Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 58
Filtrar
1.
Cancers (Basel) ; 16(13)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-39001521

RESUMO

Portal vein arterialization (PVA) is a surgical procedure that plays a crucial role in hepatic vascular salvage when hepatic artery flow restoration remains elusive. Dedicated diagnostic vascular imaging and the timely management of PVA shunts are paramount to preventing complications, such as portal hypertension and thrombosis. Regrettably, a lack of standardized postoperative management protocols for PVA has increased morbidity and mortality rates post-procedure. In response to this challenge, we developed a PVA standard operating procedure (SOP) tailored to the needs of interventional radiologists. This SOP is designed to harmonize postoperative care, fostering scientific comparability across cases. This concise brief report aims to offer radiologists valuable insights into the PVA technique and considerations for post-PVA care and foster effective interdisciplinary collaboration.

2.
Eur J Clin Invest ; 54(8): e14210, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38624140

RESUMO

AIM: To evaluate the quantity and quality of randomized controlled trials (RCTs) in hepatobiliary surgery and for identifying gaps in current evidences. METHODS: A systematic search was conducted in MEDLINE (via PubMed), Web of Science, and Cochrane Controlled Register of Trials (CENTRAL) for RCTs of hepatobiliary surgery published from inception until the end of 2023. The quality of each study was assessed using the Cochrane risk-of-bias (RoB) tool. The associations between risk of bias and the region and publication date were also assessed. Evidence mapping was performed to identify research gaps in the field. RESULTS: The study included 1187 records. The number and proportion of published randomized controlled trials (RCTs) in hepatobiliary surgery increased over time, from 13 RCTs (.0005% of publications) in 1970-1979 to 201 RCTs (.003% of publications) in 2020-2023. There was a significant increase in the number of studies with a low risk of bias in RoB domains (p < .01). The proportion of RCTs with low risk of bias improved significantly after the introduction of CONSORT guidelines (p < .001). The evidence mapping revealed a significant research focus on major and minor hepatectomy and cholecystectomy. However, gaps were identified in liver cyst surgery and hepatobiliary vascular surgery. Additionally, there are gaps in the field of perioperative management and nutrition intervention. CONCLUSION: The quantity and quality of RCTs in hepatobiliary surgery have increased over time, but there is still room for improvement. We have identified gaps in current research that can be addressed in future studies.


Assuntos
Hepatectomia , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Colecistectomia , Procedimentos Cirúrgicos do Sistema Biliar
4.
Surg Endosc ; 38(5): 2483-2496, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38456945

RESUMO

OBJECTIVE: Evaluation of the benefits of a virtual reality (VR) environment with a head-mounted display (HMD) for decision-making in liver surgery. BACKGROUND: Training in liver surgery involves appraising radiologic images and considering the patient's clinical information. Accurate assessment of 2D-tomography images is complex and requires considerable experience, and often the images are divorced from the clinical information. We present a comprehensive and interactive tool for visualizing operation planning data in a VR environment using a head-mounted-display and compare it to 3D visualization and 2D-tomography. METHODS: Ninety medical students were randomized into three groups (1:1:1 ratio). All participants analyzed three liver surgery patient cases with increasing difficulty. The cases were analyzed using 2D-tomography data (group "2D"), a 3D visualization on a 2D display (group "3D") or within a VR environment (group "VR"). The VR environment was displayed using the "Oculus Rift ™" HMD technology. Participants answered 11 questions on anatomy, tumor involvement and surgical decision-making and 18 evaluative questions (Likert scale). RESULTS: Sum of correct answers were significantly higher in the 3D (7.1 ± 1.4, p < 0.001) and VR (7.1 ± 1.4, p < 0.001) groups than the 2D group (5.4 ± 1.4) while there was no difference between 3D and VR (p = 0.987). Times to answer in the 3D (6:44 ± 02:22 min, p < 0.001) and VR (6:24 ± 02:43 min, p < 0.001) groups were significantly faster than the 2D group (09:13 ± 03:10 min) while there was no difference between 3D and VR (p = 0.419). The VR environment was evaluated as most useful for identification of anatomic anomalies, risk and target structures and for the transfer of anatomical and pathological information to the intraoperative situation in the questionnaire. CONCLUSIONS: A VR environment with 3D visualization using a HMD is useful as a surgical training tool to accurately and quickly determine liver anatomy and tumor involvement in surgery.


