Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 45
Filtrar
1.
Surg Endosc ; 38(2): 1077-1087, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38168732

RESUMEN

BACKGROUND: Robotic pancreaticoduodenectomy (RPD) is technically demanding, and 20-50 cases are required to surpass the learning curve. This study aimed to show our experience of 76 cases from the introduction of RPD and report the changes in surgical results owing to the accumulation of cases and optimization of surgical techniques. METHODS: A total of 76 patients who underwent RPD between November 2009 and May 2023 at the Fujita Health University Hospital were divided into three groups: competency (n = 23, Nov 2009-Mar 2020), proficiency (n = 31, Apr 2020-Jun 2022), and mastery (n = 22, Jul 2022-May 2023) phases. In the mastery phase, for the education of new surgeons and maintenance of surgical quality, optimization of the procedure, including hanging maneuver with or without stapling transection of the retropancreatic tissue was implemented. The surgical outcomes were compared between the groups. RESULTS: The mean operation time decreased over time despite of the participation of newly started operators in mastery phase [competency: 921.5 min (IQR 775-996 min) vs. proficiency: 802.8 min (IQR 715-887 min) vs. mastery: 609.2 min (IQR 514-699 min), p < 0.001]. Additionally, Clavien-Dindo ≥ grade IIIa complications decreased from 52.2% in competency phase to 35.5% and 9.1% in proficiency and mastery phases, respectively (p = 0.005). CONCLUSION: Operation time and major complications decreased along the learning curve from the introduction of RPD. In addition, optimization of the procedure, including hanging maneuver of the retropancreatic tissue seemed to be effective in reducing operation time and educating new RPD surgeons.


Asunto(s)
Laparoscopía , Neoplasias Pancreáticas , Procedimientos Quirúrgicos Robotizados , Robótica , Cirujanos , Humanos , Pancreaticoduodenectomía/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Japón , Curva de Aprendizaje , Estudios Retrospectivos , Neoplasias Pancreáticas/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Laparoscopía/métodos
2.
Asian J Endosc Surg ; 17(1): e13271, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38081193

RESUMEN

Pancreatic tumor enucleation is a procedure that can preserve pancreatic function and is sometimes performed using a minimally invasive approach. Recently, a single-port robotic platform called da Vinci SP has been developed. However, the technical details of pancreatic tumor enucleation using da Vinci SP have not been reported to date. We report a male patient in his 70s who underwent robotic SP pancreatic tumor enucleation for a pancreatic neuroendocrine tumor. The dissection between the tumor and pancreatic parenchyma was performed using the double bipolar technique. The operative time was 139 min, and the estimated blood loss was 4 mL. The patient had an uneventful recovery and was discharged on the sixth day after the surgery. Robotic SP pancreatic tumor enucleation appears to be a feasible procedure with lower invasiveness and better cosmesis.


Asunto(s)
Tumores Neuroendocrinos , Neoplasias Pancreáticas , Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Masculino , Procedimientos Quirúrgicos Robotizados/métodos , Neoplasias Pancreáticas/cirugía , Tumores Neuroendocrinos/cirugía , Disección
3.
Microbiol Spectr ; 11(6): e0207823, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-37966220

RESUMEN

IMPORTANCE: The World Health Organization estimated that 5-10 million people are infected with human T-cell leukemia virus type 1 (HTLV-1). This number is likely to be underestimated because reliable endemic data are available for only approximately 1.5 billion people worldwide. The point-of-care test is a powerful tool for the easy and quick detection of infections without the requirement for expensive instruments and laboratory equipment. Espline HTLV-I/II, a newly developed rapid immunochromatographic antibody test that was evaluated in this study, might significantly advance our understanding of the global epidemiology of HTLV-1 infection.


