Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 243
Filtrar
Más filtros

Base de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Artículo en Inglés | MEDLINE | ID: mdl-39314032

RESUMEN

Backgrounds/Aims: In recent years, many minimally invasive techniques have been introduced to reduce the number of ports in laparoscopic cholecystectomy (LC), offering benefits such as reduced postoperative pain and improved cosmetic outcomes. ArtiSential® is a new multi-degree-of-freedom articulating laparoscopic instrument that incorporates the ergonomic features of robotic surgery, potentially overcoming the spatial limitations of laparoscopic surgery. ArtiSential® LC can be performed using only two ports. This study aims to compare the surgical outcomes of ArtiSential® LC with those of single-fulcrum LC. Methods: This retrospective study compared ArtiSential® LC and single-fulcrum LC among LCs performed for gallbladder (GB) stones at the same center, analyzing the basic characteristics of patients; intraoperative outcomes, such as operative time, estimated blood loss, and intraoperative GB rupture; and postoperative outcomes, such as length of hospital stay, incidence of postoperative complications, and postoperative pain. Results: A total of 88 and 63 patients underwent ArtiSential® LC and single-fulcrum LC for GB stones, respectively. Analysis showed that ArtiSential® LC resulted in significantly fewer cases of surgeries longer than 60 minutes (30 vs. 35 min, p = 0.009) and intraoperative GB ruptures (2 vs. 10, p = 0.007). In terms of postoperative outcomes, ArtiSential® LC showed better results in the respective visual analog scale (VAS) scores immediately after surgery (2.59 vs. 3.73, p < 0.001), and before discharge (1.44 vs. 2.02, p = 0.01). Conclusions: ArtiSential® LC showed better results in terms of surgical outcomes, especially postoperative pain. Thus, ArtiSential® LC is considered the better option for patients, compared to single-fulcrum LC.

2.
World J Gastrointest Endosc ; 16(6): 305-317, 2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38946858

RESUMEN

While endoscopic retrograde cholangiopancreatography (ERCP) remains the primary treatment modality for common bile duct stones (CBDS) or choledocholithiasis due to advancements in instruments, surgical intervention, known as common bile duct exploration (CBDE), is still necessary in cases of difficult CBDS, failed endoscopic treatment, or altered anatomy. Recent evidence also supports CBDE in patients requesting single-step cholecystectomy and bile duct stone removal with comparable outcomes. This review elucidates relevant clinical anatomy, selection indications, and outcomes to enhance surgical understanding. The selection between trans-cystic (TC) vs trans-choledochal (TD) approaches is described, along with stone removal techniques and ductal closure. Detailed surgical techniques and strategies for both the TC and TD approaches, including instrument selection, is also provided. Additionally, this review comprehensively addresses operation-specific complications such as bile leakage, stricture, and entrapment, and focuses on preventive measures and treatment strategies. This review aims to optimize the management of CBDS through laparoscopic CBDE, with the goal of improving patient outcomes and minimizing risks.

4.
Cancer Med ; 13(14): e7459, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39030993

RESUMEN

BACKGROUND: Although adjuvant gemcitabine (GEM) monotherapy improves the overall survival (OS) of patients with resected pancreatic cancer, its efficacy requires further improvement. This multicenter, phase II study investigated the efficacy of adjuvant portal vein infusion (PVI) chemotherapy followed by GEM therapy in patients with resected pancreatic cancer. METHODS: 5-fluorouracil (250 mg/day) and heparin (2000 IU/day) PVI chemotherapy were combined with systemic administration of mitomycin C (4 mg; days 6, 13, 20, and 27) and cisplatin (10 mg; days 7, 14, 21, and 28) for 4 weeks (PI4W), followed by GEM (1000 mg/m2; days 1, 8, and 15 every 4 weeks for 6 months). The primary endpoint was relapse-free survival (RFS) and the secondary endpoints were OS and treatment completion. RESULTS: Between November 2010 and August 2013, 53 patients who underwent complete resection were enrolled, including 30, 20, and 3 patients who underwent pancreaticoduodenectomies and distal and total pancreatectomies, respectively. In total, 51 (96.2%) patients underwent R0 resection, of whom 3, 2, 12, 35, 0, and 1 had stages IA, IB, IIA, IIB, III, and IV cancer, respectively, and 47 (88.7%) patients completed PI4W. The median RFS was 22.0 months (1-, 3-, 5, and 10 years RFS: 64.9%, 38.1%, 38.1%, and 38.1%, respectively), whereas the median OS was 32.0 months (1-, 3-, 5, and 10 years OS:86.6%, 47.2%, 44.4%, and 44.4%, respectively). CONCLUSION: Treatment with PI4W followed by GEM for 6 months after surgery may be beneficial in patients undergoing curative resection of pancreatic cancer.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina , Fluorouracilo , Gemcitabina , Neoplasias Pancreáticas , Vena Porta , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Masculino , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Femenino , Persona de Mediana Edad , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante/métodos , Adulto , Resultado del Tratamiento , Infusiones Intravenosas , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Estadificación de Neoplasias
5.
Pancreas ; 53(6): e521-e527, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38888840

