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1.
Eur J Surg Oncol ; 50(4): 108010, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38394988

RESUMO

INTRODUCTION: The clinical role of lymphadenectomy (LAD) as part of hepatic resection for malignancies of the liver remains unclear. In this study, we aimed to report on the use cases and postoperative outcomes of liver resection and simultaneous LAD for hepatic malignancies (HM). MATERIALS AND METHODS: Clinicopathological data from patients who underwent surgery at 13 German centers from 2017 to 2022 (n = 3456) was extracted from the StuDoQ|Liver registry of the German Society of General and Visceral Surgery. Propensity-score matching (PSM) was performed to account for the extent of liver resection and patient demographics. RESULTS: LAD was performed in 545 (16%) cases. The most common indication for LAD was cholangiocarcinoma (CCA), followed by colorectal liver metastases (CRLM) and hepatocellular carcinoma (HCC). N+ status was found in 7 (8%), 59 (35%), and 56 cases (35%) for HCC, CCA, and CRLM, respectively (p < 0.001). The LAD rate was highest for robotic-assisted resections (28%) followed by open (26%) and laparoscopic resections (13%), whereas the number of resected lymph nodes was equivalent between the techniques (p = 0.303). LAD was associated with an increased risk of liver-specific postoperative complications, especially for patients with HCC. CONCLUSION: In this multicenter registry study, LAD was found to be associated with an increased risk of liver-specific complications. The highest rate of LAD was observed among robotic liver resections.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Colorretais , Laparoscopia , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/secundário , Neoplasias Colorretais/patologia , Estudos Retrospectivos , Hepatectomia/métodos , Colangiocarcinoma/cirurgia , Laparoscopia/métodos , Excisão de Linfonodo , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/cirurgia , Sistema de Registros , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Pontuação de Propensão
2.
J Laparoendosc Adv Surg Tech A ; 34(2): 99-105, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38294895

RESUMO

Background: Intraoperative blood loss has an unfavorable impact on the outcome of patients undergoing liver surgery. Today, the use of devices capable of minimizing this risk with high technical performance becomes mandatory. Into this scenario fits the CUSA® Clarity Ultrasonic Surgical Aspirator System. This prospective survey involving five liver surgery centers had the objective of investigating whether this innovative ultrasonic surgical aspirator is safe and effective in the transection of the liver parenchyma. Materials and Methods: This clinical study was a prospective, multicenter, single-arm Post-Market Clinical Follow-up study investigating 100 subjects who underwent liver surgery using the CUSA Clarity Ultrasonic Surgical Aspirator System at five centers during a period of 1 year and 8 months. After collecting all the patient's clinical information and instrument usage details, surgeons completed a brief survey giving their opinions on the performance of CUSA. Therefore, safety and efficacy outcomes were evaluated. Results: Surgeons had a 95% success rate in complete removal of the mass with an average overall operative time of 4 hours and 34 minutes. Overall, there were no complications or device deficiencies. Conclusion: The CUSA Clarity Ultrasonic Surgical Aspirator System performs well during liver surgery with a low complication rate. ClinicalTrials.gov Identifier: NCT04298268.


Assuntos
Hepatectomia , Ultrassom , Humanos , Seguimentos , Hepatectomia/efeitos adversos , Fígado/cirurgia , Estudos Prospectivos
3.
Ann Surg Open ; 4(4): e350, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38144486

