[Radiation therapy for the treatment of macroscopic canine anal gland tumors - a retrospective study]. / Strahlentherapie zur Behandlung makroskopischer Analbeuteltumoren des Hundes ­ eine retrospektive Studie.

INTRODUCTION: Canine anal gland tumors are locally invasive and early metastasize to the loco-regional pelvic lymph nodes. Radiation therapy is a good method for loco-regional tumor control, especially in inoperable tumors. Since the organs in the pelvic area are sensitive to both acute and late radiation damage (chronic diarrhea, bleeding, strictures or intestinal perforations) and such damage mainly depends on the fraction size, we examined the radiation protocol used in this study with a reduced number of fractions (hypofractionated) regarding effectiveness and side effects. This retrospective study describes 13 dogs with macroscopic anal gland carcinoma that were irradiated with imaging-guided, intensity-modulated radiation therapy with a hypofractionated curative protocol of 12 × 3,8 Gy. Gross pathology was either in the region of the anal gland and/or in the sublumbar lymph nodes. Ten of the 13 dogs had advanced tumor diseases (stage 3a or 3b). The acute radiation reactions were mild to moderate and had been reported for some of the dogs in a previous study. The mean study time was 572 days (range 105-1292 days). Disease progression was observed or suspected in 7/13 dogs during the study period: local or loco-regional progression occurred in 3 dogs (23 %) and distant metastases in 4 dogs (31 %). Median progression-free survival was 480 days (95 %CI, 223-908), median survival was 597 days (95 %CI, 401-908). One year after treatment, 76,9 % (95 %CI, 53,5-100) of the dogs were still alive. The likelihood of tumor progression was lower with increasing age, otherwise none of the examined tumor or patient factors showed a prognostic influence on progression or survival time. No clinically relevant late side effects were observed apart from slight alopecia, pigmentation changes or dry, scaly skin, Medium to long-term tumor control can be expected in dogs with macroscopic anal gland tumors treated with a moderately hypofractionated radiation therapy protocol (12 × 3,8 Gy). During long-term monitoring no serious side effects or side effects requiring treatment were observed.

INTRODUCTION: Les tumeurs des glandes anales canines sont localement invasives et métastasent rapidement dans les ganglions lymphatiques loco-régionaux pelviens. La radiothérapie est une bonne méthode de contrôle des tumeurs loco-régionales, en particulier pour les tumeurs inopérables. Étant donné que les organes de la région pelvienne sont sensibles aux dommages aigus et tardifs de la radiation (diarrhée chronique, saignements, sténoses ou perforations intestinales) et que ces dommages dépendent principalement de la taille des fractions, nous avons étudié le protocole de radiations utilisé dans cette étude avec un nombre réduit de fractions (hypofractionné) en terme d'efficacité et d'effets secondaires. Cette étude rétrospective décrit 13 chiens atteints de carcinome macroscopique de la glande anale qui ont été traités par une radiothérapie à modulation d'intensité guidée par imagerie avec un protocole curatif hypofractionné de 12 × 3,8 Gy. La pathologie macroscopique se trouvait soit dans la région de la glande anale et/ou dans les ganglions lymphatiques sublombaires. Dix des 13 chiens présentaient des pathologies tumorales avancées (stade 3a ou 3b). Les réactions aiguës aux radiations étaient légères à modérées et avaient été signalées pour certains des chiens dans une étude précédente. La durée moyenne de l'étude était de 572 jours (fourchette 105­1292 jours). Une progression de la maladie a été observée ou suspectée chez 7/13 chiens au cours de la période d'étude : une progression locale ou loco-régionale est survenue chez 3 chiens (23 %) et des métastases à distance chez 4 chiens (31 %). La survie médiane sans progression était de 480 jours (95 %CI, 223­908), la survie médiane était de 597 jours (95 %CI, 401­908). Un an après le traitement, 76,9 % (95 %CI, 53,5­100) des chiens étaient encore en vie. La probabilité de progression de la tumeur était plus faible avec l'âge, mais aucun des facteurs examinés concernant la tumeur ou le patient n'a montré d'influence pronostique sur la progression ou la durée de survie. Aucun effet secondaire tardif cliniquement pertinent n'a été observé, hormis une légère alopécie, des changements de pigmentation ou une peau sèche et squameuse, On peut s'attendre à un contrôle tumoral à moyen et long terme chez les chiens atteints de tumeurs macroscopiques de la glande anale traités par un protocole de radiothérapie modérément hypofractionnée (12 × 3,8 Gy). Au cours du suivi à long terme, aucun effet secondaire grave ou nécessitant un traitement n'a été observé.

