EGD)revealed an irregular, nodulated lesion with ulcers in the lower part of the stomach, for which biopsy specimens indicated poorly differentiated adenocarcinoma.Abdominal computed tomography(CT)showed a well-defined mass lesion measuring 5.3 cm in the posterior segment of the liver.Under the clinical diagnosis of advanced gastric cancer with liver metastasis, the patient received chemotherapy using S-1 and oxaliplatin.After 8 courses of chemotherapy, abdominal CT and EGD revealed that the size of liver metastasis was reduced to 2.3 cm. He underwent distal gastrectomy with D2 lymphadenectomy and resection of the liver metastases because there was no evidence of further metastatic lesions in any other organs after 10 courses of chemotherapy.The gross appearance of the surgically resected specimen showed a shrunk gastric tumor measuring 3.5×3.0 cm and a well-circumscribed, solid liver mass.Pathological examination confirmed the diagnosis of solid-type, poorly differentiated adenocarcinoma in the stomach that had invaded the submucosal layer with no lymph node metastasis, and necrotic change of the liver mass.The postoperative course was uneventful, and the patient has been well, receiving maintenance chemotherapy using S-1, without evidence of recurrence for 9 months following the operation.Conversion surgery following chemotherapy might be a proposed treatment for patients with advanced gastric cancer; however, further studies and assessments are needed to establish this treatment strategy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Idoso , Combinação de Medicamentos , Gastrectomia , Hepatectomia , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Terapia Neoadjuvante , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Ácido Oxônico/administração & dosagem , Neoplasias Gástricas/cirurgia , Tegafur/administração & dosagemRESUMO
BACKGROUND: The present study sought to evaluate an inflammation-based prognostic score (Glasgow prognostic score, GPS) and the neutrophil to lymphocyte ratio (NLR) as prognostic factors in patients receiving chemotherapy for advanced gastric cancer. METHODS: The study enrolled 224 patients who received chemotherapy for advanced gastric cancer at the Kochi Medical School from 2007 to 2014. Clinicopathological information and systemic inflammatory response data were obtained to investigate associations between baseline cancer-related prognostic variables and survival outcomes. RESULTS: The median survival time was significantly higher for patients with intestinal-type compared to diffuse-type histology (p = 0.039), a GPS 0 score compared to GPS 1 or 2 score (p = 0.004), and lower compared to higher NLR 4 (p = 0.002). Multivariate survival analysis identified high NLR 4 (HR 1.651; 95% CI 1.187-2.297; p = 0.003) and diffuse-type histology (HR 1.645; 95% CI 1.025-2.639; p = 0.039) as significant independent predictors associated with worse prognosis in the studied group of cancer patients. CONCLUSIONS: NLR and histological type are independent prognostic factors for patients receiving chemotherapy for unresectable and recurrent gastric cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores/sangue , Inflamação/sangue , Linfócitos , Neutrófilos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Prognóstico , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade , Resultado do TratamentoRESUMO
The incidence of diabetes is increasing at an unprecedented pace and has become a serious health concern worldwide during the last two decades. Despite this, adequate glycemic control using an artificial pancreas has not been established, although the 21st century has seen rapid developments in this area. Herein, we review current topics in glycemic control for both the wearable artificial pancreas for type 1 and type 2 diabetic patients and the bedside artificial pancreas for surgical diabetic patients. In type 1 diabetic patients, nocturnal hypoglycemia associated with insulin therapy remains a serious problem that could be addressed by the recent development of a wearable artificial pancreas. This smart phone-like device, comprising a real-time, continuous glucose monitoring system and insulin pump system, could potentially significantly reduce nocturnal hypoglycemia compared with conventional glycemic control. Of particular interest in this space are the recent inventions of a low-glucose suspend feature in the portable systems that automatically stops insulin delivery 2 h following a glucose sensor value <70 mg/dL and a bio-hormonal pump system consisting of insulin and glucagon pumps. Perioperative tight glycemic control using a bedside artificial pancreas with the closed-loop system has also proved safe and effective for not only avoiding hypoglycemia, but also for reducing blood glucose level variability resulting in good surgical outcomes. We hope that a more sophisticated artificial pancreas with closed-loop system will now be taken up for routine use worldwide, providing enormous relief for patients suffering from uncontrolled hyperglycemia, hypoglycemia, and/or variability in blood glucose concentrations.
Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Sistemas de Infusão de Insulina , Pâncreas Artificial , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêuticoRESUMO
An 82-year-old woman had visited her local clinic with a history of abdominal discomfort and dyspepsia related to meals over a period of several months. Esophagogastroduodenoscopy revealed a superficial spreading tumor that, on biopsy, was proven to be an adenocarcinoma, and colonoscopy revealed an ascending mass that was found to be an adenocarcinoma on biopsy, so the patient was referred to our hospital. Abdominal computed tomography revealed a mass in the ascending colon with regional lymph node swelling and a gallbladder stone measuring 1.5 cm in diameter. The patient underwent laparoscopy-assisted distal gastrectomy with cholecystectomy and right colectomy with regional lymph node dissection, resulting in a diagnosis of poorly differentiated adenocarcinoma invading the gastric submucosal layer and moderately differentiated tubular adenocarcinoma invading the colonic serosa with lymph node metastasis. Macroscopic examination of the gallbladder revealed a well-circumscribed, solid tumor measuring 0.3 x 0.3 cm with a firm consistency in the neck portion associated with lithiasis. Microscopic examination of the gallbladder tumor revealed infiltration of spindle-shaped neoplastic cells that were arranged in a fasciculated and woven pattern in abundant intersecting bundles. Immunohistochemical analyses were positive for S-100 protein and neurofilament. Although neurofibromas commonly occur in the superficial skin or subcutaneous region, isolated neurofibroma of the gallbladder is quite rare. To the best of our knowledge, this is only the 11th case of a neurofibroma of the gallbladder to be reported in English literature. In the present case, as in most previously reported cases, the tumor was found incidentally in the resected gallbladder following cholecystectomy for cholecystolithiasis.
Assuntos
Adenocarcinoma/diagnóstico , Neoplasias da Vesícula Biliar/diagnóstico , Neurofibroma/diagnóstico , Neurofibromatoses , Adenocarcinoma/cirurgia , Idoso de 80 Anos ou mais , Feminino , Vesícula Biliar , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Excisão de Linfonodo , Neurofibroma/cirurgiaRESUMO
A 34-year-old woman underwent total gastrectomy with D2 lymphadenectomy for gastric cancer, and the final diagnosis was T4N3M0, Stage III C, R0. Bilateral ovarian metastases were identified 51 months later, which were removed, and the patient received S-1 plus CDDP chemotherapy. Because the patient developed pubic bone metastasis 16 months after the second operation, we continued chemotherapy using paclitaxel with bisphosphonate. The patient was alive 70 months after the initial operation. The second patient was a 55-year-old woman who underwent total gastrectomy with D2 lymphadenectomy and was diagnosed with T2N2M0, Stage III A gastric cancer. Bilateral ovarian metastases were identified 72 months later, which were removed, and the patient received S-1 plus CDDP chemotherapy. The patient is alive with no signs of disease recurrence 96 months after the initial operation. For patients with ovarian metastases from gastric cancer, surgical resection in addition to chemotherapy might be an effective treatment. However, further studies and assessments of additional cases are needed to confirm the ideal treatment for this condition.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tumor de Krukenberg/tratamento farmacológico , Neoplasias Ovarianas/secundário , Neoplasias Gástricas/tratamento farmacológico , Adulto , Terapia Combinada , Feminino , Humanos , Tumor de Krukenberg/secundário , Tumor de Krukenberg/cirurgia , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Ovariectomia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
During the perioperative period, hyperglycemia is induced by surgical stress, which is the main risk factor for the development of postoperative infection associated with failure of neutrophil function, resulting in glucose toxicity. In elderly people with weakened immune systems, it is important to control perioperative hyperglycemia by maintaining sufficient nutrition administration. The artificial endocrine pancreas system allows strict glycemic control, which is beneficial in reducing glucose toxicity including postoperative infection not only in patients with diabetes mellitus or glucose intolerance but also in those who develop surgical diabetes during the perioperative period. Furthermore, it can contribute to the prevention of hypoglycemia and medical staff workload reduction. Therefore, the artificial pancreas is expected to come into widespread use in various fields involving glycemic control in patients.
Assuntos
Hiperglicemia/terapia , Pâncreas Artificial , Assistência Perioperatória , Idoso , Automonitorização da Glicemia , Humanos , Insulina/administração & dosagemRESUMO
This study aimed to evaluate the efficacy of protein-bound polysaccharide K (PSK)-containing chemotherapy in patients with unresectable advanced or recurrent gastric cancer (AGC). We retrospectively analyzed 190 patients with AGC who received systemic chemotherapy including 69 patients who were treated with a PSK-containing regimen. Using propensity score matching, we obtained 62 matched patients in the S-1 and S-1 plus PSK groups for outcomes analysis. There was a tendency for overall survival to be higher in the S-1 plus PSK group than in the S-1 alone group. In particular, there was a tendency for overall survival in the S-1 plus PSK group to be higher in patients with a neutrophil/lymphocyte ratio (NLR)<2.2 than in patients with a NLR<2.2. There was a tendency for fewer changes in the NLR after the beginning of treatment in the S-1 plus PSK group than in the S-1 alone group. PSK-containing chemotherapy may contribute to improved treatment outcomes of AGC patients. In particular, it may be effective in patients with a high NLR. Further investigations, including a prospective randomized controlled trial, are expected to verify the mechanisms of interaction between cancer cells and the immunoreaction.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfócitos , Neutrófilos , Neoplasias Gástricas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Combinação de Medicamentos , Humanos , Contagem de Leucócitos , Ácido Oxônico/administração & dosagem , Polissacarídeos/administração & dosagem , Polissacarídeos/efeitos adversos , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Tegafur/administração & dosagem , Resultado do TratamentoRESUMO
A 61 -year-old man underwent total gastrectomy with distal pancreatectomy and D2 lymphadenectomy for gastric cancer. The final diagnosis was UM, Post-Gre-Less, Type 3, 12 × 9 cm, T4b (SI), N3b (31/99), H0, P0, CY0, M0, tub2, ly3, v3, Stage IIIC, R0. Fifteen months after the operation, abdominal computed tomography showed a left adrenal tumor measuring 2.5 cm in diameter. Because it was a solitary tumor, we performed tumor resection, confirming adrenal metastasis that was negative for human epidermal growth factor receptor type 2 (HER2). Subsequently, the patient was treated with a chemotherapy regimen consisting of S-1 plus cisplatin. Because he developed left adrenal metastasis 6 months after tumor resection, we initiated chemotherapy with docetaxel plus irinotecan. Left adrenalectomy was performed owing to the tumor increasing to 3.6 cm despite chemotherapy. The patient is currently alive 50 months after the initial operation, without any signs of disease recurrence. For patients with solitary adrenal metastasis from gastric cancer, surgical resection in addition to chemotherapy might be the preferred choice of treatment.
Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Neoplasias Gástricas/patologia , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
A closed-loop glycemic control system using an artificial pancreas has been applied with many clinical benefits in Japan since 1987. To update this system incorporating user-friendly features, we developed a novel artificial pancreas (STG-55). The purpose of this study was to evaluate STG-55 for device usability, performance of blood glucose measurement, glycemic control characteristics in vivo in animal experiments, and evaluate its clinical feasibility. There are several features for usability improvement based on the design concepts, such as compactness, display monitor, batteries, guidance function, and reduction of the preparation time. All animal study data were compared with a clinically available artificial pancreas system in Japan (control device: STG-22). We examined correlations of both blood glucose levels between two groups (STG-55 vs. control) using Clarke's error grid analysis, and also compared mean glucose infusion rate (GIR) during glucose clamp. The results showed strong correlation in blood glucose concentrations (Pearson's product-moment correlation coefficient: 0.97; n = 1636). Clarke's error grid analysis showed that 98.4% of the data fell in Zones A and B, which represent clinically accurate or benign errors, respectively. The difference in mean GIRs was less than 0.2 mg/kg/min, which was considered not significant. Clinical feasibility study demonstrated sufficient glycemic control maintaining target glucose range between 80 and 110 (mg/dL), and between 140 and 160 without any hypoglycemia. In conclusion, STG-55 was a clinically acceptable artificial pancreas with improved interface and usability. A closed-loop glycemic control system with STG-55 would be a useful tool for surgical and critical patients in intensive care units, as well as diabetic patients.
Assuntos
Glicemia/análise , Pâncreas Artificial , Animais , Cães , Desenho de Equipamento , Feminino , Humanos , Hipoglicemia/sangue , Monitorização Fisiológica/instrumentaçãoRESUMO
In the present study, we aimed to evaluate the efficacy and safety of trastuzumab-containing regimens in patients with unresectable advanced or recurrent gastric cancer( AGC). We retrospectively analyzed 142 patients with AGC who received systemic chemotherapy, including 10 patients treated with trastuzumab-containing regimens. Among the 72 patients, 12 (16.7)% were human epidermal growth factor receptor 2 (HER2)-positive; the HER2-positive rate was significantly greater in patients with intestinal-type than diffuse-type histology( 29.0 vs 7.3%; p=0.014). The median overall survival of patients treated with trastuzumab was significantly longer than that of patients treated without trastuzumab( 22.9 vs 11.6 months; p =0.014). Seven patients continued receiving trastuzumab therapy after disease progression, and 6 patients were treated with trastuzumab after initial chemotherapy. The objective response rate of trastuzumab-containing regimens was 40%. The frequency of hematological and non-hematological toxicities was feasible. The administration of trastuzumab therapy after disease progression may contribute to improved treatment outcomes. However, further investigations, including prospective randomized controlled trials, are needed to verify this finding.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptor ErbB-2/análise , Recidiva , Estudos Retrospectivos , Neoplasias Gástricas/química , Neoplasias Gástricas/patologia , Trastuzumab , Resultado do TratamentoRESUMO
It is reported that shortage of oral magnesium intake increase the incidence of diabetes. In addition, magnesium replacement therapy improves insulin resistance and glycemic control. Low levels of magnesium in the venous blood induce the disturbances of auto-phosphylation on the insulin receptor and deteriorate insulin resistance. Since magnesium is closely related to evolution and development of metabolic syndrome including diabetes mellitus and so on, magnesium is expected as potentially effective ingredient of drug therapy in the future perspectives.
Assuntos
Diabetes Mellitus/etiologia , Diabetes Mellitus/metabolismo , Deficiência de Magnésio/complicações , Magnésio/metabolismo , Metabolismo dos Carboidratos , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/fisiopatologia , Humanos , Resistência à Insulina , Magnésio/administração & dosagem , Magnésio/fisiologia , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/metabolismo , Fosforilação , Receptor de Insulina/metabolismoRESUMO
An antibody-drug conjugate (ADC) is a promising therapeutic modality because selective and effective delivery of an anti-cancer drug is achieved by drug-conjugated antibody-targeting cancer antigen. Glypican 1 (GPC1) is highly expressed in malignant tumors, including pancreatic ductal adenocarcinoma (PDAC) and esophageal squamous cell carcinoma (ESCC). Herein, we describe the usefulness of GPC1-targeting ADC. Humanized anti-GPC1 antibody (clone T2) was developed and conjugated with monomethyl auristatin E (MMAE) via maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (mc-vc-PABC) linkers (humanized GPC1-ADC[MMAE]). Humanized GPC1-ADC(MMAE) inhibited the growth of GPC1-positive PDAC and ESCC cell lines via inducing cycle arrest in the G2/M phase and apoptosis in vitro. The binding activity of humanized GPC1-ADC(MMAE) with GPC1 was comparable with that of the unconjugated anti-GPC1 antibody. The humanized GPC1-ADC(MMAE) was effective in GPC1-positive BxPC-3 subcutaneously xenografted mice but not in GPC1-negative BxPC-3-GPC1-KO xenografted mice. To assess the bystander killing activity of the humanized GPC1-ADC(MMAE), a mixture of GPC1-positive BxPC-3 and GPC1-negative BxPC-3-GPC1-KO-Luc cells were subcutaneously inoculated, and a heterogenous GPC1-expressing tumor model was developed. The humanized GPC1-ADC(MMAE) inhibited the tumor growth and decreased the luciferase signal, measured with an in vivo imaging system (IVIS), which suggests that the suppression of the BxPC-3-GPC1-KO-Luc population. The humanized GPC1-ADC(MMAE) also inhibited the established liver metastases of BxPC-3 cells and significantly improved the overall survival of the mice. It exhibited a potent antitumor effect on the GPC1-positive PDAC and ESCC patient-derived xenograft (PDX) models. Our preclinical data demonstrate that GPC1 is a promising therapeutic target for ADC.
Assuntos
Anticorpos Monoclonais Humanizados/metabolismo , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Glipicanas/metabolismo , Imunoconjugados/metabolismo , Neoplasias Pancreáticas/metabolismo , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/metabolismo , Anticorpos Monoclonais Humanizados/administração & dosagem , Antígenos de Neoplasias/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/imunologia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/imunologia , Glipicanas/antagonistas & inibidores , Inibidores do Crescimento/administração & dosagem , Inibidores do Crescimento/metabolismo , Humanos , Imunoconjugados/administração & dosagem , Camundongos , Camundongos Knockout , Camundongos SCID , Camundongos Transgênicos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodosAssuntos
Adenocarcinoma/diagnóstico , Lipoma/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Gástricas/diagnóstico , Adenocarcinoma/cirurgia , Idoso , Endoscopia Gastrointestinal , Gastrectomia , Humanos , Masculino , Neoplasias Gástricas/cirurgia , Tomografia Computadorizada por Raios XRESUMO
We report a case of intrahepatic bile duct adenoma (BDA) detected during laparoscopic distal gastrectomy for gastric cancer. A 70-year-old man was referred to our hospital for the treatment of gastric cancer. Esophagogastroduodenoscopy revealed an irregular, nodular, and elevated lesion on the greater curvature side of the middle third of the stomach. Abdominal contrast-enhanced computed tomography showed wall thickening with homogeneous enhancement in the middle part of the stomach, and no lesions in the liver. The patient underwent laparoscopic distal gastrectomy with regional lymphadenectomy, and during the operation a small whitish nodule was observed on the lateral segment of the liver surface. The lesion was excised by partial resection of the liver for the purpose of both histological diagnosis and treatment. Pathological examination of the liver lesion revealed no structural or cellular atypia, no stromal invasion, and immunohistochemical positivity for CK7 and CK19, but negativity for p53. The final diagnosis was well-differentiated adenocarcinoma invading the gastric serosal layer without lymph node metastasis, and intrahepatic BDA measuring 0.4 × 0.3 cm. Following surgery, the patient remained symptom-free without evidence of recurrence for 5 months. To the best of our knowledge, this is the first case of BDA with gastric cancer. Because it is difficult to distinguish BDA from other liver tumors including metastatic cancer due to its characteristically small size and lack of specific morphological features on standard imaging, surgical resection should be considered as the most suitable approach for both accurate diagnosis and treatment.