Asunto(s)
Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Humanos , Infecciones por HTLV-I/diagnóstico , Infecciones por HTLV-I/epidemiología
4.
Biol Pharm Bull ; 46(9): 1269-1276, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37661406

RESUMEN

Adult T-cell leukemia/lymphoma (ATL) is a hematopoietic malignancy with a poor prognosis that develops in approximately 5% of human T-cell leukemia virus type 1 (HTLV-1) carriers. Cyclin-dependent kinase 9 (CDK9), together with Cyclin T, forms a transcription elongation factor, positive transcription elongation factor b (P-TEFb). P-TEFb promotes transcriptional elongation by phosphorylating the second serine (Ser2) of the seven amino acid repeat sequence in the C-terminal domain of RNA polymerase II (RNAP II). CDK9 inhibitors suppress cell proliferation by inducing apoptosis in chronic lymphocytic leukemia and breast cancer but there are no reports on autophagy of CDK9 inhibitors. Here, we investigated the effect of LY2857785, a novel CDK9 selective inhibitor, on cell death in ATL-related cell lines in vitro, freshly isolated cells from ATL patients ex vivo, and on ATL tumor xenografts in NOD/SCID mice in vivo. LY2857785 significantly reduced cell viability and induced apoptosis, as shown by annexin V-positive cells, cleaved poly(ADP-ribose) polymerase (PARP), and cleaved caspase-3, and suppressed the levels of anti-apoptotic protein myeloid cell leukemia-1 (MCL-1). LY2857785 decreased RNAP II Ser2 phosphorylation and downstream c-Myc protein levels. Interestingly, LY2857785 also increased microtubule-associated proteins 1A/1B light chain 3B (LC3)-II binding to autophagosome membranes. Furthermore, LY2857785 decreased the viability of freshly isolated ATL cells and induced apoptosis. Finally, LY2857785 significantly decreased the growth of ATL tumor xenografts. These results suggest that LY2857785 induces cell death of ATL cells by MCL-1-dependent apoptosis and autophagy and has anti-tumor activity.


Asunto(s)
Neoplasias de la Mama , Leucemia-Linfoma de Células T del Adulto , Linfoma , Ratones , Adulto , Animales , Humanos , Femenino , Ratones Endogámicos NOD , Ratones SCID , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Factor B de Elongación Transcripcional Positiva , Proteína 1 de la Secuencia de Leucemia de Células Mieloides , Inhibidores de Proteínas Quinasas , Apoptosis , Autofagia , Quinasa 9 Dependiente de la Ciclina
5.
Surg Endosc ; 37(11): 8384-8393, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37715084

RESUMEN

BACKGROUND: Although robotic distal pancreatectomy (RDP) has a lower conversion rate to open surgery and causes less blood loss than laparoscopic distal pancreatectomy (LDP), clear evidence on the impact of the surgical approach on morbidity is lacking. Prior studies have shown a higher rate of complications among obese patients undergoing pancreatectomy. The primary aim of this study is to compare short-term outcomes of RDP vs. LDP in patients with a BMI ≥ 30. METHODS: In this multicenter study, all obese patients who underwent RDP or LDP for any indication between 2012 and 2022 at 18 international expert centers were included. The baseline characteristics underwent inverse probability treatment weighting to minimize allocation bias. RESULTS: Of 446 patients, 219 (50.2%) patients underwent RDP. The median age was 60 years, the median BMI was 33 (31-36), and the preoperative diagnosis was ductal adenocarcinoma in 21% of cases. The conversion rate was 19.9%, the overall complication rate was 57.8%, and the 90-day mortality rate was 0.7% (3 patients). RDP was associated with a lower complication rate (OR 0.68, 95% CI 0.52-0.89; p = 0.005), less blood loss (150 vs. 200 ml; p < 0.001), fewer blood transfusion requirements (OR 0.28, 95% CI 0.15-0.50; p < 0.001) and a lower Comprehensive Complications Index (8.7 vs. 8.9, p < 0.001) than LPD. RPD had a lower conversion rate (OR 0.27, 95% CI 0.19-0.39; p < 0.001) and achieved better spleen preservation rate (OR 1.96, 95% CI 1.13-3.39; p = 0.016) than LPD. CONCLUSIONS: In obese patients, RDP is associated with a lower conversion rate, fewer complications and better short-term outcomes than LPD.


Asunto(s)
Laparoscopía , Neoplasias Pancreáticas , Procedimientos Quirúrgicos Robotizados , Humanos , Persona de Mediana Edad , Procedimientos Quirúrgicos Robotizados/efectos adversos , Neoplasias Pancreáticas/cirugía , Pancreatectomía , Resultado del Tratamiento , Laparoscopía/efectos adversos , Tempo Operativo , Tiempo de Internación , Estudios Retrospectivos
6.
Biosci Biotechnol Biochem ; 87(9): 954-959, 2023 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-37291696

RESUMEN

We present a step-economical divergent synthetic approach for isoflavene derivatives using the Suzuki-Miyaura cross coupling of a 3-boryl-2H-chromene and three aryl bromides. 3-Boryl-2H-chromene, which is not a well-explored species, was prepared via Miyaura-Ishiyama borylation of a 3-chloro-2H-chromene obtained through a Claisen rearrangement cyclization cascade reaction. Further conversion of the cross-coupling products, three isoflavene derivatives, afforded three isoflavonoid natural products with one or two additional reaction steps.