[Massive unresectable hepatocellular carcinoma in a dog treated with -intensity-modulated radiation therapy]. / Massives inoperables hepatozelluläres Karzinom bei einem Hund behandelt mittels intensitätsmodulierter Strahlentherapie.

INTRODUCTION: This case report describes a 12-year-old female spayed mixed-breed dog referred for treatment of a large, inoperable hepatocellular carcinoma. A computed tomography (CT) scan confirmed the previous ultrasonographic and laparoscopic findings of a large, lobulated, poorly defined mass on the left and central aspect of the liver. Multiple biopsies confirmed the diagnosis of hepatocellular carcinoma. Due to the large extent of the tumor, the vascular association to the Vena cava caudalis and the associated high risk of intraoperative bleeding, a resection of the mass was refrained from and a radiotherapeutic treatment was chosen. The dog underwent radiation therapy (RT) with a 6MV linear accelerator with 5×6 Gy, total dose 30 Gy. In the follow up examinations three months and one year after therapy, the dog presented in normal condition and had normal Alanine-amino-transferase (ALT) and alkaline phosphatase (AP). The tumor size measured in the CT-examinations decreased by 61% and 90%, respectively. Two years after radiation therapy the dog has a normal general condition and liver enzymes are within the normal limits.

INTRODUCTION: Ce rapport décrit le cas d'une chienne de race mixte, stérilisée, âgée de 12 ans et référée pour traitement d'un important carcinome hépatocellulaire inopérable. Une tomodensitométrie (TDM) a confirmé les résultats échographiques et laparoscopiques antérieurs, à savoir une grande masse mal définie sur la partie gauche et centrale du foie. De multiples biopsies ont confirmé le diagnostic de carcinome hépatocellulaire. En raison de l'étendue de la tumeur, de l'association à la veine cave caudale et du risque élevé associé d'hémorragies peropératoires, on a renoncé à une résection de la masse et un traitement radiothérapeutique a été choisi. Le chien a subi une radiothérapie (RT) avec un accélérateur linéaire de 6 MV avec 5 × 6 Gy, dose totale 30 Gy. Lors des examens de suivi, trois mois et un an après le traitement, le chien présentait un état normal et avait une alanine-amino­-transférase (ALT) et une phosphatase alcaline (PA) normales. La taille de la tumeur mesurée lors des examens tomodensitométriques avait diminué de 61% respectivement de 90%. Deux ans après la radiothérapie, le chien présente un état général normal et les enzymes hépatiques sont dans la norme.

[Risk stratification of emergencies during the COVID-19 pandemic within the emergency department]. / Risikostratifizierung von Notfällen während der COVID-19-Pandemie in der Zentralen Notaufnahme.

BACKGROUND: The COVID-19 pandemic represents a complex challenge for medical staff within emergency departments (ED) of hospitals at all care levels. Beside regular emergency care, rapid detection and isolation of COVID-19 cases are obligatory for prevention of internal viral transmission and efficient medical staff protection. METHODS: In this study a model of risk stratification for suspected SARS-CoV­2 and COVID-19 cases was developed on the basis of epidemiologic criteria of the Robert-Koch Institute including five risk categories (RC). The model was implemented in a hospital of basic and regular care level. By combination of risk categories with specific isolation, hygienic and personal protection procedures all areas of the ED were restructured. In a retrospective study all inpatient cases (n = 491) were re-evaluated during a 4-week interval (26 March-26 April 2020). RESULTS: In the study population 25 SARS-CoV­2 positive cases (5.2%) were identified. These cases were categorized according to the risk stratification model as follows: RC I-confirmed SARS-CoV­2 infection 36% (n = 9), RC II-reasonable suspected cases 32% (n = 8), RC III-differential diagnostic cases 12% (n = 3), RC IV-low probability 8% (n = 2) and RC V-no evidence 12% (n = 3). No viral transmission was detected during the whole period within medical staff and patients of the ED. CONCLUSIONS: Introduction of COVID-19 risk categories within the ED permits central control of important hygienic processes with respect to SARS-CoV­2 infection probability. By continuous re-evaluation of case definitions local outbreaks can be used to adapt criteria within the risk categories. Risk stratification of COVID-19 cases allows for a strict separation of COVID-19 and non-COVID-19 emergencies and thus ensures effective infection prevention of medical staff and patients.

