Alfons Kreczy

Bone bruise of the knee Histology and cryosections in 5 cases

We evaluated the histopathologic and cryosectional appearance of bone bruise injuries of the knee detected on MRI. Histologic evaluation of bone biopsies from 3 patients revealed microfractures of cancellous bone, edema and bleeding in the fatty marrow. Between intact lamellar bone trabecules, fragments of hyaline cartilage mixed with highly fragmented bone trabecules were found. Postmortem specimens were obtained from 2 more patients, killed in motor vehicle accidents. MRI revealed bone bruise injuries of the lateral femoral condyle and of the lateral tibial plateau in 1 knee and anterior cruciate ligament disruption, a medial meniscus tear and bone bruise injury of the tibial plateau and of the lateral femoral condyle in the other specimen. The specimens were embedded in physiologic saline solution and frozen to -30 degrees C. By rotationcryotomy, 1 mm slices were removed from the surface of the specimens and documented on photographs. Subchondral lesions and bleeding were found, corresponding to the MR images.

High expression of the chemokine receptor CXCR4 predicts extramedullary organ infiltration in childhood acute lymphoblastic leukaemia

Childhood acute lymphoblastic leukaemia (ALL) is a malignancy with the potential to infiltrate the liver, spleen, lymph nodes and brain. Such extramedullary presentation is important for understanding the biology of childhood ALL and also for developing new prognostic parameters. A potential mechanism in the trafficking of leukaemia cells is the interaction of the chemokine receptor CXCR4, which is expressed on ALL cells, and its ligand stromal cell‐derived factor‐1 (SDF‐1), produced by stromal cells in bone marrow and extramedullary organs. Functionality of CXCR4 was demonstrated by a high correlation between cell surface density of CXCR4 and transendothelial migration of leukaemia blasts towards a gradient of SDF‐1 (r = 0·73, P = 0·001). Inhibition of SDF‐1‐induced migration by an anti‐CXCR4 monoclonal antibody (78·33 ± 23·86% inhibition) evidenced the specificity of CXCR4 to SDF‐1. In order to evaluate clinical significance of CXCR4 expression, lymphoblasts from the bone marrow of 73 patients with and without extramedullary organ infiltration were compared. Multiparameter flow cytometry revealed that lymphoblasts from patients with high extramedullary organ infiltration, defined as ultrasonographically measured enlargement of liver or spleen, expressed the CXCR4 receptor at higher fluorescence intensity (median 66·12 ± 66·17) than patients without extramedullary organ infiltration (median 17·56 ± 19·29; P < 0·001). Consequently, high expression of CXCR4 was strongly predictive for extramedullary organ involvement, independently of the peripheral lymphoblast count. Highest CXCR4 expression was seen in mature B ALL (median 102·74 ± 92·13; P < 0·003), a disease characterized by a high incidence of extramedullary bulky disease. As high expression of the chemokine receptor CXCR4 predicts extramedullary organ infiltration in childhood ALL, we suggest that CXCR4 and its ligand play an essential role in extramedullary invasion.

Diffusion-weighted magnetic resonance imaging for monitoring diffusion changes in rectal carcinoma during combined, preoperative chemoradiation: preliminary results of a prospective study.

PURPOSE To evaluate the clinical value of diffusion-weighted magnetic resonance imaging (DW-MRI) to monitor response of primary carcinoma of the rectum to preoperative chemoradiation by measuring tumor apparent diffusion coefficient (ADC). MATERIALS AND METHODS Diffusion data of nine patients undergoing preoperative combined chemoradiation for clinical staged T3, N(0-2), M(0) carcinoma of the rectum were analyzed. Diffusion-weighted echo-planar MR images were obtained prior to and at specified intervals during chemoradiation and ADCs calculated from acquired tumor images. RESULTS Comparison of mean ADC and cumulative radiation dose showed a significant decrease of mean ADC at the 2nd (P = 0.028), 3rd (P = 0.012), and 4th (P = 0.008) weeks of treatment. Cytotoxic edema and fibrosis were considered as reasons for ADC decrease. CONCLUSION This study demonstrated tumor ADC changes via detection of therapy-induced alterations in tumor water mobility. Our results indicate that diffusion-weighted imaging may be a valuable clinical tool to diagnose the early stage of radiation-induced fibrosis.