Asunto(s)
Productos Biológicos , Bromuros , Benzopiranos , Ciclización
7.
Cancers (Basel) ; 15(8)2023 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-37190148

RESUMEN

Surgical techniques and outcomes of minimally invasive anatomic liver resection (AR) using the extrahepatic Glissonian approach for hepatocellular carcinoma (HCC) are undefined. In 327 HCC cases undergoing 185 open (OAR) and 142 minimally invasive (MIAR; 102 laparoscopic and 40 robotic) ARs, perioperative and long-term outcomes were compared between the approaches, using propensity score matching. After matching (91:91), compared to OAR, MIAR was significantly associated with longer operative time (643 vs. 579 min, p = 0.028); less blood loss (274 vs. 955 g, p < 0.0001); a lower transfusion rate (17.6% vs. 47.3%, p < 0.0001); lower rates of major 90-day morbidity (4.4% vs. 20.9%, p = 0.0008), bile leak or collection (1.1% vs. 11.0%, p = 0.005), and 90-day mortality (0% vs. 4.4%, p = 0.043); and shorter hospital stay (15 vs. 29 days, p < 0.0001). On the other hand, laparoscopic and robotic AR cohorts after matching (31:31) had comparable perioperative outcomes. Overall and recurrence-free survivals after AR for newly developed HCC were comparable between OAR and MIAR, with potentially improved survivals in MIAR. The survivals were comparable between laparoscopic and robotic AR. MIAR was technically standardized using the extrahepatic Glissonian approach. MIAR was safe, feasible, and oncologically acceptable and would be the first choice of AR in selected HCC patients.

8.
Asian J Endosc Surg ; 16(3): 588-590, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37150833

RESUMEN

Robotic surgery has technical advantages including high optical magnification and articulation of forceps. However, the surgical field tends to be narrow due to the high magnification, and the forceps have no tactile sensation. A case of severe intraoperative bleeding from the splenic artery during robotic distal pancreatectomy is presented, with a video. A man in his 80s with a cystic tumor located at the pancreatic tail underwent robotic distal pancreatectomy. During mobilization of the pancreatic tail by an inferior approach, the root of the splenic artery was injured by the joints of the robotic instruments located outside the surgical field and the bleeding became uncontrollable under the robotic operation. It is important to always be aware of what the forceps are in contact with outside the surgical field. While dissecting the left subdiaphragmatic area in robotic distal pancreatectomy, the root area of splenic artery tends to be outside the surgical field. More attention should be paid to the positional relationship between the forceps trajectory and the major blood vessels by checking the surgical field from a distant view on a regular basis.


Asunto(s)
Laparoscopía , Neoplasias Pancreáticas , Procedimientos Quirúrgicos Robotizados , Robótica , Masculino , Humanos , Pancreatectomía/efectos adversos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Páncreas/cirugía , Neoplasias Pancreáticas/cirugía
9.
Eur J Haematol ; 110(6): 639-647, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36811253

RESUMEN

Essential thrombocythemia (ET) cases without canonical JAK2, CALR, or MPL mutations, that is, triple-negative (TN) ET, have been found in 10%-20% of ET cases. Owing to the limited number of TN ET cases, its clinical significance remains unclear. This study evaluated TN ET's clinical characteristics and identified novel driver mutations. Among 119 patients with ET, 20 (16.8%) had no canonical JAK2/CALR/MPL mutations. Patients with TN ET tended to be younger and had lower white blood cell counts and lactate dehydrogenase values. We identified putative driver mutations in 7 (35%): MPL S204P, MPL L265F, JAK2 R683G, and JAK2 T875N were previously reported as candidate driver mutations in ET. Moreover, we identified a THPO splicing site mutation, MPL*636Wext*12, and MPL E237K. Four of the seven identified driver mutations were germline. Functional studies on MPL*636Wext*12 and MPL E237K revealed that they are gain-of-function mutants that increase MPL signaling and confer thrombopoietin hypersensitivity with very low efficiency. Patients with TN ET tended to be younger, although this was thought to be due to the inclusion of germline mutations, hereditary thrombocytosis. Accumulating the genetic and clinical characteristics of noncanonical mutations may help future clinical interventions in TN ET and hereditary thrombocytosis.