RESUMO

Objective: To compare the outcome of minimally invasive liver surgery (MILS) to open liver surgery (OLS) for resection of colorectal liver metastases (CRLM) on a nationwide level. Background: Colorectal cancer is the third most common malignancy worldwide. Up to 50% of all patients with colorectal cancer develop CRLM. MILS represents an attractive alternative to OLS for treatment of CRLM. Methods: Retrospective cohort study using the prospectively recorded German Quality management registry for liver surgery. Propensity-score matching was performed to account for variance in the extent of resection and patient demographics. Results: In total, 1037 patients underwent liver resection for CRLM from 2019 to 2021. MILS was performed in 31%. Operative time was significantly longer in MILS (234 vs 222 minutes, P = 0.02) compared with OLS. After MILS, median length of hospital stay (LOS) was significantly shorter (7 vs 10 days; P < 0.001). Despite 76% of major resections being OLS, postoperative complications and 90-day morbidity and mortality did not differ. The Pringle maneuver was more frequently used in MILS (48% vs 40%, P = 0.048). After propensity-score matching for age, body mass index, Eastern Cooperative Oncology Group, and extent of resection, LOS remained shorter in the MILS cohort (6 vs 10 days, P < 0.001) and operative time did not differ significantly (P = 0.2). Conclusion: MILS is not the standard for resection of CRLM in Germany. Drawbacks, such as a longer operative time remain. However, if technically possible, MILS is a reasonable alternative to OLS for resection of CRLM, with comparable postoperative complications, reduced LOS, and equal oncological radicality.

5.
Ann Surg Oncol ; 30(4): 2497-2505, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36400887

RESUMO

OBJECTIVE: The aim of this study was to evaluate the feasibility and perioperative safety of high-pressure/high-dose pressurized intraperitoneal aerosol chemotherapy (HP/HD-PIPAC) to manage peritoneal surface malignancies (PSM). METHODS: Retrospective analysis of a prospective database of about 130 consecutive patients scheduled for HP/HD-PIPACs for PSM. Doxorubicin plus cisplatin (PIPAC-C/D) or oxaliplatin (PIPAC-Ox) were nebulized into a constant capnoperitoneum of 20 mmHg at doses of 6, 30, or 120 mg/m2 of body surface area (BSA). Outcome criteria were perioperative complications (Clavien-Dindo). RESULTS: The median age of patients was 62 years (range 9-82), and the primary tumor site was of colorectal (CRC), upper gastrointestinal tract (UGI), unknown primary (CUP), malignant epithelioid mesothelioma of the peritoneum (MPM), hepato-pancreatic-biliary tract (HPB), and other origin in 30 (23.1%), 27 (20.8%), 16 (12.3%), 16 (12.3%), 6 (4.6%), and 35 (26.9%) patients, respectively. Abdominal access failed for a first, second, third, and fourth or more HP/HD-PIPAC in 12/130 (9.2%), 4/64 (6.3%), 6/40 (15.0%), and 2/33 (6.1%) patients. A total of 243 procedures were performed in 118 patients. No intraoperative complications related to increased capnoperitoneal pressure occurred, but an intraoperative bleeding complication was observed in 1/243 (0.4%) patients. The overall rate of postoperative procedure-related complications was 19.3% (47/243), while 15.3% (37/243), 1.6% (6/243), 1.6% (1/243), 0.4% (1/243), and 0.4% (1/243) were Grade I, II, III, IV, and V complications, respectively. CONCLUSIONS: Perioperative complications of HP/HD-PIPAC are comparable with standard pressure/dose PIPAC treatment protocols. Prospective studies are warranted to examine potential improvement in therapy outcomes.


Assuntos
Mesotelioma Maligno , Neoplasias Peritoneais , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Estudos Retrospectivos , Estudos de Viabilidade , Aerossóis e Gotículas Respiratórios
6.
J Pathol ; 255(3): 270-284, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34309874

RESUMO

Activation of the mechanistic target of rapamycin (mTOR) pathway is frequently found in cancer, but mTOR inhibitors have thus far failed to demonstrate significant antiproliferative efficacy in the majority of cancer types. Besides cancer cell-intrinsic resistance mechanisms, it is conceivable that mTOR inhibitors impact on non-malignant host cells in a manner that ultimately supports resistance of cancer cells. Against this background, we sought to analyze the functional consequences of mTOR inhibition in hepatocytes for the growth of metastatic colon cancer. To this end, we established liver epithelial cell (LEC)-specific knockout (KO) of mTOR (mTORLEC ) mice. We used these mice to characterize the growth of colorectal liver metastases with or without partial hepatectomy to model different clinical settings. Although the LEC-specific loss of mTOR remained without effect on metastasis growth in intact liver, partial liver resection resulted in the formation of larger metastases in mTORLEC mice compared with wildtype controls. This was accompanied by significantly enhanced inflammatory activity in LEC-specific mTOR KO livers after partial liver resection. Analysis of NF-ĸB target gene expression and immunohistochemistry of p65 displayed a significant activation of NF-ĸB in mTORLEC mice, suggesting a functional importance of this pathway for the observed inflammatory phenotype. Taken together, we show an unexpected acceleration of liver metastases upon deletion of mTOR in LECs. Our results support the notion that non-malignant host cells can contribute to resistance against mTOR inhibitors and encourage testing whether anti-inflammatory drugs are able to improve the efficacy of mTOR inhibitors for cancer therapy. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.