RESUMEN

OBJECTIVES: Endoscopic ultrasound (EUS) is an excellent diagnostic tool that provides high-resolution images of pancreatic cystic lesions. However, its role in the diagnosis of malignant intraductal papillary mucinous neoplasm (IPMN) remains limited and unclear. We aimed to determine the usefulness of this modality for such diagnosis. METHODS: Overall, 246 patients who underwent EUS for IPMN after computed tomography (CT)/magnetic resonance imaging (MRI) from April 2018 to June 2021 were followed up until March 2022. We assessed the added value of performing EUS after CT or MRI for diagnosing malignant IPMN, using receiver operating characteristic curve analysis. Walls as thick as 2 mm were considered thickened in this study if they were highly uneven. RESULTS: EUS clearly enhanced accuracy in identifying enhancing nodules and thickened walls. The areas under the receiver operating characteristic curve and corresponding 95% confidence intervals were 0.655 (0.549-0.760) and 0.566 (0.478-0.654) upon CT/MRI but 0.853 (0.763-0.942) and 0.725 (0.634-0.817) when observed using EUS. The combination of nodule size, thickened wall, and main duct size yielded the highest area under the receiver operating characteristic curve (0.944 [0.915-0.973]). CONCLUSIONS: EUS more accurately detects malignant IPMN, as uneven wall thickening and certain nodules cannot be identified with CT/MRI.


Asunto(s)
Endosonografía , Imagen por Resonancia Magnética , Neoplasias Intraductales Pancreáticas , Neoplasias Pancreáticas , Curva ROC , Tomografía Computarizada por Rayos X , Humanos , Endosonografía/métodos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X/métodos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Neoplasias Intraductales Pancreáticas/diagnóstico por imagen , Neoplasias Intraductales Pancreáticas/patología , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/diagnóstico , Adenocarcinoma Mucinoso/diagnóstico por imagen , Adenocarcinoma Mucinoso/patología , Anciano de 80 o más Años , Estudios Retrospectivos , Adulto , Reproducibilidad de los Resultados
6.
JAMA Netw Open ; 7(6): e2417625, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38888920

RESUMEN

Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking. Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy. Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months. Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection. Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively. Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89). Conclusions and Relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.


Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/mortalidad , Masculino , Persona de Mediana Edad , Femenino , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/terapia , Adenocarcinoma/patología , Anciano , Terapia Neoadyuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado del Tratamiento , Estudios de Cohortes , Oxaliplatino/uso terapéutico , Pancreatectomía
8.
Surg Endosc ; 38(5): 2411-2422, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38315197

RESUMEN

BACKGROUND: Artificial intelligence (AI) is becoming more useful as a decision-making and outcomes predictor tool. We have developed AI models to predict surgical complexity and the postoperative course in laparoscopic liver surgery for segments 7 and 8. METHODS: We included patients with lesions located in segments 7 and 8 operated by minimally invasive liver surgery from an international multi-institutional database. We have employed AI models to predict surgical complexity and postoperative outcomes. Furthermore, we have applied SHapley Additive exPlanations (SHAP) to make the AI models interpretable. Finally, we analyzed the surgeries not converted to open versus those converted to open. RESULTS: Overall, 585 patients and 22 variables were included. Multi-layer Perceptron (MLP) showed the highest performance for predicting surgery complexity and Random Forest (RF) for predicting postoperative outcomes. SHAP detected that MLP and RF gave the highest relevance to the variables "resection type" and "largest tumor size" for predicting surgery complexity and postoperative outcomes. In addition, we explored between surgeries converted to open and non-converted, finding statistically significant differences in the variables "tumor location," "blood loss," "complications," and "operation time." CONCLUSION: We have observed how the application of SHAP allows us to understand the predictions of AI models in surgical complexity and the postoperative outcomes of laparoscopic liver surgery in segments 7 and 8.