[Acromegaly due to a pituitary tumor in a dog - diagnosis, therapy and long-term follow-up]. / Akromegalie aufgrund eines Hypophysentumors bei einem Hund ­ Diagnose, Therapie und Verlauf.

INTRODUCTION: Acromegaly due to a pituitary tumor has so far only been described in 3 dogs. The present case report describes a 7-year-old male-castrated Labrador Retriever which was referred because of difficult-to-control diabetes. Physical examination revealed markedly enlarged head, tongue and paws, widened interdental spaces and thickening of the skin in the head and neck area. IGF-1 and GH were increased and the latter continued to be abnormal after somatostatin application. Computed tomography demonstrated a space-occupying lesion in the pituitary gland and the diagnosis of acromegaly due to a GH-producing tumor of the pituitary was made. The dog underwent radiation therapy with a 6MV linear accelerator (3×8Gy) and improved substantially. Two and a half years after radiation therapy the dog developed lethargy and anorexia and was euthanized. Necropsy was not permitted. This case report represents the description of a dog suffering from pituitary-dependent acromegaly which was successfully treated and had a long-term survival.

INTRODUCTION: L'acromégalie due à une tumeur hypophysaire n'a jusqu'à présent été décrite que chez 3 chiens. Le présent rapport de cas décrit un Labrador Retriever de 7 ans mâle castré, qui a été référé en raison d'un diabète difficile à contrôler. L'examen physique a révélé une tête, une langue et des pattes de taille nettement augmentée, des espaces interdentaires élargis et un épaississement de la peau dans la région de la tête et du cou. L'IGF-1 et la GH étaient augmentées et la seconde restait anormale après l'application de somatostatine. La tomodensitométrie a mis en évidence une masse dans la région de l'hypophyse et le diagnostic d'acromégalie due à une tumeur de l'hypophyse productrice de GH a été posé. Le chien a subi une radiothérapie avec un accélérateur linéaire de 6MV (3×8Gy) et son état s'est considérablement amélioré. Deux ans et demi après la radiothérapie, le chien développa une léthargie et une anorexie et fut euthanasié. L'autopsie n'a pas été autorisée. Ce rapport de cas représente la description d'un chien souffrant d'acromégalie dépendant de l'hypophyse, traité avec succès et ayant une survie à long terme.

A prospective pilot study on early toxicity from a simultaneously integrated boost technique for canine sinonasal tumours using image-guided intensity-modulated radiation therapy.

In order to overcome the common local treatment failure of canine sinonasal tumours, integrated boost techniques were tried in the cobalt/orthovoltage era, but dismissed because of unacceptable early (acute) toxicity. Intriguingly, a recent calculation study of a simultaneously integrated boost (SIB) technique for sinonasal irradiation using intensity-modulated radiation therapy (IMRT) predicted theoretical feasibility. In this prospective pilot study we applied a commonly used protocol of 10 × 4.2 Gy to the planning target volume (PTV) with a 20%-SIB dose to the gross tumour volume (GTV). Our hypothesis expected this dose escalation to be clinically tolerable if applied with image-guided IMRT. We included 9 dogs diagnosed with sinonasal tumours without local/distant metastases. For treatment planning, organs at risk were contoured according to strict anatomical guidelines. Planning volume extensions (GTV/CTV/PTV) were standardized to minimize interplanner variability. Treatments were applied with rigid patient positioning and verified daily with image guidance. After radiation therapy, we set focus on early ophthalmologic complications as well as mucosal and cutaneous toxicity. Early toxicity was evaluated at week 1, 2, 3, 8 and 12 after radiotherapy. Only mild ophthalmologic complications were found. Three patients (33%) had self-limiting moderate to severe early toxicity (grade 3 mucositis) which was managed medically. No patient developed ulcerations/haemorrhage/necrosis of skin/mucosa. The SIB protocol applied with image-guided IMRT to treat canine sinonasal tumours led to clinically acceptable side effects. The suspected increased tumour control probability and the risk of late toxicity with the used dose escalation of 20% has to be further investigated.

Dosimetric benefit of adaptive radiotherapy in the neoadjuvant management of canine and feline thymoma-An exploratory case series.

While surgery is the treatment of choice for thymomas, complete excision is not possible in a significant proportion of cases. For these patients, radiotherapy can be used as neoadjunctive, post-operative adjunctive or sole therapy. During radiotherapy, rapid biological clearance of tumour cells is often observed, requiring adaptation of the treatment plan. Adaptive radiation therapy (RT) is a dynamic process, whereby the treatment plan is altered throughout the treatment course due to changes in morphologic, functional or positioning changes. With the hypothesis, that individually adapted replanning will massively reduce the dose to organs at risk (OAR) in a fast-changing environment such as a rapidly responding thymoma, the dosimetric impact of adaptive treatment planning in 5 patients with large thymoma was measured. In all patients rapid tumour-shrinkage of the gross tumour volume was observed after 1 week of therapy, with a mean shrinkage of 31.0% ± 15.2%, or a tumour regression of 5.2% per day. In consequence, there was a considerable change in position of organs such as heart and lung, both of them moving cranially into the high dose area upon tumour regression. After mid-therapy replanning, the dose to OAR was significantly reduced, with -18.2% in the mean heart dose and -27.9% in the V20 lung dose. Adaptive planning led to a significantly reduced radiation dose and hence protection of OAR for these patients. It can be concluded that adaptive replanning should be considered for canine and feline thymoma patients receiving fractionated RT.

Safety, tolerability and pharmacokinetic properties of the novel triazene TriN 2755 in tumour bearing dogs - a phase I study†.

TriN 2755 is an alkylating antineoplastic agent for intravenous (IV) use, carrying the triazene group as the cytotoxic principal. Using a standard 3 + 3 design, a phase I study was performed in tumour bearing dogs to determine the maximum tolerated dose (MTD), the dose limiting toxicity (DLT), and pharmacokinetic (PK) profile of TriN 2755. Thirty dogs were included in the study. TriN 2755 was administered over 20 min on two consecutive weeks per month for a total of three cycles. The starting dose was 25 mg kg-1 and the MTD was 74.6 mg kg-1 . Three dogs experienced DLT, which was characterized by gastrointestinal adverse events. The PKs of TriN 2755 and its main metabolites in plasma and sputum are described in a two-compartment model. The response rate for 19 of 30 dogs was 47.3% (six partial remission, three stable disease) and the median progression-free interval (PFI) for the responders was 47 days (range: 21-450 days).

A complication probability planning study to predict the safety of a new protocol for intracranial tumour radiotherapy in dogs.

Technical advances make it possible to deliver radiation therapy for canine intracranial tumours in fewer fractions, under the assumption of equivalent tumour control. With the aim of estimating the late toxicity risk profile for various tumour sizes and locations, the present paper evaluates the normal tissue complication probability (NTCP) values for the intracranial organs at risk. By making isoeffect calculations, a new 10-fraction radiation protocol was developed with the same tumour control probability (TCP) as a currently used 20-fraction standard protocol, and complication risk profiles for brain, brainstem and optic chiasm were modelled using a representative population of 64 dogs with brain tumours. For >59% of cases, the new 10-fraction protocol yielded an acceptable, low risk estimate of late toxicity (<10%). Our calculations suggest that it may be safe to treat small to intermediate-sized tumours that are neither located near the optic chiasm nor at the brainstem with 10 daily fractions of 4.35 Gy.

Outcome in dogs with advanced (stage 3b) anal sac gland carcinoma treated with surgery or hypofractionated radiation therapy.

Stage 3b anal sac gland carcinoma (ASGC) can be life-threatening. A surgical approach is not always possible or may be declined. Dogs with stage 3b ASGC treated with surgery or conformal radiation therapy (RT) with 8 × 3.8 Gy (total dose 30.4 Gy, over 2.5 weeks) were retrospectively evaluated. Patient characteristics, median progression-free interval (PFI) and median survival time (MST) were compared. Twenty-eight dogs were included; 15 underwent surgery, 13 underwent RT. At the time of presentation, 21% showed life-threatening obstipation and 25% showed hypercalcaemia. PFI and MST for surgery cases were 159 days (95% CI: 135-184 days) and 182 days (95% CI: 146-218 days), both significantly lower than for RT cases with 347 days (95% CI: 240-454 days) and 447 days (95% CI: 222-672 days), (P = 0.01, P = 0.019). Surgery as well as RT led to a fast relief of symptoms. PFI and survival of surgical patients were significantly inferior to that of a comparable patient group treated with conformal hypofractionated RT.

Interaction of biomechanics with extracellular matrix components in abdominal aortic aneurysm wall.

OBJECTIVE: Little is known about the interactions between extracellular matrix (ECM) proteins and locally acting mechanical conditions and material macroscopic properties in abdominal aortic aneurysm (AAA). In this study, ECM components were investigated with correlation to corresponding biomechanical properties and loads in aneurysmal arterial wall tissue. METHODS: Fifty-four tissue samples from 31 AAA patients (30♂; max. diameter Dmax 5.98 ± 1.42 cm) were excised from the aneurysm sac. Samples were divided for corresponding immunohistological and mechanical analysis. Collagen I and III, total collagen, elastin, and proteoglycans were quantified by computational image analysis of histological staining. Pre-surgical CT data were used for 3D segmentation of the AAA and calculation of mechanical conditions by advanced finite element analysis. AAA wall stiffness and strength were assessed by repeated cyclical, sinusoidal and destructive tensile testing. RESULTS: Amounts of collagen I, III, and total collagen were increased with higher local wall stress (p = .002, .017, .030, respectively) and strain (p = .002, .012, .020, respectively). AAA wall failure tension exhibited a positive correlation with collagen I, total collagen, and proteoglycans (p = .037, .038, .022, respectively). α-Stiffness correlated with collagen I, III, and total collagen (p = .011, .038, and .008), while ß-stiffness correlated only with proteoglycans (p = .028). In contrast, increased thrombus thickness was associated with decreased collagen I, III, and total collagen (p = .003, .020, .015, respectively), and AAA diameter was negatively associated with elastin (p = .006). CONCLUSIONS: The present results indicate that in AAA, increased locally acting biomechanical conditions (stress and strain) involve increased synthesis of collagen and proteoglycans with increased failure tension. These findings confirm the presence of adaptive biological processes to maintain the mechanical stability of AAA wall.

Measuring and modeling patient-specific distributions of material properties in abdominal aortic aneurysm wall.

Both the clinically established diameter criterion and novel approaches of computational finite element (FE) analyses for rupture risk stratification of abdominal aortic aneurysms (AAA) are based on assumptions of population-averaged, uniform material properties for the AAA wall. The presence of inter-patient and intra-patient variations in material properties is known, but has so far not been addressed sufficiently. In order to enable the preoperative estimation of patient-specific AAA wall properties in the future, we investigated the relationship between non-invasively assessable clinical parameters and experimentally measured AAA wall properties. We harvested n = 163 AAA wall specimens (n = 50 patients) during open surgery and recorded the exact excision sites. Specimens were tested for their thickness, elastic properties, and failure loads using uniaxial tensile tests. In addition, 43 non-invasively assessable patient-specific or specimen-specific parameters were obtained from recordings made during surgery and patient charts. Experimental results were correlated with the non-invasively assessable parameters and simple regression models were created to mathematically describe the relationships. Wall thickness was most significantly correlated with the metabolic activity at the excision site assessed by PET/CT (ρ = 0.499, P = 4 × 10(-7)) and to thrombocyte counts from laboratory blood analyses (ρ = 0.445, P = 3 × 10(-9)). Wall thickness was increased in patients suffering from diabetes mellitus, while it was significantly thinner in patients suffering from chronic kidney disease (CKD). Elastic AAA wall properties had significant correlations with the metabolic activity at the excision site (PET/CT), with existent calcifications, and with the diameter of the non-dilated aorta proximal to the AAA. Failure properties (wall strength and failure tension) had correlations with the patient's medical history and with results from laboratory blood analyses. Interestingly, AAA wall failure tension was significantly reduced for patients with CKD and elevated blood levels of potassium and urea, respectively, both of which are associated with kidney disease. This study is a first step to a future preoperative estimation of AAA wall properties. Results can be conveyed to both the diameter criterion and FE analyses to refine rupture risk prediction. The fact that AAA wall from patients suffering from CKD featured reduced failure tension implies an increased AAA rupture risk for this patient group at comparably smaller AAA diameters.

Use of epothilone B (patupilone) in refractory lymphoma and advanced solid tumors in dogs.

BACKGROUND: The epothilones are microtubule-stabilizing agents with promising antitumor effect in refractory and metastatic tumors in humans. The toxicity profile is considered more favorable than in taxanes. The safety of epothilone B (patupilone) has not been evaluated in tumor-bearing dogs. OBJECTIVES: To evaluate the inhibition of proliferation in canine tumor cells after patupilone treatment. To assess toxicity profile and maximally tolerated dose of patupilone in dogs with refractory tumors. ANIMALS: Twenty client-owned dogs with various malignancies. METHODS: Prospective clinical study. The inhibition of proliferation was assessed with a proliferation assay in vitro in canine hemangiosarcoma and lymphoma cell lines. Dogs received patupilone IV once a week for 2 treatments (= 1 treatment cycle). Dose was escalated with 3 dogs per cohort and 20% increments. Adverse effects were graded according to the VCOG-CTCAE v1.0. RESULTS: Both canine cell lines were sensitive to patupilone with approximately 50% decrease in proliferative activity at 0.2-1 nM. In vivo, dose-limiting adverse effects occurred at 3.3 mg/m(2); main adverse effects were diarrhea, anorexia, vomiting, and nausea. Neither neutropenia nor peripheral neuropathy was observed. Maximally tolerated dose for 2 patupilone administrations once weekly IV is 2.76 mg/m(2). Three per 11 dogs receiving more than 1 treatment cycle showed partial remission in the short period of observation. CONCLUSIONS AND CLINICAL IMPORTANCE: Canine tumor cells show inhibition of proliferation to patupilone in vitro. Clinically, a dose of 2.76 mg/m(2) IV is well tolerated in dogs with spontaneously occurring tumors.

[Clinical pathway for total knee arthroplasty (EGON). II. The impact of enhanced patient information]. / Klinischer Behandlungspfad zur Implantation einer Oberflächenknieendoprothese (EGON). II: Effekt einer intensivierten Patienteninformation.

PURPOSE: The effects of the introduction of a clinical pathway and enhanced patient information on patients' satisfaction were investigated in the current study. MATERIAL AND METHODS: In a prospective cohort study patients were systematically interviewed about the preparation and the clinical course during implantation of a total knee arthroplasty. The study included 132 patients before (cohort I) and 128 after (cohort II) introduction of a clinical pathway. All patients of cohort II were offered the opportunity to attend an enhanced patient information lecture. The collected data were analysed in a descriptive manner. Items with more than 10% negative answers constituted the need for improvement. RESULTS: Regarding preparation of the operation there was a need for improvement of 11 items in cohort I and 4 in cohort II. With respect to the clinical course there was a slight increase from 6 to 7 items that required improvement. The enhanced information about the treatment and the clinical course were assessed positively. Patients were unsatisfied with the individual explanation of the X-rays. Of 128 patients from cohort II, 58 decided to participate in the information session for patients. The patients who had attended were more interested in receiving additional information. The success of the operation (gain in WOMAC score of at least 20%) showed a substantial effect on patient satisfaction. CONCLUSION: With increased patient information the knowledge and patient satisfaction within clinical pathways can be improved.

[Peripheral nerve blocks of the lower extremities. Clinical and practical aspects]. / Periphere Nervenblockaden an der unteren Extremität. Klinisch-praktische Aspekte.

Peripheral nerve blocks (PNBs) of the lower extremities are effective techniques for anesthesia and postoperative pain control. So far, these techniques have been used less frequently than PNBs of the upper limb. Nevertheless, growing awareness of complications of neuroaxial techniques, improved equipment and modern techniques for nerve localization have led to an increased use of PNBs of the lower limb. Anesthesiologists should be familiar with the anatomical basics and procedural details of these PNBs. They should also know the typical complications and side-effects and thoroughly inform patients about such potential problems. Continuous PNBs (perineural catheters) allow the benefits of PNBs to be prolonged into the postoperative period. Compared to continuous neuroaxial techniques continuous PNBs are equally effective for pain control but seem to be associated with fewer complications and side-effects.

[Thoracotomy and scoliosis surgery in a patient with a univentricular heart]. / Thorakotomie und Skoliosekorrektur bei univentrikulärem Herzen.

We report the case of a 15-year-old boy with a single left ventricle who underwent total cavopulmonary connection (Fontan circulation). Due to a progredient idiopathic scoliosis he had to undergo two surgical correction procedures of the vertebral column. Fontan circulation is characterized by the functional absence of the right ventricle. Blood from the systemic circulation passively flows directly into the pulmonary artery. Therefore, central venous preload as well as pulmonary vascular resistance gain essential significance for cardiac output. After volume preload, in both procedures anaesthesia was induced with etomidate and maintained intravenously with propofol and fentanyl but without N(2)O. Increases of the systemic and pulmonary vascular resistance were avoided. A central venous pressure of 20 mmHg was clinically associated with the most stable haemodynamics. In view of the elective nature of the present surgical procedures and with regard to an individual advantage vs risk estimation, tactical algorithms of action must be predefined on the basis of the individual physiology/pathophysiology to keep reaction times for necessary interventions brief.

Simultaneous evaluation of T- and B-cell clonality, t(11;14) and t(14;18), in a single reaction by a four-color multiplex polymerase chain reaction assay and automated high-resolution fragment analysis: a method for the rapid molecular diagnosis of lymphoproliferative disorders applicable to fresh frozen and formalin-fixed, paraffin-embedded tissues, blood, and bone marrow aspirates.

Current polymerase chain reaction (PCR) methods for the molecular diagnosis of B- and T-cell lymphomas by determination of clonality of immunoglobulin heavy chain (IgH) and T-cell receptor-gamma rearrangements and by detection of the chromosomal translocations t(14;18) and t(11;14), require several laborious and costly PCR assays for each of these diagnostic tests. We have developed a multiplex PCR assay for the simultaneous determination of B- and T-cell clonality and the detection of the chromosomal translocations t(14;18) and t(11;14) in a single reaction, using four-color fluorescence and automated high-resolution fragment analysis. The 26 primers combined in the multiplex PCR correspond to the sequences of >90% of the 69 variables and 6 join IgH genes and 100% of the T-cell receptor-gamma variables and join genes that could participate in the respective rearrangements. In addition, they detect the major and the minor breakpoint regions of the t(14;18) and the major breakpoint region of the t(11;14), and amplify the beta-globin gene as an internal control. The specificity of the multiplex PCR was confirmed by analysis of 39 T-cell lymphomas and 58 B-cell lymphomas, including 11 mantle cell lymphomas bearing the t(11;14) and 25 follicular lymphomas bearing the t(14;18), with known rearrangements and/or translocations. Fifteen samples of reactive lymphadenitis remained negative.

Metastatic primitive neuroectodermal tumor of the kidney in adults.

OBJECTIVE: Primitive neuroectodermal tumors (PNET) of the kidney are rare and highly aggressive malignancies. The purpose of our study was to present information about the management of patients with metastatic disease. METHODS: The records of 2 patients (30-year-old female and 32-year-old male) with metastatic PNET of the kidney were reviewed and our data compared with the literature. RESULTS: Neither clinical evaluation nor radiological methods allowed to distinguish PNET from renal cell carcinoma. Immunohistochemistry revealed strong positivity for CD99 in tumor 1 and weak positivity for NSE and vimentin in both tumors. In tumor 2, EWS/FLI1 translocation was detected by RT-PCR. Patient 1 underwent nephrectomy, seven cycles of polychemotherapy, two cycles of high-dose chemotherapy, autologous bone marrow rescue, radiotherapy of suspicious skeletal foci and is without evidence of recurrent disease 28 months after therapy. Patient 2 underwent six cycles of polychemotherapy, nephrectomy, high-dose chemotherapy with cyclophosphamide and abdominal radiotherapy. Because of relapse high-dose chemotherapy with stem cell rescue was not performed. He underwent three further cycles of polychemotherapy and died one year after diagnosis due to cerebral metastasis. CONCLUSIONS: The diagnosis of renal PNET must be considered in young patients with renal neoplasm, particularly those with advanced disease at presentation. Achieving exact diagnosis has important clinical consequences because polychemotherapy and high-dose chemotherapy may lead to dramatic tumor reduction or even complete remission.

Hepatitis C virus infection: 10 years after the discovery of the virus.

The hepatitis C virus (HCV) causes an acute but very often chronic liver disease. An estimated 3% of the world population is chronically infected with HCV. Chronic hepatitis C is the major cause of cirrhosis and hepatocellular carcinoma (HCC), which most often lead to liver transplantation. HCV is a single-stranded enveloped RNA virus; it belongs to the flaviviridae family. The virus has been classified into six genotypes, some of which are distributed worldwide, others of which are confined to more restricted areas. The genotype is an independent predictor of response to antiviral treatment. Blood transfusion was a major risk factor for acquiring HCV infection before donor screening for surrogate marker testing for non-A, non-B (NANB) hepatitis began in the mid-1980s, followed by screening for antibody to HCV in 1990. Today, intravenous drug use and high-risk sexual activity are the most frequently identified risk factors associated with HCV infection. The prevalence of people with unknown HCV infection worldwide is high, so it is necessary to screen people with risk factors. The treatment of patients with chronic HCV infection who have not been treated previously should consist of interferon alpha (IFN-alpha) and ribavirin.

Enhanced expression of interferon-regulated genes in the liver of patients with chronic hepatitis C virus infection: detection by suppression-subtractive hybridization.

Hepatitis C virus (HCV) infection causes acute and often also chronic liver disease. Worldwide, prevalence of infection is estimated to exceed that of human immunodeficiency virus infection fourfold. Because of the lack of appropriate animal models, knowledge of interactions between virus and host is still limited. Assumptions regarding pathogenesis or the activation status of innate antiviral host responses, for instance, derive mainly from clinical observations and from expression analyses of selected genes. To obtain a more objective insight into virus-host interrelationships, we used suppression-subtractive hybridization to compare gene expression in HCV-infected and non-HCV-infected liver tissues samples. Four differentially expressed genes were found: (i) the gamma interferon (IFN-gamma)-inducible chemokine IP-10 gene; (ii) the IFN-alpha/beta-inducible antiviral MxA gene; (iii) the gene encoding IFN-alpha/beta-inducible p44, shown to be associated with ultrastructural cytoplasmic entities within hepatocytes of non-A, non-B hepatitis-infected chimpanzees; and (iv) the gene encoding IFN-alpha/beta/gamma-inducible IFI-56K, a protein recently shown to interact with the eukaryotic translation initiation factor eIF-3. Compared to hepatic gene expression in patients with liver diseases unrelated to viral infections, expression in patients with chronic HCV infection was up to 50-fold higher. While in patients with chronic HBV infection IP-10 was slightly activated as well, the IFN-alpha/beta-regulated genes were not. Revealing a dominance of hepatic interferon-regulated processes in chronic HCV infection, data on the enhanced expression of the IFN-gamma regulated IP-10 support earlier findings and may explain the composition of the hepatic cellular infiltrate. The data on enhanced expression of IFN-alpha/beta inducible genes might be germane to therapeutic considerations.