Assuntos
Imageamento Tridimensional , Tomografia Computadorizada por Raios X , Realidade Virtual , Humanos , Tomografia Computadorizada por Raios X/métodos , Feminino , Masculino , Hepatectomia/métodos , Hepatectomia/educação , Adulto , Adulto Jovem , Tomada de Decisão Clínica , Interface Usuário-Computador , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/diagnóstico por imagem
5.
Cancers (Basel) ; 16(4)2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38398162

RESUMO

BACKGROUND: ALPPS popularity is increasing among surgeons worldwide and its indications are expanding to cure patients with primarily unresectable liver tumors. Few reports recommended limitations or even contraindications of ALPPS in perihilar cholangiocarcinoma (phCC). Here, we discuss the results of ALPPS in patients with phCC in a systematic review as well as a pooled data analysis. METHODS: MEDLINE and Web of Science databases were systematically searched for relevant literature up to December 2023. All studies reporting ALPPS in the management of phCC were included. A single-arm meta-analysis of proportions was carried out to estimate the overall rate of outcomes. RESULTS: After obtaining 207 articles from the primary search, data of 18 studies containing 112 phCC patients were included in our systematic review. Rates of major morbidity and mortality were calculated to be 43% and 22%, respectively. The meta-analysis revealed a PHLF rate of 23%. One-year disease-free survival was 65% and one-year overall survival was 69%. CONCLUSIONS: ALPPS provides a good chance of cure for patients with phCC in comparison to alternative treatment options, but at the expense of debatable morbidity and mortality. With refinement of the surgical technique and better perioperative patient management, the results of ALPPS in patients with phCC were improved.

6.
Cancers (Basel) ; 15(23)2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38067316

RESUMO

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a two-stage procedure that can potentially cure patients with large cholangiocarcinoma. The current study evaluates the impact of modifications on the outcomes of ALPPS in patients with cholangiocarcinoma. In this single-center study, a series of 30 consecutive patients with cholangiocarcinoma (22 extrahepatic and 8 intrahepatic) who underwent ALPPS between 2011 and 2021 was evaluated. The ALPPS procedure in our center was modified in 2016 by minimizing the first stage of the surgical procedure through biliary externalization after the first stage, antibiotic administration during the interstage phase, and performing biliary reconstructions during the second stage. The rate of postoperative major morbidity and 90-day mortality, as well as the one- and three-year disease-free and overall survival rates were calculated and compared between patients operated before and after 2016. The ALPPS risk score before the second stage of the procedure was lower in patients who were operated on after 2016 (before 2016: median 6.4; after 2016: median 4.4; p = 0.010). Major morbidity decreased from 42.9% before 2016 to 31.3% after 2016, and the 90-day mortality rate decreased from 35.7% before 2016 to 12.5% after 2016. The three-year survival rate increased from 40.8% before 2016 to 73.4% after 2016. Our modified ALPPS procedure improved perioperative and postoperative outcomes in patients with extrahepatic and intrahepatic cholangiocarcinoma. Minimizing the first step of the ALPPS procedure was key to these improvements.

