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1.
Chirurgie (Heidelb) ; 95(1): 27-33, 2024 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-38051317

RESUMO

The trend to minimally invasive surgery has also made its way into the surgical treatment of incisional hernias. Unlike other areas of visceral surgery, recent years have seen a resurgence of open sublay repair in incisional hernia procedures, primarily due to the recognition of the retromuscular layer as the optimal mesh placement site. Additionally, with the growing availability of robotic systems in visceral surgery, these procedures are increasingly being offered in the form of minimally invasive procedures. These methods can be categorized based on the access routes: robotic-assisted transperitoneal procedures (e.g., r­Rives, r­TARUP, r­TAR) and total extraperitoneal hernia repair (e.g., r­eTEP, r­eTAR). Notably, the introduction of transversus abdominis muscle release enables the robotic-assisted treatment of larger and more complex hernia cases with complete fascial closure. With respect to the comparison with open surgery required in retromuscular hernia treatment, the currently available literature on incisional hernia repair seems to show initial advantages of robotic-assisted surgery in the perioperative course. New technologies create new possibilities. In the context of surgical training the use of surgical robot systems with double consoles opens up completely new perspectives. Furthermore, the robot enables the implementation of models of artificial intelligence and augmented reality and could therefore open up novel dimensions in surgery.


Assuntos
Hérnia Incisional , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Hérnia Incisional/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Inteligência Artificial , Laparoscopia/métodos , Telas Cirúrgicas
2.
Chirurgie (Heidelb) ; 94(2): 147-154, 2023 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-36280627

RESUMO

BACKGROUND: As in many other fields of surgery, robotically assisted surgical procedures have been established in the treatment of ventral hernias in recent years. The use of the robot can combine the demands of a minimally invasive approach and retromuscular mesh placement. In addition to a transabdominal approach, these procedures can also be performed using an extraperitoneal approach. OBJECTIVES: The purpose of this study is to demonstrate that robotic total extraperitoneal management of abdominal wall hernias is safe and efficient. MATERIALS AND METHODS: A retrospective analysis of all robotically operated patients on ventral hernia using extraperitoneal eTEP technique from September 2019 to May 2022 was performed. RESULTS: A total of 61 ventral hernias were operated on using the robotic eTEP technique during the study period. In 14 patients retro-rectal dissection was extended laterally by an extraperitoneal transversus abdominis release (eTAR) because of the hernia size or a lateral hernia localization. In all cases, an uncoated synthetic mesh was placed in the retromuscular position with complete closure of the hernia defects. The median hernia defect area was 30 cm² (4-308 cm²). The median mesh size was 540 cm² (300-1350 cm²). The median mesh defect ratio (MDR) was 17.78 (3.06-145). One intraoperative and three postoperative complications were encountered. Neither conversion nor reoperation were required. CONCLUSION: The robotic extraperitoneal eTEP technique enables the required retromuscular mesh placement in a minimally invasive approach. With the possibility of a combination with a transversus abdominis release, even complex findings can be treated using this technique.


Assuntos
Hérnia Ventral , Hérnia Incisional , Laparoscopia , Robótica , Humanos , Hérnia Incisional/cirurgia , Estudos Retrospectivos , Laparoscopia/métodos , Hérnia Ventral/cirurgia , Músculos Abdominais/cirurgia , Herniorrafia/efeitos adversos , Herniorrafia/métodos
3.
Chirurg ; 93(1): 82-88, 2022 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-33876252

RESUMO

BACKGROUND: In recent years there has been a rise in robotic techniques and approaches regarding hernia repair with extraperitoneal mesh placement. METHODS: A retrospective analysis of the first 50 patients who underwent robotic ventral hernia repair between May 2019 and November 2020 at the department of general surgery of the Kempten Clinic was performed. RESULTS: This case series consisted of 36 incisional hernias, 12 primary hernias (8 umbilical and 3 epigastric hernias in combination with a diastasis recti abdominis as well as 1 Spigelian hernia) and 2 parastomal hernias. A complete closure of the hernia was achieved in all cases. Extraperitoneal mesh placement in the retromuscular or preperitoneal space was achieved in 98 % of the ventral procedures. We used an extraperitoneal approach with retromuscular mesh implantation (r-eTEP= robotic enhanced view total extraperitoneal plasty) in 22 cases, 3 of those along with a transversus abdominis release (r-eTAR= robotic extraperitoneal transversus abdominis release) and 26 operations were carried out transperitoneally. These included 11 preperitoneal (r-vTAPP= robotic ventral TAPP), 7 retrorectus (TARUP= robotic transabdominal retromuscular umbilical prosthetic hernia repair) and 1 intraperitoneal onlay mesh placements (r-IPOM= robotic intraperitoneal onlay mesh) as well as 7 transperitoneal transversus abdominis releases with retromuscular mesh placement. The 2 parastomal hernias were treated with an intraperitoneal 3D funnel mesh. After the initial treatment of smaller hernias the indications could be rapidly extended to complex hernias in 38 % of this case series. One conversion to an open operation was necessary due to technical problems in closing the posterior rectus sheath. The complication rate was 12 % and the reintervention rate 4 %. CONCLUSION: Robotic surgery of ventral hernia is safe and effective. Even complex hernias can be treated minimally invasively with closure of the hernia defect and extraperitoneal mesh placement.