Asunto(s)
Trombocitemia Esencial , Trombocitosis , Humanos , Trombocitemia Esencial/diagnóstico , Trombocitemia Esencial/genética , Receptores de Trombopoyetina/genética , Receptores de Trombopoyetina/metabolismo , Calreticulina/genética , Mutación , Janus Quinasa 2/genética , Janus Quinasa 2/metabolismo
10.
Asian J Surg ; 46(8): 3052-3057, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36283877

RESUMEN

BACKGROUND & AIMS: Optimizing treatments balancing prognosis and therapeutic invasiveness is important in the management of pancreatic cancer (PC) owing to global ageing. This study aimed to verify the different utility of biomarkers by patients' age. MATERIALS & METHODS: This is a single-center, retrospective cohort analysis involving 160 patients who undertook pancreaticoduodenectomy (PD) for PC. After comparing clinicopathological factors and survival after PD between aged (≥70 y/o) and young (<70 y/o) patients, we compared neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), controlling nutrition (CONUT) score, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 as well as clinicopathological factors between long and short survivors in each group. We also performed Kaplan-Meyer analysis between patients stratified by biomarkers. RESULTS: Overall survival (OS) was significantly worse in aged patients (p = 0.002). In aged patients, CEA was significantly higher in short survivors. In young patients, CONUT score and CA19-9 were higher in short survivors. Kaplan-Meyer analysis showed that NLR and CEA stratified OS in aged patients, whereas CONUT score and CA19-9 could stratify OS in young patients. CONCLUSION: Our current results suggest that these biomarkers had different impact on survivals according to the patients' age.


Asunto(s)
Antígeno Carcinoembrionario , Neoplasias Pancreáticas , Humanos , Pronóstico , Pancreaticoduodenectomía , Antígeno CA-19-9 , Estudios Retrospectivos , Neoplasias Pancreáticas/patología , Linfocitos , Biomarcadores de Tumor , Neutrófilos , Neoplasias Pancreáticas
11.
DEN Open ; 3(1): e143, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35898824

RESUMEN

The diagnosis of bile duct tumors can be difficult at times. A transpapillary bile duct biopsy findings with endoscopic retrograde cholangiopancreatography sometimes contradict diagnostic imaging findings. In bile duct tumors, inflammatory polyps in the extrahepatic bile duct are relatively rare with extrahepatic cholangitis. The disease's clinical relevance, including its natural history and prognosis, is not always clear. We show here a rare case of an inflammatory polyp in the common bile duct. A 69-year-old woman with abdominal pain was diagnosed with cholangitis. The findings of contrast-enhanced computed tomography and magnetic resonance cholangiopancreatography suggested that she had extrahepatic cholangiocarcinoma. The examination and therapy of cholangitis were performed by endoscopic retrograde cholangiopancreatography. The cholangiography revealed a suspected tumor in the hilar bile duct with some common bile duct stones. Then, after endoscopic sphincterotomy to remove tiny common bile duct stones, further detailed examinations were performed at the same time using an oral cholangioscope revealed a papillary raised lesion with a somewhat white surface in the bile duct; a biopsy was conducted on the same spot, and epithelial cells with mild atypia appeared in the shape of a papilla. Since the malignant tumor or the intraductal papillary neoplasm of the bile duct could not be ruled out, extrahepatic bile duct resection was conducted with the patient's informed consent. Bile duct inflammatory polyp was the histopathological diagnosis.