7.
Eur J Surg Oncol ; 49(11): 107080, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37738873

RESUMO

INTRODUCTION: Outcomes of major surgeries in tertiary educational hospitals have been complicated by the referral of high-risk patients and the participation of trainees in surgical procedures. We analyzed outcomes of major hepatectomies in a tertiary academic setting emphasizing the role of training and obesity on textbook outcomes (TO). MATERIALS AND METHODS: 971 adult patients who underwent open major hepatectomy (Mesohepatectomy [n = 111], hemihepatectomy [n = 610], and extended hepatectomy [n = 250]) were evaluated. A TO was defined as: a negative resection margin, no grade B/C bile leak, no major complications, no in-hospital mortality, and no 30-day readmission. TOs were compared following operations performed by senior surgeons and those performed by junior surgeons under the supervision of senior surgeons and between patients with and without obesity. RESULTS: TO was achieved in 70.1% of patients overall (78.4% in mesohepatectomy, 73.1% in hemihepatectomy, and 59.2% in extended hepatectomy). The rate of TO was similar following operations performed by and supervised by a senior surgeon (69.3% vs 71.0%, p = 0.570). The rate of TO was significantly lower in patients with obesity (41.5% vs 74.6%, p < 0.001). Factors including increased age (odds ratio [OR] for 10-year increase = 0.83, 95% confidence interval [CI]: 0.73-0.96, p = 0.009), obesity (OR = 0.25, 95%CI: 0.16-0.37, p < 0.001), biliodigestive anastomosis (OR = 0.27, 95%CI: 0.19-0.40, p < 0.001), and portal vein resection (OR = 0.49, 95%CI: 0.28-0.87, p = 0.014) lower the rate of TO. CONCLUSION: Promising outcomes are possible after major hepatectomy in an academic setting. Obese patients and those undergoing more complex surgeries had a higher risk of poor postoperative outcomes.


Assuntos
Neoplasias Hepáticas , Fígado , Adulto , Humanos , Hepatectomia/métodos , Obesidade/complicações , Obesidade/epidemiologia , Veia Porta , Encaminhamento e Consulta , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Neoplasias Hepáticas/cirurgia , Resultado do Tratamento
8.
Cancer Med ; 12(19): 19548-19559, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37737550

RESUMO

BACKGROUND: Statins, metformin, and aspirin have been reported to reduce the incidence of hepatocellular carcinoma (HCC). However, the effect of their perioperative use on survival outcomes of HCC patients following curative liver resection still remains unclear. METHOD: Three hundred and fifty three patients with a first diagnosis of HCC who underwent curative liver resection were included. Propensity score matching analysis with a users: nonusers ratio of 1:2 were performed for each of the medications (statins, metformin, and aspirin). Overall survival (OS) and recurrence-free survival (RFS) were evaluated and multivariable Cox proportional hazard analysis was performed. RESULTS: Sixty two patients received statins, 48 patients used metformin, and 53 patients received aspirin for ≥90 days before surgery. None of the medications improved OS. RFS of statin users was significantly longer than that of nonusers (p = 0.021) in the matched cohort. Users of hydrophilic statins, but not lipophilic ones had a significantly longer RFS than nonusers. Multivariable analysis showed that statin use significantly improved RFS (hazard ratio [HR]: 0.41, 95% confidence interval [CI]: 0.17-0.97, p = 0.044). No difference was seen in RFS between metformin users and nonusers. Among patients with diabetes, RFS was nonsignificantly longer in metformin users than in non-metformin users (84.1% vs. 60.85%, p = 0.069) in the matched cohort. No difference in postoperative RFS was seen between aspirin users and nonusers. CONCLUSION: Preoperative use of statins in patients with HCC can increase RFS after curative liver resection, but metformin and aspirin were not associated with improved survival. Randomized controlled trials are needed to confirm the findings of the present study.


Assuntos
Carcinoma Hepatocelular , Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias Hepáticas , Metformina , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Metformina/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Pontuação de Propensão , Aspirina/efeitos adversos , Estudos Retrospectivos , Hepatectomia/efeitos adversos
9.
J Robot Surg ; 17(5): 2513-2526, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37531044