Assuntos
Hérnia Umbilical , Hérnia Ventral , Hérnia Incisional , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Hérnia Ventral/cirurgia , Herniorrafia , Humanos , Hérnia Incisional/cirurgia , Estudos Retrospectivos , Telas Cirúrgicas
4.
J Child Orthop ; 13(2): 196-205, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30996745

RESUMO

PURPOSE: The treatment of early onset scoliosis continues to be a major challenge, even when using motorized growth-sparing implants. We report on 30 cases operated on with magnetically controlled growing rods (MCGRs) at our institution, analyzing radiological parameters and complications, comparing our results with the literature and presenting a special implant fixation technique. A separate focus highlights the challenges of conversion from previous non-motorized implants. METHODS: Consecutive case series. The nature and effects of complications were recorded for all patients. Radiographic evaluations were performed for patients with a minimum follow-up of two years. Separate analyses were carried out for patients who were previously treated with non-motorized growth-sparing implants. RESULTS: There were 12 documented complications in 11/30 (37%) patients leading to 13 unplanned returns to the operating room. In all, 18/30 patients had a minimum follow-up of two years. Major curve and main kyphosis, as well as T1 to T12 and T1 to S1 distances significantly improved with MCGR implantation, however, less in patients converted from previous growth-sparing surgical treatment. While the achieved correction of the major curve was maintained, there was a loss of kyphosis correction with subsequent implant lengthening. Gain in implant length decreased with increasing number of extensions. CONCLUSION: Despite improved patient's comfort, MCGR show a considerable complication rate. Coronal plane deformities can be well controlled, but diminished implant lengthening is already apparent within two years after MCGR implantation. Central databases should help to clarify unresolved aspects and optimize the treatment of these young patients. LEVEL OF EVIDENCE: IV.

5.
Bone ; 120: 25-37, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30240961

RESUMO

Clinical retrospective studies have only reported limited improvements in hip fracture classification accuracy using finite element (FE) models compared to conventional areal bone mineral density (aBMD) measurements. A possible explanation is that state-of-the-art quasi-static models do not estimate patient-specific loads. A novel FE modeling technique was developed to improve the biofidelity of simulated impact loading from sideways falling. This included surrogate models of the pelvis, lower extremities, and soft tissue that were morphed based on subject anthropometrics. Hip fracture prediction models based on aBMD and FE measurements were compared in a retrospective study of 254 elderly female subjects from the AGES-Reykjavik study. Subject fragility ratio (FR) was defined as the ratio between the ultimate forces of paired biofidelic models, one with linear elastic and the other with non-linear stress-strain relationships in the proximal femur. The expected end-point value (EEV) was defined as the FR weighted by the probability of one sideways fall over five years, based on self-reported fall frequency at baseline. The change in maximum volumetric strain (ΔMVS) on the surface of the femoral neck was calculated between time of ultimate femur force and 90% post-ultimate force in order to assess the extent of tensile tissue damage present in non-linear models. After age-adjusted logistic regression, the area under the receiver-operator curve (AUC) was highest for ΔMVS (0.72), followed by FR (0.71), aBMD (0.70), and EEV (0.67), however the differences between FEA and aBMD based prediction models were not deemed statistically significant. When subjects with no history of falling were excluded from the analysis, thus artificially assuming that falls were known a priori with no uncertainty, a statistically significant difference in AUC was detected between ΔMVS (0.85), and aBMD (0.74). Multivariable linear regression suggested that the variance in maximum elastic femur force was best explained by femoral head radius, pelvis width, and soft tissue thickness (R2 = 0.79; RMSE = 0.46 kN; p < 0.005). Weighting the hip fracture prediction models based on self-reported fall frequency did not improve the models' sensitivity, however excluding non-fallers lead to significant differences between aBMD and FE based models. These findings suggest that an accurate assessment of fall probability is necessary for accurately identifying individuals predisposed to hip fracture.


Assuntos
Análise de Elementos Finitos , Fraturas do Quadril/classificação , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Estudos de Coortes , Feminino , Fêmur/patologia , Humanos , Islândia , Masculino , Probabilidade , Curva ROC , Estudos Retrospectivos
6.
Artigo em Inglês | MEDLINE | ID: mdl-29542838

RESUMO

BACKGROUND: A large proportion of age-related fecal incontinence is attributed to weakness or degeneration of the muscles composing the anal continence organ. However, the individual role of these muscles and their functional interplay remain poorly understood. METHODS: This study employs a novel technique based on the combination of MR imaging and FLIP measurements (MR-FLIP) to obtain anatomical and mechanical information simultaneously. Unlike previous methods used to assess the mechanics of the continence organ, MR-FLIP allows inter-individual comparisons and statistical analysis of the sphincter morpho-mechanical parameters. The anatomy as well as voluntary and involuntary mechanical properties of the anal continence organ were characterized in 20 healthy senior volunteers. RESULTS: Results showed that the external anal sphincter (EAS) forms a funnel-like shape with wall thickness increasing by a factor of 2.5 from distal (6 ± 0 mm) to proximal (15 ± 3 mm). Both voluntary and involuntary mechanical properties in this region correlate strongly with the thickness of the muscle. The positions of least compliance and maximal orifice closing were both located toward the proximal EAS end. In addition, maximal contraction during squeeze maneuvers was reached after 2 s, but high muscle fatigue was measured during a 7 s holding phase, corresponding to about 60% loss of the energy produced by the muscles during the contraction phase. CONCLUSIONS: This work reports baseline parameters describing the morpho-mechanical condition of the sphincter muscle of healthy elderly volunteers. New parameters were also proposed to quantify the active properties of the muscles based on the mechanical energy associated with muscle contraction and fatigue. This information could be used to assess patients suffering from AI or for the design of novel implants.

7.
Colorectal Dis ; 19(8): 764-771, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27997766

RESUMO

AIM: Continence results from a complex interplay between anal canal (AC) muscles and sensorimotor feedback mechanisms. The passive ability of the AC to withstand opening pressure - its compliance - has recently been shown to correlate with continence. A functional lumen imaging probe (FLIP) is used to assess AC compliance, although it provides no anatomical information. Therefore, assessment of the compliance specific anatomical structures has not been possible, and the anatomical position of critical functional zones remains unknown. In addition, the FLIP technique assumes a circular orifice cross-section, which has not been shown for the AC. To address these shortcomings, a technique combining FLIP with a medical imaging modality is needed. METHOD: We implemented a new research method (MR-FLIP) that combines FLIP with MR imaging. Twenty healthy volunteers underwent MR-FLIP and conventional FLIP assessment. MR-FLIP was validated by comparison with FLIP results. Anatomical markers were identified, and the cross-sectional shape of the orifice was investigated. RESULTS: MR-FLIP provides compliance measurements identical to those obtained by conventional FLIP. Anatomical analysis revealed that the least compliant AC zone was located at the proximal end of the external anal sphincter (EAS). The cross-sectional shape of the AC was found to deviate only slightly from circularity in healthy volunteers. CONCLUSION: The proposed method is equivalent to classical FLIP. It establishes for the first time direct mapping between local tissue compliance and anatomical structure, which is key to gaining novel insights into (in)continence. In addition, MR-FLIP provides a tool for better understanding conventional FLIP measurements in the AC by quantifying its limitations and assumptions.


Assuntos
Canal Anal/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Manometria/métodos , Músculo Liso/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Canal Anal/anatomia & histologia , Canal Anal/fisiologia , Fenômenos Biomecânicos , Estudos Transversais , Incontinência Fecal/diagnóstico por imagem , Incontinência Fecal/fisiopatologia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Liso/anatomia & histologia , Músculo Liso/fisiologia , Pressão , Estudos Prospectivos
8.
Transplant Proc ; 43(10): 3762-8, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22172843

RESUMO

Due to the lack of donor organs for orthotopic liver transplantation (OLT) in Germany, a larger proportion of patients advance to multi-organ failure (MOF) before OLT. Twenty-three patients on the waiting list for OLT were admitted to our intensive care unit (ICU) from January 2007 until September 2009. They consisted of 16 men and 7 women of median (25th-75th percentile) age of 60 years (54-65). Acute Physiology and Chronic Health Evaluation (APACHE II) score upon ICU admission was 26 (19-34); Model of End-Stage Liver Disease (MELD) score was 29 (22-41); Sequential Organ Failure Assessment (SOFA) score was 12 (8-16). The 90-day mortality rate was 39%. A decrease in MELD score during the first 48 hours (-2 [-5-0] vs 2 [-1-4]; P=.019) was associated with survival. Thirteen patients underwent transplantation from the ICU. By the time of the OLT, the MELD scores had deteriorated to 38 (33-39) and SOFA scores to 19 (18-19). All patients were mechanically ventilated and received hemodynamic support with catecholamines. Ten of 13 patients (77%) received renal replacement therapy and/or single pass albumin dialysis. Eight of 13 patients (62%) had a SOFA score of 3 or 4 (organ failure) in each of the respective subscores for the cardiovascular, renal, and respiratory systems at the time of OLT. The 90-day mortality rate after OLT was 38% and the 1-year-mortality rate was 54%. Patients who did not survive 90 days post OLT showed lower MELD scores on admission (33 [18-35] vs 44 [32-46]; P=.045), an increased MELD during the first 48 hours (3 [1-4] vs -2 [-8-1]; P=.002), and a longer ICU stay before OLT (32 [18-37] vs 8 [2-15]; P=.006). In conclusion, OLT may be successful treatment for cirrhotic patients with MOF. Outcomes of MOF in cirrhotic patients may improve after OLT but are generally worse than acceptable. A shorter ICU waiting time seemed to be beneficial.


Assuntos
Cirrose Hepática/cirurgia , Transplante de Fígado , Insuficiência de Múltiplos Órgãos/cirurgia , APACHE , Idoso , Catecolaminas/uso terapêutico , Distribuição de Qui-Quadrado , Estado Terminal , Feminino , Alemanha , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Seleção de Pacientes , Terapia de Substituição Renal , Respiração Artificial , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Vasoconstritores/uso terapêutico , Listas de Espera
9.
Toxicol In Vitro ; 25(6): 1203-8, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21621600

RESUMO

Gold standard for in vitro toxicity tests and drug screenings is primary human hepatocytes (hHeps). Because of their limited availability efforts have been made to provide alternatives, e.g., monocyte-derived NeoHepatocytes. In the past years it has been critically discussed if gaining hepatocyte features is associated with trans-differentiation of monocytes or their activation towards a macrophage phenotype. Generating NeoHepatocytes in the presence of six different human AB sera, fetal calf serum (FCS) or autologous serum showed that yield and quality of NeoHepatocytes is inversely correlated to macrophage activation. Using autologous serum constantly the highest amount of cells with the best metabolic capacity was obtained. Focus of this study was to further analyze bio-transformation capacity of the optimized NeoHepatocytes for use as in vitro toxicity test-system. Treatment of the optimized NeoHepatocytes with two different pro-teratogenic substances with corresponding metabolites and eight known hepatotoxins showed comparable toxicity to hHeps. Bio-transformation rates, assessed by testosterone metabolism, were comparable in both cell types. Our data reveal that use of autologous serum reduced macrophage activation which improved yield and function of NeoHepatocytes resulting in bio-transformation and toxicity profiles comparable to hHeps. Thus, their easy accessibility makes them an ideal candidate for in vitro toxicity studies.


Assuntos
Hepatócitos/efeitos dos fármacos , Monócitos/metabolismo , Testes de Toxicidade/métodos , Animais , Bovinos , Transdiferenciação Celular , Sangue Fetal/metabolismo , Hepatócitos/metabolismo , Humanos , Macrófagos/metabolismo , Teratogênicos/toxicidade , Testosterona/metabolismo
10.
Br J Surg ; 98(6): 768-83, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21462364

RESUMO

BACKGROUND: The standard treatment for resectable oesophageal squamous cell carcinoma (OSCC) is surgical resection with adequate lymphadenectomy. Most Western patients receive neoadjuvant chemotherapy or chemoradiotherapy (CRT). In recent years some patients have received CRT alone (definitive CRT, dCRT). This meta-analysis sought to clarify the benefits of neoadjuvant and definitive treatment for OSCC. METHODS: Eligible randomized controlled trials (RCTs) were identified using the Cochrane database, MEDLINE and Embase. Only RCTs with intention-to-treat analysis, and published hazard ratios (HRs) or estimates from survival data, were included. RESULTS: Nine RCTs involving neoadjuvant CRT versus surgery, eight involving neoadjuvant chemotherapy versus surgery, and three involving neoadjuvant treatment followed by surgery or surgery alone versus dCRT were identified. The HR for overall survival was 0·81 (95 per cent confidence interval 0·70 to 0·95; P = 0·008) after neoadjuvant CRT and 0·93 (0·81 to 1·08; P = 0·368) after neoadjuvant chemotherapy. The likelihood of R0 resection was significantly higher after neoadjuvant treatment (CRT: HR 1·15, P = 0·043; chemotherapy: HR 1·16, P = 0·006). Morbidity rates were not increased after neoadjuvant CRT (HR 0·94, P = 0·363) but 30-day mortality was non-significantly higher with combined treatment. Morbidity (HR 1·03, P = 0·638) and mortality (HR 1·04, P = 0·810) rates after neoadjuvant chemotherapy and surgery did not differ from those after surgery alone. None of the RCTs reporting outcome after dCRT demonstrated a significant survival benefit, but treatment-related mortality rates were lower (HR 7·60, P = 0·007) than with neoadjuvant treatment followed by surgery or surgery alone. CONCLUSION: For patients with resectable OSCC, a significant survival benefit for neoadjuvant CRT was evident, with no increase in morbidity rate. dCRT did not demonstrate any survival benefit over other curative strategies. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.


Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Células Escamosas/mortalidade , Quimioterapia Adjuvante , Neoplasias Esofágicas/mortalidade , Humanos , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , Radioterapia Adjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Med Eng Phys ; 33(3): 340-6, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21130015

RESUMO

The spine is a complex structure that provides motion in three directions: flexion and extension, lateral bending and axial rotation. So far, the investigation of the mechanical and kinematic behavior of the basic unit of the spine, a motion segment, is predominantly a domain of in vitro experiments on spinal loading simulators. Most existing approaches to measure spinal stiffness intraoperatively in an in vivo environment use a distractor. However, these concepts usually assume a planar loading and motion. The objective of our study was to develop and validate an apparatus, that allows to perform intraoperative in vivo measurements to determine both the applied force and the resulting motion in three dimensional space. The proposed setup combines force measurement with an instrumented distractor and motion tracking with an optoelectronic system. As the orientation of the applied force and the three dimensional motion is known, not only force-displacement, but also moment-angle relations could be determined. The validation was performed using three cadaveric lumbar ovine spines. The lateral bending stiffness of two motion segments per specimen was determined with the proposed concept and compared with the stiffness acquired on a spinal loading simulator which was considered to be gold standard. The mean values of the stiffness computed with the proposed concept were within a range of ±15% compared to data obtained with the spinal loading simulator under applied loads of less than 5 Nm.


Assuntos
Teste de Materiais/métodos , Fenômenos Mecânicos , Movimento , Coluna Vertebral/fisiologia , Coluna Vertebral/cirurgia , Animais , Fenômenos Biomecânicos , Teste de Materiais/instrumentação , Ovinos , Suporte de Carga
12.
Dig Dis Sci ; 56(1): 244-51, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20824504

RESUMO

AIM: The aim of this trial was to evaluate the impact of conversion from a calcineurin-inhibitor (CNI)-based immunosuppressive regimen to mycophenolate mofetil (MMF) and reduced-dose CNI on long-term renal function and survival in a series of 63 liver transplant patients with CNI-induced renal dysfunction. METHODS: CNI dosage was significantly tapered after introduction of 2,000 mg MMF per day. Renal function was assessed by determination of serum creatinine levels and calculated creatinine clearance (CCl). The impact of relevant clinical parameters on renal function and survival post-conversion was analyzed by univariate and multivariate analysis. RESULTS: At 60 months post-conversion, mean creatinine level had significantly declined from 197.2±58.3 µmol/l at baseline to 160.0±76.5 µmol/l, and mean CCl has significantly increased from 38.4±13.4 ml/min at baseline to 47.9±21.1 ml/min (p<0.001), respectively. Forty-six patients (73.1%) demonstrated sustained renal response to modified immunosuppression. Full-dose MMF medication (p=0.006) and the early conversion (p=0.02) were identified as independent predictors of persistent renal function improvement. Sustained renal response to MMF plus reduced-dose CNI was identified as the most relevant independent promoter of long-term survival (hazard ratio 6.9). Five-year survival rate post-conversion was 93.9% in renal responders and 64.3% in renal non-responders (log rank<0.001). CONCLUSIONS: Sustained renal response to MMF and CNI dose reduction promotes long-term survival in liver transplant patients with CNI-induced renal dysfunction.


Assuntos
Inibidores de Calcineurina , Nefropatias/induzido quimicamente , Nefropatias/mortalidade , Transplante de Fígado , Ácido Micofenólico/análogos & derivados , Complicações Pós-Operatórias , Adulto , Ciclosporina/efeitos adversos , Ciclosporina/farmacologia , Ciclosporina/uso terapêutico , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Rim/efeitos dos fármacos , Rim/fisiopatologia , Testes de Função Renal , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Ácido Micofenólico/uso terapêutico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida , Tacrolimo/efeitos adversos , Tacrolimo/farmacologia , Tacrolimo/uso terapêutico
13.
Interface Focus ; 1(3): 450-61, 2011 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-22670213

RESUMO

The challenge of modelling cancer presents a major opportunity to improve our ability to reduce mortality from malignant neoplasms, improve treatments and meet the demands associated with the individualization of care needs. This is the central motivation behind the ContraCancrum project. By developing integrated multi-scale cancer models, ContraCancrum is expected to contribute to the advancement of in silico oncology through the optimization of cancer treatment in the patient-individualized context by simulating the response to various therapeutic regimens. The aim of the present paper is to describe a novel paradigm for designing clinically driven multi-scale cancer modelling by bringing together basic science and information technology modules. In addition, the integration of the multi-scale tumour modelling components has led to novel concepts of personalized clinical decision support in the context of predictive oncology, as is also discussed in the paper. Since clinical adaptation is an inelastic prerequisite, a long-term clinical adaptation procedure of the models has been initiated for two tumour types, namely non-small cell lung cancer and glioblastoma multiforme; its current status is briefly summarized.

14.
Br J Cancer ; 103(10): 1571-9, 2010 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-20978507

RESUMO

PURPOSE: Tumour hypoxia activates hypoxia-inducible factor-1 (HIF-1) and indluences angiogenesis, cell survival and invasion. Prolyl hydroxylase-3 (PHD3) regulates degradation of HIF-1α. The effects of PHD3 in tumour growth are largely unknown. EXPERIMENTAL DESIGN: PHD3 expression was analysed in human pancreatic cancer tissues and cancer cell lines by real-time quantitative PCR and immunohistochemistry. PHD3 overexpression was established by stable transfection and downregulation by short interfering RNA technology. VEGF was quantified by enzyme-linked immunosorbent assay. Matrigel invasion assays were performed to examine tumour cell invasion. Apoptosis was measured by annexin-V staining and caspase-3 assays. The effect of PHD3 on tumour growth in vivo was evaluated in an established orthotopic murine model. RESULTS: PHD3 was upregulated in well-differentiated human tumours and cell lines, and regulated hypoxic VEGF secretion. PHD3 overexpression mediated tumour cell growth and invasion by induction of apoptosis in a nerve growth factor-dependent manner by the activation of caspase-3 and phosphorylation of focal adhesion kinase HIF-1 independently. In vivo, PHD3 inhibited tumour growth by abrogation of tumour angiogenesis. CONCLUSION: Our results indicate essential functions of PHD3 in tumour growth, apoptosis and angiogenesis and through HIF-1-dependent and HIF-1-independent pathways.


Assuntos
Dioxigenases/genética , Neovascularização Patológica/patologia , Neoplasias Pancreáticas/patologia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Animais , Anexina A5/análise , Apoptose , Carcinoma Ductal Pancreático/enzimologia , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Caspase 3/metabolismo , Diferenciação Celular , Linhagem Celular Tumoral , Dioxigenases/fisiologia , Ensaio de Imunoadsorção Enzimática , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Prolina Dioxigenases do Fator Induzível por Hipóxia , Camundongos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Neoplasias Pancreáticas/enzimologia , Neoplasias Pancreáticas/cirurgia , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , RNA Neoplásico/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transplante Heterólogo , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/análise
15.
Eur J Pediatr Surg ; 20(5): 316-20, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20577951

RESUMO

BACKGROUND: Greenstick fractures suffered during growth have a high risk for refracture and posttraumatic deformity, particularly at the forearm diaphysis. The use of a preemptive completion of the fracture by manipulation of the concave cortex is controversial and data supporting this approach are few. AIM: Aim of this study was to determine the factors which predispose to refracture and deformities, and to define therapeutic strategies. METHODS: We prospectively gathered clinical and radiographic data over a period of one year on greenstick fractures of the middle third of the forearm in children as part of a multi-centre study. Endpoint was a follow-up visit at one year. Radiographic deformity, state of consolidation at resumption of physical activities and refracture rate were analysed statistically (ANOVA, Student's t-test and Pearson's chi-square test) with regard to patient age, gender, fracture type, therapy and time in plaster. RESULTS: We collected the data of 103 patients (63 boys, 40 girls), average age 6.6 years (1.3-14.5 years), the vast majority of whom had a combined greenstick fracture of the radius and ulna. 6.7% of the patients sustained a refracture within 49 days (29-76) after plaster removal. They were significantly older (p=0.017) with a significantly higher incidence of manual completion of the fracture with radiographic signs of partial consolidation (p=0.025). Residual deformities were significantly smaller after completion of the fracture compared to reduction without completion (p=0.019) or plaster fixation alone (p<0.005). CONCLUSIONS: Completion of a greenstick fracture does not prevent refracture. Nevertheless, it diminishes the extent of secondary deformities in cases where the primary angulation exceeds the remodelling capacity. Prevention of refracture should include a routine radiographic follow-up 4-6 weeks after injury with continuation of plaster fixation in cases of partial consolidation.


Assuntos
Fraturas do Rádio/cirurgia , Fraturas da Ulna/cirurgia , Adolescente , Remodelação Óssea , Moldes Cirúrgicos , Criança , Pré-Escolar , Feminino , Consolidação da Fratura , Humanos , Lactente , Masculino , Estudos Prospectivos , Radiografia , Fraturas do Rádio/diagnóstico por imagem , Fraturas do Rádio/epidemiologia , Fraturas do Rádio/fisiopatologia , Recidiva , Fatores de Risco , Fraturas da Ulna/diagnóstico por imagem , Fraturas da Ulna/epidemiologia , Fraturas da Ulna/fisiopatologia
16.
J Biomech ; 43(5): 836-42, 2010 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-20006338

RESUMO

The optical characteristics of the human cornea depends on the mechanical balance between the intra-ocular pressure and intrinsic tissue stiffness. A wide range of ophthalmic surgical procedures alter corneal biomechanics to induce local or global curvature changes for the correction of visual acuity. Due to the large number of surgical interventions performed every day, a deeper understanding of corneal biomechanics is needed to improve the safety of these procedures and medical devices. The aim of this study is to propose a biomechanical model of the human cornea, based on stromal microstructure. The constitutive mechanical law includes collagen fiber distribution based on X-ray scattering analysis, collagen cross-linking, and fiber uncrimping. Our results showed that the proposed model reproduced inflation and extensiometry experimental data [Elsheikh et al., Curr. Eye Res., 2007; Elsheikh et al., Exp. Eye Res., 2008] successfully. The mechanical properties obtained for different age groups demonstrated an increase in collagen cross-linking for older specimens. In future work such a model could be used to simulate non-symmetric interventions, and provide better surgical planning.


Assuntos
Córnea/anatomia & histologia , Córnea/fisiologia , Pressão Intraocular/fisiologia , Modelos Biológicos , Simulação por Computador , Módulo de Elasticidade/fisiologia , Humanos
17.
Adv Med Sci ; 54(2): 158-69, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20022858

RESUMO

BACKGROUND: Radical esophagectomy with lymphadenectomy remains the only curative therapy for patients with resectable esophageal squamous cell cancer (ESCC), however, combined treatment modalities may improve survival. Based upon more than 1300 consecutive esophageal resections, we present our current multidisciplinary ESCC approach with analysis in the context of recently published RCTs. METHODS: Subject to tumor staging, patients with resectable ESCC receive either a neoadjuvant radiochemotherapy (uT3N+) or are referred to primary surgery (uT1/2N0). By Medline searches (1997-2009), all published RCTs containing multimodal ESCC therapy concepts were identified and a systematic review was generated. RESULTS: From July 2007 to June 2009, 62 patients with ESCC were treated in our department (40 multimodal treatment concept, 21 primary surgery, 1 definite radiochemotherapy). The R0 resection rate was 78%, in hospital mortality 4.8%. 60% of patients showed a good response to neoadjuvant treatment. 18-month follow-up data revealed absence of tumor recurrence in 7 patients (18%). Our approach is aligned to the current published literature including 12 studies in this review. In line with our institutional experience, neodjuvant radiochemotherapy tends to improve overall survival and increases the likelihood of R0 resection. However, postoperative morbidity and mortality rates are increased. Adjuvant treatment failed to demonstrate any improvement in prognosis. For palliation, concurrent radiochemotherapy is the treatment of choice. CONCLUSION: The MRI approach can be aligned to the most recent published data. Surgical resection remains the principle treatment for patients with resectable ESCC. Although multimodal therapy concepts tend to improve survival rates, postoperative morbidity and mortality rates are increased.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Imageamento por Ressonância Magnética , Terapia Neoadjuvante , Idoso , Carcinoma de Células Escamosas/secundário , Causas de Morte , Quimioterapia Adjuvante , Esofagectomia , Feminino , Seguimentos , Humanos , Excisão de Linfonodo , Masculino , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Cuidados Paliativos , Tomografia por Emissão de Pósitrons , Prognóstico , Radioterapia Adjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Resultado do Tratamento
18.
Clin Transplant ; 23 Suppl 21: 37-41, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19930315

RESUMO

Acute liver failure is a life threatening disease mostly triggered by drug-induced or toxic liver damage or viral hepatitis. Herpes Simplex virus (HSV) hepatitis is rare and accounts for only 1% of all acute liver failures. The importance of HSV-induced acute liver failure is based on its extremely severe clinical course with lethality rates of almost 75%. HSV hepatitis is just one of several clinical manifestations of HSV sepsis leading more frequently to encephalitis, pneumonia and esophagitis. Local herpes infection or recurrence of dermal lesions (herpes labialis, herpes genitalis), however, is common and account for the high prevalence of HSV-1 or HSV-2 infection in adults. Another rare entity is visual dissemination, which mostly affects immunocompromised patients. Compromised cellular immunity is a major risk factor for HSV sepsis because of either primary infection or reactivation of occult chronic HSV infection. Delayed diagnosis without antiviral therapy significantly contributes to the unfavorable outcome. Typically, anicteric hepatitis is seen in patients with HSV hepatitis. Because of its low incidence, however, and the lack of dermal manifestations, HSV hepatitis is rarely considered in the context of acute liver failure. In addition, diagnostic tests might not always be available. Therefore, it is a generally accepted consensus to begin antiviral therapy pre-emptively with acyclovir in cases of acute liver failure of unknown origin, in which high urgency (HU) liver transplantation remains the only therapeutical option. Even in the case of early specific therapy, sepsis may prevail and the indication for HU transplantation must be evaluated carefully. The outcome after liver transplantation for HSV-induced liver failure with reported survival rates of more than 40% is good. Because of the risk of recurrence, lifelong prophylaxis with acyclovir is recommended.


Assuntos
Herpes Simples/complicações , Falência Hepática Aguda/virologia , Sepse/virologia , Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Herpes Simples/diagnóstico , Herpes Simples/tratamento farmacológico , Humanos , Reação em Cadeia da Polimerase
19.
Chirurg ; 80(1): 14-21, 2009 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-19011818

RESUMO

Benign and low malignant tumors of the middle pancreatic segment can be resected by extended pancreaticoduodenectomy or distal pancreatic resection. Both procedures involve unavoidably extensive loss of normal pancreatic parenchyma, leading to deteriorated endocrine and exocrine pancreatic function. Segmental pancreatic resection represents an organ-preserving surgical procedure. Normal pancreatic tissue can be preserved as only the tumor with a pancreatic segment is resected. Several reports confirm lower mortality and minimal risk of postoperative endocrine or exocrine insufficiency than with standard pancreatic resections. The indication should be limited exclusively to benign or low malignant pancreatic tumors, metastases from other tumors, and focal chronic pancreatitis, as this type of resection cannot be deemed oncologic. Segmental pancreatic resections are technically more demanding and therefore should be performed in experienced centers.


Assuntos
Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Pancreatite/cirurgia , Lesões Pré-Cancerosas/cirurgia , Adulto , Insuficiência Pancreática Exócrina/etiologia , Insuficiência Pancreática Exócrina/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Pancreatite/patologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/prevenção & controle , Lesões Pré-Cancerosas/patologia , Taxa de Sobrevida
20.
Environ Technol ; 29(2): 123-30, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18613611

RESUMO

This paper present the possible alternative options for the remove of trace elements from drinking water supplies in the trace. Arsenic and chromium are two of the most toxic pollutants, introduced into natural waters from a variety of sources and causing various adverse effects on living bodies. The performance of three filter bed methods was evaluated in the laboratory. Experiments were conducted to investigate the sorption of arsenic and chromium on carbon steel and removal of trace elements from drinking water with a household filtration process. The affinity of the arsenic and chromium species for Fe/Fe3C (iron/iron carbide) sites is the key factor controlling the removal of the elements. The method is based on the use of powdered block carbon, powder carbon steel and ceramic spheres in the ion-sorption columns as a cleaning process. The modified powdered block carbon is a satisfactory and economical sorbent for trace elements (arsenite and chromate) dissolved in water due to its low unit cost of about $23 and compatibility with the traditional household filtration system.


Assuntos
Carbono/química , Oligoelementos/análise , Poluentes da Água/análise , Purificação da Água/métodos , Água/química , Arsênio/análise , Cromo/análise , Meio Ambiente , Monitoramento Ambiental , Concentração de Íons de Hidrogênio , Íons , Ferro/química , Microscopia Eletrônica de Varredura , Modelos Químicos , Prótons
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