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1.
Zentralbl Chir ; 149(1): 46-55, 2024 Feb.
Artículo en Alemán | MEDLINE | ID: mdl-38442883

RESUMEN

Today, endoscopy plays a decisive role not only in the detection of colorectal adenomas and carcinomas, but also in the treatment of precancerous lesions, in particular flat adenomas and early carcinomas. In recent years, endoscopic submucosal dissection (ESD) has become increasingly important alongside classic polypectomy and mucosal resection after saline injection using a snare (EMR). Using ESD the lesion is marked, injected submucosally using viscous substances and the mucosa incised and tunneled with a transparent cap and a fine diathermy knife. Particularly in the case of widespread and high-risk lesions ESD enables a quasi-surgical "en bloc" resection almost regardless of size, with a histological R0 resection rate of far over 90% in specialized centers. ESD enables an excellent histopathological evaluation and has a low recurrence risk of 1-3%. Endoscopic full-thickness resection using a dedicated device (FTRD system) represents another addition to the armamentarium. It can be used for circumscribed submucosal, suspicious or scarred changes up to 2 cm in the middle and upper rectum. Endoscopic intermuscular dissection (EID) enables histopathological analysis of the complete submucosa beyond the mucosa and upper submucosal layer by including the circular inner muscle layer within the resection specimen. It reduces basal R1 situations and offers a new perspective for T1 carcinomas through curative, organ-preserving endoscopic therapy, especially in the case of deep submucosal infiltration alone, without other risk factors for metastases. Indications, the procedure itself and significance of the various techniques for premalignant and early malignant lesions in the rectum are presented.


Asunto(s)
Adenoma , Carcinoma , Lesiones Precancerosas , Humanos , Recto/cirugía , Endoscopía , Lesiones Precancerosas/cirugía , Adenoma/cirugía
2.
Z Gastroenterol ; 62(2): 175-182, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36669527

RESUMEN

OBJECTIVES: Endoscopic trans-anal colonic decompression (ECD) may be requested in the case of massive colon distension, but evidence regarding success and safety issues remains scarce. The aim of this analysis is to examine the technical success, complications and clinical outcome in a large series of patients undergoing an ECD in various clinical scenarios. A standardized evaluation system was used to identify the pre-interventional risk parameters that might be helpful to guide clinical decision making. METHODS: In this single-centre retrospective study, the modified Clavien-Dindo classification (CDC) was applied to assess technical success, complications and clinical outcome of 125 consecutive patients who underwent ECD between 2007 and 2020. PRIMARY ENDPOINT: post interventional 90-day mortality. Secondary endpoints: periprocedural complications (CDC event IV-V) and technical success rate. All Martin criteria for standardized reporting of complications were met. Uni- and multivariable analyses for prediction of complications were carried out. RESULTS: The overall technical success rate was 90%. The periprocedural complication rate was low with 3%. Overall 90-day mortality was 31%. Univariable analyses showed a significant correlation between 90-day mortality and ASA≥4 (p<0.001, odds ratio [OR] 15.33), general anaesthesia (p=0.05, OR 21.42) and elevated serological infection parameters (p 0.028, OR 1.004). The pre-interventional multivariable model identified ASA ≥4 (p <0.001; OR 10.94) as the only independent risk factor. CONCLUSIONS: ECD is a safe, easily available, technical feasible, inexpensive and successful tool for colonic decompression in various colonic obstruction scenarios, even in critically ill patients. ASA Score ≥IV can be helpful to identify patients at risk for complications/mortality after ECD.


Asunto(s)
Endoscopía , Obstrucción Intestinal , Humanos , Estudios Retrospectivos , Colon , Descompresión/efectos adversos
3.
Pediatr Transplant ; 26(5): e14298, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35460136

RESUMEN

BACKGROUND: Portal vein complications (PVCs) after pediatric liver transplantation (LT) are sometimes asymptomatic, especially in the early phase, and can threaten both the graft and patient's survival. Therefore, the purpose of this study is to analyze the risk factors for portal vein thrombosis (PVT) and portal vein stenosis (PVS) after pediatric LT. METHODS: All pediatric patients (n = 115) who underwent primary LT at Regensburg University Hospital between January 2010 and April 2017 were included in this study. The pre-, intra-, and postoperative parameters of all patients were retrospectively reviewed and risk factors for both PVT and PVS were analyzed. RESULTS: Of the 115 patients, living donor LT was performed on 57 (49.5%) patients, and biliary atresia was the primary diagnosis in 65 patients (56%). After pediatric LT, 9% of patients developed PVT, and 16.5% developed PVS. Patient weight ≤7 kg [odds ratio (OR) 9.35, 95% confidence interval (CI) 1.03-84.9, p = .04] and GRWR >3% (OR 15.4, 95% CI 1.98-129.5, p = .01) were the independent risk factors for the development of PVT and PVS, respectively upon multivariate analysis. The overall patient survival rates at 1, 3, and 5 years were 91%, 90%, and 89%, respectively, and there was no difference in patient survival among those with and without PVCs. CONCLUSIONS: Pediatric patients with body weight <7 kg and/or receiving a graft with GRWR >3% may develop PVCs and so require certain surgical modifications, close follow-up, and prophylactic anticoagulant therapy following transplant.


Asunto(s)
Trasplante de Hígado , Trombosis de la Vena , Niño , Constricción Patológica/complicaciones , Humanos , Trasplante de Hígado/efectos adversos , Donadores Vivos , Vena Porta/cirugía , Estudios Retrospectivos , Trombosis de la Vena/complicaciones , Trombosis de la Vena/etiología
4.
Clin Transplant ; 30(6): 741-8, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27160359

RESUMEN

BACKGROUND: The 12-month (M) PROTECT study showed that de novo liver transplant recipients (LTxR) who switched from a calcineurin inhibitor (CNI)-based immunosuppression to a CNI-free everolimus (EVR)-based regimen showed numerically better renal function. Here, we present the five-yr follow-up data. METHODS: PROTECT was a randomized controlled study in which LTxR received basiliximab and CNI-based immunosuppression ± corticosteroids. Patients were randomized 1:1 to receive EVR or continue CNI. Patients completing the core study could enter the extension study on their randomized treatment. RESULTS: A total of 81 patients entered the extension study (41, EVR; 40, CNI). At M59 post-randomization, the adjusted mean eGFR was significantly higher in the EVR group, with a benefit of 12.4 mL/min using Cockcroft-Gault (95% CI: 1.2; 23.6; p = 0.0301). Also, there was a significant benefit for adjusted and unadjusted eGFR using the four-variable Modification of Diet in Renal Disease (MDRD4) or Nankivell formula. During the extension period, treatment failure rates were similar. SAEs occurred in 26 (63.4%) and 28 (70.0%) of the patients in EVR and CNI groups, respectively. CONCLUSION: Compared with the CNI-based treatment, EVR-based CNI-free immunosuppression resulted in significantly better renal function and comparable patient and graft outcomes after five-yr follow-up.


Asunto(s)
Inhibidores de la Calcineurina/administración & dosificación , Everolimus/administración & dosificación , Rechazo de Injerto/tratamiento farmacológico , Supervivencia de Injerto/efectos de los fármacos , Hepatopatías/cirugía , Trasplante de Hígado/efectos adversos , Privación de Tratamiento , Adulto , Femenino , Estudios de Seguimiento , Rechazo de Injerto/etiología , Humanos , Inmunosupresores/administración & dosificación , Pruebas de Función Renal , Masculino , Estudios Prospectivos , Resultado del Tratamiento
5.
Langenbecks Arch Surg ; 401(1): 43-53, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26627084

RESUMEN

PURPOSE: According to current treatment guidelines, surgical resection of hepatocellular carcinoma (HCC) is mostly restricted to a limited subgroup of patients. Due to improved surgical techniques and perioperative management, liver resections may also be performed more extendedly and also in cirrhotic livers with clinical signs of portal hypertension in selected patients. In this study, the clinical and long-term outcomes of liver resection in HCC patients with or without liver cirrhosis were evaluated. METHODS: One hundred fifty-eight patients undergoing liver resection for primary HCC at our institution were identified. Logistic and Cox regression analyses were used to identify prognostic parameters for postoperative complications and survival. RESULTS: In our cohort of patients, there was no association between clinical parameters or extent of surgical resection and postoperative morbidity. Only Barcelona Clinic Liver Cancer (BCLC) stage C patients were at significantly higher risk for major complications (OR 5.27, P = 0.009). Risk factors influencing long-term survival were patient age (HR 1.026, P = 0.027) and BCLC stage C (HR 3.47, P = 0.002). Compared to patients without liver cirrhosis, BCLC stage A and B patients undergoing resection were at similar risk for the development of severe complications and long-term mortality. CONCLUSION: Liver resection as potentially curative therapy can be performed in selected patients in BCLC stage B, as well as in patients with clinical signs of portal hypertension. The resection of HCC-classified BCLC stage C is feasible but associated with significant morbidity and mortality.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Hepatectomía , Neoplasias Hepáticas/cirugía , Adulto , Anciano , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Femenino , Humanos , Hipertensión Portal/diagnóstico , Hipertensión Portal/etiología , Hipertensión Portal/terapia , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento
6.
Eur Radiol ; 26(4): 1125-33, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26186960

RESUMEN

OBJECTIVES: To determine whether liver function as determined by indocyanine green (ICG) clearance can be estimated quantitatively from hepatic magnetic resonance (MR) relaxometry with gadoxetic acid (Gd-EOB-DTPA). METHODS: One hundred and seven patients underwent an ICG clearance test and Gd-EOB-DTPA-enhanced MRI, including MR relaxometry at 3 Tesla. A transverse 3D VIBE sequence with an inline T1 calculation was acquired prior to and 20 minutes post-Gd-EOB-DTPA administration. The reduction rate of T1 relaxation time (rrT1) between pre- and post-contrast images and the liver volume-assisted index of T1 reduction rate (LVrrT1) were evaluated. The plasma disappearance rate of ICG (ICG-PDR) was correlated with the liver volume (LV), rrT1 and LVrrT1, providing an MRI-based estimated ICG-PDR value (ICG-PDRest). RESULTS: Simple linear regression model showed a significant correlation of ICG-PDR with LV (r = 0.32; p = 0.001), T1post (r = 0.65; p < 0.001) and rrT1 (r = 0.86; p < 0.001). Assessment of LV and consecutive evaluation of multiple linear regression model revealed a stronger correlation of ICG-PDR with LVrrT1 (r = 0.92; p < 0.001), allowing for the calculation of ICG-PDRest. CONCLUSIONS: Liver function as determined using ICG-PDR can be estimated quantitatively from Gd-EOB-DTPA-enhanced MR relaxometry. Volume-assisted MR relaxometry has a stronger correlation with liver function than does MR relaxometry. KEY POINTS: • Measurement of T1 relaxation times in Gd-EOB-DTPA-enhanced MR imaging quantifies liver function. • Volume-assisted Gd-EOB-DTPA-enhanced MR relaxometry has stronger correlation with ICG-PDR than does Gd-EOB-DTPA-enhanced MR relaxometry. • Gd-EOB-DTPA-enhanced MR relaxometry may provide robust parameters for detecting and characterizing liver disease. • Gd-EOB-DTPA-enhanced MR relaxometry may be useful for monitoring liver disease progression. • Gd-EOB-DTPA-enhanced MR relaxometry has the potential to become a novel liver function index.


Asunto(s)
Medios de Contraste , Gadolinio DTPA , Aumento de la Imagen/métodos , Hepatopatías/fisiopatología , Hígado/fisiopatología , Imagen por Resonancia Magnética/métodos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Pruebas de Función Hepática/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Análisis de Regresión
7.
Stem Cells Transl Med ; 4(8): 899-904, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26041737

RESUMEN

Mesenchymal stem cells and multipotent adult progenitor cells (MAPCs) have been proposed as novel therapeutics for solid organ transplant recipients with the aim of reducing exposure to pharmacological immunosuppression and its side effects. In the present study, we describe the clinical course of the first patient of the phase I, dose-escalation safety and feasibility study, MiSOT-I (Mesenchymal Stem Cells in Solid Organ Transplantation Phase I). After receiving a living-related liver graft, the patient was given one intraportal injection and one intravenous infusion of third-party MAPC in a low-dose pharmacological immunosuppressive background. Cell administration was found to be technically feasible; importantly, we found no evidence of acute toxicity associated with MAPC infusions.


Asunto(s)
Células Madre Adultas/trasplante , Cirrosis Hepática/terapia , Trasplante de Hígado/métodos , Trasplante de Células Madre Mesenquimatosas , Adulto , Rechazo de Injerto , Humanos , Inmunomodulación , Terapia de Inmunosupresión , Cirrosis Hepática/patología , Masculino , Células Madre Mesenquimatosas/citología , Células Madre Multipotentes/trasplante
8.
World J Hepatol ; 7(11): 1509-20, 2015 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-26085910

RESUMEN

In 1953, the pioneer of human orthotopic liver transplantation (LT), Thomas E Starzl, was the first to attempt an orthotopic liver transplant into a 3 years old patient suffering from biliary atresia. Thus, the first LT in humans was attempted in a disease, which, up until today, remains the main indication for pediatric LT (pLT). During the last sixty years, refinements in diagnostics and surgical technique, the introduction of new immunosuppressive medications and improvements in perioperative pediatric care have established LT as routine procedure for childhood acute and chronic liver failure as well as inherited liver diseases. In contrast to adult recipients, pLT differs greatly in indications for LT, allocation practice, surgical technique, immunosuppression and post-operative life-long aftercare. Many aspects are focus of ongoing preclinical and clinical research. The present review gives an overview of current developments and the clinical outcome of pLT, with a focus on alternatives to full-size deceased-donor organ transplantation.

9.
Langenbecks Arch Surg ; 400(3): 361-9, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25854503

RESUMEN

PURPOSE: In-situ split (ISS) liver resection is a novel method to induce rapid hypertrophy of the contralateral liver lobe in patients at risk for postoperative liver failure due to insufficient liver remnant. So far, no data about oncological long-term survival after ISS liver resection is available. METHODS: We retrospectively analyzed our patients treated with ISS liver resection at the Department of Surgery of the University of Regensburg, the first center worldwide to perform ISS. RESULTS: Between 2007 and 2014, ISS liver resection was performed in 16 patients. Two patients (12.5 %) were lost in early postoperative phase (90 days) and one was lost to follow-up. Thirteen patients with a follow-up period of more than 3 months were included into oncologically focused analyses. Median follow-up was 26.4 months (range 3.2-54.6). Seven patients had suffered from colorectal liver metastases (CRLM) and six from various other liver malignancies (non-CRLM). The ISS procedure had led to a median increase of 86.3 % of the left lateral liver lobe after a median of 9 days (range 4-28 days). Median disease-free survival (DFS) was 14.6 months and median overall survival (OS) was 41.7 months (26.4 months when including 90-days mortality). Three-year survival was calculated with 56.4 and 48.9 % when including perioperative mortality, respectively (CRLM 64.3 % vs. non-CRLM 50 %). CONCLUSION: ISS liver resection can provide long-term survival of selected patients with advanced liver malignancies that otherwise are not eligible for liver resection due to insufficient liver remnant.


Asunto(s)
Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Tiempo de Internación/estadística & datos numéricos , Fallo Hepático/mortalidad , Fallo Hepático/prevención & control , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Resultado del Tratamiento
10.
BMC Cancer ; 14: 810, 2014 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-25369977

RESUMEN

BACKGROUND: Purpose of this study was to analyse the surgical management and long-term clinical outcome of patients diagnosed with colorectal liver metastases (CLM) over a period of 10 years using data from a German tumour registry. METHODS: Retrospective analysis of 5772 patients diagnosed with colorectal adenocarcinoma between 2002 and 2007. Follow-up was continued until 2012. RESULTS: 1426 patients (24.7%) had CLM; 1019 patients (71%) had synchronous, 407 patients (29%) developed metachronous CLM. Hepatic resection was performed in 374 of the 1426 CLM patients (26%). A significant increase in liver resection rate from 16.6% for the 2002 cohort to 32% in later cohorts was observed. In centers specialized in liver surgery, CLM resection rates reached 46.6%. However, up to 52% of patients diagnosed with three or less CLM did not undergo liver surgery, although, if resected, patients with 1 CLM show a similar long-time survival as CRC patients who do not develop any CLM. Univariate and multivariate analyses adjusted for age, sex, year of resection, time of CLM diagnosis and number of CLM revealed a significant survival benefit for CLM resection (HR =0.355; CI 0.305-0.414). Furthermore, significant impact on OS was seen for age at diagnosis, perioperative chemotherapy and number of CLM. CONCLUSIONS: We here present the first long-term, population-based analysis of the surgical management of CLM in Germany. Significant increase in hepatic resection rates, translating to a significant benefit in OS, was seen over years. However, we still see a striking potential for further improvements in interdisciplinary CLM management.


Asunto(s)
Adenocarcinoma/patología , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Adenocarcinoma/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/epidemiología , Terapia Combinada , Femenino , Alemania/epidemiología , Humanos , Incidencia , Neoplasias Hepáticas/epidemiología , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Sistema de Registros , Resultado del Tratamiento , Adulto Joven
11.
BMC Health Serv Res ; 14: 584, 2014 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-25421753

RESUMEN

BACKGROUND: The majority of pancreases, offered in allocation, are not transplanted. This pancreas under-utilisation is a phenomenon observed in all transplant systems in North-America and Europe. It was the aim of this study to analyse factors predictive of pancreas non-transplantation in Germany. METHODS: Routine Eurotransplant data of 3,666 deceased German donors (from 2002-2011) were used for multivariate modelling. Socio-demographic and medical factors were considered as independent variables in logistic regression models with non-transplantation as dependent variable. RESULTS: Male gender, advanced age, overweight/obesity, long ICU stay, a history of smoking, non-traumatic brain death, elevated levels of sodium, serum glucose, lipase/amylase and the liver not being considered for procurement were significant independent predictors of non-transplantation. CONCLUSION: In line with previous research, advanced age, high BMI, long ICU stay and the liver not being considered for procurement were the strongest predictors of pancreas non-transplantation in Germany. About three quarters of the variance remained unexplained, suggesting that factors not assessed or unknown may play a decisive role.


Asunto(s)
Trasplante de Páncreas/estadística & datos numéricos , Donantes de Tejidos/estadística & datos numéricos , Receptores de Trasplantes/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , Anciano , Niño , Femenino , Predicción , Alemania , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Factores Sexuales , Factores Socioeconómicos , Adulto Joven
12.
BMC Surg ; 14: 78, 2014 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-25319372

RESUMEN

BACKGROUND: Free jejunal interposition is a useful technique for reconstruction of the cervical esophagus. However, the distal anastomosis between the graft and the remaining thoracic esophagus or a gastric conduit can be technically challenging when located very low in the thoracic aperture. We here describe a modified technique for retrograde stapling of a jejunal graft to a failed gastric conduit using a circular stapler on a delivery system. CASE PRESENTATION: A 56 year-old patient had been referred for esophageal squamous cell carcinoma at 20 cm from the incisors. On day 8 after thoracoabdominal esophagectomy with gastric pull-up, an anastomotic leakage was diagnosed. A proximal-release stent was successfully placed by gastroscopy and the patient was discharged. Two weeks later, an esophagotracheal fistula occurred proximal to the esophageal stent. Cervical esophagostomy was performed with cranial closure of the gastric conduit, which was left in situ within the right hemithorax. Three months later, reconstruction was performed using a free jejunal interposition. The anvil of a circular stapler (Orvil®, Covidien) was placed transabdominally through an endoscopic rendez-vous procedure into the gastric conduit. A free jejunal graft was retrogradely stapled to the proximal end of the conduit. Microvascular anastomoses were performed subsequently. The proximal anastomosis of the conduit was completed manually after reperfusion. CONCLUSIONS: This modified technique allows stapling of a jejunal interposition graft located deep in the thoracic aperture and is therefore a useful method that may help to avoid reconstruction by colonic pull-up and thoracotomy.


Asunto(s)
Carcinoma de Células Escamosas/cirugía , Neoplasias Esofágicas/cirugía , Esofagectomía/métodos , Esófago/cirugía , Yeyuno/cirugía , Anastomosis Quirúrgica/métodos , Carcinoma de Células Escamosas de Esófago , Humanos , Masculino , Persona de Mediana Edad , Grapado Quirúrgico/métodos
14.
World J Gastroenterol ; 20(18): 5331-44, 2014 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-24833863

RESUMEN

In 1967, Starzl et al performed the first successful liver transplantation for a patient diagnosed with hepatoblastoma. In the following, liver transplantation was considered ideal for complete tumor resection and potential cure from primary hepatic malignancies. Several reports of liver transplantation for primary and metastatic liver cancer however showed disappointing results and the strategy was soon dismissed. In 1996, Mazzaferro et al introduced the Milan criteria, offering liver transplantation to patients diagnosed with limited hepatocellular carcinoma. Since then, liver transplantation for malignant disease is an ongoing subject of preclinical and clinical research. In this context, several aspects must be considered: (1) Given the shortage of deceased-donor organs, long-term overall and disease free survival should be comparable with results obtained in patients transplanted for non-malignant disease; (2) In this regard, living-donor liver transplantation may in selected patients help to solve the ethical dilemma of optimal individual patient treatment vs organ allocation justice; and (3) Ongoing research focusing on perioperative therapy and anti-proliferative immunosuppressive regimens may further reduce tumor recurrence in patients transplanted for malignant disease and thus improve overall survival. The present review gives an overview of current indications and future perspectives of liver transplantation for malignant disease.


Asunto(s)
Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Supervivencia de Injerto , Humanos , Inmunosupresores/uso terapéutico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Donadores Vivos , Factores de Riesgo , Resultado del Tratamiento
16.
J Immunol ; 192(4): 1954-61, 2014 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-24415778

RESUMEN

We studied the developmental and functional mechanisms behind NK cell-mediated antitumor responses against metastatic colorectal carcinoma (CRC) in mice. In particular, we focused on investigating the significance of T-box transcription factors and the immunotherapeutic relevance of IL-15 in the development and function of tumor-reactive NK cells. Pulmonary CRC metastases were experimentally seeded via an adoptive i.v. transfer of luciferase-expressing CT26 CRC cells that form viewable masses via an in vivo imaging device; genetically deficient mice were used to dissect the antitumor effects of developmentally different NK cell subsets. IL-15 precomplexed to IL-15 receptor-α was used in immunotherapy experiments. We found that mice deficient for the T-box transcription factor T-bet lack terminally differentiated antitumor CD27(low)KLRG1(+) NK cells, leading to a terminal course of rapid-onset pulmonary CRC metastases. The importance of this NK cell subset for effective antitumor immunity was shown by adoptively transferring purified CD27(low)KLRG1(+) NK cells into T-bet-deficient mice and, thereby, restoring immunity against lung metastasis formation. Importantly, immunity to metastasis formation could also be restored in T-bet-deficient recipients by treating mice with IL-15 precomplexed to IL-15 receptor-α, which induced the development of eomesodermin(+)KLRG1(+) NK cells from existing NK cell populations. Thus, contingent upon their T-bet-dependent development and activation status, NK cells can control metastatic CRC in mice, which is highly relevant for the development of immunotherapeutic approaches in the clinic.


Asunto(s)
Neoplasias Colorrectales/patología , Células Asesinas Naturales/inmunología , Neoplasias Pulmonares/secundario , Receptores Inmunológicos/metabolismo , Proteínas de Dominio T Box/genética , Traslado Adoptivo , Animales , Diferenciación Celular/inmunología , Células Cultivadas , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/terapia , Proteínas de Homeodominio/genética , Inmunoterapia , Interferón gamma/genética , Interleucina-15/metabolismo , Células Asesinas Naturales/citología , Lectinas Tipo C , Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/terapia , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Perforina , Proteínas Citotóxicas Formadoras de Poros/genética , Receptores de Interleucina-15/metabolismo , Proteínas Recombinantes de Fusión/uso terapéutico , Proteínas de Dominio T Box/deficiencia , Proteínas de Dominio T Box/metabolismo , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/metabolismo
17.
Viszeralmedizin ; 30(6): 394-400, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26285602

RESUMEN

BACKGROUND: Acute thrombosis of the portal vein (PV) and/or the mesenteric vein (MV) is a rare but potentially life-threatening disease. A multitude of risk factors for acute portal vein thrombosis (PVT)/mesenteric vein thrombosis (MVT) have been identified, including liver cirrhosis, malignancy, coagulation disorders, intra-abdominal infection/inflammation, and postoperative condition. METHODS: This article analyses the treatment options for acute PVT/MVT. RESULTS: Initially, the clinical management should identify patients with an intra-abdominal focus requiring immediate surgical intervention (e.g. bowel ischaemia). Subsequently, emphasis is placed on the recanalization of the PV/MV or at least the prevention of thrombus extension to avoid long-term complications of portal hypertension. Several therapeutic options are currently available, including anticoagulation therapy, local/systemic thrombolysis, interventional or surgical thrombectomy, and a combination of these procedures. Due to the lack of prospective randomized studies, a comparison between these therapeutic approaches regarding the efficacy of PV/MV recanalization is difficult, if not impossible. CONCLUSION: In patients with acute PVT/MVT, an individualized treatment based on the clinical presentation, the underlying disease, the extent of the thrombosis, and the patients' comorbidities is mandatory. Therefore, these patients should be considered for an interdisciplinary therapy in specialized centres with the option to utilise all therapeutic approaches currently available.

18.
Clin Hemorheol Microcirc ; 58(2): 343-52, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-23380964

RESUMEN

AIM: Identification of acute and subacute complications following pancreas and renal transplantation using contrast enhanced ultrasound (CEUS) in comparison with Magnetic Resonance Tomography (MRI), Computed Tomography (CT), Digital Subtraction Angiography (DSA) or Ultrasound (US). The study evaluated whether CEUS could confirm the preliminary diagnosis or even provide additional information, relevant for the therapeutic strategy. MATERIAL AND METHODS: Retrospective evaluation of 19 patients (13 male, 6 female, age 26-77 years, mean 53.2 years) following renal transplantation and 10 patients (4 male, 6 female, age 35-56 years, mean 45.7 years) following combined pancreas and renal transplantation. CEUS was used as an additional diagnostic method when obscure diagnostic findings occurred in US, CT, MRI or DSA. Fundamental B-scan, Color Coded Doppler Sonography (CCDS) and CEUS were performed in all patients by an experienced examiner using a multifrequency convex transducer (1-5 MHz). After a bolus injection of up to 2.4 ml SonoVue® [BRACCO, Italy] digital raw data was stored as cine-loops up to 5 minutes in length. RESULTS: In all patients, the pathological features and suspected diagnostic findings identified in the other imaging modalities could be confirmed using CEUS (100%). In 25 out of 29 patients (86.2%), new clinically relevant findings were detected. In 27 patients, the diagnosis of CEUS was confirmed during surgery (7), DSA (5), follow-up CEUS (13), CT (1) and MRI (1). In 4 patients renal AV-fistulas were found following biopsy, 3 patients showed post-operative allograft arterial stenosis or dissection, 1 patient demonstrated a stenosis of the common iliac artery and 2 patients were diagnosed with post-operative allograft venous thrombosis or stenosis. In 2 patients, a definite diagnosis of a benign lesion following renal transplantation was possible. In 1 patient a malignant lesion was suspected and confirmed following surgery. In 6 patients, normal perfusion of the pancreas and renal parenchyma and the corresponding vessels was diagnosed, in 5 patients the parenchymal perfusion was diminished and 1 patient suffered from pancreatitis. CONCLUSION: These first results show that CEUS can provide additional, clinically relevant informations in patients with acute and subacute complications following pancreas and renal transplantation. Thus, an early application within the diagnostic course seems favorable.


Asunto(s)
Trasplante de Riñón/efectos adversos , Páncreas/patología , Ultrasonografía Doppler en Color/métodos , Adulto , Anciano , Medios de Contraste , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
19.
Cardiovasc Intervent Radiol ; 37(4): 949-57, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24091757

RESUMEN

PURPOSE: This study evaluated technical efficacy and safety of stent angioplasty of the inferior vena cava (IVC) after liver transplantation or liver resection and analysis of changes in creatinine levels and patients' weight. METHODS: Between October 2004 and February 2011, 16 patients (mean age, 52.6 years) with symptomatic IVC stenoses after liver transplantation (n = 10) or liver resection (n = 6) were subjected to stent angioplasty. Enrollment criteria included edema and/or ascites. The smallest diameter of the IVC, serum creatinine values, and patients' weight were assessed before and after stent placement and respective values were compared. Technical and clinical success, patency rates, related complications, and patients' survival were analyzed. RESULTS: Stent placement was technically successful in 16 patients (100 %). Clinical success was achieved in 13 patients (81.25 %), reflecting two patients with early restenosis and one patient suffering from thrombosis distal to the stent. Mean follow-up was 372 days. Primary patencies were 75 % (n = 12). Primary assisted patencies were 93.75 % (n = 15). Serum creatinine levels decreased significantly (p = 0.01) from 1.68 mg/dl before to 1.08 mg/dl after stent placement. Patients' weight decreased (mean 2.1 %). No angioplasty-related complications occurred. CONCLUSIONS: Stent angioplasty of the IVC is an effective and safe treatment of stenoses after liver transplantation and resection and has a positive effect on creatinine levels.


Asunto(s)
Angioplastia/métodos , Hepatectomía , Trasplante de Hígado , Complicaciones Posoperatorias/cirugía , Stents , Vena Cava Inferior/cirugía , Adolescente , Adulto , Anciano , Peso Corporal , Niño , Constricción Patológica/cirugía , Creatinina/sangre , Diagnóstico por Imagen , Femenino , Humanos , Hepatopatías/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Grado de Desobstrucción Vascular
20.
BMC Surg ; 13: 47, 2013 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-24152541

RESUMEN

BACKGROUND: Most offered pancreases are not transplanted. This study investigates the factors that inform and influence the transplant surgeon's decision to select an offered pancreas. METHODS: Semi-standardized interviews were conducted with 14 highly qualified transplant surgeons from all 14 German transplant centers performing > 5 pancreas transplantations per year. The interviews focused on medical and non-medical criteria on which the individual accept/refuse decision depends. Interviews were recorded, transcribed and underwent content analysis. RESULTS: The interviewees agreed upon certain main selection criteria, e.g. donor age, lab results, ICU stay. However, there was no consistency in judging these parameters, and clear cut-offs did not exist. The pancreas macroscopy is a pivotal factor, as well as knowing (and trusting) the donor surgeon. 3/14 surgeons reported that they had occasionally refused a pancreas because of staff shortage. Some interviewees followed a restrictive acceptance policy, whereas others preferred to accept almost any pancreas and inspect it personally before deciding. CONCLUSION: The assessment of medical donor characteristics is highly inconsistent. Both very cautious as well as very permissive acceptance policies may render the allocation process less efficient. A more standardized policy should be discussed. Finally, better training for donor surgeons seems advisable, in order to increase trust and thus pancreas utilization.


Asunto(s)
Actitud del Personal de Salud , Toma de Decisiones , Selección de Donante/métodos , Trasplante de Páncreas , Selección de Donante/normas , Alemania , Humanos , Entrevistas como Asunto , Guías de Práctica Clínica como Asunto , Investigación Cualitativa
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