RESUMO

The use of robots in donor nephrectomy has increased in recent years. However, whether robot-assisted methods have better outcomes than traditional laparoscopic methods and how surgical experience influences these outcomes remains unclear. This meta-analysis compares the outcomes of robot-assisted donor nephrectomy (RADN) with those of laparoscopic donor nephrectomy (LDN) and to investigate the effects of surgical experience on these outcomes. A systematic literature search was conducted in Medline (through PubMed) and Web of Science databases. Perioperative data were extracted for meta-analysis. To assess the impact of the learning curve, a subgroup analysis was performed to compare outcomes between inexperienced and experienced surgeons. Seventeen studies with 6970 donors were included. Blood loss was lower (mean difference [MD] = - 13.28, p < 0.01) and the warm ischemia time was shorter (MD = - 0.13, p < 0.05) in the LDN group than the RADN group. There were no significant differences in terms of conversion to open surgery, operation time, surgical complications, hospital stay, costs, and delayed graft function between the groups. Subgroup analysis revealed that operation time (MD = - 1.09, p < 0.01) and length of hospital stay (MD = - 1.54, p < 0.05) were shorter and the rate of conversion to open surgery (odds ratios [OR] = 0.14, p < 0.0001) and overall surgical complications (OR = 0.23, p < 0.05) were lower in experienced RADN surgeons than in experienced LDN surgeons. Surgical experience enhances the perioperative outcomes following RADN more than it does following LDN. This suggests that RADN could be the method of choice for living donor nephrectomy as soon as surgeons gain sufficient experience in robotic surgery.


Assuntos
Transplante de Rim , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Doadores Vivos , Curva de Aprendizado , Nefrectomia/métodos , Transplante de Rim/métodos , Resultado do Tratamento , Procedimentos Cirúrgicos Robóticos/métodos , Laparoscopia/métodos , Tempo de Internação , Estudos Retrospectivos
11.
HPB (Oxford) ; 25(8): 907-914, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37149487

RESUMO

BACKGROUND: The present study evaluates the impact of the pandemic on outcomes after surgical treatment for primary liver cancer in a high-volume hepatopancreatobiliary surgery center. METHODS: Patients, who underwent liver resection for primary liver resection between January 2019 and February 2020, comprised pre-pandemic control group. The pandemic period was divided into two timeframes: early pandemic (March 2020-January 2021) and late pandemic (February 2021-December 2021). Liver resections during 2022 were considered as the post-pandemic period. Peri-, and postoperative patient data were gathered from a prospectively maintained database. RESULTS: Two-hundred-eighty-one patients underwent liver resection for primary liver cancer. The number of procedures decreased by 37.1% during early phase of pandemic, but then increased by 66.7% during late phase, which was comparable to post-pandemic phase. Postoperative outcomes were similar between four phases. The duration of hospital stay was longer during the late phase, but not significantly different compared to other groups. CONCLUSION: Despite an initial reduction in number of surgeries, COVID-19 pandemic had no negative effect on outcomes of surgical treatment for primary liver cancer. The structured standard operating protocol in a high-volume and highly specialized surgical center can withstand negative effects, a pandemic may have on treatment of patients.


Assuntos
COVID-19 , Neoplasias Hepáticas , Humanos , COVID-19/epidemiologia , Pandemias , Bases de Dados Factuais , Padrões de Referência , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/cirurgia
12.
Cancers (Basel) ; 15(5)2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36900157

RESUMO

BACKGROUND: Liver transplantation is the only promising treatment for end-stage liver disease and patients with hepatocellular carcinoma. However, too many organs are rejected for transplantation. METHODS: We analyzed the factors involved in organ allocation in our transplant center and reviewed all livers that were declined for transplantation. Reasons for declining organs for transplantation were categorized as major extended donor criteria (maEDC), size mismatch and vascular problems, medical reasons and risk of disease transmission, and other reasons. The fate of the declined organs was analyzed. RESULTS: 1086 declined organs were offered 1200 times. A total of 31% of the livers were declined because of maEDC, 35.5% because of size mismatch and vascular problems, 15.8% because of medical reasons and risk of disease transmission, and 20.7% because of other reasons. A total of 40% of the declined organs were allocated and transplanted. A total of 50% of the organs were completely discarded, and significantly more of these grafts had maEDC than grafts that were eventually allocated (37.5% vs. 17.7%, p < 0.001). CONCLUSION: Most organs were declined because of poor organ quality. Donor-recipient matching at time of allocation and organ preservation must be improved by allocating maEDC grafts using individualized algorithms that avoid high-risk donor-recipient combinations and unnecessary organ declination.