The Rectogenital Septum: Morphology, Function, and Clinical Relevance

PURPOSE: The rectogenital septum (known in clinical literature as Denonvilliers’ fascia) forms an incomplete partition between the rectum and the urogenital organs in both men and women. It is composed of collagenous and elastic fibers and smooth muscle cells intermingled with nerve fibers emerging from the autonomic inferior hypogastric plexus. The aim of this study was to investigate the fetal development of the rectogenital septum, and the origin and innervation of the longitudinal smooth muscle cells within the septum, as well as to consider possible effects on function of operations that compromise the integrity of these structures. METHODS: Macroscopic dissections on embalmed human pelves and plastination histology of 40 fetal and newborn pelvic specimens were performed. By means of conventional and immunohistochemical staining methods using monoclonal and polyclonal antibodies for tissue analysis and neuronal labeling, the motor and sensory innervation of the longitudinal muscle bundles within the septum was defined. RESULTS: The rectogenital septum is formed by a local condensation of mesenchymal connective tissue in the early fetal period. The longitudinal muscle bundles could be traced back to the longitudinal layer of the rectal wall, and, using the septum as a guiding structure, it was possible to identify autonomic nerve fibers and ganglion cells innervating the muscle cells and crossing the midline without detectable gender differences. CONCLUSIONS: Because of a coinnervation of the rectal muscle layers and the adjacent longitudinal muscle fibers of the septum, a functional correlation between the two structures during defecation is postulated. On the basis of these findings, a safer dissection of the anterior rectal wall during rectal resection is postulated, thus limiting functional disturbance and preventing neural damage.

Steroid- and ATG-Resistant Rejection After Double Forearm Transplantation Responds to Campath-1H

We herein report on immunological and histological observations in the first bilateral forearm transplant recipient. The last of three rejection episodes occurring on day 95 after transplantation was resistant to steroid and antithymocyte globulin (ATG) treatment. Histology demonstrated lymphocytic infiltrates, apoptotic and necrotic keratinocytes and focal desquamation of the epidermis. Therapy with Campath‐1H, however, resulted in complete restitution of normal skin. This is the first report on a successful rescue therapy with Campath‐1H in a severe, steroid‐ and ATG‐resistant rejection. Hence, Campath‐1H treatment might be a novel and powerful therapeutic option for multiresistant allograft rejection.

Renal hypoplasia and postnatally acquired cortical loss in children with vesicoureteral reflux

We reviewed histologically 86 nephrectomy specimens from patients with vesicoureteral reflux (with or without ureterovesical obstruction) to investigate the relationship between coexisting hypoplasia and postnatally acquired cortical damage. Hypoplasia was assessed independently of the acquired cortical loss using medullary ray glomerular counting. Severe hypoplasia (glomerular number <25% of normal) was detected in 47 of 86 patients. These patients underwent nephrectomy at a significantly younger age than those with minimal or no hypoplasia (P<0.01). There was no significant relationship between the severity of hypoplasia and the presence or absence of obstruction. Severe acquired cortical loss was found in 68 of 86 patients. There was no significant association between the severity of cortical loss and the presence or absence of obstruction, age at nephrectomy or degree of coexisting hypoplasia. The findings suggest a strong association of hypoplasia and vesicoureteral reflux. Therefore, early postnatal presentation with minimal renal function need not necessarily reflect a failure of management but rather a pre-existing limitation of renal capacity. Further-more, in a significant proportion of fetuses with ultrasonographic evidence of urinary tract abnormality, renal pathology may be present prior to the time at which in utero surgical intervention may be considered.

Necrotizing sialometaplasia in two patients with bulimia and chronic vomiting

The purpose of this report was to present two unusual cases of necrotizing sialometaplasia of the hard palate, in which the patients were suffering from bulimia and chronic self-induced vomiting. It emphasizes the importance of confirming the diagnosis by incisional biopsy and discusses local mucosal trauma as a possible etiologic factor.

Diagnostic value of different PCR assays for the detection of mycobacterial DNA in granulomatous lymphadenopathy.

Diagnosis of mycobacterial infection is made by assessment of characeristic histological features, staining of acid‐fast bacilli, or agar culture. Recent advances in molecular biology have provided alternative approaches for the detection of mycobacteria, but only limited data are available dealing with the comparative evaluation of these methods. In order to determine the diagnostic applicability of polymerase chain reaction (PCR)‐based assays, 20 formalin‐fixed and paraffin‐embedded lymph nodes with bacille Calmette–Guérin (BCG) lymphadenitis were investigated which in Löwenstein Jensen agar culture were either positive or negative (ten cases each); ten lymph nodes with non‐specific lymphadenitis served as negative controls. Ziehl–Neelsen staining as well as three different PCR assays (including nested PCR), amplifying a specific sequence of theMycobacterium tuberculosis complex or sequences of the 65 kD antigen gene, were performed. Positive culture was only obtained from lymph nodes which had been surgically removed within 20 weeks after vaccination (P<0·001). In contrast to microscopic examination, which yielded no more information than agar culture, PCR detection of mycobacterial DNA was unrelated to culture findings. Combined use of different assays, as well as DNA extraction from at least three paraffin sections from each specimen, resulted in the detection of mycobacterial DNA in all lymph nodes with amplifiable DNA (18 out of 20 cases). Controls remained consistently negative. Thus, the combined use of different PCR assays is proposed as a rapid and sensitive technique for the detection of mycobacterial DNA in formalin‐fixed and paraffin‐embedded tissue.