Asunto(s)
Inteligencia Artificial , Hepatectomía , Laparoscopía , Neoplasias Hepáticas , Humanos , Laparoscopía/métodos , Hepatectomía/métodos , Femenino , Masculino , Persona de Mediana Edad , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Anciano , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Tempo Operativo , Adulto
10.
Ann Surg Oncol ; 31(2): 1347-1357, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37952022

RESUMEN

BACKGROUND: Advancements in multiagent chemotherapy have expanded the surgical indications for pancreatic cancer. Although pancreaticoduodenectomy (PD) with portal vein resection (PVR) has become widely adopted, distal pancreatectomy (DP) with PVR remains rarely performed because of its technical complexity. This study was designed to assess the feasibility of DP-PVR compared with PD-PVR for pancreatic body cancers, with a focus on PV complications and providing optimal reconstruction techniques when DP-PVR is necessary. METHODS: A retrospective review was conducted on consecutive pancreatic body cancer patients who underwent pancreatectomy with PVR between 2005 and 2020. An algorithm based on the anatomical relationship between the arteries and PV was used for optimal surgical selection. RESULTS: Among 119 patients, 32 underwent DP-PVR and 87 underwent PD-PVR. Various reconstruction techniques were employed in DP-PVR cases, including patch reconstruction, graft interposition, and wedge resection. The majority of PD-PVR cases involved end-to-end anastomosis. The length of PVR was shorter in DP-PVR (25 vs. 40 mm; p < 0.001). Although Clavien-Dindo ≥3a was higher in DP-PVR (p = 0.002), inpatient mortality and R0 status were similar. Complete PV occlusion occurred more frequently in DP-PVR than in PD-PVR (21.9% vs. 1.1%; p < 0.001). A cutoff value of 30 mm for PVR length was determined to be predictive of nonrecurrence-related PV occlusion after DP-PVR. The two groups did not differ significantly in recurrence or overall survival. CONCLUSIONS: DP-PVR had higher occlusion and postoperative complication rates than PD-PVR. These findings support the proposed algorithm and emphasize the importance of meticulous surgical manipulation when DP-PVR is deemed necessary.


Asunto(s)
Pancreatectomía , Neoplasias Pancreáticas , Humanos , Pancreatectomía/métodos , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía/métodos , Estudios Retrospectivos , Complicaciones Posoperatorias/cirugía , Vena Porta/cirugía , Resultado del Tratamiento
11.
Hepatol Res ; 54(6): 562-574, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38133587

RESUMEN

AIM: C-reactive protein (CRP) is both an inflammatory and prognostic marker in various cancers. This study aimed to elucidate the characteristics of CRP and the prognostic factors in patients who were administered with atezolizumab plus bevacizumab (ATZ + BEV) for unresectable hepatocellular carcinoma (HCC). METHODS: A total of 213 patients who received ATZ + BEV for HCC from November 2020 to March 2023 at 15 hospitals were enrolled in this retrospective study. The prognosis was analyzed by subdividing the patients based on baseline characteristics, radiologic response, and treatment lines. Accuracy of survival prediction was assessed using CRP, alpha fetoprotein (AFP), C-reactive protein and alpha fetoprotein in immunotherapy (CRAFITY), and Glasgow Prognostic Score. RESULTS: Compared with patients with baseline CRP <1 mg/dL, those with baseline CRP ≥1 mg/dL (n = 45) had a significantly higher baseline albumin-bilirubin score and AFP levels, significantly lower disease control rate (62.2%), and significantly shorter median overall survival (hazards ratios 2.292; 95% confidence interval 1.313-5.107; log-rank test, p < 0.001). Multivariate analysis identified CRP ≥1 mg/dL, AFP ≥100 ng/mL, and modified albumin-bilirubin grade as the significant prognostic factors. The baseline CRP, AFP, CRAFITY, and Glasgow Prognostic Score demonstrated higher discrimination for 1-year survival prediction after first-line ATZ + BEV administration, compared with beyond second line, with area under the receiver operating characteristic curves of 0.759, 0.761, 0.805, and 0.717, respectively. CONCLUSIONS: CRP was a significant biomarker in patients treated with ATZ + BEV for HCC. Elevated CRP levels may indicate aggressive cancer progression and potential resistance to ATZ + BEV therapy.

12.
J Hepatobiliary Pancreat Sci ; 31(3): 143-151, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38148501

RESUMEN

BACKGROUND: Recent advancements in systemic therapy for hepatocellular carcinoma (HCC) necessitate the establishment of resectability criteria for advanced HCC. METHODS: A questionnaire survey sought to clarify the perspectives of Japanese expert hepatobiliary surgeons regarding surgical indications for HCC. Thirty-one questions were used to determine when surgery is strongly recommended (resectable: R) or not recommended (unresectable: UR). RESULTS: A total of 351 responses were obtained. While 64.7% of the respondents considered solitary tumors as being R, irrespective of size, opinions diverged on the upper limit of the number of tumors/tumor size for R: (1) up to three nodules with no size limit (27.9%), (2) up to three nodules ≤5 cm in diameter each (21.4%) and (3) up to three nodules ≤3 cm in diameter each (19.4%). Vp1, Vp2, Vp3, and Vp4 were considered as being R by 90.9%, 70.7%, 39.0%, and 8.0% of respondents, respectively. Half of the respondents indicated they would consider resection even for cases with extrahepatic spread under limited conditions. CONCLUSIONS: The current views of Japanese expert surgeons on the resectability criteria for HCC were clarified for the first time. The findings could serve as a basis for preparing expert consensus statements on the resectability criteria for HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Cirujanos , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Japón , Encuestas y Cuestionarios
13.
Gene ; 893: 147916, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-37866661

RESUMEN

Pancreatic neuroendocrine carcinoma (NEC) and mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) are rare pancreatic malignant tumors, and comprehensive gene analyses are scarce. In this study, six NECs and six MiNENs were collected, immunohistochemistry for synaptophysin, chromogranin A, INSM1, Ki-67, and Rb was conducted, and KRAS mutational status was examined. Among these cases, comprehensive gene expression analysis of oncogene pathways using nCounter® were performed with six NECs and four MiNENs, and those data were compared with that of three pancreatic ductal adenocarcinomas (PDACs), with that of three normal pancreatic ducts, and with each other. By dividing NEC and MiNEN cases into KRAS-mutated group and KRAS-wild group, the difference of clinicopathological data and gene expression profiling data were examined between the two groups. Compared to the data of normal pancreatic epithelium, all 13 cancer-related pathways were upregulated in PDAC, MiNEN, and NEC group with more upregulation in this order. Compared to the data of PDAC, genes of DNA Damage repair pathway was most upregulated both in NECs and MiNENs. Regarding the difference between KRAS-mutated and KRAS-wild groups, several genes were differentially expressed between the two, where MMP7 was the upregulated gene with highest p-value and NKD1 was the downregulated gene with highest p-value in KRAS-mutated group. From the extent of upregulation of 13 pathways, MiNEN was considered more progressed stage than PDAC, and NEC was considered more progressed than MiNEN. From the comparison of KRAS-mutated and KRAS-wild NECs and MiNENs, several differentially expressed genes were identified in this study.


Asunto(s)
Carcinoma Neuroendocrino , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Proteínas Proto-Oncogénicas p21(ras)/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Carcinoma Neuroendocrino/genética , Carcinoma Neuroendocrino/patología , Perfilación de la Expresión Génica , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/patología , Proteínas Represoras/genética
14.
Surg Today ; 2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-38055106

RESUMEN

PURPOSE: Hepatic veno-occlusive disease (HVOD) after liver transplantation (LT) is almost always a fatal complication. We assessed the outcomes of HVOD in a single institute and analyzed a literature-based cohort. METHODS: We reviewed the medical records of recipients of LT performed between 1995 and 2020 at our institute and the literature on HVOD after LT. We then analyzed the clinical features based on a "pooled" cohort of cases identified in our institute and reported in the literature. RESULTS: HVOD was diagnosed in 3 of 331 LT recipients, all of whom died in hospital, on days 164, 12, and 13, respectively. Our comprehensive review of the literature, as well as our cases, identified eight cases of HVOD that developed within 14 days after LT (early-onset type). Early-onset HVOD had a significantly worse prognosis than HVOD that developed beyond 2 weeks after LT (non-early-onset type), which was identified in 22 cases (25.0% vs. 86.1% of the 3-month graft survival rate). The most common causes of early-onset and non-early-onset types were acute cellular rejection (50%) and drug-induced disease (50%), respectively. CONCLUSION: Early-onset HVOD developing within 14 days after LT has a poor prognosis.