13.
Front Med (Lausanne) ; 9: 1043674, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36523786

RESUMO

Background: Use of intraoperative prothrombin complex concentrates (PCC) and fibrinogen concentrate administration has been linked to thrombotic events. However, it is unknown if its use is associated with thrombotic events after liver transplant. Methods and analysis: We conducted a post hoc analysis of a prospectively conducted registry database study on patients who underwent liver transplant between 2004 and 2017 at Heidelberg University Hospital, Heidelberg, Germany. Univariate and multivariate analyses were used to determine the association between PCC and fibrinogen concentrate administration and thrombotic complications. Results: Data from 939 transplantations were included in the analysis. Perioperative PCC or fibrinogen administration was independently associated with the primary composite endpoint Hepatic artery thrombosis (HAT), Portal vein thrombosis (PVT), and inferior vena cava thrombosis [adjusted HR: 2.018 (1.174; 3.468), p = 0.011]. PCC or fibrinogen administration was associated with the secondary endpoints 30-day mortality (OR 4.225, p < 0.001), graft failure (OR 3.093, p < 0.001), intraoperative blood loss, red blood cell concentrate, fresh frozen plasma and platelet transfusion, longer hospitalization, and longer length of stay in intensive care units (ICUs) (all p < 0.001). PCC or fibrinogen administration were not associated with pulmonary embolism, myocardial infarction, stroke, or deep vein thrombosis within 30 days after surgery. Conclusion: A critical review of established strategies in coagulation management during liver transplantation is warranted. Perioperative caregivers should exercise caution when administering coagulation factor concentrate during liver transplant surgery. Prospective randomized controlled trials are needed to establish causality for the relationship between coagulation factors and thrombotic events in liver transplantation. Further studies should be tailored to identify patient subgroups that will likely benefit from PCC or fibrinogen administration.

14.
J Hepatocell Carcinoma ; 9: 1137-1147, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338431

RESUMO

Purpose: Although surgery is associated with an acceptable cure rate, tumor recurrence is still a challenging issue in hepatocellular carcinoma (HCC) patients. Red blood cell distribution width (RDW) is considered an inflammatory marker for predicting overall mortality in a wide spectrum of malignancies. In the current study, the prognostic role of pre- and postoperative RDW in HCC recurrence after liver resection (LRx) is investigated. Patients and Methods: In 395 patients, RDW levels were evaluated preoperatively as well as six and twelve months after curative LRx. The RDW cutoff values were determined using receiver operating characteristic curves (ROCs) according to the recurrence-free survival (RFS). Survival analyses were performed using the Kaplan-Meier, and differences were compared using the Log rank test. Results: The RFS was significantly higher among patients with low RDW at the 6th month and 12th month, postoperatively (P < 0.001 and P = 0.028). RDW levels of higher than 16.15% at the 6th (HR: 2.047, P <0.001) and higher than 15.85% at 12th (HR: 3.105, P < 0.002) months after liver resection were independent predictors of RFS. Conclusion: Postoperative RDW values seem to be predictive of tumor recurrence in HCC patients. RDW levels at the 6th and 12th months postoperatively were independent predictors of recurrence after LRx.

16.
J Am Coll Surg ; 235(2): 257-266, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35839400

RESUMO

BACKGROUND: Mesohepatectomy is a viable treatment option for patients diagnosed with centrally located liver tumors (CLLTs). There are several reports from Eastern centers, but few data are available on this topic from Western centers. STUDY DESIGN: Data of 128 consecutive patients who underwent mesohepatectomy between September 2000 and September 2020 in our center were analyzed from a prospectively collected database. Patient demographic data, liver tumor characteristics, and intraoperative data were collected. In addition, posthepatectomy bile leakage (PHBL), posthepatectomy hemorrhage (PHH), posthepatectomy liver failure (PHLF), and 90-day mortality after mesohepatectomy were assessed. Long-term outcomes were also reported, and factors that may influence disease-free survival were evaluated. RESULTS: Of 128 patients, 113 patients (88.3%) had malignant hepatic tumors (primary and metastatic tumors in 41 [32%] and 72 [56.3%] patients, respectively), and 15 patients suffered from benign lesions (11.7%). Among the relevant surgical complications (grade B or C), PHBL was the most common complication after mesohepatectomy and occurred in 11.7% of patients, followed by PHLF in 3.1% of patients and PHH in 2.3% of patients. Only four patients (3.1%) died within 90 days after mesohepatectomy. The 5-year overall survival and overall recurrence (for malignant lesion) rates were 76.5% and 45.1%, respectively. CONCLUSION: Mesohepatectomy is a safe and feasible surgical treatment with low morbidity and mortality for patients with CLLT. Long-term outcomes can be improved by increased surgical expertise.


Assuntos
Carcinoma Hepatocelular , Falência Hepática , Neoplasias Hepáticas , Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Humanos , Falência Hepática/cirurgia , Estudos Retrospectivos
17.
Br J Surg ; 109(7): 580-587, 2022 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-35482020

RESUMO

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a relatively rare malignancy. The aim of this meta-analysis was to evaluate outcomes of repeat liver resection and non-surgical approaches for treatment of recurrent ICC. METHODS: PubMed, Embase, and Web of Science databases were searched from their inception until March 2021 for studies of patients with recurrent ICC. Studies not published in English were excluded. Two meta-analyses were performed: a single-arm meta-analysis of studies reporting pooled short- and long-term outcomes after repeat liver resection for recurrent ICC (meta-analysis A), and a meta-analysis of studies comparing 1-, 3-, and 5-year overall survival (OS) rates after repeat liver resection and non-surgical approaches for recurrent ICC (meta-analysis B). RESULTS: Of 543 articles retrieved in the search, 28 were eligible for inclusion. Twenty-four studies (390 patients) were included in meta-analysis A and nine studies (591 patients) in meta-analysis B. After repeat liver resection, 1-, 3-, and 5-year OS rates were 87 (95 per cent c.i. 81 to 91), 58 (48 to 68), and 39 (29 to 50) per cent respectively. The 1-, 3-, and 5-year OS rates were higher after repeat liver resection than without surgery: odds ratio 2.70 (95 per cent c.i. 1.28 to 5.68), 2.89 (1.15 to 7.27), and 5.91 (1.59, 21.90) respectively. CONCLUSION: Repeat liver resection is a suitable strategy for recurrent ICC in selected patients. It improves short- and long-term outcomes compared with non-surgical treatments.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/cirurgia , Hepatectomia , Humanos , Recidiva Local de Neoplasia , Estudos Retrospectivos
18.
Basic Clin Pharmacol Toxicol ; 130(4): 542-552, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35040273

RESUMO

Pancreatic surgery is complicated by untreated fluid leakage, but no tenable techniques exist to detect and close leakage sites during surgery. A novel hydrogel called SmartPAN has been developed to meet this need and is here assessed for safety before trials on human patients. First, resazurin assays were used to test the cytotoxic effects of SmartPAN's active bromothymol blue (BTB) indicator and its solution of phosphate-buffered saline (PBS) on normal (HPDE: human pancreatic duct epithelial) or carcinomic (FAMPAC) human pancreatic cells. Cells incubated with BTB showed no significant reduction in cell viability below threshold safety levels. However, PBS had a mild cytotoxic effect on FAMPAC cells. Second, SmartPAN's pathological effects were evaluated in vivo by applying 4-ml SmartPAN to a porcine (Sus scrofa domesticus) model of pancreatic resection. There were no significant differences in macroscopic and microscopic pathologies between pigs treated with SmartPAN or saline. Third, measurements using HPLC-MS/MS demonstrate that BTB does not cross into the bloodstream and was eliminated from the body within 2 days of surgery. Overall, SmartPAN appears safe in the short term and ready for first-in-human trials because its components are either biocompatible or quickly neutralized by dilution and drainage.


