RESUMEN
BACKGROUND: The surgical approach of choice in the treatment of symptomatic cholecystolithiasis is considered to be elective laparoscopic cholecystectomy (CCE) as the established gold standard. Today, approximately 80-90% of CCE are performed using a laparoscopic approach whereas the remaining portion undergoes primary conventional CCE, however, in 6% conversion is necessary. AIM: Since pathological aspects found intraoperatively and finally requiring conversion are correlated to an increased risk for complications, it appears reasonable to assess the risk factors prior to operation. PATIENTS AND METHODS: Through a well defined study period of 9 years, all consecutive patients who underwent CCE for cholecystolithiasis at the Municipal Hospital "HELIOS Klinikum Aue" were enrolled in a registry comparing laparoscopic and conversion CCE. Diverse parameters were tested as to whether they increase significantly the risk for conversion. The intensity of each factor-associated impact on a possible conversion was determined. RESULTS: From 2001 to 2009 1477 patients underwent CCE at the Municipal Hospital "Helios Klinikum Aue", out of them 131 (8.9%) cases were primarily treated by conventional CCE whereas in the vast majority (1346 subjects [91.1%]), laparoscopic CCE was the initial approach. However, conversion became necessary in 106 individuals resulting in a conversion rate of 7.9%. Comparing data obtained from laparoscopic CCE with those from open procedure after conversion, there were significant differences in operating time, complication rate and postoperative hospital stay (p = 0.01). Over the study period, there were 5 cases (0.37%) with iatrogenic injuries of the biliary system. Hospital mortality was 0.08% in the laparoscopic and 2.8% in the conversion group. The following parameters were found to have a significant impact on the risk for conversion (univariate analysis): elevation of CRP, preoperative ERCP, renal insufficiency, previous laparotomy, histological grade M3 (ulcerous, haemorrhagic necrotising cholecystitis, perforation of the gall bladder) and M4 (carcinoma of the gall bladder). While in the spectrum of preoperative factors former ERCP, elevation of CRP and terminal renal insufficiency were most relevant (2- to 3-fold each), histological grade M3 and M4, 7- and 14-fold, respectively, showed the greatest impact on conversion rate highlighting the profile of postoperative parameters. CONCLUSION: The main focus is directed to keep the conversion rate low. In case of diagnosing a severely inflamed gall bladder, a primarily open procedure or an early decision for conversion should be considered.
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Colecistectomía Laparoscópica/estadística & datos numéricos , Colecistolitiasis/cirugía , Conversión a Cirugía Abierta/estadística & datos numéricos , Complicaciones Intraoperatorias/cirugía , Adulto , Anciano , Comorbilidad , Estudios Transversales , Femenino , Neoplasias de la Vesícula Biliar/epidemiología , Neoplasias de la Vesícula Biliar/cirugía , Alemania , Humanos , Complicaciones Intraoperatorias/epidemiología , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Tempo Operativo , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Hepatic recurrence is seen in approximately 40â% of patients undergoing hepatectomy for colorectal metastases. The authors assessed the benefit and the main prognostic factors for a second liver resection of recurrent colorectal metastases. METHODS: This study reports the experience with second liver resections for recurrent liver metastases at a German University Hospital. A total of 39 parameters from 60 patients were identified from a prospective database and analysed as to their influence on recurrence-free survival and overall survival. RESULTS: At a median follow-up of 26 months (range: 2-173 months) after second hepatic resection, recurrence-free survival at 3 and 5 years were 50â% and 37â%, respectively. The overall survival at three and five years were 61â% and 52â%, respectively. Recurrence was identified in 58.3â% of the patients. Recurrences involved exclusively the liver in 19 patients (31.6â%). By multivariate analysis (Cox proportional hazard model), a time interval between diagnosis of the liver metastases of less than 24 months after operation for colorectal primary carcinoma (HR: 6.47, p = 0.002), a CEA level of 4.0 ng/mL or more (HR: 3.48, p = 0.004) at the time of first liver metastases and a size of second liver metastases of 80 mm or more (HR: 4.73, p = 0.007) were independent prognostic factors for a reduced recurrence-free survival. A repeat recurrence of liver metastases without the option of curative resection was the only risk factor for overall survival after second hepatic resection (p = 0.009). In these cases, mortality risk was 4.51-fold, however, when the second liver recurrence was resectable, the mortality risk increased only 1.4-fold. CONCLUSIONS: Technically resectable recurrent colorectal hepatic metastases should be resected the same as the first metastases. Characteristics of the primary metastasis as well as parameters of the hepatic recurrence are shown to influence the prognosis of patients after resection of recurrent liver metastases. Repeat resection of colorectal liver metastases allows for improved survival in patients even after two previous liver operations.
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Neoplasias Colorrectales/cirugía , Hepatectomía , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia/cirugía , Adulto , Anciano , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Conducta Cooperativa , Supervivencia sin Enfermedad , Femenino , Alemania , Hospitales Universitarios , Humanos , Comunicación Interdisciplinaria , Hígado/patología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Pronóstico , Modelos de Riesgos Proporcionales , Reoperación , Carga TumoralRESUMEN
AIMS/HYPOTHESIS: Immunosuppressive drugs used in human islet transplantation interfere with the balance between beta cell renewal and death, and thus may contribute to progressive graft dysfunction. We analysed the influence of immunosuppressants on the proliferation of transplanted alpha and beta cells after syngeneic islet transplantation in streptozotocin-induced diabetic mice. METHODS: C57BL/6 diabetic mice were transplanted with syngeneic islets in the liver and simultaneously abdominally implanted with a mini-osmotic pump delivering BrdU alone or together with an immunosuppressant (tacrolimus, sirolimus, everolimus or mycophenolate mofetil [MMF]). Glycaemic control was assessed for 4 weeks. The area and proliferation of transplanted alpha and beta cells were subsequently quantified. RESULTS: After 4 weeks, glycaemia was significantly higher in treated mice than in controls. Insulinaemia was significantly lower in mice treated with everolimus, tacrolimus and sirolimus. MMF was the only immunosuppressant that did not significantly reduce beta cell area or proliferation, albeit its levels were in a lower range than those used in clinical settings. CONCLUSIONS/INTERPRETATION: After transplantation in diabetic mice, syngeneic beta cells have a strong capacity for self-renewal. In contrast to other immunosuppressants, MMF neither impaired beta cell proliferation nor adversely affected the fractional beta cell area. Although human beta cells are less prone to proliferate compared with rodent beta cells, the use of MMF may improve the long-term outcome of islet transplantation.
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Terapia de Inmunosupresión/métodos , Células Secretoras de Insulina/efectos de los fármacos , Trasplante de Islotes Pancreáticos , Animales , Glucemia/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Inmunohistoquímica , Inmunosupresores/farmacología , Ratones , Ratones Endogámicos C57BLRESUMEN
Peripheral arterial occlusive disease is one manifestation of the systemic disease atherosclerosis. The initial therapy for every arteriosclerotic disease is aimed at reducing cardiovascular risk factors by lifestyle modification and medication. Patients who require surgical revascularisation need long-term antiplatelet therapy or anticoagulation. This therapy has to be differentiated according to the vascular territory involved and the method used for revascularisation. After local thrombendarterectomy, alloplastic bypass graft surgery of the aortic, aorto-iliac, aorto-femoral or femoro-popliteal region above the knee, long-term ASA 100 mg/d or clopidogrel 75 mg/d should be initiated. After alloplastic bypass grafting below the knee the combination of ASA 100 mg/d and clopidogrel 75 mg/d should be used. In contrast, after venous grafts the patency rate is improved by anticoagulation with vitamin K antagonists (INR 2-3), if there is a low risk of bleeding. If there is a contraindication to vitamin K antagonists, ASA 100 mg/d should be used. After revascularisation, a structured surveillance programme should be implemented aiming at controlling cardiovascular risk factors and monitoring the vascular state, as well as the anticoagulation and the antiplatelet therapy.
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Enfermedades de la Aorta/cirugía , Implantación de Prótesis Vascular/métodos , Endarterectomía/métodos , Medicina Basada en la Evidencia , Fibrinolíticos/administración & dosificación , Enfermedad Arterial Periférica/cirugía , Complicaciones Posoperatorias/tratamiento farmacológico , Enfermedades de la Aorta/diagnóstico , Aspirina/administración & dosificación , Clopidogrel , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Arteria Femoral/cirugía , Estudios de Seguimiento , Humanos , Arteria Ilíaca/cirugía , Relación Normalizada Internacional , Enfermedad Arterial Periférica/sangre , Enfermedad Arterial Periférica/diagnóstico , Tereftalatos Polietilenos , Politetrafluoroetileno , Arteria Poplítea/cirugía , Complicaciones Posoperatorias/sangre , Diseño de Prótesis , Ticlopidina/administración & dosificación , Ticlopidina/análogos & derivados , Venas/trasplante , Vitamina K/antagonistas & inhibidoresRESUMEN
The dominant role for the emergence and establishment of intensive care medicine can be attributed to surgery. The first critical care units were developed in surgical university hospitals. Numerous scientific findings and interventional procedures have been contributed to intensive care medicine by surgeons and surgical disease symptoms shaped the character of the intensive care units. Currently 40% of the intensive care beds in Germany are assigned to surgical disciplines and surgery is the prerequisite for this operative intensive care. Nevertheless, both the human and ideational impact of surgery on intensive care medicine has decreased in recent decades. Through the formation of large interdisciplinary intensive care units, surgery continues to be threatened with losing its influence even further. Now and in the future, the role of surgery has to be the maintenance and enhancement of surgical specialized intensive care medicine. Surgery has to make surgical intensive care medicine interesting and attractive for physicians again.
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Cuidados Críticos/tendencias , Cirugía General/tendencias , Comunicación Interdisciplinaria , Selección de Profesión , Conducta Cooperativa , Curriculum/tendencias , Predicción , Cirugía General/educación , Alemania , Hospitales Universitarios , Humanos , Satisfacción en el Trabajo , Mejoramiento de la Calidad/tendencias , Especialidades Quirúrgicas/educación , Especialidades Quirúrgicas/tendenciasRESUMEN
Morbidity and mortality conferences have been entitled the "golden hour" of surgical education. There is a long-standing tradition for these conferences in the USA and the United Kingdom. In Germany they are still not fully integrated in the daily clinical work although the positive influence on quality improvement, patient safety and surgical education has been repeatedly proven. Some factors are still hampering the establishment of M & M conferences: the lack of time, worrying about shame and blame and last not least some deficit for a culture of discussions. The commitment of surgeons in leading positions is required for the establishment and further support of -these conferences. In addition to patient safety, one of the main goals is the continuing education of young surgeons. Structuring M & M conferences as well as an intelligent moderation by an experienced surgeon and lively, open and interactive discussions - all these factors are obviously of great importance for improving success in surgery.
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Educación Médica Continua/organización & administración , Cirugía General/educación , Capacitación en Servicio/organización & administración , Errores Médicos/prevención & control , Mejoramiento de la Calidad/organización & administración , Alemania , Humanos , Liderazgo , Evaluación de Resultado en la Atención de Salud/organización & administración , Seguridad del Paciente , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & controlRESUMEN
Infectious agents are likely to play a role in the pathogenesis of chronic inflammatory diseases, including abdominal aortic aneurysms (AAAs). The goal of this study was to determine if Borrelia burgdorferi sensu lato (sl), a microorganism responsible for Lyme disease, is involved in the etiology of AAAs. The presence of serum antibodies against B. burgdorferi sl was measured with enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blotting in 96 AAA and 108 peripheral artery disease (PAD) patients. Polymerase chain reaction (PCR) was used for the detection of Borrelia-specific DNA in the aneurysm wall. Among AAA patients 34% and among PAD patients 16% were seropositive for B. burgdorferi sl antibodies (Fisher's exact test, p = 0.003; odds ratio [OR] 2.79; 95% confidence interval [CI] 1.37-5.85). In the German general population, 3-17% are seropositive for Borrelia antibodies. No Borrelia DNA was detected in the aneurysm wall. Our findings suggest a relationship between AAAs and B. burgdorferi sl. We hypothesize that the underlying mechanism for B. burgdorferi sl in AAA formation is similar to that by the spirochete Treponema pallidum; alternatively, AAAs could develop due to induced autoimmunity via molecular mimicry due to similarities between some of the B. burgdorferi sl proteins and aortic proteins.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Aneurisma de la Aorta Abdominal/epidemiología , Aneurisma de la Aorta Abdominal/etiología , Grupo Borrelia Burgdorferi/inmunología , Enfermedad de Lyme/complicaciones , Anciano , Anciano de 80 o más Años , Western Blotting , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: The creation of a center for interdisciplinary operative intensive care through the fusion of several smaller intensive care units from various specialties is mainly driven by economic reasons. To specify some conditions for making such a fusion less expensive and to identify the impact of larger intensive care units on the quality of patients' treatment and on surgical training are the subjects of this study. MATERIALS AND METHODS: Based on a review of the literature and on our own experience in this field, the influence of the size of the unit should be analysed not just regarding the economic aspects but also concerning the medical and surgical training issues. RESULTS: The economic advantages of scale of a larger unit are limited because of management problems when reaching a number of more than ten to twelve patients. This number probably leads to an optimal quality in medical care - especially if the patients are treated by specialists. The claim for a specific surgical training is thereby conceeded. The economical and medical advantages by connecting subunits to a larger operative intensive care unit will be achieved by economies of scale. For coordinating and running such a large unit an experienced intensive care doctor should be appointed. CONCLUSION: The concept of an interdisciplinary surgical ICU is obviously most practicable and reasonable if subunits with approximately twelve beds are concentrated in one centre for operative intensive care. This offers an advantage concerning the organisation and for the philosophy of treating special diseases by specialised medical teams. The size maintains the advantage of economies of scale as well the economies of scope and also promises effective logistics. For the management, an experienced intensive care specialist, either an anaesthesiologist or a surgeon should be assigned. All subject-specific advanced skills in intensive care have to be covered by an interdisciplinary continuing education.
Asunto(s)
Conducta Cooperativa , Cuidados Críticos/tendencias , Comunicación Interdisciplinaria , Programas Nacionales de Salud/tendencias , Grupo de Atención al Paciente/tendencias , Ahorro de Costo/tendencias , Cuidados Críticos/economía , Cuidados Críticos/organización & administración , Grupos Diagnósticos Relacionados/economía , Grupos Diagnósticos Relacionados/organización & administración , Grupos Diagnósticos Relacionados/tendencias , Educación Médica Continua/tendencias , Predicción , Cirugía General/educación , Alemania , Necesidades y Demandas de Servicios de Salud/economía , Necesidades y Demandas de Servicios de Salud/tendencias , Humanos , Programas Nacionales de Salud/economía , Grupo de Atención al Paciente/economía , Grupo de Atención al Paciente/organización & administración , Calidad de la Atención de Salud/economía , Calidad de la Atención de Salud/organización & administración , Calidad de la Atención de Salud/tendenciasRESUMEN
Cysts of the pancreas most often develop after chronic or acute inflammation of the pancreas. Cystic neoplasia of the pancreas have been increasingly recognized in clinical practice and 90% are represented by four types: serous microcystic (SCN), mucinous cystic (MCN), intraductal papillary-mucinous (IPMN) and solid pseudopapillary (SPN) neoplasia. IPMN is the most common form nowadays and main duct and branch duct types can be differentiated by morphology. This classification is of prognostic and therapeutic relevance. While main duct IPMNs have a high risk of malignant progression and resection is therefore recommended, branch duct IPMNs have a much lower risk of harboring malignancy. Small branch duct IPMNs (<2 cm) without symptoms or mural nodules can be managed by periodic surveillance. Recently, it has become clear that IPMN constitutes a heterogeneous group with at least four subtypes. Their stratification reveals that the various subtypes of IPMN have different biological properties with different prognostic implications, but the subclassification is usually not known prior to surgery. Moreover, even differentiation between inflammatory and neoplastic cysts can be challenging. Clear indications for resection are local complications (jaundice or gastric outlet obstruction), large and increasing tumors, symptoms or secretion of mucinous fluid from the papilla of Vater.
Asunto(s)
Quiste Pancreático/cirugía , Neoplasias Pancreáticas/cirugía , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/cirugía , Cistadenocarcinoma Mucinoso/diagnóstico , Cistadenocarcinoma Mucinoso/patología , Cistadenocarcinoma Mucinoso/cirugía , Cistadenocarcinoma Papilar/diagnóstico , Cistadenocarcinoma Papilar/patología , Cistadenocarcinoma Papilar/cirugía , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/cirugía , Diagnóstico Diferencial , Humanos , Páncreas/patología , Pancreatectomía , Quiste Pancreático/diagnóstico , Quiste Pancreático/patología , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , PronósticoRESUMEN
Training in technical skills is essential for advanced surgical education. Training is moving more and more from the operating room to surgical training laboratories. A crucial impulse for this development came from Davos, where the first skills course was organized in 1984 after the formation of the Working Group for Gastro-intestinal (GI) Surgery (AGC Davos). Since this first course more than 5,000 residents have successfully completed the GI skills training course in Davos and many of the alumni are themselves teaching surgery today. The level and quality of this course has remained stable for 27 years on a high quality level although teaching has continuously been adjusted to modern techniques. The language of this international workshop is English. The number of applications exceeds the course capacity every year, which is an indication for the need of such training courses and should be principally included into the skills curriculum for surgeons.
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Procedimientos Quirúrgicos del Sistema Digestivo/educación , Educación de Postgrado en Medicina/normas , Cirugía General/educación , Sociedades Médicas , Competencia Clínica , Simulación por Computador , Curriculum/normas , Humanos , Internado y Residencia , Laparoscopía , Modelos Anatómicos , Suiza , Interfaz Usuario-ComputadorRESUMEN
Vascular injuries are an uncommon finding. In times of peace vascular injuries occur in approximately 1-4 % during traffic accidents. Especially challenging is the treatment of open fractures combined with arterial lesions. These fractures are usually accompanied with severe soft tissue damage and injuries to neurological structures. The overall prognosis of these trauma patients is dependent on fast and sufficient diagnostics and therapy. In particular, for unstable patients time-consuming diagnostics can be dispensed and a primarily operative therapy should be targeted. Vascular reconstruction by direct suture is sometimes only possible with interposition and should be the primary goal. Interposition should be performed with autologous vein material because of the high risk of infection. Here we demonstrate on the basis of our patients the interdisciplinary -management of such trauma patients in our hospital.
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Arterias/lesiones , Fracturas Abiertas/cirugía , Traumatismos de los Tejidos Blandos/cirugía , Adolescente , Adulto , Anciano , Amputación Quirúrgica , Anastomosis Quirúrgica , Arterias/cirugía , Trasplante Óseo , Fijadores Externos , Extremidades/irrigación sanguínea , Femenino , Fracturas Abiertas/mortalidad , Alemania , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Traumatismo Múltiple/mortalidad , Traumatismo Múltiple/cirugía , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/cirugía , Reoperación , Traumatismos de los Tejidos Blandos/mortalidad , Colgajos Quirúrgicos , Venas/trasplante , Adulto JovenRESUMEN
BACKGROUND: Skill courses for surgery offer a good but cost and personnel-intensive possibility to obtain practical and theoretical knowledge by the employment of a close teacher-pupil contact of a large group of surgeons. The goal of the study presented here was to evaluate the satisfaction and benefits of the practical course for visceral surgery in Warnemünde after 10 years of course experience. MATERIAL AND METHODS: All participants in the annual course for visceral surgery were included since 1999. During this 1-week course conventional and laparoscopic exercises are performed under direct guidance of an experienced tutor. The participants are divided into 3 groups based on their surgical experience (e.g. <3 years, 3-5 years, >5 years). All participants received a standardised questionnaire before and after successful course completion for the collection of relevant data (e.g. demography, training, surgical experience and course evaluation). RESULTS: A total of 1,062 participants (435 female, 627 male, mean age 37 years) participated in the course. The average surgical experience of the participants was 5 years. Of the participants 489 came from a hospital of basic medical care, 499 from a hospital of maximum medical care and 74 from a university hospital. Of the participants 96% had no or only little experience with skill courses (1,020 out of 1,065) and 827 participants had no or only few possibilities for training outside of the operation room (78%). The conventional part of the course was evaluated by 77% of the participants as very good and by 50% as very good for the laparoscopic part. Only 8.3% of the participants were willing to finance the costs of the course by themselves. CONCLUSIONS: The practical course for visceral surgery leads to a subjective success in learning. Participation in the course leads to a high satisfaction and offers a cost-intensive possibility for a standardised surgical training. But there are too few experiences with skill courses and possibilities for surgical training outside the operation room so far.
Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo/educación , Educación Médica Continua , Adulto , Actitud del Personal de Salud , Curriculum , Femenino , Estudios de Seguimiento , Alemania , Humanos , Laparoscopía , Masculino , Evaluación de Programas y Proyectos de SaludRESUMEN
Diabetes mellitus is a common disease among patients with pancreatic cancer and chronic pancreatitis, disorders of the exocrine pancreas. Different clinical features of diabetes are associated with these two conditions: hyperinsulinemia and peripheral insulin resistance are the prevailing diabetic traits in pancreatic cancer, whereas reduced islet cell mass and impaired insulin secretion are typically observed in chronic pancreatitis. Whether or not a causal relationship exists between diabetes and pancreatic carcinoma is an intriguing but unanswered question. Diabetes often precedes pancreatic cancer and is thus regarded as a potential risk factor for malignancy. Conversely, pancreatic cancer may secrete diabetogenic factors. Given these findings, there is increasing interest in whether close monitoring of the glycemic profile may aid early detection of pancreatic tumor lesions.
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Complicaciones de la Diabetes , Enfermedades Pancreáticas/etiología , Animales , Carcinoma Ductal Pancreático/complicaciones , Carcinoma Ductal Pancreático/metabolismo , Complicaciones de la Diabetes/epidemiología , Diabetes Mellitus/etiología , Humanos , Enfermedades Pancreáticas/complicaciones , Enfermedades Pancreáticas/epidemiología , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/metabolismo , Factores de RiesgoRESUMEN
Kallikreins play an important role in tumour microenvironment and as cancer biomarkers in different cancer entities. Previous studies suggested an upregulation of KLK10 and KLK6 in pancreatic ductal adenocarcinoma (PDAC). Therefore, we evaluated the clinicopathological role of these kallikreins and their value as biomarkers in PDAC.Differential expression was validated by DNA-microarrays and immunohistochemistry in normal and malignant pancreatic tissues. Sera concentrations of both kallikreins were evaluated using ELISA. In silico analysis of possible protein interactions and gene silencing of KLK10 in vitro using siRNAs gave further insights in the pathomechanisms.Gene expression analysis and immunohistochemistry demonstrated a strong expression for KLK10 and KLK6 in PDAC. Statistical analysis showed that co-expression of these kallikreins correlated with an R1-resection status (P=0.017) and worse outcome for overall survival (P=0.031). Multivariate analysis proofed that co-expression is an independent prognostic factor for survival (P=0.043). Importantly, KLK10 knockdown in AsPC-1 cells significantly reduced cell migration, whereas computational analysis suggested interaction of KLK6 with angiogenetic factors as an important mechanism.Co-expression of KLK10 and KLK6 plays an unfavourable role in PDAC. Our results suggest that this effect is likely mediated by an interaction with the factors of the extracellular matrix and enhancement of cancer cell motility.
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Adenocarcinoma/química , Carcinoma Ductal Pancreático/química , Calicreínas/análisis , Neoplasias Pancreáticas/química , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Movimiento Celular , Proteínas del Ojo/fisiología , Perfilación de la Expresión Génica , Silenciador del Gen , Humanos , Inmunohistoquímica , Calicreínas/genética , Calicreínas/fisiología , Factores de Crecimiento Nervioso/fisiología , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Pronóstico , Serpinas/fisiologíaRESUMEN
BACKGROUND: The formation of sporadic abdominal aortic aneurysm (AAA) is explained by a remodelling of the extracellular matrix (ECM) and breakdown of structural components of the vascular wall. Matrix metalloproteinases are the principle matrix-degrading proteases and are known to play a major role in the remodelling of the extracellular matrix in arterial vessels. Their activity is controlled by tissue inhibitors of metalloproteinases (TIMPs). Decreased TIMP-1 and TIMP-2 expression in the extracellular matrix of the walls of AAAs has been demonstrated in several studies. This case-control study was designed to investigate the possible impact of genetic variants of the TIMP-2 gene in the aetiology of AAA and to reproduce a recently described significant difference in allele frequency of the SNP 303G>A in a German population. METHODS: TIMP-2 single nucleotide polymorphisms (SNPs) were analysed in a study sample of 50 patients with AAA and 41 controls. Differences in genotype and allele frequencies of the identified polymorphisms were determined after sequencing the entire coding region and selected parts of the promoter using the automated laser fluorescence technique. RESULTS: Six polymorphisms were identified, one of which is described for the first time, located in the intron, (231+23C>T). An association of the SNP 303G>A with the phenotype was not confirmed in our study (p=0.648). However, the CT genotype of the SNP -479C>T was more frequent in patients with AAA than in the control group (p=0.054). CONCLUSIONS: In our analysis of the TIMP-2 gene, we identified one new SNP. A previously published association of the SNP 303G>A with the phenotype could not be validated in our population. However, we detected an association for the CT genotype of one polymorphism in the promoter region (g-479C>T) and AAA. This result has to be proved in a second study sample.
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Aneurisma de la Aorta Abdominal/genética , Polimorfismo de Nucleótido Simple/genética , Anciano , Anciano de 80 o más Años , Alelos , Femenino , Frecuencia de los Genes , Pruebas Genéticas , Genética de Población , Genotipo , Humanos , Intrones/genética , Masculino , Persona de Mediana Edad , Fenotipo , Regiones Promotoras Genéticas/genética , Inhibidor Tisular de Metaloproteinasa-2RESUMEN
Familial tumors of the gastrointestinal tract, which often appear as autosomal-dominantly inherited tumor syndromes, account for only a small proportion of all gastrointestinal tumors. With the opportunities of modern molecular diagnostics, identifying the pathogenic mutation in families is often possible, with the option of predictive molecular testing and differentiation between mutation carriers and noncarriers. Thus a good chance exists for detection of early tumor stages by individually tailored surveillance programs and for improving prognosis by early intervention and prophylactic resection. Clinical manifestation, molecular basis at the root, individual surveillance programs, and their consequences for the treatment of familial gastric cancer, familial adenomatous polyposis coli, hereditary nonpolyposis colorectal cancer, Peutz-Jeghers syndrome, juvenile polyposis, hyperplastic polyposis, and familial pancreatic cancer are presented.
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Síndromes Neoplásicos Hereditarios , Poliposis Adenomatosa del Colon/diagnóstico , Poliposis Adenomatosa del Colon/genética , Poliposis Adenomatosa del Colon/cirugía , Adolescente , Adulto , Anciano , Niño , Colonoscopía , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/cirugía , Femenino , Gastrectomía , Humanos , Masculino , Persona de Mediana Edad , Síndromes Neoplásicos Hereditarios/diagnóstico , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/cirugía , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirugía , Síndrome de Peutz-Jeghers/diagnóstico , Síndrome de Peutz-Jeghers/genética , Síndrome de Peutz-Jeghers/cirugía , Guías de Práctica Clínica como Asunto , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirugíaRESUMEN
BACKGROUND/AIMS: The advent of contrast-enhanced ultrasound (CEUS) has called into question the efficacy of standard ultrasonographic techniques. In this study, we evaluated B-mode and color-duplex imaging and CEUS in the detection of liver metastases, using intraoperative and histological findings as a reference. MATERIALS AND METHODS: Before laparotomy, 108 patients suspected of having liver metastases were prospectively examined with B-mode and color-duplex imaging, followed by contrast-enhanced ultrasound (2.4 ml SonoVue). Patients with unresectable tumors (n=8) were excluded from the analysis. The sonographic diagnosis in the remaining 100 patients was compared to the intraoperative and histological findings. RESULTS/FINDINGS: CEUS improved the sensitivity for detecting liver lesions from 56.3% (B-mode) to 83.8% (CEUS) (p=0.004). In particular, the contrast agent led to an improvement in ultrasonographic detection in the following cases: nodular metastases smaller than one centimeter; after adjuvant chemotherapy; for tumors near the surface of the liver; and for lesions situated around the ligamentum teres. INTERPRETATION/CONCLUSIONS: CEUS provides significant improvement in the detection of liver metastases, and should therefore, be performed routinely in the surveillance of cancer patients.
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Medios de Contraste , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Fosfolípidos , Hexafluoruro de Azufre , Ultrasonografía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease and one of the cancer entities with the lowest life expectancy. Beside surgical therapy, no effective therapeutic options are available yet. Here, we show that 4-phenylbutyrate (4-PB), a known and well-tolerable inhibitor of histone deacetylases (HDAC), induces up to 70% apoptosis in all cell lines tested (Panc 1, T4M-4, COLO 357, BxPc3). In contrast, it leads to cell cycle arrest in only half of the cell lines tested. This drug increases gap junction communication between adjacent T3M-4 cells in a concentration-dependent manner and efficiently inhibits cellular export mechanisms in Panc 1, T4M-4, COLO 357 and BxPc3 cells. Consequently, in combination with gemcitabine 4-PB shows an overadditive effect on induction of apoptosis in BxPc3 and T3M-4 cells (up to 4.5-fold compared to single drug treatment) with accompanied activation of Caspase 8, BH3 interacting domain death agonist (Bid) and poly (ADP-ribose) polymerase family, member 1 (PARP) cleavage. Although the inhibition of the mitogen-activated protein kinase-pathway has no influence on fulminant induction of apoptosis, the inhibition of the JNK-pathway by SP600125 completely abolishes the overadditive effect induced by the combined application of both drugs, firstly reported by this study.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Carcinoma Ductal Pancreático/tratamiento farmacológico , Comunicación Celular/efectos de los fármacos , Uniones Comunicantes/efectos de los fármacos , Inhibidores de Histona Desacetilasas , Neoplasias Pancreáticas/tratamiento farmacológico , Fenilbutiratos/farmacología , Antracenos/farmacología , Apoptosis/efectos de los fármacos , Caspasa 8/metabolismo , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Sinergismo Farmacológico , Activación Enzimática/efectos de los fármacos , Humanos , Factores de Tiempo , Células Tumorales Cultivadas , GemcitabinaRESUMEN
HISTORY AND CLINICAL FINDINGS: A 55 year old female patient was diagnosed because of painless jaundice and weight loss. She had undergone conventional cholecystectomy 15 years before. INVESTIGATIONS: Bilirubin level before ERCP and stent implantation was 287 micromol/l at maximum. A subtotal stenosis was found in the proximal common hepatic duct. Endosonographically, a mass of 14 mm diameter was seen. She was suspected of having a Klatskin tumour Bismuth type II. Tumour markers (CEA, CA19-9) were within normal ranges. TREATMENT AND COURSE: One month after stent implantation open surgery was performed suspecting a malignant tumour of the bile duct. A solid tumour at the hepatic bifurcation was resected completely. Reconstruction was performed by hepatico-jejunostomy was formed and the blind end of the jejunum was anastomosed to the gastric antrum to form an "access loop". Upon histological analysis no malignancy was found. However, a distinct fibrosis within the suspicious area was seen, formed around braided suture material. CONCLUSION: Preoperative distinction between benign and malignant bile duct stenosis can be difficult, even impossible. Thus, every resectable bile duct tumour should undergo surgery even and especially if a histological diagnosis cannot be reached preoperatively and the condition of the patient is adequate.