Balloon-expandable stents for recoarctation of the aorta in small children. Two centre experience.

BACKGROUND: In young patients with native aortic coarctation (CoA), the management of choice is surgery. However, in re-coarctation (re-CoA) surgery is associated with increased morbidity and even mortality. Some children with native CoA present relative contraindications for surgery. METHODS: From 2006 to 2017, thirty-four patients (male n = 20; 59%) from two centres with re-CoA (31) and native CoA (3) were managed by stent implantation with premounted balloon expandable stents. Inclusion criteria were age < 3 years and >1 month, weight < 16 kg. Median age was 6,5 months (min. 1; max. 34 months), median weight 6,2 kg (min. 3,7; max. 16 kg). Thirteen patients (38%) had Re-CoA and hypoplastic left heart syndrome (HLHS). In three patients (9%) the native CoA was stented due to contraindications for surgical treatment. RESULTS: All procedures were successful. The median peak invasive systolic pressure gradient declined from 31 mm Hg (max. 118; min. 4) to 0 mm Hg (max. 32; min.-7) (p < 0.001). The median minimal diameter of the narrowed segment of aorta increased from 3 mm (max. 6,9; min. 1,0) to 7 mm (max. 11,5; min. 3,5) (p < 0.001). There were no serious complications. The median follow-up time was 12,5 months (max. 88; min. 0 month). During this time ten patients (29%) required re-dilatation and two of them re-stenting. CONCLUSION: Percutaneous stent implantation for Re-CoA and in selected patients for native CoA can be performed successfully in very young patients with a good immediate hemodynamical result. However, repeated stent angioplasties and further on interventional 'opening' of the stent is necessary to augment the aorta to adult size.

Frequent down-regulation of major histocompatibility class I antigen expression on individual micrometastatic carcinoma cells.

An astoundingly high frequency of micrometastatic cells have been found in bone marrow aspirates of patients with colon carcinomas (G. Schlimok et al., J. Clin. Oncol., 8:831-837, 1990), although these tumors very rarely metastasize to the skeleton. This observation has raised questions about the malignant potential of such cells. In a first attempt to characterize this potential, we have assessed the expression of major histocompatibility complex (MHC) class I antigens on bone marrow micrometastases, inasmuch as down-regulation of these molecules is a potential mechanism to escape from MHC class I-restricted lysis by cytotoxic T-cells. The two groups of cancer patients compared were those with tumors known to rarely (stomach and colon cancer) or frequently (breast cancer) manifest skeleton metastases. Bone marrow aspirates taken from these patients were probed for individual disseminated tumor cells using the immunoalkaline phosphatase technique with monoclonal antibody CK2 to the epithelial differentiation antigen cytokeratin 18 (CK-18), as described previously (G. Schlimok et al., Proc. Natl. Acad. Sci. USA, 84:8672-8676, 1987). Specimens containing CK18-positive cells were colabeled with monoclonal antibody W6/32 directed to a framework (or nonpolymorphic) antigenic determinant of MHC class I heavy chains associated with beta 2-microglobulin. W6/32-positive CK-18-positive cells could be detected in 25 of 54 patients (46.3%) with significantly higher incidences in 26 breast cancer patients (61.9%) as compared to 28 patients with carcinomas of the stomach and colon (27.3 and 29.4%). Independent from the origin of the primary carcinoma, the incidence of W6/32-negative CK18-positive cells was positively correlated to both the differentiation grade of the primary tumor (P less than 0.05) and appeared to be linked to the occurrence of regional lymph node metastases (statistically not significant) determined by conventional histological examination. The present results demonstrate for the first time that down-regulation of MHC expression on individual micrometastatic cells correlates to the differential pattern of metastasis obtained by comparing breast and gastrointestinal carcinomas. This finding together with the suggestive link to clinical risk factors supports the significance of reduced MHC class I expression for the survival of residual metastatic cells which is a major determinant of prognosis for patients with solid tumors.

Radiotherapy of the chest wall following mastectomy for early-stage breast cancer: impact on local recurrence and overall survival.

INTRODUCTION: Recent studies have renewed an old controversy about the efficacy of adjuvant radiotherapy following mastectomy for breast cancer. Radiotherapy is usually recommended for advanced disease, but whether or not to use it in pT1-T2 pN0 situations is still being debated. This study was designed to clarify whether or not routine radiotherapy of the chest wall following mastectomy reduces the risk of local recurrence and if it influences the overall survival rate. METHODS: Retrospective analysis of patients treated with mastectomy for pT1-T2 pN0 tumors and no systemic treatment. Patients treated with radiotherapy of the chest wall following mastectomy (Group A) are compared with those treated with mastectomy alone (Group B). RESULTS: A total of 918 patients underwent mastectomy. Patients who received adjuvant radiotherapy after mastectomy (n = 114) had a significantly lower risk for local recurrence. Ten years after the primary diagnosis, 98.1% of the patients with radiotherapy were disease free compared to 86.4% of the patients without radiotherapy. The average time interval from primary diagnosis until local recurrence was 8.9 years in Group A and 2.8 years in Group B. The Cox regression analysis including radiotherapy, tumor size and tumor grading found the highest risk for local recurrence for patients without radiotherapy (p < 0.0004). In terms of overall survival however, the Kaplan-Meier analysis showed no difference between the two groups (p = 0.8787) and the Cox regression analysis failed to show any impact on overall survival. CONCLUSION: With observation spanning over 35 years, this study shows that adjuvant radiotherapy of the chest wall following mastectomy reduces the risk for local recurrence in node-negative patients with pT1-T2 tumors but has no impact on the overall survival rate.

Matched pair analysis of survival after chest-wall recurrence compared to mammary recurrence: a long-term follow up.

BACKGROUND: Local recurrence remains a major concern after primary treatment of breast cancer and has a major impact on subsequent survival. While most studies report a poorer survival rate in patients with a local recurrence after mastectomy than after breast conservation, it remains controversial whether different risk profiles at the time of primary diagnosis may account for this difference. METHOD: Matched pair analysis of 134 patients with newly diagnosed locoregional recurrence of breast cancer without evidence of systemic disease. Matching criteria included the primary surgical treatment, tumor size, nodal status, and age. The significance of various prognostic parameters at the time of primary diagnosis and at the time of recurrence were evaluated, by univariate and multivariate analyses, with respect to survival after recurrence. The median follow-up was 8.4 years. RESULTS: Risk factors at the time of presentation, such as tumor size and lymph node status, were comparable between both groups. Local recurrence occurred on an average 9 months earlier in patients after mastectomy (P = 0.08). Univariate analysis showed that lymph node status (P = 0.0001) and disease-free interval from primary treatment to local recurrence (P = 0.0002) were the most significant single prognostic factors for subsequent survival after local recurrence. The primary surgical treatment modality was shown to be of marginal statistical influence (only P = 0.05). CONCLUSION: Local recurrence after mastectomy seems to be associated with worse survival than after breast-conserving therapy. Early onset of chest-wall recurrence, moreover, represents the highest independent risk for cancer-associated death.

Cardiac output determination in children: equivalence of the transpulmonary thermodilution method to the direct Fick principle.

OBJECTIVE: To show the equivalence of the transpulmonary thermodilution method to the direct Fick principle in children. DESIGN: Prospective single-centre study. SETTING: A 16-bed paediatric cardiac ICU and a cardiac catheterisation laboratory at an university affiliated centre for paediatric cardiology and congenital heart disease. PATIENTS: We consecutively investigated 18 patients (mean age 12.1 +/- 6.4 years) during cardiac catheterisation and after corrective cardiac operation. METHODS AND RESULTS: We prospectively defined limits of equivalence for cardiac index (CI) for both methods of +/- 0.25 l/min x m(2). We measured oxygen consumption for determination of CI by Fick as the clinical "gold standard" and performed a set of three transpulmonary thermodilution measurements. The mean CI(Fick) was 2.88 +/- 1.07 l/min x m(2) (range 1.10-4.62 l/min x m(2)) and CI(TPID)was 2.85 +/- 1.03 l/min x m(2)(range 1.02-4.49 l/min x m(2)). The mean difference between CI(Fick) and CI(TPID)was 0.030 +/- 0.168 l/min x m(2), and limits of agreement -0.306 to 0.366 l/min x m(2)(90% confidence interval -0.040 to 0.099 l/min x m(2)). The regression equation was : CI(Fick)=1.0244 x CI(TPID)-0.040, r(2) = 0.976, P < 0.0001. The intraclass coefficient of reliability for three repeated measurements of CI(TPID) was 0.97, the corresponding lower limit of the 95% confidence interval was 0.94. CONCLUSION: We demonstrated the equivalence of CI measurement by transpulmonary thermodilution and the Fick principle in children. This new method may improve hemodynamic monitoring and management in seriously ill children.

[Giant-cell reaction of the short tubular bones of the hand and foot]. / Die riesenzellige Reaktion der kurzen Röhrenknochen von Hand und Fuss.

Giant cell reactions in the short tubular bones comprise mainly enchondromas, aneurysmal bone cysts and giant cell tumours. In both cases a history of trauma can be related. We therefore agree with Aegerter and Lorenzo that an intra-osseous haematoma due to minor trauma is likely to be of pathogenic significance.

Computed tomographic findings in myogenic gastric tumors.

Computed tomographic findings in leiomyoma, leiomyosarcoma and benign leiomyoblastoma of the stomach are discussed. Gastroscopic biopsy was unsuccessful in every case, but CT was able to show the extragastric extension in all tumors. In one case, gastric leiomyoma and renal hypernephroma occurred simultaneously. Both tumors showed similar contrast medium enhancement, leading to a misdiagnosis.

Mass output and particle size distribution of glucocorticosteroids emitted from different inhalation devices depending on various inspiratory parameters.

Efficient inhalation therapy depends on successful delivery of the drug to the lung. The efficacy of drug delivery is not only influenced by the characteristics of the inhalation device, but also by the patient's handling of the device and by the inspiratory maneuver achieved through the device. We analyzed the output characteristics of three different chlorofluorocarbon (CFC)-free breath-actuated inhalers for inhaled glucocorticosteroids (BUD Turbohaler, FP Diskus/Accuhaler and HFA-BDP Autohaler, respectively). Mass output and particle size distribution of drug aerosol delivered by the inhalers were determined depending on different inhalation parameters in vitro using an Andersen cascade impactor. We found that, beside the peak inspiratory flow (PIF), other factors such as flow acceleration and inhalation volume also have significant effects on aerosol generation with respect to mass output and particle size distribution. Thus, these parameters should be taken into account when a suitable device for an individual patient is to be selected. The dependency on inspiratory parameters was most pronounced for the dry powder inhalers. The Turbohaler showed by far the highest variance in particle output (fine particle fraction ranging from 3.4% to 22.1% of label claim), whereas the Diskus was less dependent on variations in inhalation (10.6% to 18.5% of label claim). The most constant aerosol output was found for the Autohaler, which also released the highest fine particle fraction (43.1% to 56.6% of label claim).

Intraductal carcinoma (DCIS) of the breast. Risk-adapted tumor surgery with axillary lymphadenectomy?

Between 1963 and April 1994, 3823 women were treated both at the Universitäts-Frauenklinik Berlin-Charlottenburg as well as at the I. Frauenklinik der Universität München, for a malignant condition of the breast gland. 161 of these (4.2%) exhibited an intraductal carcinoma stage pTis, whilst 99 (61.5%) were axillary lymphadenectomised. During the observation time-span of up to 24 years, 9 patients (5.6%) developed local recurrence. In neither patients of the group with axillary nor without axillary dissection could a regional recurrence be observed within this period. Also, a generalisation of this condition was not recorded in any patient. On the basis of our own results and those from the literature we postulate that, under the auspices of a risk adapted tumor surgery, axillary lymphadenectomy is no longer necessary under certain conditions in non-invasive breast carcinoma.

[Hemodynamic effect of captopril in children with dilated cardiomyopathy]. / Hämodynamische Effekte von Captopril bei Kindern mit dilativer Kardiomyopathie.

Hemodynamic effects of captopril were prospectively studied in 12 children suffering from dilative cardiomyopathy. Before the administration of the drug all patients were put on a stable medication of diuretics and/or glycosides. A median daily dose of 1.83 mg captopril/kg body weight was given in 3 or 4 single doses depending on age. Median body weight of the children was 18.6 kg (range 2.7-42.2) and the median age was 5.8 years (range 0.2-15). Left ventricular volume was determined in systole and diastole using 2-D echo, and the stroke volume als well as the ejection fraction were calculated. Cardiac index (CI) and systemic resistance (Rs) were measured by Doppler echo. Blood pressure and heart rate were recorded at each echo registration. ESVI (-32%), EDVI (-21%) and SVI (-7%) were significantly (p less than 0.05) reduced by short-term captopril treatment. This effect was maintained under long-term therapy. EF, CI, Rs, blood pressure and heart rate showed only minor changes under captopril. Adverse effects were recorded only in one child. They disappeared after dose reduction.

Site of coronary sinus drainage does not significantly affect coronary flow reserve in patients long term after Fontan operation.

This study was designed to investigate the impact of postoperative coronary sinus drainage pressure on coronary flow reserve (CFR) assessed by Doppler guidewire in patients long term after Fontan operation. Twenty-nine patients (median age, 17.4 years female, 11) at a median of 10.6 years after Fontan operation were examined with intracoronary Doppler guidewire during cardiac catheterization. Fourteen patients had coronary sinus (CS) drainage to the systemic venous atrium and 15 patients had CS drainage to the pulmonary venous atrium after Fontan operation. Median CS drainage pressure was significantly higher in systemic venous CS drainage compared to pulmonary venous CS drainage (11 vs 5 mmHg, p < 0.0001). Median CFR values for the right and left coronary artery did not differ significantly with respect to CS drainage. There was a positive correlation between coronary flow reserve and pulmonary arteriolar resistance (p < 0.05) in multivariate regression analysis. The site of coronary drainage into the systemic atrium or the pulmonary venous atrium did not significantly affect CFR. Our data do not support a surgical strategy of elective redirection of coronary sinus blood to a low-pressure compartment but support an early staged approach. The positive correlation between CFR and pulmonary resistance demands further evaluation.

Stenting of a stenosed sano shunt in a neonate with hypoplastic left heart syndrome.

We report on successful stenting of a proximally stenosed Sano shunt in a newborn with hypoplastic left heart syndrome after a stage I Norwood operation.

[Atmocausis vaporization. Most severe internal burns following intrauterine use of steam]. / Atmokausis-Vaporisation. Schwerste innere Verbrennungen nach intrauteriner Anwendung von strömenden Wasserdampf.

The article gives a brief historical review of the now obsolete method of atmocausis and reports on two cases of very deep internal burns after direct intrauterine application of superheated steam; one of the patients died as a result of this procedure. In the thirties this method was used especially to arrest intrauterine perimenopausal bleeding, but has since been abandoned.

Immunohistochemical detection of keratins 1 and 13 as differentiation markers in the hormone-dependent human vaginal epithelium.

Human vaginal epithelium provides a good model to study hormonally regulated differentiation. Differentiation in this tissue can be characterized by the expression of the keratins 1 and 13 which represent the epidermal and nonkeratinizing pathway in stratified epithelia, respectively. In the present study immunohistochemistry was applied on sections of vaginal epithelium derived from women at various stages of the menstrual cycle or during pregnancy. Our results demonstrate that both pathways are realized simultaneously during sexual maturity and that the maximum for synthesis of keratins 1 and 13 is seen during the first half of the cycle. In contrast keratin 1 is not detectable at the end of pregnancy, thus reflecting a completely suppressed epidermal differentiation. As the levels of the female sex hormones, i.e. estrogens, is significantly increased in pregnant women over that in nonpregnant women, these results suggest a possible role of estrogens in downregulating the epidermal differentiation pathway.

A comparison between the results of simple mastectomy and tumorectomy for breast cancer: the problem of local recurrence.

Between 1963 and 1981, 1139 patients had surgery for unilateral breast cancer at the Charlottenburg Gynaecological Clinic of the Free University Berlin. A total of 948 patients had a simple mastectomy and 191 patients had an extended tumorectomy (or lumpectomy) with subsequent radiotherapy (40 Gy). Retrospective analysis of "matched cases" treated by tumorectomy or mastectomy showed the rate of local recurrence after tumorectomy to be nearly double that after simple mastectomy (8.7% after tumorectomy, 4.7% after mastectomy). Life expectancy with a local recurrence after conservative surgery, was however, better than that after simple mastectomy.

Comparison of the serum protein binding of digoxin in premature and mature newborns, infants and adults.

Infants require higher therapeutic doses (per unit body weight and surface area) and also tolerate higher doses of digoxin than adults. In contrast premature and even mature newborns are more susceptible to digoxin intoxications. Serum protein binding contributes to the apparent volume of distribution. Since the volume of distribution for digoxin shows an age-dependency, the present study was designed to determine the plasma protein binding of digoxin in premature and mature newborns as well as in infants and adults. Using the equilibrium dialysis method the fraction of digoxin bound to serum protein averages 30% in all groups studied. Thus protein binding could not account for the differences in dosage and susceptibility of digoxin in newborns and infants as compared to adults.