15.
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
16.
Hepatol Commun ; 7(10)2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37782459

RESUMEN

BACKGROUND: NAFLD caused by abnormalities in hepatic lipid metabolism is associated with an increased risk of developing HCC. The molecular mechanisms underlying the progression of NAFLD-related HCC are not fully understood. We investigated the molecular mechanism and role of KDM6B downregulation in NAFLD-related HCC after the KDM6B gene was identified using microarray analysis as commonly downregulated in mouse NAFLD-related HCC and human nonhepatitis B and nonhepatitis C viral-HCC. METHODS: The 5-hydroxymethylcytosine levels of KDM6B in HCC cells were determined using glycosylated hydroxymethyl-sensitive PCR. Microarray and chromatin immunoprecipitation analyses using KDM6B-knockout (KO) cells were used to identify KDM6B target genes. Lipotoxicity was assessed using a palmitate-treated cell proliferation assay. Immunohistochemistry was used to evaluate KDM6B expression in human HCC tissues. RESULTS: KDM6B expression levels in HCC cells correlated with the 5-hydroxymethylcytosine levels in the KDM6B gene body region. Gene set enrichment analysis revealed that the lipid metabolism pathway was suppressed in KDM6B-KO cells. KDM6B-KO cells acquired resistance to lipotoxicity (p < 0.01) and downregulated the expression of G0S2, an adipose triglyceride lipase/patatin like phospholipase domain containing 2 (ATGL/PNPLA2) inhibitor, through increased histone H3 lysine-27 trimethylation levels. G0S2 knockdown in KDM6B-expressed HCC cells conferred lipotoxicity resistance, whereas ATGL/PNPLA2 inhibition in the KDM6B-KO cells reduced these effects. Immunohistochemistry revealed that KDM6B expression was decreased in human NAFLD-related HCC tissues (p < 0.001), which was significantly associated with decreased G0S2 expression (p = 0.032). CONCLUSIONS: KDM6B-disrupted HCC acquires resistance to lipotoxicity via ATGL/PNPLA2 activation caused by epigenetic downregulation of G0S2 expression. Reduced KDM6B and G0S2 expression levels are common in NAFLD-related HCC. Targeting the KDM6B-G0S2-ATGL/PNPLA2 pathway may be a useful therapeutic strategy for NAFLD-related HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Ratones , Humanos , Animales , Enfermedad del Hígado Graso no Alcohólico/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Lipasa/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Histona Demetilasas con Dominio de Jumonji/genética
17.
Biomedicines ; 11(8)2023 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-37626774

RESUMEN

Accumulation of 4-hydroxynonenal (4-HNE), a marker of lipid peroxidation, has various favorable and unfavorable effects on cancer cells; however, the clinicopathological significance of its accumulation in hepatocellular carcinoma (HCC) and its metabolic pathway remain unknown. This study analyzed 4-HNE accumulation and its clinicopathological significance in HCC. Of the 221 cases, 160 showed relatively low accumulation of 4-HNE in HCC tissues, which was an independent prognostic predictor. No correlation was found between 4-HNE accumulation and the expression of the antioxidant enzymes glutathione peroxidase 4, ferroptosis suppressor protein 1, and guanosine triphosphate cyclohydrolase 1. Therefore, we hypothesized that 4-HNE metabolism is up-regulated in HCC. A database search was focused on the transcriptional regulation of aldo-keto reductases, alcohol dehydrogenases, and glutathione-S-transferases, which are the metabolic enzymes of 4-HNE, and seven candidate transcription factor genes were selected. Among the candidate genes, the knockdown of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4) increased 4-HNE accumulation. Immunohistochemical analysis revealed an inverse correlation between 4-HNE accumulation and SMARCA4 expression. These results suggest that SMARCA4 regulates 4-HNE metabolism in HCC. Therefore, targeting SMARCA4 provides a basis for a new therapeutic strategy for HCC via 4-HNE accumulation and increased cytotoxicity.

18.
Pancreatology ; 23(6): 697-703, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37574438

RESUMEN

OBJECTIVES: The dorsal pancreatic artery (DPA) is a pancreatic branch with various anatomical variations. Previous studies mostly focused on the origin of the DPA, and its pathways and branching patterns have rarely been examined. The purpose of this study was to investigate the branching patterns and pathways of the DPA. METHODS: This study included 110 patients who underwent computed tomography scans. We examined the pathways and branching patterns of the DPA. RESULTS: The DPA was identified in 101 patients (92%), and originated from the splenic artery in 30 patients (31%), the common hepatic artery in 17 patients (17%), the celiac trunk in 10 patients (10%), the superior mesenteric artery in 27 patients (27%), the replaced right hepatic artery in 7 patients (7%), the inferior pancreaticoduodenal artery in 5 patients (5%), and other arteries in 3 patients (3%). Four distinct types of branches were identified as follows: the superior branch (32%), the inferior branch (86%), the right branch (80%), and the accessory middle colic artery (12%). Additionally, the arcs of Buhler and Riolan were observed in two patients each and their anastomotic vessels followed almost the same pathway as the DPA. CONCLUSION: A number of variations of the DPA were observed with regard to its origin and branching pattern; however, the DPA and its branches always ran along the same pathway, as summarized in Fig. 4. The anatomical information gained from this study may contribute to performing safe pancreatic resections.


Asunto(s)
Páncreas , Arteria Esplénica , Humanos , Arteria Esplénica/diagnóstico por imagen , Arteria Esplénica/cirugía , Páncreas/diagnóstico por imagen , Páncreas/cirugía , Páncreas/irrigación sanguínea , Arteria Mesentérica Superior/diagnóstico por imagen , Arteria Mesentérica Superior/anatomía & histología , Arteria Celíaca/diagnóstico por imagen , Arteria Celíaca/cirugía , Desarrollo Embrionario
19.
Pancreatology ; 23(6): 712-720, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37336669

RESUMEN

Locally advanced pancreatic cancer (LAPC), which progresses locally and surrounds major vessels, has historically been deemed unresectable. Surgery alone failed to provide curative resection and improve overall survival. With the advancements in treatment, reports have shown favorable results in LAPC after undergoing successful chemotherapy therapy or chemoradiation therapy followed by surgical resection, so-called "conversion surgery", at experienced high-volume centers. However, recognizing significant regional and institutional disparities in the management of LAPC, an international consensus meeting on conversion surgery for LAPC was held during the Joint Congress of the 26th Meeting of the International Association of Pancreatology (IAP) and the 53rd Annual Meeting of Japan Pancreas Society (JPS) in Kyoto in July 2022. During the meeting, presenters reported the current best multidisciplinary practices for LAPC, including preoperative modalities, best systemic treatment regimens and durations, procedures of conversion surgery with or without vascular resections, biomarkers, and genetic studies. It was unanimously agreed among the experts in this meeting that "cancer biology is surpassing locoregional anatomical resectability" in the era of effective multiagent treatment. The biology of pancreatic cancer has yet to be further elucidated, and we believe it is essential to improve the treatment outcomes of LAPC patients through continued efforts from each institution and more international collaboration. This article summarizes the agreement during the discussion amongst the experts in the meeting. We hope that this will serve as a foundation for future international collaboration and recommendations for future guidelines.


Asunto(s)
Gastroenterología , Neoplasias Pancreáticas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Japón , Terapia Neoadyuvante/métodos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/cirugía
20.
Surg Today ; 53(10): 1160-1172, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37272972

RESUMEN

PURPOSE: Acute liver failure is a life-threatening condition for which ABO-incompatible living donor liver transplantation (ABOi-LDLT) is sometimes the only life-saving treatment option. We reviewed a single-center experience of adult ABOi-LDLT treatment for acute liver failure (ALF). METHODS: Preoperative treatment, immune indices (B cell marker, anti-donor blood-type antibody), and postoperative outcomes were compared between ALF and non-ALF groups. RESULTS: There were 5 and 33 patients in the ALF and non-ALF groups, respectively. The ALF group received higher doses of steroids, underwent more rounds of plasma exchange (PE), and underwent transplantation for ALF with a shorter interval following preoperative rituximab (RTx) administration (median: 2 vs 13 days; P < 0.05) than the non-ALF group. Preoperatively, CD19-positive lymphocytes in the peripheral blood were sufficiently depleted in all of the non-ALF group patients, whereas they were poorly depleted in the ALF group. Postoperatively, neither group suffered anti-donor blood-type antibody titer rebound or antibody-mediated rejection. The ALF group had a comparable 5-year survival rate to the non-ALF group (80.0% vs 77.9%). CONCLUSIONS: Despite the delayed preoperative administration of RTx, the ALF group showed an uneventful immunological response and acceptable long-term survival rate. Thus, ABOi-LDLT seems a viable treatment option for ALF.


Asunto(s)
Fallo Hepático Agudo , Trasplante de Hígado , Adulto , Humanos , Sistema del Grupo Sanguíneo ABO , Incompatibilidad de Grupos Sanguíneos , Rechazo de Injerto , Fallo Hepático Agudo/cirugía , Fallo Hepático Agudo/tratamiento farmacológico , Donadores Vivos , Rituximab/uso terapéutico
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA