The volume effect in irradiated mouse colorectum

Damage of the colorectum is the dose-limiting normal tissue complication following radiotherapy of prostate and cervical cancers. One approach for decreasing complications is to physically reduce the treatment volume. Mathematical models have been previously developed to describe the change in associated toxicity with a change in irradiated volume, i.e. the "volume effect", for serial-type normal tissues including the colorectum. The first goal of this thesis was to test the hypothesis that there would not be a threshold length in the development of obstruction after irradiation of mouse colorectum, as predicted by the Probability model of the volume effect. The second goal was to examine if there were differences in the threshold and in the incidence of colorectal obstruction after irradiation of two mouse strains, C57B1/6 (C57) and C3Hf/Kam (C3H), previously found to be fibrosis-prone and-resistant, respectively, after lung irradiation due, in part, to genetic differences. The hypothesis examined was that differences in incidence between strains were due to the differential expression of the fibrogenic cytokines $\rm TGF\beta$ and $\rm TNF\alpha.$ Various lengths of C57 and C3H mouse colorectum were irradiated and the incidence of colorectal obstruction was followed up to 15 months. A threshold length was observed for both mouse strains, in contradiction of model predictions. The mechanism of the threshold was epithelial regeneration after irradiation. C57 mice had significantly higher incidence of colorectal obstruction compared to C3H mice, especially at smaller irradiated lengths. Colorectal tissue was obtained at various times after irradiation and prepared for histology, immunohistochemistry and RNase protection assay for measurement of $\rm TGF\beta 1,$ 2, 3 and $\rm TNF\alpha$ mRNA. Distinct strain differences in the histological time of appearance and spatial locations of fibrosis were observed. However, there were no consistent strain difference in mRNA levels or immunolocalization for any of the cytokines examined. The data indicate the need for volume effect models that account for biologically important processes, such as the effect of epithelial regeneration after irradiation. As well, changes in fibrogenic cytokines at the mRNA level do not contribute to the strain difference in radiation-induced colorectal obstruction. ^

Bouveret's syndrome: presentation of two cases with review of the literature and development of a surgical treatment strategy

BACKGROUND Bouveret's syndrome causes gastric outlet obstruction when a gallstone is impacted in the duodenum or stomach via a bilioenteric fistula. It is a rare condition that causes significant morbidity and mortality and often occurs in the elderly with significant comorbidities. Individual diagnostic and treatment strategies are required for optimal management and outcome. The purpose of this paper is to develop a surgical strategy for optimized individual treatment of Bouveret's syndrome based on the available literature and motivated by our own experience. CASE PRESENTATION Two cases of Bouveret's syndrome are presented with individual management and restrictive surgical approaches tailored to the condition of the patients and intraoperative findings. CONCLUSIONS Improved diagnostics and restrictive individual surgical approaches have shown to lower the mortality rates of Bouveret's syndrome. For optimized outcome of the individual patient: The medical and perioperative management and time of surgery are tailored to the condition of the patient. CT-scan is most often required to secure the diagnosis. The surgical approach includes enterolithotomy alone or in combination with simultaneous or subsequent cholecystectomy and fistula repair. Lower overall morbidity and mortality are in favor of restrictive surgical approaches. The surgical strategy is adapted to the intraoperative findings and to the risk for secondary complications vs. the age and comorbidities of the patient.

Imaging findings in uncorrected tetralogy of Fallot and pulmonary atresia with major aortopulmonary collateral arteries and septic embolism.

Tetralogy of Fallot (TOF) is one of the most common congenital heart malformations comprising a ventricular septal defect, right ventricular outflow tract obstruction, right ventricular hypertrophy, and overriding aorta. A rare variant includes pulmonary atresia and major aortopulmonary collateral arteries. Altered hemodynamics within the functional single-ventricle results in turbulent flow and predisposes to endocardial vegetation formation which may consequently lead to thromboembolic events. We present a rare case of an adult survivor of uncorrected TOF with pulmonary atresia.

Intracranial meningiomas associated with cervical syringohydromyelia in a cat

Eine dreizehnjährige, weibliche, nicht kastrierte Hauskatze wurde zur chirurgischen Therapie eines multiplen Meningeoms in der Kleintierklinik des Tierspital Bern vorgestellt. Eine leichtgradige generalisierte Ataxie wurde beobachtet, die Propriozeption war generalisiert herabgesetzt und der Drohreflex war beidseitig reduziert. Es wurden eine prä- und eine postoperative Magnetrezonanztomographie durchgeführt. Drei supratentoriale extra-axiale Raumforderungen wurden diagnostiziert. Eine vierte Masse wurde infratentorial extra-axial über der linken zerebellären Hemisphere lokalisiert. Eine Herniation des kaudoventralen Kleinhirn (Vermis) von ungefähr einem Zentimeter Länge durch das Foramen magnum wurde beobachtet. Eine zervikale Syringohydromyelie wurde als Zufallsbefund diagnostiziert. Die Meningeome wurden durch 3 Kraniotomiestellen entfernt. Zwei Jahre nach der Operation ist die Katze normal. Anhand der vorhandenen Literatur wird die tumor-assoziierte Syringohydromyelie besprochen. Die Therapie der Syringohydromyelie sollte gegen den kausalen pathologischen Prozess (z.B. intrakranieller Tumor) für die Liquorzirkulationsstörung gerichtet sein.

Genetics of upper and lower airway diseases in the horse.

Genetic predispositions for guttural pouch tympany, recurrent laryngeal neuropathy and recurrent airway obstruction (RAO) are well documented. There is also evidence that exercise-induced pulmonary haemorrhage and infectious diseases of the respiratory tract in horses have a genetic component. The clinical expression of equine respiratory diseases with a genetic basis results from complex interactions between the environment and the genetic make-up of each individual horse. The genetic effects are likely to be due to variations in several genes, i.e. they are polygenic. It is therefore unlikely that single gene tests will be diagnostically useful in these disorders. Genetic profiling panels, combining several genetic factors with an assessment of environmental risk factors, may have greater value, but much work is still needed to uncover diagnostically useful genetic markers or even causative variants for equine respiratory diseases. Nonetheless, chromosomal regions associated with guttural pouch tympany, recurrent laryngeal neuropathy and RAO have been identified. The association of RAO with other hypersensitivities and with resistance to intestinal parasites requires further study. This review aims to provide an overview of the available data and current thoughts on the genetics of equine airway diseases.

Late toxicity and five year outcomes after high-dose-rate brachytherapy as a monotherapy for localized prostate cancer

BACKGROUND To determine the 5-year outcome after high-dose-rate brachytherapy (HDR-BT) as a monotherapy. METHODS Between 10/2003 and 06/2006, 36 patients with low (28) and intermediate (8) risk prostate cancer were treated by HDR-BT monotherapy. All patients received one implant and 4 fractions of 9.5 Gy within 48 hours for a total prescribed dose (PD) of 38 Gy. Five patients received concomitant androgen deprivation therapy (ADT). Toxicity was scored according to the common terminology criteria for adverse events from the National Cancer Institute (CTCAE) version 3.0. Biochemical recurrence was defined according to the Phoenix criteria and analyzed using the Kaplan Meier method. Predictors for late grade 3 GU toxicity were analyzed using univariate and multivariate Cox regression analyses. RESULTS The median follow-up was 6.9 years (range, 1.5-8.0 years). Late grade 2 and 3 genitourinary (GU) toxicity was observed in 10 (28%) and 7 (19%) patients, respectively. The actuarial proportion of patients with late grade 3 GU toxicity at 5 years was 17.7%. Late grade 2 and 3 gastrointestinal (GI) toxicities were not observed. The crude erectile function preservation rate in patients without ADT was 75%. The 5 year biochemical recurrence-free survival (bRFS) rate was 97%. Late grade 3 GU toxicity was associated with the urethral volume (p = 0.001) and the urethral V120 (urethral volume receiving ≥120% of the PD; p = 0.0005) after multivariate Cox regression. CONCLUSIONS After HDR-BT monotherapy late grade 3 GU was observed relatively frequently and was associated with the urethral V120. GI toxicity was negligible, the erectile function preservation rate and the bRFS rate was excellent.

The use of bougie-guided insertion of a laryngeal mask airway device in neonatal piglets after unexpected complications

After marked airway obstruction with laryngeal mask (LM) placement in neonate piglets, anatomical observations in cadavers revealed a large epiglottis advancing markedly over the soft palate. CT imaging in vivo confirmed that the LM pushes the epiglottis caudally thereby obstructing the larynx. As a new approach, in 20 piglets a flexible PVC bougie placed under laryngoscopy was used to guide the LM to the correct position at the larynx. Placement of the bougie was easy and the LM was positioned successfully in all piglets at first attempt. In 14 piglets, the epiglottis was positioned dorsal to the soft palate before LM insertion and had to be pushed downwards to advance the bougie. In case of failure of LM placement with potential airway obstruction, the use of a bougie to guide the LM over the epiglottis was simple, rapid, and improved the success rate without complication.

Blastomycosis granuloma involving the cranial vena cava associated with chylothorax and cranial vena caval syndrome in a dog

A four-year-old, sexually intact, male dachshund was diagnosed with pulmonary blastomycosis. Itraconazole was administered for 60 days, and the dog was considered to be disease-free at three- and 12-month reevaluations. Two years following discontinuation of itraconazole, the dog developed a granuloma of the cranial vena cava resulting in chylothorax and cranial vena caval obstruction. To the authors' knowledge, this is the first case of a blastomycotic granuloma involving the vena cava reported in the dog. Blastomycosis should be considered as a differential diagnosis for both chylothorax and cranial vena caval syndrome in the dog.

Is thermochemotherapy with the Synergo system a viable treatment option in patients with recurrent non-muscle-invasive bladder cancer?

OBJECTIVES To prospectively evaluate the outcome of combined microwave-induced bladder wall hyperthermia and intravesical mitomycin C instillation (thermochemotherapy) in patients with recurrent non-muscle-invasive bladder cancer. METHODS Between 2003 and 2009, 21 patients (median age 70 years, range 35-95 years) with recurrent non-muscle-invasive bladder cancer (pTaG1-2 n = 9; pTaG3 n = 3; pT1 n = 9; concurrent pTis n = 8) were prospectively enrolled. Of 21 patients, 15 (71%) had received previous intravesical instillations with bacillus Calmette-Guérin, mitomycin C and/or farmorubicin. Thermochemotherapy using the Synergo system was carried out in 11 of 21 patients (52%) with curative intent, and in 10 of 21 patients (48%) as prophylaxis against recurrence. RESULTS The median number of thermochemotherapy cycles per patient was six (range 1-12). Adverse effects were frequent and severe: urinary urgency/frequency in 11 of 21 patients (52%), pain in eight of 21 patients (38%) and gross hematuria in five of 21 patients (24%). In eight of 21 patients (38%), thermochemotherapy had to be abandoned because of the severity of the adverse effects (pain in 3/8, severe bladder spasms in 2/8, allergic reaction in 2/8, urethral perforation in 1/8). Overall, six of 21 patients (29%) remained free of tumor after a median follow up of 50 months (range 1-120), six of 21 patients (29%) had to undergo cystectomy because of multifocal recurrences or cancer progression and seven of 21 patients (33%) died (2/7 of metastatic disease, 5/7 of non-cancer related causes). CONCLUSIONS Given the high rate of severe side-effects leading to treatment discontinuation, as well as the limited tumor response, thermochemotherapy should be offered only in highly selected cases of recurrent non-muscle-invasive bladder cancer.

Die akute Hanrverhaltung in der Praxis

Acute urinary retention is a common emergency condition in elderly men. Transurethral and suprapubic catheterization are easy and safe procedures provided that a few simple rules are followed. Primarily, a transurethral catheter is placed if there is no urethral injury or stricture. Local anaesthesia of the urethra up to the sphincter region and a well-stretched penis warrant an atraumatic insertion of the catheter into the bladder. The use of a thick catheter with a round tip or of a catheter with a bended tip under rectal guidance facilitate the insertion of the catheter in difficult conditions. Alternatively, a suprapubic catheterization can be performed provided that no contraindication such as history or suspicion of transitional cell carcinoma is present. Optimal interventional conditions using ultrasound-guidance are mandatory in patients after abdominal surgery and with hemorrhagic diathesis in view of a safe and straight-forward placement of the suprapubic catheterization. In case of persistent bleeding after insertion of a suprapubic catheter, the suprapubic catheter should be replaced by one with a balloon blocked and kept under tension for several minutes.

Favourable mid-term outcome after heart transplantation for late Fontan failure.

OBJECTIVES Fontan failure (FF) represents a growing and challenging indication for paediatric orthotopic heart transplantation (OHT). The aim of this study was to identify predictors of the best mid-term outcome in OHT after FF. METHODS Twenty-year multi-institutional retrospective analysis on OHT for FF. RESULTS Between 1991 and 2011, 61 patients, mean age 15.0 ± 9.7 years, underwent OHT for failing atriopulmonary connection (17 patients = 27.8%) or total cavopulmonary connection (44 patients = 72.2%). Modality of FF included arrhythmia (14.8%), complex obstructions in the Fontan circuit (16.4%), protein-losing enteropathy (PLE) (22.9%), impaired ventricular function (31.1%) or a combination of the above (14.8%). The mean time interval between Fontan completion and OHT was 10.7 ± 6.6 years. Early FF occurred in 18%, requiring OHT 0.8 ± 0.5 years after Fontan. The hospital mortality rate was 18.3%, mainly secondary to infection (36.4%) and graft failure (27.3%). The mean follow-up was 66.8 ± 54.2 months. The overall Kaplan-Meier survival estimate was 81.9 ± 1.8% at 1 year, 73 ± 2.7% at 5 years and 56.8 ± 4.3% at 10 years. The Kaplan-Meier 5-year survival estimate was 82.3 ± 5.9% in late FF and 32.7 ± 15.0% in early FF (P = 0.0007). Late FF with poor ventricular function exhibited a 91.5 ± 5.8% 5-year OHT survival. PLE was cured in 77.7% of hospital survivors, but the 5-year Kaplan-Meier survival estimate in PLE was 46.3 ± 14.4 vs 84.3 ± 5.5% in non-PLE (P = 0.0147). Cox proportional hazards identified early FF (P = 0.0005), complex Fontan pathway obstruction (P = 0.0043) and PLE (P = 0.0033) as independent predictors of 5-year mortality. CONCLUSIONS OHT is an excellent surgical option for late FF with impaired ventricular function. Protein dispersion improves with OHT, but PLE negatively affects the mid-term OHT outcome, mainly for early infective complications.

The ADO index as a predictor of two-year mortality in general practice-based chronic obstructive pulmonary disease cohorts.

BACKGROUND Existing prediction models for mortality in chronic obstructive pulmonary disease (COPD) patients have not yet been validated in primary care, which is where the majority of patients receive care. OBJECTIVES Our aim was to validate the ADO (age, dyspnoea, airflow obstruction) index as a predictor of 2-year mortality in 2 general practice-based COPD cohorts. METHODS Six hundred and forty-six patients with COPD with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages I-IV were enrolled by their general practitioners and followed for 2 years. The ADO regression equation was used to predict a 2-year risk of all-cause mortality in each patient and this risk was compared with the observed 2-year mortality. Discrimination and calibration were assessed as well as the strength of association between the 15-point ADO score and the observed 2-year all-cause mortality. RESULTS Fifty-two (8.1%) patients died during the 2-year follow-up period. Discrimination with the ADO index was excellent with an area under the curve of 0.78 [95% confidence interval (CI) 0.71-0.84]. Overall, the predicted and observed risks matched well and visual inspection revealed no important differences between them across 10 risk classes (p = 0.68). The odds ratio for death per point increase according to the ADO index was 1.50 (95% CI 1.31-1.71). CONCLUSIONS The ADO index showed excellent prediction properties in an out-of-population validation carried out in COPD patients from primary care settings.

Primum et super omnium: nihil nocere Operationsindikation im Wandel bei Divertikulitis

Diverticulitis is a common disease in western countries and its incidence is increasing especially among young patients. Colonic diverticulosis, incidentally diagnosed by endoscopy or CT-scanning, has no immediate clinical consequences. Progression to diverticulitis develops in only 4 % of cases. In the last decades management of diverticular disease evolved and expectative treatment and less invasive techniques have gained importance. Elective resection has traditionally been advised after a second episode of diverticulitis or after a first episode if the patient was less than 50 years of age or complicated disease occurred. Recent changes in understanding the natural history of diverticular disease have substantially modified treatment paradigms. Elective resection in case of recurrent diverticular disease should be performed on a individual basis and in cases with complications like intestinal obstruction or fistulas. Primary anastomosis is an option even in emergency surgery due to colonic perforation, while diverting operations are indicated for selected patient groups with a high risk profile. Several prospective studies showed good results for laparoscopic drainage and lavage in the setting of perforated diverticulitis with generalized peritonitis, though this concept needs to be controlled with randomized clinical trials before application into the daily practice. This article should provide a short overview of trends in the surgical treatment of diverticulitis, help to understand the natural history of the disease and thereby explain the currently lower frequency of surgical interventions for diverticulitis.

Arterial stiffness is increased in asthmatic children.

UNLABELLED Altered arterial stiffness is a recognized risk factor of poor cardiovascular health. Chronic inflammation may increase arterial stiffness. We tested whether arterial stiffness is increased children with asthma, a chronic disease characterized by fluctuating airway and systemic inflammation. Arterial stiffness, expressed as carotid-femoral pulse wave velocity (PWVcf), was measured in 37 mild-to-moderate asthmatic children: 11 girls, median (range) age 11.1 years (6-15). PWVcf in asthma was compared to PWVcf in 65 healthy controls matched for age, height, and gender previously studied in Germany and was correlated with airway inflammation and obstruction. PWVcf was higher in asthmatic children compared to controls: PWVcf median (interquartile range) was 4.7 m/s (4.5-4.9) vs. 4.3 m/s (4.1-4.7), p < 0.0001. In asthmatic children, PWVcf was inversely associated (r (2) = 0.20, p = 0.004) with forced expiratory volume in 1 s (FEV1). This association remained significant after adjusting for possible confounders including body mass index, blood pressure, steroid use, and FeNO. CONCLUSION Arterial stiffness is increased in children with mild-to-moderate asthma. The association between impaired lung function and increased arterial stiffness suggests that severity of disease translates into detrimental effects on the cardiovascular system.

Orthotopic Ileal Bladder Substitution in Women: Factors Influencing Urinary Incontinence and Hypercontinence.

BACKGROUND Urinary incontinence or the inability to void spontaneously after ileal orthotopic bladder substitution is a frequent finding in female patients. OBJECTIVE To evaluate how hysterectomy and nerve sparing affect functional outcomes and whether these relate to pre- and postoperative urethral pressure profile (UPP) results. DESIGN, SETTING, AND PARTICIPANTS Prospectively performed pre- and postoperative UPPs of 73 female patients who had undergone cystectomy and bladder substitution were correlated with postoperative voiding and continence status. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Outcome analyses were performed with the Kruskal-Wallis test, Wilcoxon-Mann-Whitney, or two-group post hoc testing with the Bonferroni correction. Chi-square or Fisher exact tests were applied for the categorical data. RESULTS AND LIMITATIONS Of postoperatively continent or hypercontinent patients, 22 of 43 (51.2%) had the uterus preserved; of incontinent patients, only 4 of 30 (13.3%, p<0.01) had the uterus preserved. Of postoperatively continent or hypercontinent patients, 27 of 43 patients (62.8%) had bilateral and 15 of 43 (34.9%) had unilateral attempted nerve sparing. In incontinent patients, 11 of 30 (36.7%) had bilateral and 16 of 30 (53.3%) had unilateral attempted nerve sparing (p=0.02). When compared with postoperatively incontinent patients, postoperatively continent patients had a longer functional urethral length (median: 32mm vs 24mm; p<0.001), a higher postoperative urethral closing pressure at rest (56cm H2O vs 35cm H2O; p<0.001) as well as a higher preoperative urethral closing pressure at rest (74cm H2O vs 47.5cm H2O; p=0.01). The main limitation was the limited number of patients. CONCLUSIONS In female patients undergoing radical cystectomy and bladder substitution, preservation of the uterus and attempted nerve sparing results in better functional outcomes. The preoperative UPPs correlate with postoperative voiding and continence status and may predict which patients are at a higher risk of functional failure after bladder substitution. PATIENT SUMMARY If preservation of the urethra's innervation is not possible during cystectomy, poor functional results with bladder substitutes are likely.