Assuntos
Fístula Pancreática , Espectrometria de Massas em Tandem , Drenagem/efeitos adversos , Drenagem/métodos , Humanos , Pâncreas/cirurgia , Fístula Pancreática/complicações , Fístula Pancreática/etiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Fatores de Risco
19.
J Cell Biol ; 221(1)2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34860252

RESUMO

Transforming growth factor ß (TGF-ß) signaling plays a fundamental role in metazoan development and tissue homeostasis. However, the molecular mechanisms concerning the ubiquitin-related dynamic regulation of TGF-ß signaling are not thoroughly understood. Using a combination of proteomics and an siRNA screen, we identify pVHL as an E3 ligase for SMAD3 ubiquitination. We show that pVHL directly interacts with conserved lysine and proline residues in the MH2 domain of SMAD3, triggering degradation. As a result, the level of pVHL expression negatively correlates with the expression and activity of SMAD3 in cells, Drosophila wing, and patient tissues. In Drosophila, loss of pVHL leads to the up-regulation of TGF-ß targets visible in a downward wing blade phenotype, which is rescued by inhibition of SMAD activity. Drosophila pVHL expression exhibited ectopic veinlets and reduced wing growth in a similar manner as upon loss of TGF-ß/SMAD signaling. Thus, our study demonstrates a conserved role of pVHL in the regulation of TGF-ß/SMAD3 signaling in human cells and Drosophila wing development.


Assuntos
Proteólise , Transdução de Sinais , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Animais , Drosophila melanogaster/metabolismo , Células HCT116 , Células HeLa , Humanos , Ligação Proteica , Domínios Proteicos , Proteína Smad2/metabolismo , Proteína Smad3/química , Ubiquitina-Proteína Ligases/metabolismo
20.
Ann Surg Open ; 3(4): e221, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37600287

RESUMO

To compare the outcomes of modified-Associating Liver Partition and Portal vein Ligation for Staged hepatectomy (ALPPS) techniques with those of conventional-ALPPS. Background: ALPPS is an established technique for treating advanced liver tumors. Methods: PubMed, Web of Science, and Cochrane databases were searched. The outcomes were assessed by single-arm and 2-arm analyses. Results: Seventeen studies containing 335 modified-ALPPS patients were included in single-arm meta-analysis. The estimated blood loss was 267 ± 29 mL (95% confidence interval [CI], 210-324 mL) during the first and 662 ± 51 mL (95% CI, 562-762 mL) during the second stage. The operation time was 166 ± 18 minutes (95% CI, 131-202 minutes) during the first and 225 ± 19 minutes (95% CI, 188-263 minutes) during the second stage. The major morbidity rate was 14% (95% CI, 9%-22%) after the first stage. The future liver remnant hypertrophy rate was 65.2% ± 5% (95% CI, 55%-75%) and the interstage interval was 16 ± 1 days (95% CI, 14-17 days). The dropout rate was 9% (95% CI, 5%-15%). The overall complication rate was 46% (95% CI, 37%-56%) and the major complication rate was 20% (95% CI, 14%-26%). The postoperative mortality rate was 7% (95% CI, 4%-11%). Seven studies containing 215 patients were included in comparative analysis. The hypertrophy rate was not different between 2 methods (mean difference [MD], -5.01; 95% CI, -19.16 to 9.14; P = 0.49). The interstage interval was shorter for partial-ALPPS (MD, 9.43; 95% CI, 3.29-15.58; P = 0.003). The overall complication rate (odds ratio [OR], 10.10; 95% CI, 2.11-48.35; P = 0.004) and mortality rate (OR, 3.74; 95% CI, 1.36-10.26; P = 0.01) were higher in the conventional-ALPPS. Conclusions: The hypertrophy rate in partial-ALPPS was similar to conventional-ALPPS. This shows that minimizing the first stage of the operation does not affect hypertrophy. Moreover, the postoperative overall morbidity and mortality rates were lower following partial-ALPPS.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA