Primäre Lymphome im Gastrointestinaltrakt

Gastointestinal lymphomas represent a heterogeneous group. The various subtypes are characterized by histological, immunohistochemical and molecular genetic properties. After arriving at a diagnosis a staging procedure is necessary as the histological type and stage of the lymphoma determine the therapeutic strategy which comprises eradication of Helicobacter pylori, chemotherapy, radiation or a combination of these. Surgery no longer plays a role.     

Prim?r bili?re Zirrhose

Primary biliary cirrhosis (PBC) is characterized by immune-mediated destruction of small intrahepatic bile ducts and subsequent development of liver fibrosis and cirrhosis, occuring mainly in middle-aged women. PBC is diagnosed on the basis of a cholestatic serum enzyme pattern, elevated serum IgM, the presence of antimitochondrial antibodies (AMA) in serum directed against the E₂ subunit of the pyruvate dehydrogenase complex, and a ?florid bile duct lesion” of mid size intrahepatic bile ducts and bile duct paucity. The cholestatic serum enzyme pattern and serum AMA are mandatory for the diagnosis. PBC is frequently associated with other autoimmune disorders such as Sjögren’s syndrome, Hashimoto’s thyroiditis, and celiac disease. Early diagnosis and medical therapy with ursodeoxycholic acid aim to hinder progression of the disease toward cirrhosis. Additional medical treatments are under evaluation. Liver transplantation is an effective treatment of end-stage PBC.     

Prim?re Katheterablation von Vorhofflimmern

Hintergrund: Die primäre Katheterablation von Vorhofflimmern stellt eine neue, kurative Behandlungsoption für Patienten mit therapieresistentem Vorhofflimmern dar. Sie hat den langfristig stabilen Sinusrhythmus zum Ziel, mit daraus folgernder koordinierter Vorhofkontraktion. Ablationsmethoden: Zwei verschiedene Ablationsstrategien haben sich in den letzten Jahren etabliert: Die Triggerelimination versucht auslösende atriale Extrasystolen (meistens innerhalb der Pulmonalvenen) zu identifizieren und durch fokale Hochfrequenzstromapplikation auszuschalten oder innerhalb der Pulmonalvenen zu isolieren. Durch die Substratmodifikation sollen mittels Anlage langer Ablationslinien die Eigenschaften des Vorhofmyokards so verändert werden, dass Vorhofflimmern nicht mehr aufrechterhalten werden kann. Bewertung: Beide Behandlungskonzepte müssen ihre Effektivität noch im Rahmen von sorgfältigen Nachbeobachtungsstudien unter Beweis stellen, bevor sie für den generellen Einsatz bei Patienten mit Vorhofflimmern empfohlen werden können. Background: Primary catheter ablation of atrial fibrillation is a new and curative option for the treatment of patients with drug-refractory atrial fibrillation. It is aiming at a long-term restoration of sinus rhythm and thereby causing a coordinated atrial contraction. Ablation Methods: Two different ablation strategies have been established: The "trigger elimination" tries to identify triggering atrial extrasystoles (mostly within the pulmonary veins), followed by focal ablation or isolation within the pulmonary veins. The "substrate modification" changes by long linear radiofrequency-induced lesions the ability of the atrial myocardium to sustain atrial fibrillation. Valuation: Both treatment options still have to prove their effectiveness in carefully monitored follow-up, before they can be offered to the general patient population with atrial fibrillation.     

Therapie des akuten Myokardinfarkts — Primäre PTCA oder Thrombolyse?

Since reperfusion of the infarct-related coronary artery has been established as a mainstay in the treatment of acute myocardial infarction (AMI) mechanical recanalization by direct angioplasty has been used as an alternative to the standard treatment with thrombolysis. Direct PTCA is more efficient than thrombolysis in terms of reperfusion rates, whereas thrombolysis is more readily available. Thrombolysis reduces mortality from AMI by approximately 25%. The clinical efficacy is strongly time-dependent, and treatment within the first hour of AMI improves survival by nearly 50% by preventing transmural infarction in a significant proportion of the patients. The disadvantage of thrombolysis is its limited efficacy in terms of rapid, complete and sustained patency of the infarct vessel yielding optimal results in only 50% of the patients. Direct PTCA is generally agreed to be more efficient to recanalize the infarct vessel, but its clinical advantage remains controversial. The first randomized studies of direct PTCA in AMI from highly specialized centers in selected patients reported success rates of coronary reperfusion up to 97% resulting in a trend to less death and reinfarction; but the differences were significant only in a meta-analysis of these small studies. The real world of direct PTCA has been depicted by a large registry in Germany of the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte (ALKK) now including more than 4,000 direct PTCA-procedures since 1994. In this registry, the success rate of direct PTCA was 87% as defined by a final TIMI-grade 3 perfusion of the infarct vessel which is close to the data of the MITI-registry and the GUSTO IIb study. Failed PTCA was associated with an exceptionally high mortality rate of 36% confirming earlier observational reports. The non-randomized comparison of thrombolysis and direct PTCA in the MITI-registry showed no difference in survival or reinfarction rates, and the randomized GUSTO IIb substudy of direct PTCA versus front-loaded alteplase showed a small advantage in death and reinfarction rates at 30 days which dissipated over time leaving no significant clinical advantage of direct PTCA over thrombolysis at 6 months. Thus, in myocardial infarction in general the advantage of direct PTCA over thrombolysis is at best minimal. The reason is very probably the longer time lag until the procedure is started, the lower success rate as compared to the first reports of some specialized centers, and the clearly negative impact of failed PTCA on survival. Moreover, the immediate success of direct PTCA seems to be overestimated by the operator as demonstrated by comparison of central and local estimates of the TIMI flow rates in GUSTO IIb. Improvements of direct PTCA in AMI might be possible by coronary stenting which has markedly increased to more than 60% during the last year in the ALKK-registry. This was accompanied by a slight decrease in death and reinfarction rates. Further improvements can be expected from GP IIb/IIIa platelet antagonists which are under clinical investigation. It has been claimed, that in cardiogenic shock direct PTCA is more effective than thrombolysis. This hypothesis is based on comparison of failed versus successful PTCA-attempts, but this comparison is not valid since failed procedures clearly increase mortality. In the GUSTO-I study patients with cardiogenic shock had lower mortality with than without an early coronary angiogram. This survival advantage, however, was independent of revascularization since only half of the patients with an early angiogram had PTCA. The same was observed in the International Shock Registry, reflecting significant selection bias in that patients in relatively better condition will be taken to the cathlab whereas apparently hopeless cases will not. In the ALKK-registry half of the patients in cardiogenic shock died after direct PTCA casting doubt on the presumed high clinical efficacy of this strategy. A definitive answer to the role of PTCA in cardiogenic shock could only be given by randomized studies, but these have been stopped prematurely for poor patient recruitment. Thus, the consensus to prefer PTCA over thrombolysis in cardiogenic shock is not based on firm clinical data.     

Primäre Hyperoxalurie

The three currently known forms of primary hyperoxaluria (PH) types I, II and III are autosomal recessive inherited defects of glyoxylate metabolism resulting in overproduction of endogenous oxalate and hence extremely elevated urinary oxalate excretion (>1 mmol/1.73 m² body surface area per day; normal <0.5). Primary clinical hallmarks of PH are recurrent urolithiasis and/or progressive nephrocalcinosis. These and chronic inflammatory processes often lead to early renal failure in most PH type I and in 20% of PH type II patients resulting in systemic deposition of calcium oxalate crystals, which makes PH an often fatal multisystemic disease. Diagnosis is often missed or delayed until end-stage renal disease (ESRD) or when isolated kidney transplantation has failed due to recurrent oxalosis. Treatment options are scarce, even in patients with an early diagnosis. High fluid intake and medication to increase urine solubility of oxalate, e.g. alkaline citrate, are the therapy of choice. Pyridoxine treatment in PH type I may reduce oxalate excretion in about one third of the patients. In ESRD time on dialysis should be short to avoid severe systemic oxalosis, which would worsen transplantation outcome. Transplantation methods are different depending on the PH type and the individual clinical course, but combined or sequential liver/kidney transplantation is still the method of choice in PH I, whereas isolated kidney transplantation is performed in PH II. No patient with PH III has yet been reported to develop ESRD.     

Primäre ziliäre Dyskinesie

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder with defective structure or function of normally motile cilia, leading to chronic upper and lower respiratory tract infections, fertility problems and organ site abnormalities. The PCD is a genetically heterogeneous condition entailing a broad range of different disease variants. Diagnosing these different PCD phenotypes requires a combined approach using complementary methods for detection of defects of ciliary function, ultrastructure and composition as well as low nasal nitric oxide values and biallelic genetic mutations. To date, mutations in 31 different genes have been linked to PCD permitting a genetic diagnosis in approximately 60?% of cases. Due to the lack of adequate trials evidence-based knowledge on the epidemiology, disease course and management of PCD is currently lacking. An international PCD registry has been developed to overcome these limitations (www.pcdregistry.eu) and is currently recruiting patients. Current treatment regimens have to rely on expert opinions and on experience gained from other respiratory diseases. The management of PCD includes surveillance of pulmonary function, culturing upper and lower airway secretions and diagnostic imaging. Daily airway clearance techniques as well as prompt antibiotic treatment of infections are the cornerstones of PCD treatment regimens.     

Primäre und sekundäre Osteoporose

Bone metabolism as an important part of internal medicine is covered by endocrinologists, rheumatologists and nephrologists. Primary osteoporosis is an inheritable metabolic bone disease, which can be strongly modified by lifestyle, ageing and underlying diseases. Chronic inflammatory diseases, disorders of metabolism and nutritional deficits enhance the risk. Secondary osteoporosis is caused by endocrinological disorders and drugs such as glucocorticoids. It is the task of internists to clinically recognise and diagnose prominent individual risk factors for primary osteoporosis and underlying diseases for secondary osteoporosis. The key competence of internal medicine in metabolism, hormone-related disorders, malignant diseases and in handling complex medical treatment modalities represents an indispensable segment of an interdisciplinary network approach in patient care, research and teaching. This network includes orthopaedic surgery, paediatrics and gynaecology in addition to other specialities.     

Primäre und sekundäre Neutropenie

Severe chronic neutropenia (SCN) comprises a heterogeneous group of disorders with a common hematological and clinical phenotype characterized by absolute neutrophil counts (ANC) below 0,5???10⁹/l and increased risk of severe bacterial infections. The differentiation between primary and secondary neutropenia and the identification of causative gene mutations is of great importance for the estimation of prognosis. During childhood primary autoimmune neutropenia is the most frequent diagnosis, while secondary neutropenia predominates in adulthood. Despite the rarity, congenital, genetic neutropenias are of great value for research on normal and pathological hematopoiesis and have a fundamental impact on the current knowledge on hematopoiesis. To date mutations in more than 10 genes have been described which are mainly associated with an increased risk for leukemia. The treatment with hematopoietic growth factors has improved the long-term prognosis of SCN patients dramatically: Bacterial infections can be prevented and a normal participation in everyday life is possible.     

Primäre Prävention des Typ-2-Diabetes durch Lebensstilmodifikation

Background

Large landmark studies, such as the Finnish Diabetes Prevention Study (DPS) and the American Diabetes Prevention Program (DPP) could conclusively show that prevention of type 2 diabetes or a significant delay in the manifestation of diabetes is possible by lifestyle modifications in persons with an increased risk of diabetes. However, the lifestyle interventions in these studies were carried out in a relatively resource-intensive individual setting and measures were employed which are far too costly to be implemented in practice. A group approach is clearly more economical and less resource-intensive.

Aim

The objective of this prospective, randomized trial was to investigate whether the results of the large, high-quality clinical trials for the prevention of type 2 diabetes could be translated into practical affordable interventions that are deliverable in the real world healthcare system in Germany. The effectiveness of the newly developed Prevention of Diabetes Self-Management Program (PREDIAS) for groups was investigated for people with increased risk of diabetes with respect to a successful weight reduction after 1 year.

Material and methods

The PREDIAS group program for lifestyle modification and primary prevention of type 2 diabetes consists of 12 course-hours extending over a period of 12 months. A total of 182 persons with an elevated diabetes risk participated in this study and were randomly assigned to the intervention group (PREDIAS) or the control group (CG). Patients in the CG received written information about diabetes prevention.

Results

After 12 months participants in the PREDIAS program achieved a significantly higher average weight loss than the CG (??3.8?±?5.2 kg versus ??1.4?±?4.0 kg, p?=?0.001). Fasting glucose was reduced in the PREDIAS group, whereas it rose slightly in the CG (??4.3?±?11.3 mg/dl versus 1.8?±?13.1 mg/dl, p?=?0.001). The duration of physical activity per week was significantly increased in the PREDIAS group than in the CG (46.6?±?95.5 min/week versus 17.9?±?63.8 min/week, p=0.034). Indicators of a modified eating behavior also showed a significantly greater improvement in PREDIAS than in the CG (cognitive restraint 3.9?±?3.8 versus 1.5?±?4.7, p?=?0.001 and disinhibition ??1.2?±?2.7 versus ??0.4?±?2.6, p?=?0.049). There were no significantly greater improvements with regard to lipids or blood pressure in the PREDIAS group compared with the CG.

Conclusion

The improvements in the risk factors achieved with the PREDIAS group program were broadly equivalent to the 1 year data of the DPP or the DPS, which were both conducted in an extensive and time-consuming individual setting.     

Mikroskopische Erkrankungen des Gastrointestinaltrakts – eine Domäne der Pathologie?

Microscopic colitis is defined as a chronic inflammatory disease of the colon which can be diagnosed only under the microscope. The term summarizes the colorectal inflammation of collagen colitis and lymphocytic colitis. Presently, these diseases are considered to be special entities of inflammatory bowel diseases. Although patients become symptomatic with chronic diarrhea they show an endoscopic non-inflammatory mucosa but characteristic microscopical changes. Therefore, in patients with a history of chronic diarrhea biopsies should be taken even from normal mucosa. Even rarer than microscopic inflammatory colitis are pericryptic eosinophilic enterocolitis, lymphocytic esophagitis as well as lymphocytic and collagenous gastritis.     

Prim?r- und Sekund?rpr?vention des Schlaganfalls

Despite considerable advances in acute stroke therapy, stroke prevention remains the most promising approach for reducing the burden of stroke. A healthy lifestyle and the treatment of cardiometabolic risk factors are the cornerstones of both primary and secondary stroke prevention. Due to a proportionately higher risk of bleeding complications, platelet inhibitors are not recommended for primary stroke prevention. Platelet inhibitors are effective in the secondary prevention of stroke with acetyl salicylic acid (ASS) and clopidogrel showing the most consistent data. New oral anticoagulants are slightly more effective than coumarin and significantly reduce the risk of intracranial hemorrhage. They offer the opportunity to bring more patients with atrial fibrillation at risk for stroke into anticoagulation particularly those on ASS therapy. Surgery for patients with asymptomatic carotid artery stenosis should be viewed critically with respect to an only marginal benefit and improvement in medical therapies. Carotid endarterectomy remains the gold standard for patients with symptomatic carotid stenosis because of an increased procedural stroke risk with carotid stenting. Patients with symptomatic intracranial stenosis or cryptogenic stroke and a patent foramen ovale should receive only medical treatment.     

Prim?r- und Sekund?rpr?vention des Typ-1-Diabetes

Type 1 diabetes (T1D) is the most common autoimmune disease in children and adolescents with a worldwide rising incidence. In particular, small children are becoming more and more affected. Despite the improvement of insulin therapy complications, such as retinopathy and nephropathy cannot be avoided in many cases. These complications are predominantly suspected in children with an early onset and a long duration of diabetes. Therefore, the development of effective preventive strategies is an important medical and also economic goal. Primary prevention in genetically predisposed individuals intervenes before diabetes-associated antibodies occur. Secondary prevention aims to arrest the progression to T1D in subjects with autoantibodies.     

Kosteneffektivit?t der Prim?rpr?vention des Typ-2-Diabetes

Type 2 diabetes mellitus (T2DM) represents a large burden for patients and society and its prevalence is increasing worldwide. There is evidence that T2DM can be delayed or prevented by interventions such as pharmacological and lifestyle interventions in individuals with pre-diabetes. However, the question emerges whether the implementation of these interventions is cost-effective. This article presents studies concerning the cost-effectiveness of interventions targeting primary prevention of T2DM which have been identified in a systematic review of the literature. In all 11 identified studies primary prevention of T2DM was shown to be potentially cost-effective.     

Pathologie prim?r pulmonaler Lymphome

Pulmonary involvement in malignant lymphoma is rare. In most cases it represents either secondary organ manifestation in late stage disease or direct infiltration from a mediastinal process, where lymphomas occur frequently. However, some types of lymphoma exist that may originate from the lung. They are a rare differential diagnosis in the evaluation of single or multiple pulmonary masses. An overview of the lymphoma entities that occur in the lung is given.