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1.
Langenbecks Arch Surg ; 408(1): 22, 2023 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-36635466

RESUMEN

STUDY DESIGN: A randomized, controlled, prospective multicenter clinical trial with a parallel group design was initiated in eight surgical centers to compare a large-pore polypropylene mesh (Ultrapro®) to a small-pore polypropylene mesh (Premilene®) within a standardized retromuscular meshplasty for incisional hernia repair. METHODS: Between 2004 and 2006, patients with a fascial defect with a minimum diameter of 4 cm after vertical midline laparotomy were recruited for the trial. Patients underwent retromuscular meshplasty with either a large-pore or a small-pore mesh to identify the superiority of the large-pore mesh. Follow-up visits were scheduled at 5 and 21 days and 4, 12, and 24 months after surgery. A clinical examination, a modified short form 36 (SF-36®), a daily activity questionnaire, and an ultrasound investigation of the abdominal wall were completed at every follow-up visit. The primary outcome criterion was foreign body sensation at the 12-month visit, and the secondary endpoint criteria were the occurrence of hematoma, seroma, and chronic pain within 24 months postoperatively. RESULTS: In 8 centers, 181 patients were included in the study. Neither foreign body sensation within the first year after surgery (27.5% Ultrapro®, 32.2% Premilene®) nor the time until the first occurrence of foreign body sensation within the first year was significantly different between the groups. Regarding the secondary endpoints, no significant differences could be observed. At the 2-year follow-up, recurrences occurred in 5 Ultrapro® patients (5.5%) and 4 Premilene® patients (4.4%). CONCLUSION: Despite considerable differences in theoretical and experimental works, we have not been able to identify differences in surgical or patient-reported outcomes between the use of large- and small-pore meshes for retromuscular incisional hernia repair. TRIAL REGISTRATION: Clinical Trials NCT04961346 (16.06.2021) retrospectively registered.


Asunto(s)
Cuerpos Extraños , Hernia Ventral , Hernia Incisional , Humanos , Hernia Incisional/cirugía , Polipropilenos , Estudios Prospectivos , Hernia Ventral/cirugía , Mallas Quirúrgicas , Cuerpos Extraños/cirugía , Herniorrafia/efectos adversos
2.
PLoS One ; 17(8): e0272853, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35972977

RESUMEN

BACKGROUND: The Global Trigger Tool (GTT) has become a worldwide used method for estimating adverse events through a retrospective patient record review. However, little is known about the facilitators and the challenges in the GTT-implementation process. Thus, this study followed two aims: First, to apply a comprehensive set of feasibility criteria to qualitatively and systematically assess the GTT-implementation process in three departments of German university hospitals. Second, to identify the facilitators and the obstacles met in the GTT-implementation process and to derive recommendations for supporting other hospitals in implementing the GTT in clinical practice. METHODS: The study used a qualitative documentary method based on process documentation, with written and verbal feedback from the reviewer, as well as evaluating the study sites during the implementation process. The study was conducted in three departments, each in a different German university hospital. The authors applied a comprehensive set of 22 feasibility criteria assessing the level of challenge in GTT implementation. The results were synthesized and they focused on the facilitators and the challenges. RESULTS: Of these 22 feasibility criteria, nine were assessed as a low-level challenge, eleven regarded as a moderate-level challenge, and two with a problematic level of challenge. In particular, the lack of time and staff resources, the quality of the information in the patient records, organizational procedures, and local issues, posed major challenges in the implementation process. By contrast, the use of local coordinators and an external expert made important contributions to the GTT implementation. CONCLUSIONS: Considering the facilitators and the obstacles beforehand may help with the implementation of the GTT in routine practice. In particular, early and effective planning can reduce or prevent critical challenges in terms of time, staff resources, and organizational aspects.