12.
J Hepatobiliary Pancreat Sci ; 30(1): 72-90, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35737850

RESUMEN

BACKGROUND/PURPOSE: Surgical outcomes and utility of robotic liver resection (RLR) are undefined. METHODS: We retrospectively studied perioperative and long-term outcomes of the single-center 120 RLRs including non-anatomic (NAR, n = 58) and anatomic (AR, n = 62) resections. To evaluate the feasibility and safety of RLR, perioperative outcomes of RLR (n = 103) were compared to those of open (OLR, n = 495) or laparoscopic (LLR, n = 451) resection in liver-only resections without reconstruction, using 1:1 propensity score matching (PSM). The changing trends from the earlier to the later RLR cases were assessed. Long-term outcomes were compared between RLR and LLR. RESULTS: Various types of RLR with different surgical difficulties were performed, with mostly comparable postoperative morbidity between AR and NAR, or among AR subtypes. In segmentectomy and sectionectomy cases, perioperative outcomes significantly improved in the later period. In comparison between PSM-selected OLR and RLR cases (87:87), RLR had significantly longer operative time, less blood loss, and shorter hospital stay. PSM-selected LLR and RLR cases (91:91) showed comparable perioperative outcomes. Overall and recurrence-free survivals after RLR for newly diagnosed hepatocellular carcinoma and colorectal metastasis were comparable to those after LLR. CONCLUSIONS: RLR is applicable to various types of liver resection with acceptable perioperative and long-term outcomes in select patients.


Asunto(s)
Carcinoma Hepatocelular , Laparoscopía , Neoplasias Hepáticas , Procedimientos Quirúrgicos Robotizados , Humanos , Neoplasias Hepáticas/secundario , Estudios Retrospectivos , Tiempo de Internación , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Hepatectomía , Puntaje de Propensión , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/cirugía
13.
Surg Oncol ; 45: 101857, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36252411

RESUMEN

BACKGROUND: Conventional open distal pancreatectomy with en bloc celiac axis resection (DP-CAR) using the ventral approach is technically challenging, highly invasive, and not easy to ensure ample dorsal surgical margins. Hence, we describe a novel minimally invasive strategy for DP-CAR using the retroperitoneal-first laparoscopic approach (Retlap), i.e., Retlap DP-CAR, for locally advanced pancreatic body cancer (LAPC), and assess its utility. METHODS: Retlap DP-CAR was performed in 10 patients with LAPC that was categorized as either unresectable (UR-LA, n = 4) or borderline (BR-A, n = 6). Neoadjuvant chemotherapy was applied on 8 patients and upfront surgery on 2. Retlap was used to create a working space in the retroperitoneal cavity between the pancreatic body and the left kidney and confirm technical resectability, such as securing the celiac axis and preserving the superior mesenteric artery in an early operative stage. Retlap DP-CAR was laparoscopic in 8 patients and robotic in 2. Surgical procedures are directly manipulated from the dorsal side of the pancreas and tumor, facilitating confirmation of technical resectability and obtaining ample dorsal margins in a no-touch isolation approach. Once technical resectability was confirmed, the procedure was converted to the ventral approach for completing DP-CAR. RESULTS: Median operating time and blood loss during Retlap were 271 min and 10 mL, respectively, while median resection time and intraoperative blood loss were 582 min and 412 mL, respectively. Tumor-free resection margins were obtained in all cases. The major morbidity rate (C-D > IIIa) was 10%. No mortality was recorded within 90 days. Median overall survival was 53.8 months [95% confidence interval 32.7-75.0]. CONCLUSIONS: Retlap DP-CAR is a novel minimally invasive procedure for resecting LAPC located close to the celiac axis. It is both safe and feasible, enables determination of technical resectability, achieves dorsal surgical margins, and can improve outcomes and QOL in patients with LAPC.


Asunto(s)
Laparoscopía , Neoplasias Primarias Secundarias , Neoplasias Pancreáticas , Humanos , Pancreatectomía/métodos , Márgenes de Escisión , Calidad de Vida , Neoplasias Pancreáticas/patología , Páncreas/patología , Páncreas/cirugía , Laparoscopía/métodos , Neoplasias Primarias Secundarias/cirugía
14.
Langenbecks Arch Surg ; 407(7): 2881-2892, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36102966

RESUMEN

PURPOSE: Anatomic isolated liver segmentectomy 8 (ILSeg8) for malignancies remains technically challenging. The feasibility, safety, and oncologic validity of laparoscopic ILSeg8 are undefined, and thus were evaluated in comparison with the open approach. METHODS: This study enrolled 35 open and 29 laparoscopic ILSeg8 cases of hepatocellular carcinoma (n = 47), metastatic liver tumors (n = 16), and intrahepatic cholangiocarcinoma (n = 1) at our institution. The surgical techniques were based on the pre-hepatectomy extrahepatic Glissonian pedicle control, followed by cranial-to-caudal parenchymal dissection from the hepatic vein root side. The short- and long-term outcomes after ILSeg8 were retrospectively evaluated and compared between the open and laparoscopic approaches using 1:1 propensity score matching (PSM). RESULTS: Both before and after PSM, the laparoscopic ILSeg8 group had significantly less blood loss, lower postoperative serum bilirubin level, and a shorter postoperative hospital stay than the open group. The overall survival rates were comparable between the laparoscopic and open groups before (P = 0.017) and after (P = 0.043) PSM, with the similar recurrence-free survival rates between the groups. In a multivariable analysis of the cohort before PSM (n = 64), the laparoscopic approach was identified to be an independent factor for favorable overall survival (hazard ratio = 0.20, P = 0.039). CONCLUSION: Laparoscopic ILSeg8 using the extrahepatic Glissonian approach and hepatic vein root at first parenchymal dissection was feasible, safe, and oncologically acceptable. In ILSeg8 for malignancy, the laparoscopic approach potentially confers short-term advantages over the open approach with comparable long-term outcomes in select patients.


Asunto(s)
Neoplasias de los Conductos Biliares , Carcinoma Hepatocelular , Laparoscopía , Neoplasias Hepáticas , Humanos , Hepatectomía/métodos , Puntaje de Propensión , Estudios Retrospectivos , Neumonectomía , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Laparoscopía/métodos , Conductos Biliares Intrahepáticos , Neoplasias de los Conductos Biliares/cirugía , Tiempo de Internación
15.
Chem Pharm Bull (Tokyo) ; 70(7): 492-497, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35786568

RESUMEN

Formamides are useful starting materials for pharmaceutical syntheses. Although various synthetic methods have been documented in this regard, the use of N-formylcarbazole as a formylation reagent for amines has not yet been reported. We report here the first examples of the use of N-formylcarbazole for the formylation of amines. The characteristic reactivity of N-formylcarbazole enables the selective formylation of sterically less hindered aliphatic primary and secondary amines. In contrast, sterically bulkier amines and weakly nucleophilic amines such as anilines are less reactive under the reaction conditions.


Asunto(s)
Aminas , Carbazoles , Compuestos de Anilina
16.
FEBS J ; 289(12): 3477-3488, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35029032

RESUMEN

Adult T-cell leukemia/lymphoma (ATL) develops after a long period of human T-cell leukemia virus (HTLV)-1 infection and is associated with host aging in addition to genetic abnormalities in HTLV-1 infected cells. SIRT1 is a histone deacetylase involved in cell cycle and apoptosis. We previously showed the high expression of SIRT1 protein in peripheral blood mononuclear cells from patients with ATL. There have been many reports that SIRT1 inhibitors show tumor-suppressive effects. On the other hand, SIRT1 activator SRT1720 induces the cell death of multiple myeloma and breast cancer cells. However, the effect of SRT1720 on ATL is unknown. This study aimed to evaluate the effect of SRT1720 on cell death in leukemic cell lines in vitro and freshly isolated ATL cells ex vivo and in an ATL in vivo mouse model. SRT1720 reduced cell viability in vitro and ex vivo. Additionally, SRT1720 increased the number of apoptotic cells, as shown by annexin V positive cells, cleaved poly (ADP-ribose) polymerase 1, cleaved caspase-3, and fragmented DNA. SRT1720 also induced mitochondrial outer membrane permeabilization with the generation of mitochondrial reactive oxygen species and autophagy. However, SIRT1 knockdown did not attenuate SRT1720-induced cell death in leukemic cell lines. Finally, SRT1720 treatment decreased the growth of human ATL tumor xenografts in immunodeficient mice. Our study shows that while SRT1720 does not target SIRT1, it induces cell death in ATL cells via apoptosis and autophagy and has antitumor activity.


Asunto(s)
Compuestos Heterocíclicos de 4 o más Anillos , Leucemia-Linfoma de Células T del Adulto , Animales , Apoptosis , Muerte Celular , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Humanos , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Leucemia-Linfoma de Células T del Adulto/genética , Leucemia-Linfoma de Células T del Adulto/metabolismo , Leucocitos Mononucleares/metabolismo , Ratones , Sirtuina 1/genética , Sirtuina 1/metabolismo
17.
BMC Cancer ; 22(1): 119, 2022 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-35093003

RESUMEN

BACKGROUND: Borderline resectable pancreatic cancer (BRPC) is a category of pancreatic cancer that is anatomically widely spread, and curative resection is uncommon with upfront surgery. Intensity-modulated radiation therapy (IMRT) is a form of radiation therapy that delivers precise radiation to a tumor while minimizing the dose to surrounding normal tissues. Here, we conducted a phase 2 study to estimate the curability and efficacy of neoadjuvant chemoradiotherapy using IMRT (NACIMRT) for patients with BRPC with arterial abutment (BRPC-A). METHODS: A total of 49 BRPC-A patients were enrolled in this study and were treated at our hospital according to the study protocol between June 2013 and March 2021. The primary endpoint was microscopically margin-negative resection (R0) rates and we subsequently analyzed safety, histological effect of the treatment as well as survivals among patients with NACIMRT. RESULTS: Twenty-nine patients (59.2%) received pancreatectomy after NACIMRT. The R0 rate in resection patients was 93.1% and that in the whole cohort was 55.1%. No mortality was encountered. Local therapeutic effects as assessed by Evans classification showed good therapeutic effect (Grade 1, 3.4%; Grade 2a, 31.0%; Grade 2b, 48.3%; Grade 3, 3.4%; Grade 4, 3.4%). Median disease-free survival was 15.5 months. Median overall survival in the whole cohort was 35.1 months. The only independent prognostic pre-NACIMRT factor identified was serum carbohydrate antigen 19-9 (CA19-9) > 400 U/ml before NACIMRT. CONCLUSIONS: NACIMRT showed preferable outcome without significant operative morbidity for BRPC-A patients. NACIMRT contributes to good local tumor control, but a high initial serum CA19-9 implies poor prognosis even after neoadjuvant treatment. TRIAL REGISTRATION: UMIN-CTR Clinical Trial: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011776 Registration number: UMIN000010113. Date of first registration: 01/03/2013.


Asunto(s)
Terapia Neoadyuvante , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/terapia , Radioterapia de Intensidad Modulada , Anciano , Antígenos de Carbohidratos Asociados a Tumores/sangre , Arterias , Femenino , Humanos , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Pancreatectomía , Estudios Prospectivos , Resultado del Tratamiento
18.
Pancreatology ; 22(1): 123-129, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34736838

RESUMEN

BACKGROUND: /Objectives: Although the presence of lymph node metastasis (LNM) defines malignant potential, preoperative prediction of LNM has not been established for non-functional pancreatic neuroendocrine neoplasm (NF-PNEN). We sought to develop a prediction system using only preoperatively available factors that would stratify the risk of LNM for NF-PNEN. METHODS: We retrospectively reviewed patients who underwent R0/1 resection of NF-PNEN at Kyoto University (2007-2019) and the University of California, San Francisco (2010-2019). Risk stratification of LNM was developed using preoperative factors by the logistic regression analysis. Long-term outcomes were compared across the risk groups. RESULTS: A total of 131 patients were included in this study. Lymph nodes were pathologically examined in 116 patients, 23 (20%) of whom had LNM. Radiological tumor size [1.5-3.5 cm (odds ratio: 13.5, 95% confidence interval: 1.77-398) and >3.5 cm (72.4, 9.06-2257) against ≤1.5 cm], <50% cystic component (8.46 × 10^6, 1.68 × 10^106-), and dilatation of main pancreatic duct ≥5 mm (31.2, 3.94-702) were independently associated with LNM. When patients were classified as the low-risk (43 patients), intermediate-risk (44 patients), and high-risk groups (29 patients), proportions of LNM differed significantly across the groups (0%, 14%, and 59%, respectively). Recurrence-free survival (RFS) of the low- and intermediate-risk groups were significantly better than that of the high-risk group (5-year RFS rates of 92.2%, 85.4%, and 47.1%, respectively). CONCLUSIONS: The prediction system using preoperative radiological factors stratifies the risk of LNM for NF-PNEN. This stratification helps to predict malignant potential and determine the surgical procedure and necessity of regional lymphadenectomy.


Asunto(s)
Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Neoplasias Pancreáticas/patología , Anciano , California , Femenino , Humanos , Japón , Ganglios Linfáticos/cirugía , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Neoplasias Pancreáticas/cirugía , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo
19.
Surg Oncol ; 38: 101577, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33887674

RESUMEN

BACKGROUND: Minimally invasive pancreaticoduodenectomy (MIPD), including laparoscopic pancreaticoduodenectomy (LPD) and robotic pancreaticoduodenectomy (RPD), is technically demanding because of pancreaticojejunostomy (PJ). Postoperative pancreatic fistula (POPF) is the most serious complication of MIPD and open pancreaticoduodenectomy (OPD). Contrary to expectations, conventional PJ in MIPD did not improve POPF rate and length of hospital stay. High POPF rates are attributed to technical issues encountered during MIPD, which include motion restriction and insufficient water tightness. Therefore, we developed wrapping double-mattress anastomosis, the Kiguchi method, which is a novel PJ technique that can improve MIPD. Herein, we describe the Kiguchi method for PJ in MIPD and compare the outcomes between this technique and conventional PJ in OPD. METHODS: The current retrospective study included 83 patients in whom the complete obstruction of the main pancreatic duct by pancreatic tumors was absent on preoperative imaging. This research was performed from September 2016 to August 2020 at Fujita Health University Hospital. All patients were evaluated as having a soft pancreatic texture, which is the most important factor associated with POPF development. Briefly, 50 patients underwent OPD with conventional PJ (OPD group). Meanwhile, 33 patients, including 15 and 18 who had LPD and RPD, respectively, underwent MIPD using the Kiguchi method (MIPD group). After a 1:1 propensity score matching, 30 patients in the OPD group were matched to 30 patients in the MIPD group. RESULTS: The patients' preoperative data did not differ. The grade B/C POPF rate was significantly lower in the MIPD group than in the OPD group (6.7% vs 40.0%, p = 0.002). The MIPD group had a significantly shorter median length of hospital stay than the OPD group (24 vs 30 days, p = 0.004). CONCLUSION: The novel Kiguchi method in MIPD significantly reduced the POPF rate in patients without complete obstruction of the main pancreatic duct.


Asunto(s)
Anastomosis Quirúrgica/métodos , Laparoscopía , Fístula Pancreática/prevención & control , Pancreaticoduodenectomía , Pancreatoyeyunostomía , Complicaciones Posoperatorias/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Tiempo de Internación , Masculino , Análisis por Apareamiento , Persona de Mediana Edad , Neoplasias Pancreáticas/cirugía , Puntaje de Propensión , Estudios Retrospectivos
20.
Surg Case Rep ; 7(1): 72, 2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33742297

RESUMEN

BACKGROUND: Although duodenal neuroendocrine neoplasms (DuNENs) usually have indolent phenotypes, some DuNENs exhibit aggressive clinical manifestations. Tumor size > 1 cm, lymph node metastasis, and high grade have been associated with poor prognosis. However, preoperative risk evaluation is often difficult, because Ki-67 index on biopsy is frequently underestimated due to the intratumor heterogeneity. Here, we present a case of a subcentimeter DuNEN with a low Ki-67 index on endoscopic biopsy, who developed lymph node metastasis and high-grade liver metastasis. CASE PRESENTATION: The patient was a 52-year-old female who presented an epigastric pain. Esophagogastroduodenoscopy revealed a duodenal submucosal lesion with a size of 8 mm. The endoscopic biopsy showed DuNEN with a Ki-67 index of 3.3% (G2 categorized by the World Health Organization 2019 classification). We performed an open partial duodenectomy with adjacent lymph node dissection. Pathological examination of the resected specimens revealed a Ki-67 index of 13.5% (G2) in the "hot spot" and lymph node metastasis. A hepatic low-density area detected on preoperative contrast-enhanced computed tomography appeared to be a liver metastasis on postoperative gadoxetic acid-enhanced magnetic resonance imaging. Subsequently, we performed a laparoscopic partial hepatectomy. Pathological examination of the liver specimen showed a metastatic neuroendocrine tumor with a Ki-67 index of 27.5% (NET-G3). The patient has been alive for 14 months since the hepatectomy. CONCLUSIONS: This case shows the possibility of high malignant potential of DuNEN even if the primary lesion is < 1 cm and has a low Ki-67 index on biopsy.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...