Assuntos
Neoplasias do Colo/patologia , Hepatócitos/metabolismo , Neoplasias Hepáticas/secundário , Serina-Treonina Quinases TOR/metabolismo , Animais , Neoplasias Hepáticas/metabolismo , Camundongos , Camundongos Knockout , Metástase Neoplásica/patologia
7.
Case Rep Gastroenterol ; 14(3): 658-667, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33442346

RESUMO

Combined hepatocellular-cholangiocarcinoma (cHCC/CCA) represents a rare type of primary liver cancer with a very limited prognosis. Although just recently genomic studies have contributed to a better understanding of the disease's genetic landscape, therapeutic options, especially for advanced-stage patients, are limited and often experimental, as no standardized treatment protocols have been established to date. Here, we report the case of a 38-year-old male patient who was diagnosed with extensive intrahepatic cHCC/CCA in an otherwise healthy liver without signs of chronic liver disease. An interdisciplinary stepwise therapeutic approach including locoregional liver-targeted therapy, systemic chemotherapy, liver transplantation, surgical pulmonary metastasis resection, and next-generation sequencing-based targeted therapy led to a prolonged overall survival beyond 5 years with an excellent quality of life. This case report comprises several provocative treatment decisions that are extensively discussed in light of the existing literature on this rare but highly aggressive malignancy.

8.
Ann Med Surg (Lond) ; 25: 6-11, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29326811

RESUMO

BACKGROUND: Liver failure remains a life-threatening complication after liver resection, and is difficult to predict preoperatively. This retrospective cohort study evaluated different preoperative factors in regard to their impact on posthepatectomy liver failure (PHLF) after extended liver resection and previous portal vein embolization (PVE). METHODS: Patient characteristics, liver function and liver volumes of patients undergoing PVE and subsequent liver resection were analyzed. Liver function was determined by the LiMAx test (enzymatic capacity of cytochrome P450 1A2). Factors associated with the primary end point PHLF (according to ISGLS definition) were identified through multivariable analysis. Secondary end points were 30-day mortality and morbidity. RESULTS: 95 patients received PVE, of which 64 patients underwent major liver resection. PHLF occurred in 7 patients (11%). Calculated postoperative liver function was significantly lower in patients with PHLF than in patients without PHLF (67 vs. 109 µg/kg/h; p = 0.01). Other factors associated with PHLF by univariable analysis were age, future liver remnant, MELD score, ASA score, renal insufficiency and heart insufficiency. By multivariable analysis, future liver remnant was the only factor significantly associated with PHLF (p = 0.03). Mortality and morbidity rates were 4.7% and 29.7% respectively. CONCLUSION: Future liver remnant is the only preoperative factor with a significant impact on PHLF. Assessment of preoperative liver function may additionally help identify patients at risk for PHLF.

9.
Int J Nanomedicine ; 12: 5933-5940, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28860758

RESUMO

Superparamagnetic iron oxide nanoparticles (SPION) may be used for local tumor treatment by coupling them to a drug and accumulating them locally with magnetic field traps, that is, a combination of permanent magnets and coils. Thereafter, an alternating magnetic field generates heat which may be used to release the thermosensitively bound drug and for hyperthermia. Until today, only superficial tumors can be treated with this method. Our aim was to transfer this method into an endoscopic setting to also reach the majority of tumors located inside the body. To find the ideal endoscopic magnetic field trap, which accumulates the most SPION, we first developed a biophysical model considering anatomical as well as physical conditions. Entities of choice were esophageal and prostate cancer. The magnetic susceptibilities of different porcine and rat tissues were measured with a superconducting quantum interference device. All tissues showed diamagnetic behavior. The evaluation of clinical data (computed tomography scan, endosonography, surgical reports, pathological evaluation) of patients gave insight into the topographical relationship between the tumor and its surroundings. Both were used to establish the biophysical model of the tumors and their surroundings, closely mirroring the clinical situation, in which we could virtually design, place and evaluate different electromagnetic coil configurations to find optimized magnetic field traps for each tumor entity. By simulation, we could show that the efficiency of the magnetic field traps can be enhanced by 38-fold for prostate and 8-fold for esophageal cancer. Therefore, our approach of endoscopic targeting is an improvement of the magnetic drug-targeting setups for SPION tumor therapy as it holds the possibility of reaching tumors inside the body in a minimal-invasive way. Future animal experiments must prove these findings in vivo.


Assuntos
Biofísica/métodos , Sistemas de Liberação de Medicamentos/métodos , Endoscopia/métodos , Nanopartículas de Magnetita/administração & dosagem , Modelos Teóricos , Animais , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/tratamento farmacológico , Compostos Férricos/administração & dosagem , Humanos , Campos Magnéticos , Masculino , Neoplasias/tratamento farmacológico , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/tratamento farmacológico , Ratos , Suínos , Tomografia Computadorizada por Raios X
10.
J Hepatol ; 67(4): 749-757, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28668580

RESUMO

BACKGROUND & AIMS: Cholangiocarcinoma (CCA) represents a primary hepatic malignancy with incidence and mortality rising globally. Surgical treatment has remained the only potentially curative treatment option, but it is still unclear which patients benefit most from extended liver surgery, highlighting the need for new pre-operative stratification strategies. Osteopontin is a secreted extracellular glyco-phosphoprotein that has been associated with inflammation, metabolic disorders and cancer. Here, we examined the potential of circulating osteopontin serum levels as a diagnostic or prognostic biomarker in patients with CCA undergoing extended liver surgery. METHODS: Osteopontin expression levels were analysed in human and murine CCA tumour samples, using semi-quantitative reverse transcriptase PCR and immunohistochemistry. Osteopontin serum concentrations were measured by enzyme-linked immunosorbent assay in 107 patients with CCA undergoing elective tumour resection as well as 55 healthy controls. Results were correlated with clinical data. RESULTS: Correlating with an upregulation in CCA tumour cells and the tumour stroma, serum levels of osteopontin were elevated in patients with cholangiocarcinoma compared to healthy controls and patients with primary sclerosing cholangitis. Importantly, pre- and postoperative elevations of osteopontin showed a striking association with poor postoperative survival. CONCLUSIONS: Serum osteopontin concentrations represent a promising prognostic biomarker in patients resectable CCA which could help to guide preoperative treatment decisions and to identify patients that will particularly benefit from extended liver surgery. Lay summary: Extended liver surgery is the only potentially curative treatment for patients with cholangiocarcinoma (CCA/biliary cancer), but it is currently unclear which patients benefit most from surgery. Detecting serum levels of osteopontin - a specific secreted glycoprotein involved in multiple human diseases - in CCA patients might help to identify those patients that particularly benefit from tumour resection.


Assuntos
Neoplasias dos Ductos Biliares/sangue , Biomarcadores Tumorais/sangue , Colangiocarcinoma/sangue , Osteopontina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/cirurgia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Colangiocarcinoma/genética , Colangiocarcinoma/cirurgia , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos , Pessoa de Meia-Idade , Osteopontina/genética , Osteopontina/metabolismo , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo
11.
Hepatobiliary Pancreat Dis Int ; 16(6): 617-623, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-29291781

RESUMO

BACKGROUND: The potential effect of graft steatosis on the postoperative liver function is discussed controversially. The present study aimed to evaluate the effect of the donor liver microvesicular steatosis on the postoperative outcome after liver transplantation. METHODS: Ninety-four patients undergoing liver transplantation at the University Hospital Aachen were included in this study. The patient cohort was divided into three groups according to the grade of microvesicular steatosis (MiS): MiS <30% (n=27), MiS 30%-60% (n=41) and MiS >60% (n=26). The outcomes after liver transplantation were evaluated, including the 30-day and 1-year patient and graft survival rates and the incidences of early allograft dysfunction (EAD) and primary nonfunction (PNF). RESULTS: The incidences of EAD and PNF did not differ significantly between the groups. We observed 5 cases of PNF, one occurred in the MiS <30% group and 4 in the MiS 30%-60% group. The 30-day and 1-year graft survivals did not differ significantly between groups. The 30-day patient survival rates were 100% in all groups. The 1-year patient survival rates were 94.4% in the MiS <30% group, 87.9% in the MiS 30%-60% group and 90.9% in the MiS >60% group. CONCLUSION: Microvesicular steatosis of donor livers has no negative effect on the postoperative outcome after liver transplantation.


Assuntos
Transplante de Fígado/métodos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Doadores de Tecidos , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Feminino , Alemanha/epidemiologia , Sobrevivência de Enxerto , Hospitais Universitários , Humanos , Incidência , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Disfunção Primária do Enxerto/diagnóstico , Disfunção Primária do Enxerto/epidemiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
12.
Z Gastroenterol ; 55(1): 56-62, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27706546

RESUMO

We report the case of a 53-year-old female patient who was transplanted with the liver of a 71-year-old male donor for advanced primary sclerosing cholangitis (PSC) and who additionally was diagnosed with a histologically non-classifiable colitis shortly before transplantation. Upon follow-up abdominal ultrasound 4 months after transplantation, a liver lesion measuring 16 × 23 mm was detected in the transplanted liver. This lesion had not been noticed immediately after transplantation and showed a pattern suspicious for malignancy in contrast-enhanced ultrasound. In line, a biopsy revealed the presence of a metastasis of an adenocarcinoma of colorectal origin, suggesting that a colitis- and PSC-associated colorectal cancer of the recipient might have been overseen upon the initial diagnostic workup. Despite two negative follow-up colonoscopies, this hypothesis was further supported by a strong positive signal in projection to the cecum in a subsequently performed PET/CT-scan. However, surgical resection of the right colon that was performed simultaneously with the atypical resection of the liver metastasis only revealed an inflamed diverticulum but no malignancy in the resected colon segment. Moreover, cytogenetic and molecular genetic testing on the resected specimens clearly attributed the metastasis to the male donor. On the one hand, this case underlines the necessity of endoscopic surveillance of patients with PSC and/or inflammatory bowel disease as well as the challenges in diagnosis of colitis-associated cancer. On the other hand, it shows that the acceptance of organs from elderly donors in times of organ shortage might be linked to an increased risk of donor transmitted malignancies.


Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/secundário , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Transplante de Fígado/efeitos adversos , Equipe de Assistência ao Paciente/organização & administração , Adenocarcinoma/etiologia , Idoso , Diagnóstico Diferencial , Seleção do Doador/métodos , Feminino , Alemanha , Humanos , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Doadores de Tecidos
13.
J Vasc Interv Radiol ; 28(1): 60-63, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28007080

RESUMO

Patients with locally advanced pancreatic cancer who undergo distal pancreatectomy with resection of the celiac axis (CA) are at risk for postoperative hepatic or gastric ischemia if collateral blood flow from the superior mesenteric artery (SMA) via the gastroduodenal artery is insufficient. This study presents a technique for preoperative angiographic evaluation of these collateral vessels by using an AMPLATZER Vascular Plug to temporarily occlude the CA or common hepatic artery while simultaneously performing digital subtraction angiography of the SMA. If collateral vessels are deemed sufficient, the plug can subsequently be released for permanent occlusion with the intent to enhance the blood flow in these collateral vessels.


Assuntos
Artéria Celíaca/cirurgia , Duodeno/irrigação sanguínea , Embolização Terapêutica/métodos , Artéria Hepática , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Circulação Esplâncnica , Estômago/irrigação sanguínea , Idoso , Angiografia Digital , Artéria Celíaca/diagnóstico por imagem , Artéria Celíaca/fisiopatologia , Circulação Colateral , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/instrumentação , Desenho de Equipamento , Feminino , Artéria Hepática/diagnóstico por imagem , Artéria Hepática/fisiopatologia , Humanos , Circulação Hepática , Masculino , Artéria Mesentérica Superior/diagnóstico por imagem , Artéria Mesentérica Superior/fisiopatologia , Pessoa de Meia-Idade , Pancreatectomia/efeitos adversos , Neoplasias Pancreáticas/patologia , Complicações Pós-Operatórias/prevenção & controle , Resultado do Tratamento
14.
J Surg Res ; 206(2): 525-535, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27884351

RESUMO

BACKGROUND: The nuclear factor-erythroid 2-related factor 2 (Nrf2) -antioxidant response element (ARE) pathway is important for the regulation of antioxidative stress response and detoxification. To activate the expression of its target genes, such as heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase (quinone) 1 (NQO1), Nrf2 binds to the ARE within the promoter region of these genes. Partial hepatectomy and consecutive liver regeneration lead to oxidative stress with activation of the Nrf2-ARE pathway. The aim of this study was to investigate ARE activity in vivo during liver regeneration after partial hepatectomy. MATERIALS AND METHODS: Transgenic ARE-luc mice were used. In these mice, the luciferase reporter gene is under the control of an ARE promoter element. Following 2/3 partial hepatectomy (PHx), mice underwent in vivo bioluminescence imaging up until the ninth postoperative day. In addition, liver tissue was analyzed by immunohistochemistry (Nrf2 and HO-1), quantitative reverse transcription-PCR (HO-1 and NQO1) and in vitro luminescence assays. RESULTS: Bioluminescence imaging revealed a significant increase in Nrf2-ARE activity after PHx. The signal maximum was recorded on the third day after PHx. Seven days postoperatively, the signal almost reached baseline levels. In immunohistochemistry, significantly more hepatocytes were positive for Nrf2 and HO-1 on the third postoperative day compared with baseline levels. The mRNA expression of HO-1 and NQO1 were significantly increased on day 3 as measured by qRT-PCR. CONCLUSIONS: This study demonstrated the time-dependent activation of the Nrf2-ARE system during liver regeneration in vivo. The transgenic ARE-luc mouse provided a convenient model for studying Nrf2-mediated gene expression noninvasively and may facilitate further experiments with therapeutic modulation of the antioxidative stress response.


Assuntos
Elementos de Resposta Antioxidante/fisiologia , Heme Oxigenase-1/metabolismo , Hepatectomia , Regeneração Hepática/fisiologia , Proteínas de Membrana/metabolismo , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Biomarcadores/metabolismo , Feminino , Heme Oxigenase-1/genética , Imuno-Histoquímica , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , NAD(P)H Desidrogenase (Quinona)/genética , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo , Período Pós-Operatório , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
15.
Clin Transl Med ; 5(1): 39, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27709523

RESUMO

BACKGROUND: Elevated expression levels of S100A6, a calcium-binding low-molecular-weight protein, were demonstrated in various malignancies. Moreover, increased serum levels of S100A6 were suggested as a novel biomarker for various inflammatory and malignant diseases including lung and gastric cancer. However, up to now, serum concentrations of S100A6 have not been analyzed in patients with cholangiocarcinoma (CCA). METHODS: S100A6 mRNA expression levels were analyzed in human and murine CCA tumor samples, using semi-quantitative reverse transcriptase PCR. S100A6 serum concentrations were measured using an enzyme-linked immunosorbent assay in 112 patients with CCA referred to surgery for curative resection and were compared to those of 42 healthy controls. Results were correlated with clinical data. RESULTS: S100A6 mRNA expression levels were significantly up-regulated in tumor samples of CCA patients and in tumor tissue of a CCA mouse model. In contrast, serum levels of S100A6 were not significantly altered in patients with CCA compared to healthy controls. Whereas no differences became apparent within the different clinical subgroups of CCA, patients with primary sclerosing cholangitis (PSC)-based CCA displayed higher levels of S100A6 compared to the other patients. Nevertheless, patients with higher S100A6 serum concentrations showed a trend towards an impaired prognosis compared to patients with lower levels. Finally, within our cohort of patients both the diagnostic and prognostic potentials of S100A6 were similar to those of the clinically established biomarkers CEA and CA19-9. CONCLUSION: Although S100A6 was expressed at significantly higher levels in human and murine CCA tumor samples, S100A6 serum levels were not regulated in patients with CCA and are thus not suitable for diagnosis of CCA. However, CCA-patients with elevated S100A6 displayed a trend toward an impaired prognosis compared to patients with lower S100A6 levels, supporting its further evaluation as a prognostic biomarker in CCA.

16.
Ann Transplant ; 21: 185-93, 2016 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-27029495

RESUMO

BACKGROUND: Organ shortage is a major problem in liver transplantation. The use of extended criteria donors has become the most important strategy for increasing the donor pool. However, the role of donor body mass index has not yet been thoroughly investigated. The aim of our study was to compare outcomes after liver transplantation in patients who received a liver from a donor with a BMI <30, 30-39, and ≥40, with special regard to the incidence of early allograft dysfunction (EAD) and primary non-function (PNF). MATERIAL AND METHODS: One hundred and sixty-three patients who underwent liver transplantation at the University Hospital Aachen between June 2010 and January 2014 were included in this analysis. The outcome of liver transplantation was evaluated by the 30-day and 1-year patient and graft survival rates and the incidences of post-reperfusion syndrome (PRS), EAD, and PNF. RESULTS: The BMI 30-39 group had a higher incidence of EAD than the BMI <30 and BMI ≥40 groups. We observed 5 cases of PNF in the BMI <30 group. The incidence of acute renal failure was significantly higher in the BMI 30-39 and BMI ≥40 groups than in the BMI <30 group. Patient and graft survival did not differ significantly among the 3 groups. CONCLUSIONS: Based on the findings of this study, grafts from obese donors with a BMI >30 can be safely transplanted. Therefore, the donor pool can be enlarged to include such obese donors without a negative impact on the long-term patient outcome after liver transplantation.


Assuntos
Índice de Massa Corporal , Seleção do Doador/métodos , Transplante de Fígado , Disfunção Primária do Enxerto/etiologia , Doadores de Tecidos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Disfunção Primária do Enxerto/epidemiologia , Estudos Retrospectivos , Adulto Jovem
17.
Viszeralmedizin ; 31(3): 194-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26468315

RESUMO

BACKGROUND: Cholestatic liver diseases (CD) account for 11% of all liver transplantations (LT) in the Eurotransplant region. Despite the excellent long-term outcome that is considerably superior to all other indications for LT, transplant surgeons and physicians face nowadays - in the era of MELD (Model of End-Stage Liver Disease)-based allocation, organ shortage, and extended allocation policies - more and more challenges in this patient cohort, especially since there is no curative medical treatment for these entities. METHODS: Based on a literature review and personal experience in liver transplantation for CD, we show the status quo of indication, allocation, and outcome as well as potential strategies to overcome long waiting times and organ shortage. RESULTS: Concerning graft and patient survival, CD remain the 'best indications' for LT. Since the implementation of MELD-based allocation results in patients with primary sclerosing cholangitis (PSC) could be preserved on good levels only by the implementation and revision of standard exceptions. Recurrence of PSC after LT remains a challenge for transplant surgeons and physicians. New data has kindled a debate on biliary reconstruction in LT for PSC. Promising data on living donor LT motivate to push the boundaries in this direction. CONCLUSION: CD are excellent indications for liver transplantation since excellent long-term outcomes are achievable when the transplant is performed at the right time. The decisions concerning evaluation, listing, and allocation should be made by an interdisciplinary team of gastroenterologists and transplant surgeons.

18.
Exp Clin Transplant ; 13(4): 301-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26295179

RESUMO

Liver transplant is not a standard therapy for cholangiocarcinoma; complete surgical resection of the tumor is currently the treatment of choice. Palliative options offer only short-term survival. After initial recurrence rates after liver transplant for cholangiocarcinoma in the 1990s were unacceptably high, cholangiocarcinoma has been regarded widely as a contraindication to liver transplant. Ubiquitous organ shortage further supports this conviction. Careful patient selection and a rigorous perioperative treatment by radiochemotherapy have produced some impressive survival data in specialized transplant centers in recent years. Although the graft shortage is aggravating in the Western world, the issue of liver transplant as a treatment for irresectable cholangiocarcinoma is being discussed. This review article provides an update and overview on the current status of liver transplant as a potential option for patients with irresectable cholangiocarcinoma.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Transplante de Fígado , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Seleção de Pacientes , Medição de Risco , Fatores de Risco , Doadores de Tecidos/provisão & distribuição , Resultado do Tratamento
19.
J Cachexia Sarcopenia Muscle ; 6(2): 155-63, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26136191

RESUMO

BACKGROUND: Sarcopenia, obesity and sarcopenic obesity have been linked to impaired outcome after liver surgery. Preoperative liver function of sarcopenic, obese and sarcopenic-obese patients might be reduced, possibly leading to more post-operative morbidity. The aim of this study was to explore whether liver function and volume were influenced by body composition in patients undergoing liver resection. METHODS: In 2011 and 2012, all consecutive patients undergoing the methacetin breath liver function test were included. Liver volumetry and muscle mass analysis were performed using preoperative CT scans and Osirix(®) software. Muscle mass and body-fat% were calculated. Predefined cut-off values for sarcopenia and the top two body-fat% quintiles were used to identify sarcopenia and obesity, respectively. Histologic assessment of the resected liver gave insight in background liver disease. RESULTS: A total number of 80 patients were included. Liver function and volume were comparable in sarcopenic(-obese) and non-sarcopenic(-obese) patients. Obese patients showed significantly reduced liver function [295 (95-508) vs. 358 (96-684) µg/kg/h, P = 0.018] and a trend towards larger liver size [1694 (1116-2685) vs. 1533 (869-2852) mL, P = 0.079] compared with non-obese patients. Weight (r = -0.40), body surface area (r = -0.32), estimated body-fat% (r = -0.43) and body mass index (r = -0.47) showed a weak but significant negative (all P < 0.05) correlation with liver function. Moreover, body-fat% was identified as an independent factor negatively affecting the liver function. CONCLUSION: Sarcopenia and sarcopenic obesity did not seem to influence liver size and function negatively. However, obese patients had larger, although less functional, livers, indicating dissociation of liver function and volume in these patients.

20.
HPB (Oxford) ; 17(8): 732-5, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26096195

RESUMO

BACKGROUND: Pyogenic liver abscesses are currently treated by either percutaneous computer tomography (CT)-guided drainage or by laparoscopic and a conventional liver resection when conservative treatment fails but may be associated with substantial morbidity and mortality. METHODS: A minimally invasive technique involving debridement of right liver abscesses was employed using a minimally invasive video-assisted hepatic abscess debridement (VAHD) after unsuccessful percutaneous CT-guided drainage. Clinical data, complication rates and outcomes of patients were recorded retrospectively. RESULTS: Between 2011 and 2014, VAHD was performed on 10 patients at two centres with no observed recurrence of a liver abscess. The median age of the patients was 57 years (range 42-78) with a median pre-operative size of a liver abscess of 78 mm (range 40-115). The median operation time was 47 min (range 23-75), and the median postoperative hospital stay was 9 days (range 7-69). One patient developed a subcutaneous abscess that required further surgery. No patient died, and there were no major complications related to the VAHD. CONCLUSIONS: Video-assisted hepatic abscess debridement is a feasible technique that shows promising results for the treatment of a recurrent right liver abscess.


Assuntos
Desbridamento , Tempo de Internação , Abscesso Hepático/cirurgia , Duração da Cirurgia , Cirurgia Vídeoassistida , Adulto , Idoso , Estudos de Viabilidade , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Cirurgia Vídeoassistida/métodos
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