Asunto(s)
Registros Médicos , Estudios de Factibilidad , Humanos , Factores Desencadenantes , Estudios Retrospectivos
3.
Eur J Endocrinol ; 186(2): 223-231, 2022 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-34871180

RESUMEN

AIM: Calcitonin (Ctn) measurement in patients with thyroid disease could potentially increase the detection rates of medullary thyroid carcinoma (MTC) but remains a controversial issue. The aim of this study was to evaluate routine preoperative Ctn measurements. METHODS: All patients with thyroid surgery documented in the prospective StuDoQ|Thyroid registry between March 2017 and September 2020 were included. Cutoff levels for Ctn were determined with receiver-operating characteristic analyses to assess the preoperative diagnosis of MTC in subgroups for females and males. FINDINGS: In 29 590 of 39 679 patients (75%) participating in the registry, routine preoperative Ctn testing was performed. In 357 patients (227 females and 130 males), histopathology confirmed MTC with a mean tumor size of 14.7 mm (±12.43). Biochemical cure was achieved in 71.4% of the patients. Ctn levels between 11 and 20 pg/mL were seen in 2.6% of the patients, and only 0.7% of the patients had Ctn levels above 21 pg/mL. Cutoff levels for the diagnosis of MTC were 7.9 pg/mL for females and 15 pg/mL for males (P < 0.001). The sensitivity and specificity for females were 95 and 98%, and 96 and 97% for males, respectively. CONCLUSION: Routine Ctn testing is a reliable predictor for MTC and provides the opportunity for earlier thyroidectomy before lymph node metastases occur, resulting in a better prognosis. Females with Ctn levels >7.9 pg/mL and males >15 pg/mL without any other extrathyroidal sources for an elevated Ctn should be monitored. Thyroid surgery should be considered if Ctn levels are increasing or ultrasound detects suspicious thyroid lesions.


Asunto(s)
Biomarcadores de Tumor/sangre , Calcitonina/sangre , Carcinoma Neuroendocrino/sangre , Periodo Preoperatorio , Enfermedades de la Tiroides/cirugía , Neoplasias de la Tiroides/sangre , Adulto , Anciano , Anciano de 80 o más Años , Austria/epidemiología , Carcinoma Neuroendocrino/patología , Carcinoma Neuroendocrino/cirugía , Femenino , Alemania/epidemiología , Humanos , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Neoplasia Endocrina Múltiple Tipo 2a/epidemiología , Pronóstico , Valores de Referencia , Sensibilidad y Especificidad , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Ultrasonografía
4.
J Patient Saf ; 16(4): e340-e351, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33215895

RESUMEN

OBJECTIVE: The aim of the study was to assess the feasibility and potential of the Global Trigger Tool (GTT) for identifying adverse events (AEs) in different specialties in German hospitals. METHODS: A total of 120 patient records were randomly selected from two surgical and one neurosurgery departments of three university hospitals in Germany for a period of 2 months per department between January and July 2017. The records were reviewed using an adaptation of the German version of the Institute for Healthcare Improvement GTT. RESULTS: Thirty-nine records (32.5%) contained at least one AE. A total of 53 AEs were found in these 39 records. The incidences of AEs were 18.9% and 35.9% in the two surgical departments and 45.3% in neurosurgery. This corresponded to AE rates of 25.5 to 72.1 per 1000 patient-days and from 25.0 to 60.0 per 100 admissions across the three departments. A total of 71.7% of all identified AEs resulted in temporary harm (category E), 26.4% in temporary harm, requiring prolonged hospitalization (category F), and 1.9% in permanent patient harm. We also identified practical challenges, such as the necessary adaptation of the GTT relative to the respective department. CONCLUSIONS: The application of the GTT is feasible and represents an effective instrument for quality measurement when adapted to the departmental specifics. The trigger detection with the GTT is a valuable addition for proactive analyses of high-risk processes.


Asunto(s)
Cirugía General/normas , Errores Médicos/estadística & datos numéricos , Neurocirugia/métodos , Seguridad del Paciente/normas , Indicadores de Calidad de la Atención de Salud/normas , Gestión de Riesgos/métodos , Estudios Transversales , Alemania , Humanos , Estudios Retrospectivos
5.
JCI Insight ; 4(2)2019 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-30674727

