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1.
Cancer Sci ; 114(3): 1165-1179, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36382538

RESUMEN

Acinar cell carcinoma (ACC) of the pancreas is a malignant tumor of the exocrine cell lineage with a poor prognosis. Due to its rare incidence and technical difficulties, few authentic human cell lines are currently available, hampering detailed investigations of ACC. Therefore, we applied the organoid culture technique to various types of specimens, such as bile, biopsy, and resected tumor, obtained from a single ACC patient. Despite the initial propagation, none of these organoids achieved long-term proliferation or tolerated cryopreservation, confirming the challenging nature of establishing ACC cell lines. Nevertheless, the biopsy-derived early passage organoid developed subcutaneous tumors in immunodeficient mice. The xenograft tumor histologically resembled the original tumor and gave rise to infinitely propagating organoids with solid features and high levels of trypsin secretion. Moreover, the organoid stained positive for carboxylic ester hydrolase, a specific ACC marker, but negative for the duct cell marker CD133 and the endocrine lineage marker synaptophysin. Hence, we concluded the derivation of a novel ACC cell line of the pure exocrine lineage, designated HS-1. Genomic analysis revealed extensive copy number alterations and mutations in EP400 in the original tumor, which were enriched in primary organoids. HS-1 displayed homozygous deletion of CDKN2A, which might underlie xenograft formation from organoids. Although resistant to standard cytotoxic agents, the cell line was highly sensitive to the proteasome inhibitor bortezomib, as revealed by an in vitro drug screen and in vivo validation. In summary, we document a novel ACC cell line, which could be useful for ACC studies in the future.


Asunto(s)
Carcinoma de Células Acinares , Neoplasias Pancreáticas , Humanos , Ratones , Animales , Carcinoma de Células Acinares/genética , Carcinoma de Células Acinares/metabolismo , Carcinoma de Células Acinares/patología , Homocigoto , Eliminación de Secuencia , Neoplasias Pancreáticas/patología , Organoides/metabolismo , Línea Celular , Neoplasias Pancreáticas
2.
Dig Endosc ; 2022 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-35502924

RESUMEN

OBJECTIVES: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) plays a crucial role in the diagnosis of pancreatic tumors. The present study aimed to investigate the current status of needle tract seeding (NTS) after EUS-TA of pancreatic tumors based on a nationwide survey in Japan. METHODS: Patients who underwent surgical resection of primary pancreatic tumors after EUS-TA performed between April 2010 and March 2018 were surveyed. The incidence rates of NTS were determined, and compared in patients with pancreatic ductal adenocarcinomas (PDACs) and other tumors, and in patients who underwent transgastric and transduodenal EUS-TA of PDACs. The detailed features and prognosis of patients with NTS were also assessed. RESULTS: A total of 12,109 patients underwent surgical resection of primary pancreatic tumors after EUS-TA. The overall incidence rate of NTS was 0.330%, and the NTS rate was significantly higher in patients with PDAC than in those with other tumors (0.409% vs. 0.071%, P=0.004). NTS was observed in 0.857% of patients who underwent transgastric EUS-TA, but in none of those who underwent transduodenal EUS-TA. Of the patients with NTS of PDACs, the median time from EUS-TA to occurrence of NTS and median patient survival were 19.3 and 44.7 months, respectively, with 97.4% of NTS located in the gastric wall and 65.8% of NTS resected. The patient survival was significantly longer in patients who underwent NTS resection than in those without NTS resection (P=0.037). CONCLUSIONS: NTS appeared only after transgastric not after transduodenal EUS-TA. Careful follow-up provides an opportunity to remove localized NTS lesions by gastrectomy.

3.
Pancreas ; 52(5): e288-e292, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-37922344

RESUMEN

OBJECTIVE: We aimed to elucidate the feasibility of surveillance of patients with mucinous cystic neoplasm (MCN). METHODS: We performed a retrospective, multi-institutional study of 328 patients who underwent surgery for MCN at 18 Japanese institutions. Patients with MCN were divided into an immediate surgery group and a surveillance group, which underwent surgery after surveillance. RESULTS: The median surveillance period until surgery in the surveillance group was 27 months (range, 7-165 months). Compared with the immediate surgery group, the surveillance group showed smaller tumor diameter (46 vs 50 mm, P = 0.01), more frequent laparoscopic approach (58% vs 37%, P < 0.01), and less frequent malignancy (7% vs 15%, P = 0.03). The new appearance of mural nodules and elevation of serum tumor markers were associated with malignancy in the surveillance group. Two patients in the surveillance group experienced postoperative recurrence, although there was no significant difference in recurrence or disease-free survival between the two groups. In the surveillance group, the 1-, 5-, and 10-year cumulative incidence rates of malignant MCN were 0.8%, 5.6%, and 36.5%, respectively. CONCLUSION: As the risk of progression to malignant MCNs increases over the long term, MCNs should be resected rather than subjected to unnecessary surveillance.


Asunto(s)
Neoplasias Quísticas, Mucinosas y Serosas , Neoplasias Pancreáticas , Humanos , Estudios Retrospectivos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Pueblos del Este de Asia , Estudios de Factibilidad , Páncreas/patología , Neoplasias Quísticas, Mucinosas y Serosas/cirugía , Neoplasias Quísticas, Mucinosas y Serosas/patología , Hormonas Pancreáticas
7.
Pancreas ; 49(2): 181-186, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-32011526

RESUMEN

OBJECTIVE: The aim of the study was to develop a formula for predicting the probability of malignancy of mucinous cystic neoplasm (MCN) of the pancreas with ovarian-type stroma. METHODS: A total of 364 patients were enrolled. A total score was calculated as the sum of the approximate integers of the odds ratios of the predictive factors identified by multivariate analysis. The relationship between the total score and pathological results was assessed. RESULTS: A total of 321 patients had benign MCN and 43 had malignant MCN. Five possible predictive factors were analyzed: 56 years or older, high serum carcinoembryonic antigen level, high carbohydrate antigen 19-9 level, tumor size of 51 mm or greater, and the presence of mural nodules. The total score was significantly higher in patients with malignant MCN (median, 24; range, 0-37) compared with benign MCN (median, 5; range, 0-33; P < 0.001). Receiver operating characteristic curve analysis demonstrated that the area under the curve was 0.86, and the sensitivity and specificity of the total score for discriminating malignant MCNs were 72% and 83%, respectively, using a cut-off value of 22. CONCLUSIONS: The current simple formula can predict the malignancy of MCN and may thus contribute to the adequate management of patients with MCN.


Asunto(s)
Neoplasias Quísticas, Mucinosas y Serosas/patología , Ovario/patología , Neoplasias Pancreáticas/patología , Células del Estroma/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígeno CA-19-9/sangre , Antígeno Carcinoembrionario/sangre , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Neoplasias Quísticas, Mucinosas y Serosas/sangre , Neoplasias Quísticas, Mucinosas y Serosas/diagnóstico , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/diagnóstico , Probabilidad , Sensibilidad y Especificidad , Adulto Joven
8.
Sci Rep ; 9(1): 16187, 2019 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-31700023

RESUMEN

Overall survival in a phase III study for metastatic pancreatic cancer has significantly improved with gemcitabine (GEM) plus nab-paclitaxel. However, to date, there is limited data on the efficacy and safety of its use for patients with locally advanced (LA) or borderline resectable pancreatic cancer (BRPC). Here, we investigated the efficacy and safety of first-line GEM plus nab-paclitaxel for LA or BRPC. We retrospectively analysed consecutive patients with pathologically confirmed, untreated LA or BRPC who started receiving first-line GEM plus nab-paclitaxel. A total of 30 patients (LA, n = 22; BRPC, n = 8) were analysed. Twelve patients (40%) without distant metastasis received additional chemoradiotherapy using S-1. Laparotomy was performed on 8 patients and 6 (20%; LA, n = 3; BR, n = 3) achieved R0 resection. Objective response rate was 44.8%. For all patients, median progression-free survival and overall survival were 14.8 and 29.9 months, respectively. Median overall survival for LA was 24.1 months with a 2-year survival rate of 50.8%. The most frequently observed grade 3 or 4 toxicities were neutropenia (73%) and biliary infection (13%). First-line GEM plus nab-paclitaxel was well-tolerated and feasible with an encouraging survival for LA or BRPC.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Pancreáticas , Anciano , Albúminas/administración & dosificación , Quimioradioterapia , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Femenino , Humanos , Laparotomía , Masculino , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/terapia , Tasa de Supervivencia , Gemcitabina
9.
Cancer Chemother Pharmacol ; 80(1): 195-202, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28597040

RESUMEN

PURPOSE: S-1 has systemic activity for locally advanced pancreatic cancer (LAPC). Here, the efficacy and safety of induction gemcitabine (GEM) and S-1 (GS) followed by chemoradiotherapy (CRT) and systemic chemotherapy using S-1 for LAPC were assessed. METHODS: The treatment consisted of four cycles of induction GS (S-1 60, 80, or 100 mg/day based on body surface area for 14 days every 3 weeks plus GEM 1000 mg/m2 on days 8 and 15), followed by S-1 (80, 100, or 120 mg/day based on body surface area on days 1-14 and 22-35) and concurrent radiotherapy (50.4 Gy in 28 fractions). Maintenance chemotherapy with S-1 was started 1-4 weeks after CRT until disease progression or unacceptable toxicity was observed. The primary endpoint was 1-year survival. RESULTS: A total of 30 patients with LAPC were enrolled. The median survival and progression-free survival were 21.3 and 12.7 months, respectively. Overall survival rates at 1, 2, 3, and 4 years were 73.3, 36.7, 23.3, and 16.7%, respectively. The median survival of 23 patients who received CRT was 22.9 months, with a 3-year survival rate of 30.4%. The two most common grade 3 or 4 adverse events during induction GS were neutropenia (63.3%) and biliary tract infection (20%). Toxicities during CRT or maintenance chemotherapy were generally mild. CONCLUSIONS: This regimen was feasible and highly active resulting in encouraging survival in patients with LAPC. Further investigations are warranted to elucidate the effectiveness of this treatment strategy in future studies. Clinical trials information: UMIN000006332.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/métodos , Neoplasias Pancreáticas/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Quimioterapia de Inducción/métodos , Quimioterapia de Mantención/métodos , Masculino , Persona de Mediana Edad , Ácido Oxónico/administración & dosificación , Neoplasias Pancreáticas/patología , Estudios Prospectivos , Tasa de Supervivencia , Tegafur/administración & dosificación , Resultado del Tratamiento , Gemcitabina
10.
Case Rep Gastroenterol ; 8(3): 353-7, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25520605

RESUMEN

A 73-year-old woman was admitted because of obstructive jaundice. Computed tomography revealed a stricture in the lower bile duct with enhanced bile duct wall. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a tapering stenosis at the lower bile duct. Transpapillary histological biopsy using biopsy forceps through ERCP was performed; the diagnosis of signet ring cell carcinoma (SRCC) of the bile duct was established. Regional lymph node enlargement and distant metastases were not detected on diagnostic imaging. Pancreaticoduodenectomy with pylorus preservation was performed. Histological examination of the resected specimen confirmed SRCC of the extrahepatic bile duct coexisting with adenocarcinoma (ADC) of the extrahepatic bile duct with negative resection margins. However, tumor cells directly invaded the pancreatic parenchyma and the muscle layer of the duodenum, prompting us to administer adjuvant chemotherapy to the patient, with no sign of tumor recurrence at 1-year follow-up. Almost all tumors originating from the extrahepatic bile duct are ADC and other histological variants are rare. Of these, SRCC is extremely rare and only four cases have been reported. Furthermore, to the best of our knowledge, this is the first case report regarding the preoperative diagnosis of SRCC of the bile duct. Current reports indicate that younger age and Asian ethnicity are the clinical features of SRCC of the extrahepatic bile duct. Immunohistochemical staining of CK7, CK20 and MUC2 may be useful for predicting prognosis. Chemotherapy has not resulted in increased survival rates and only surgical resection currently serves as a curative treatment.

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