RESUMEN

Polypropylene meshes that are commonly used for inguinal hernia repair may trigger granulomatous foreign body reactions. Here, we show that asymptomatic patients display mesh-associated inflammatory granulomas long after surgery, which are dominated by monocyte-derived macrophages expressing high levels of inflammatory activation markers. In mice, mesh implantation by the onlay technique induced rapid and strong myeloid cell accumulation, without substantial attenuation for up to 90 days. Myeloid cells segregated into distinct macrophage subsets with separate spatial distribution, activation profiles, and functional properties, showing a stable inflammatory phenotype in the tissue surrounding the biomaterial and a mixed, wound-healing phenotype in the surrounding stromal tissue. Protein mass spectrometry confirmed the inflammatory nature of the foreign body reaction, as characterized by cytokines, complement activation, and matrix-modulating factors. Moreover, immunoglobulin deposition increased over time around the implant, arguing for humoral immune responses in association with the cell-driven inflammation. Intravital multiphoton microscopy revealed a high motility and continuous recruitment of myeloid cells, which is partly dependent on the chemokine receptor CCR2. CCR2-dependent macrophages are particular drivers of fibroblast proliferation. Thus, our work functionally characterizes myeloid cell-dependent inflammation following mesh implantation, thereby providing insights into the dynamics and mechanisms of foreign body reactions to implanted biomaterials.

6.
Int J Colorectal Dis ; 34(1): 55-61, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30250969

RESUMEN

PURPOSE: While many hospitals consider a continuous sutured colonic anastomosis with monofilamental fiber the current state of the art, others have advocated for interrupted sutures as the gold standard. The aim of the study was to evaluate the influence of suture technique on leakage rate (primary endpoint), wound infections, postoperative stay, and mortality. METHODS: Retrospective analyses of 347 patients (273 elective, 74 urgent) over 6 years with a handsewn colonic anastomosis (190 interrupted, 157 continuous), excluding sigma and rectum anastomosis. Demographic and surgical baseline characteristics were used as competing predictors. RESULTS: Overall leakage rate was 9% but strongly dependent on suture technique (interrupted: 16%; continuous: 2.5%; p = 0.001) yielding an odds ratio of 5.10 [95% CI: 2.55, 6.71] (relative risk of leakage). No other variable showed a significant influence on leakage rate. Postoperative stay was prolonged in the interrupted suture group (23 ± 15 vs. 16 ± 11 days; p = 0.000, attributable effect 7.5 days [4.7, 10.3]). CONCLUSIONS: Our results indicate a highly significant reduction of anastomotic leakage rate and postoperative stay that generalize to the underlying population by continuous sutures in handsewn colonic anastomosis. In the absence of randomized prospective studies, the current results provide the yet strongest evidence for the superiority of continuous sutures.


Asunto(s)
Fuga Anastomótica/etiología , Técnicas de Sutura/efectos adversos , Suturas , Anciano , Colectomía , Determinación de Punto Final , Femenino , Humanos , Válvula Ileocecal/cirugía , Masculino , Estudios Retrospectivos
7.
Hepatobiliary Pancreat Dis Int ; 18(1): 28-37, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30115516

RESUMEN

BACKGROUND: Hepatocellular carcinoma is the most common innate liver tumor. Due to improved surgical techniques, even extended resections are feasible, and more patients can be treated with curative intent. As the liver is the central metabolic organ, preoperative metabolic assessment is crucial for risk stratification. Sarcopenia, obesity and sarcopenic obesity characterize body composition and metabolic status. Here we present the impact of body composition on survival after liver resection in patients with hepatocellular carcinoma. METHODS: A retrospective database analysis of 70 patients who were assigned for liver resection due to hepatocellular carcinoma was conducted. For assessment of sarcopenia and obesity, skeletal muscle surface area was measured at lumbar vertebra 3 level (L3) in preoperative four-phase contrast enhanced abdominal CT scans, and L3 muscle index and body fat percentage were calculated. RESULTS: Univariate analysis comparing the survival curves using the score test demonstrated superior postoperative overall survival for sarcopenic (P = 0.035) and sarcopenic obese (P = 0.048) patients as well as a trend favoring obese (P = 0.130) subjects. Whereas multivariate analysis could not identify significant difference in postoperative survival regarding sarcopenia, obesity or sarcopenic obesity. Only large tumor size, multifocal disease and male gender were risk factors for long-term survival. CONCLUSIONS: Sarcopenia, obesity and sarcopenic obesity are indeed no risk factors for poor postoperative survival in this study. Our data do not support the evaluation of sarcopenia, obesity and sarcopenic obesity before liver resection in hepatocellular carcinoma patients.


Asunto(s)
Composición Corporal , Carcinoma Hepatocelular/cirugía , Hepatectomía , Neoplasias Hepáticas/cirugía , Obesidad/fisiopatología , Sarcopenia/fisiopatología , Adiposidad , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Bases de Datos Factuales , Femenino , Estado de Salud , Hepatectomía/efectos adversos , Hepatectomía/mortalidad , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Músculo Esquelético/fisiopatología , Obesidad/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Sarcopenia/mortalidad , Factores de Tiempo , Resultado del Tratamiento
8.
Lymphat Res Biol ; 16(6): 525-532, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30281382

RESUMEN

Background: In the past, measurement of upper limb lymphedema was done by water displacement (WD), which is frequently cited as the gold standard. For various reasons, however, the use of WD is restricted in clinical settings. A more precise and easy-to-use method would be favorable. The high precision of three-dimensional (3D) imaging in comparison to WD has already been reported for healthy subjects. The aim of this study is to determine the validity and reliability of 3D imaging by comparing it to the WD method in women with unilateral upper limb lymphedema. Methods and Results: Thirty-nine women with unilateral breast cancer-related lymphedema (BCRL) were included, of which 37 completed two volume measurement techniques (3D and WD) on the BCRL and contralateral healthy arm. Slightly larger volumes were measured by the WD method in healthy arms (+9.8 mL; p = 0.058) and also in BCRL arms (+18.5 mL; p < 0.001). All measurements were performed twice by the same researcher to evaluate reliability. There was no significant difference between the two measurements for healthy arms (p = 0.323) or BCRL arms (p = 0.807) in 3D imaging. Bland-Altman plots showed a high limit of agreement between the single measurements. 3D imaging had a high intrarater reliability (Intraclass Correlation Coefficient = 0.999). Conclusion: Results show that 3D imaging is an innovative method for measuring upper limb volume in BCRL patients. Even though image processing is time consuming, 3D imaging combines high reproducibility with high precision. By software automation, this technique could easily be integrated into clinical routine. It is for this reason that we would recommend implementing the Vectra 3D imaging technique for measurement of BCRL.


Asunto(s)
Linfedema del Cáncer de Mama/diagnóstico por imagen , Neoplasias de la Mama/complicaciones , Imagenología Tridimensional/métodos , Fotograbar/métodos , Extremidad Superior/diagnóstico por imagen , Adulto , Anciano , Análisis de Varianza , Linfedema del Cáncer de Mama/etiología , Linfedema del Cáncer de Mama/patología , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Estudios Transversales , Femenino , Humanos , Imagenología Tridimensional/instrumentación , Imagenología Tridimensional/normas , Persona de Mediana Edad , Fotograbar/instrumentación , Fotograbar/normas , Reproducibilidad de los Resultados , Extremidad Superior/patología
9.
J Clin Med ; 7(11)2018 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-30373147

RESUMEN

For colorectal liver metastases (CRLM), surgical resection is the only potentially curative therapy, but even successfully resected patients often face disease recurrence, leading to 5-year survival rate below 50%. Despite available preoperative stratification strategies, it is not fully elucidated which patients actually benefit from CRLM resection. Here we evaluated osteopontin, a secreted glyco-phosphoprotein, as a biomarker in the context of CRLM resection. Tissue levels of osteopontin were analysed in CRLM using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. Pre- and postoperative osteopontin serum concentrations were analysed by enzyme-linked immunosorbent assay (ELISA) in 125 patients undergoing resection of CRLM as well as 65 healthy controls. Correlating with an upregulation of osteopontin tissue expression in CRLM, osteopontin serum levels were significantly elevated in patients with CRLM compared to healthy controls. Importantly, high pre- and post-operative osteopontin serum levels were associated with a poor prognosis after tumour resection. Patients with initial osteopontin serum levels above our ideal cut-off value of 264.4 ng/mL showed a significantly impaired median overall survival of 304 days compared to 1394 days for patients with low osteopontin levels. Together, our data suggest a role of osteopontin as a prognostic biomarker in patients with resectable CRLM that might help to identify patients who particularly benefit from liver resection.

10.
J Clin Med ; 7(7)2018 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-30011858

RESUMEN

The tumor necrosis factor⁻related weak inducer of apoptosis (TWEAK) belongs to the tumor necrosis factor ligand superfamily, which was shown to play an important role in inflammatory and malignant gastrointestinal diseases, including colitis or colorectal cancer. However, in contrast to other members of the TNF ligand superfamily, its role as a biomarker in pancreatic cancer is currently unknown. We analyzed serum levels of A proliferation-inducing ligand (APRIL) and TWEAK in 134 patients with pancreatic cancer. Results were compared with 50 healthy controls and correlated with clinical data. Intratumoral expression of APRIL and TWEAK in pancreatic cancer was analysed using the datasets made available by the TCGA-LIHC project. APRIL serum levels were significantly elevated in patients with pancreatic cancer compared to healthy controls, which is in line with previous findings. Notably, the diagnostic accuracy of circulating APRIL levels was similar to CA19-9, an established tumor marker for pancreatic cancer. In contrast, serum concentrations of TWEAK were decreased in pancreatic cancer patients. Interestingly, no differences in TWEAK concentrations became apparent between different clinical subgroups of pancreatic cancer. Moreover, within our cohort of patients, TWEAK levels did not correlate with the patients' prognosis and the diagnostic as well as prognostic potential of TWEAK was lower than CA 19-9, when analyzed in this setting. Finally, using data from the TCGA-LIHC project, we demonstrate that expression levels of TWEAK and APRIL represent prognostic markers for patients' survival according to Kaplan-Meier curve analyses. TWEAK and APRIL serum concentrations are regulated differently in patients with pancreatic cancer, highlighting diverse roles of variant TNF ligands in this type of cancer.

11.
Oncotarget ; 9(43): 27027-27038, 2018 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-29930748

RESUMEN

BACKGROUND: In colorectal cancer (CRC), the liver is the most common site of metastasis. Surgical resection represents the standard therapy for patients with colorectal liver metastases (CRLM). However, 5-year survival rates after resection do not exceed 50%, and despite existing preoperative stratification algorithms it is still debated which patients benefit most from surgical treatment. The soluble urokinase plasminogen activator receptor (suPAR) has recently evolved as a promising biomarker for distinct clinical conditions. Here, we examined a potential role of suPAR as a biomarker in patients undergoing resection of CRLM. RESULTS: Correlating with upregulated uPAR tissue expression in resected metastases, serum concentrations of suPAR were significantly elevated in CRLM patients compared to healthy controls. Importantly, patients with preoperative suPAR serum levels above the identified ideal cut-off value of 4.83 ng/ml showed a significantly reduced overall survival after resection of CRLM, both in right- and left-sided primary CRC. Moreover, multivariate Cox regression analysis revealed preoperative suPAR serum levels as a prognostic factor for mortality. Additionally, elevated preoperative suPAR but not creatinine levels were a predictor of acute kidney injury (AKI) after CRLM resection, correlating with a longer postoperative hospitalization. CONCLUSION: SuPAR represents a promising novel biomarker in CRLM patients that might help to guide preoperative treatment decisions regarding patients' outcome and to identify patients particularly susceptible to AKI. METHODS: Expression levels of uPAR were analyzed in CRLM tissue using RT-PCR and immunohistochemistry. SuPAR serum levels were measured by ELISA in 104 CRC patients undergoing hepatic resection for CRLM and 50 healthy controls.

12.
J Surg Res ; 222: 85-92, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29273379

RESUMEN

BACKGROUND: Abdominal adhesions are one of the most common complications after abdominal surgery, and fibrin is suspected to be a crucial component. The aim of the current study was an in vivo evaluation of a new recombinant fibrinogenase (AK03) in two animal models. METHODS: Sixty-four rats were randomly divided into four groups (sodium chloride [NaCl], icodextrin, AK03 low dose, and AK03 high dose) and evaluated at two time endpoints. Adhesion model comprised both a visceral defect (terminal ileum) and parietal defect. Test (AK03) and control substances (NaCl and icodextrin) were administered intraperitoneally after setting the intraabdominal defects. A second dose was administered 24 h after surgery. Plasma fibrinogen values were taken at baseline and after 7 and 21 d, respectively. Rats were sacrificed after 7 or 21 d for macroscopic (Diamond score) and immunohistochemical investigations. RESULTS: After 7 and 21 d, the Diamond score of postsurgical adhesions were significantly lower in both AK03-treated groups compared with NaCl control group (P = 0.02). There were no unspecific systemic side effects in both treatment groups and no decrease in plasma fibrinogen concentration. In none of the four groups was there any evidence for impaired wound repair. Microscopically in the area of the parietal defect, we saw less cluster of differentiation 3+ T-lymphocytes and cluster of differentiation 68+ macrophages in both groups receiving AK03 compared with the NaCl and icodextrin control groups. CONCLUSIONS: The results of this study indicate that the new recombinant fibrinogenase AK03 effectively prevents peritoneal adhesions without causing side effects, notably systemic fibrinogen depletion, bleeding, or impaired wound repair. Due to these results, future clinical studies may be promising.


Asunto(s)
Adherencias Tisulares/prevención & control , Animales , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Ciclooxigenasa 2/metabolismo , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Femenino , Fibrinógeno/metabolismo , Masculino , Peritoneo/inmunología , Peritoneo/metabolismo , Distribución Aleatoria , Ratas Sprague-Dawley , Porcinos , Porcinos Enanos , Vimentina/metabolismo
13.
Sci Rep ; 7(1): 16975, 2017 12 05.
Artículo en Inglés | MEDLINE | ID: mdl-29208940

RESUMEN

Cholangiocarcinoma (CCA) represents a rare form of primary liver cancer with increasing incidence but dismal prognosis. Surgical treatment has remained the only potentially curative treatment option, but it remains unclear which patients benefit most from liver surgery, highlighting the need for new preoperative stratification strategies. In clinical routine, CA19-9 represents the most widely used tumor marker in CCA patients. However, data on the prognostic value of CA19-9 in CCA patients are limited and often inconclusive, mostly due to small cohort sizes. Here, we investigated the prognostic value of CA19-9 in comparison with other standard laboratory markers in a large cohort of CCA patients that underwent tumor resection. Of note, while CA19-9 and CEA were able to discriminate between CCA and healthy controls, CEA showed a higher accuracy for the differentiation between CCA and patients with primary sclerosing cholangitis (PSC) compared to CA19-9. Furthermore, patients with elevated levels of C-reactive protein (CRP), CA19-9 or CEA showed a significantly impaired survival in Kaplan-Meier curve analysis, but surprisingly, only CEA but not CA19-9 represented an independent predictor of survival in multivariate Cox-regression analysis. Our data suggest that CEA might help to identify CCA patients with an unfavourable prognosis after tumor resection.


Asunto(s)
Neoplasias de los Conductos Biliares/cirugía , Antígeno CA-19-9/sangre , Antígeno Carcinoembrionario/sangre , Colangiocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de los Conductos Biliares/mortalidad , Biomarcadores de Tumor/sangre , Estudios de Casos y Controles , Colangiocarcinoma/mortalidad , Colangitis Esclerosante/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios , Pronóstico , Resultado del Tratamiento
14.
Oncotarget ; 8(49): 86253-86263, 2017 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-29156792

RESUMEN

Non-invasive molecular analysis of circulating tumor DNA (ctDNA) is a promising application in personalized cancer management, although there is still much to learn about the biological characteristics of ctDNA. The present study compared absolute amounts of KRAS mutated ctDNA and total circulating cell-free DNA (cfDNA) in colorectal cancer (CRC) patients (n=50) from various stages and healthy controls (n=8) by Intplex allele-specific and digital droplet PCR. In addition, the impact of two prominent extraction techniques (silica-based membrane vs. magnetic beads) on cfDNA and ctDNA recovery was analyzed in 38 paired samples from CRC patients and specific spike-in DNA controls. CfDNA fragment size was assessed using the Agilent 2100 Bioanalyzer. Relative quantities of total cfDNA quantities were measured using the Qubit fluorometer. Statistical analysis on total cfDNA yield revealed a strong correlation (r=0.976) between Qubit and absolute Intplex allele-specific PCR measurements in cancer patients and healthy controls. Total cfDNA was significantly increased in cancer patients compared to healthy controls, with the highest yield in distant metastatic disease. In line, the highest amount of ctDNA (1.35 ng/µL) was found in patients with distant organ metastasis. Of great interest, the silica-based membrane method significantly promoted extraction of long cfDNA fragments. In contrast, the magnetic bead system more efficiently recovered short cfDNA fragments in serum of cancer patients. Further, a decreased KRAS allele frequency was observed in serum compared to plasma. This study suggests that the source of cfDNA and choice of pre-analytical extraction systems needs to be more carefully validated in routine clinical practice.

15.
J Hepatol ; 67(4): 749-757, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28668580

RESUMEN

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.


Asunto(s)
Neoplasias de los Conductos Biliares/sangre , Biomarcadores de Tumor/sangre , Colangiocarcinoma/sangre , Osteopontina/sangre , Adulto , Anciano , Anciano de 80 o más Años , Animales , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/cirugía , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Estudios de Casos y Controles , Colangiocarcinoma/genética , Colangiocarcinoma/cirugía , Estudios de Cohortes , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Ratones , Persona de Mediana Edad , Osteopontina/genética , Osteopontina/metabolismo , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo
16.
Z Gastroenterol ; 55(1): 56-62, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27706546

RESUMEN

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.


Asunto(s)
Adenocarcinoma/diagnóstico , Adenocarcinoma/secundario , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundario , Trasplante de Hígado/efectos adversos , Grupo de Atención al Paciente/organización & administración , Adenocarcinoma/etiología , Anciano , Diagnóstico Diferencial , Selección de Donante/métodos , Femenino , Alemania , Humanos , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Donantes de Tejidos
17.
Ann Vasc Surg ; 39: 287.e15-287.e20, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27671449

RESUMEN

Aortoesophageal fistulas (AEFs) are rare and life-threatening conditions. Till date, an association between an AEF and sarcoidosis has not been reported yet. The aim of this report is to demonstrate a case of AEF secondary to sarcoidosis and its multistage interdisciplinary surgical therapy. A 66-year-old male was diagnosed with sarcoidosis in 2014. He has been treated with glucocorticoids since then and no severe health restrictions due to the disease have occurred. In December 2015, the patient presented with acute thoracic pain and hematemesis: an esophagogastroscopy revealed an AEF. First, stent-graft implantation in the thoracic aorta was urgently performed as a "bridging" procedure. Second, esophagectomy and local debridement were performed, followed by explantation of the stent graft and reconstruction by means of xenograft replacement of the stented aorta in a third operation. Finally, retrosternal gastric pull-up was performed in a fourth operative procedure. Sixteen days after the last operation the patient could be discharged to a rehabilitation clinic. Follow-up is uneventful so far; the antibiotic therapy was stopped at the time of hospital discharge. The pathogenesis of sarcoidosis, a rare autoimmunological disease, has not been completely clarified yet. The diagnosis relies on clinical symptoms and radiological as well as histopathological findings. Many cases of sarcoidosis show spontaneous regression, but severe complications may occur. While tracheoesophageal fistulas have been described in the literature, AEFs related to sarcoidosis have not been mentioned yet. Despite surgical and antibiotic treatment, the morbidity and mortality rates of AEF are high. Because the endovascular treatment has been established for emergency procedures of the aorta, it is considered as an appropriate first-line "bridging" treatment option. To achieve good long-term results, surgical treatment has to involve esophagectomy with secondary reconstruction of the upper gastrointestinal tract, as well as open aortic replacement using xenograft or homograft material. Sarcoidosis may lead to AEF as demonstrated in this case. Successful treatment can be realized by a multistage interdisciplinary surgical approach.


Asunto(s)
Aorta Torácica/cirugía , Enfermedades de la Aorta/cirugía , Implantación de Prótesis Vascular , Remoción de Dispositivos , Procedimientos Quirúrgicos del Sistema Digestivo , Fístula Esofágica/cirugía , Grupo de Atención al Paciente , Sarcoidosis/complicaciones , Fístula Vascular/cirugía , Anciano , Antibacterianos/uso terapéutico , Aorta Torácica/diagnóstico por imagen , Enfermedades de la Aorta/diagnóstico por imagen , Enfermedades de la Aorta/etiología , Aortografía/métodos , Prótesis Vascular , Implantación de Prótesis Vascular/instrumentación , Angiografía por Tomografía Computarizada , Desbridamiento , Urgencias Médicas , Fístula Esofágica/diagnóstico por imagen , Fístula Esofágica/etiología , Esofagectomía , Esofagostomía , Gastroscopía , Glucocorticoides/uso terapéutico , Xenoinjertos , Humanos , Comunicación Interdisciplinaria , Masculino , Sarcoidosis/diagnóstico , Sarcoidosis/tratamiento farmacológico , Stents , Resultado del Tratamiento , Fístula Vascular/diagnóstico por imagen , Fístula Vascular/etiología
18.
BMC Med Educ ; 16: 45, 2016 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-26842357

RESUMEN

BACKGROUND: In recent years the focus on practical skills in the German curriculum of medical school has increased greatly. In this study we evaluate the value of a practical surgery course for medical students as a tool for surgical education, as a way of enhancing interest in surgical fields, and as a method of influencing medical students to subsequently choose a surgical career. METHODS: The "Feel like a surgeon"-course is an optional practical surgery course in which topographical anatomy and realistic surgical training using fresh human cadavers are combined for medical students of the RWTH Aachen University. Between 2010 and 2015 every student completed a survey before starting and after completing our course, and in 2015 a follow-up was performed. Using a standardized questionnaire, course quality, learning success and impact on post-instructional career and choice of profession was evaluated. RESULTS: In total, 82 students attended our course between 2010 and 2015 and took part in the evaluation. Evaluation of the course was positive overall, with an average grade of 1.4° ± °0.50. Significant improvement of basic, as well as more complex surgical skills and theoretical knowledge was noted. Furthermore, self-confidence for patient related assignments improved as well. In the follow-up evaluation, a high level of recommendation for surgical residents was seen, as was a high influence of the course on our students' career choice, although no significant change in career plans before and after taking the course was noted. CONCLUSIONS: Our results indicate that a practical surgical course can be a valuable tool to prepare students for a surgical residency and to improve their practical skills generally.


Asunto(s)
Competencia Clínica/normas , Educación Médica/organización & administración , Cirugía General/educación , Estudiantes de Medicina/psicología , Adulto , Cadáver , Selección de Profesión , Educación Médica/métodos , Femenino , Alemania , Humanos , Masculino , Modelos Educacionales , Evaluación de Programas y Proyectos de Salud , Adulto Joven
19.
Int J Colorectal Dis ; 30(11): 1571-80, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26260480

RESUMEN

PURPOSE: Intestinal anastomosis is a fundamental procedure in general surgery and required to restore intestinal continuity following resection. The aim of this study was to evaluate whether a gentamicin-coated polyvinylidene fluoride (PVDF) suture material has beneficial effect on anastomotic healing. METHODS: Ninety Sprague-Dawley rats were divided into three groups: a PVDF-suture group, a gentamicin-coated PVDF (GPVDF)-suture group and a control group using Maxon® (polyglycolid-co-trimethylene carbonate). For each animal, a colonic anastomosis was performed. Ten animals from each group were sacrificed on postoperative days 3, 5, and 14. Measurements of anastomotic bursting pressure were performed on days 3 and 5. At each time, collagen type I/III ratio, MMP 2 and MMP-9 expression and the proliferation index (Ki67) were analyzed. RESULTS: In total, 90 animals underwent surgery without postoperative complications. Bursting strength in the GPVDF group was significantly elevated on day 5. Immunohistochemistry showed significant increase of the collagen type I/III ratio for PVDF and GPVDF on days 3 and 5. MMP2 was significantly increased for PVDF on days 3 and 5 and for GPVDF on day 5. The analysis of MMP9 revealed significant increase compared to control on day 3 and 5 (GPVDF) as well as on day 5 (PVDF). Staining for Ki67 revealed a significant elevation on postoperative day 3 for the PVDF and the GPVDF group. CONCLUSIONS: The present data shows the feasibility of PVDF as suture material for colonic anastomosis and confirms the ability of gentamicin to increase the stability of colonic anastomosis when used as coating material.


Asunto(s)
Gentamicinas , Intestinos/cirugía , Polivinilos , Inhibidores de la Síntesis de la Proteína , Suturas , Cicatrización de Heridas/efectos de los fármacos , Anastomosis Quirúrgica , Animales , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Antígeno Ki-67/metabolismo , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Modelos Animales , Ratas Sprague-Dawley , Resistencia a la Tracción , Cicatrización de Heridas/fisiología
20.
HPB (Oxford) ; 17(8): 732-5, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26096195

RESUMEN

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.


Asunto(s)
Desbridamiento , Tiempo de Internación , Absceso Hepático/cirugía , Tempo Operativo , Cirugía Asistida por Video , Adulto , Anciano , Estudios de Factibilidad , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Cirugía Asistida por Video/métodos
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