High-Dose-Rate Intraoperative Brachytherapy (IOHDR) Using Flab Technique in the Treatment of Soft Tissue Sarcomas

Background: Adjuvant radiotherapy has been shown to improve local control in patients with soft tissue sarcoma. Additional brachytherapy represents a means of enhancing the therapeutic ratio, as biological and dosimetric advantage over single external-beam irradiation (EBRT) can be expected. High-dose-rate intraoperative brachytherapy (IOHDR) as a boost therapy should therefore be able to further diminish the rate of local recurrence even when performing marginal resection. There are sparse data on IOHDR using flab applicators as adjuvant boost to EBRT in combination with marginal resection of soft tissue sarcomas. Patients and Methods: Within a period of 8 years, we prospectively studied 39 adult patients treated by marginal resection, IOHDR using the flab technique and EBRT for soft tissue sarcomas. There were 32 high-grade and seven low-grade tumors, 35 were > 5 cm. Mean follow-up was 26 months (range 3–59 months). Results: We could not detect any local recurrences. No treatment-related loss of limb or life occurred. There were no neurologic or vascular complications, all patients maintained functioning extremities as evidenced by a mean Musculoskeletal Tumor Society (MSTS) functional score of 88.5 (70–100). Treatment-related wound morbidity occurred in eleven patients necessitating revision surgery in eight. Metastatic disease developed in seven patients, six of them had died. The 2-year actuarial disease-free survival was 84%. Conclusions: IOHDR using the flab technique in combination with EBRT and marginal resection is an efficient treatment technique leading to optimal local control rates and limited functional impairment.Hintergrund: Die adjuvante perkutane Strahlentherapie hat unter Beweis gestellt, dass sie die lokale Kontrolle von Weichteilsarkomen verbessern kann. Eine zusätzliche Brachytherapie könnte die therapeutische Wirksamkeit weiter erhöhen, da mit einem biologischen und dosimetrischen Vorteil gegenüber der alleinigen perkutanen Strahlentherapie zu rechnen ist. Die intraoperative Hochdosisbrachytherapie (IOHDR) als Boost-Therapie sollte daher in der Lage sein, die Lokalrezidivrate weiter zu senken, selbst wenn der Tumor nur marginal reseziert wird. Bis jetzt gibt es nur sehr wenige Daten über die IOHDR unter Verwendung von Flab-Applikatoren und marginaler Resektion von Weichteilsarkomen. Patienten und Methodik: Innerhalb einer Zeitspanne von 8 Jahren haben wir prospektiv den Verlauf von 39 erwachsenen Patienten verfolgt, die wegen eines Weichteilsarkoms mit marginaler Tumorresektion, IOHDR unter Verwendung von Flab-Applikatoren und perkutaner Strahlentherapie behandelt wurden. Es lagen 32 hochmaligne und sieben niedrigmaligne Tumoren vor, 35 Tumoren waren > 5 cm. Die mittlere Nachuntersuchungszeit betrug 26 Monate (3–59 Monate). Ergebnisse: Es ließen sich keine Lokalrezidive feststellen. Auch kam es zu keinem Extremitätenverlust oder therapiebedingten Todesfällen. Es traten keine Nerven- oder Gefäßkomplikationen auf, bei allen Patienten konnten funktionstüchtige Extremitäten erhalten werden, was sich in einem mittleren Musculoskeletal-Tumor-Society-(MSTS-)Funktionswert von 88,5 (70–100) zeigte. Wundheilungsstörungen stellten sich bei elf Patienten ein, die aber nur in acht Fällen chirurgisch versorgt werden mussten. Fernmetastasen traten bei sieben Patienten auf, von denen in der Zwischenzeit sechs verstorben sind. Die aktuarische krankheitsfreie 2-Jahres-Überlebensrate betrug 84%. Schlussfolgerungen: Die IOHDR in Verbindung mit perkutaner Strahlentherapie und marginaler Tumorresektion stellt eine effektive Behandlungstechnik dar, die den Tumor lokal optimal kontrolliert und die Extremitätenfunktion nur geringfügig einschränkt.

Goldenhar's syndrome: congenital hearing deficit of conductive or sensorineural origin? Temporal bone histopathologic study.

Background Oculoauriculovertebral dysplasia (OAVD) (Goldenhars syndrome) is a congenital syndrome with ipsilateral deformity of the ear and face, epibulbar lipodermoids, coloboma, and vertebral anomalies. Goldenhars anomaly has often been associated with a degree of congenital hearing deficits, almost always of a conductive origin, but a sensorineural component is also suspected in some cases, evident through malformations of the inner ear. Patients and Methods Both temporal bones of a 10-day-old deceased patient with oculoauriculovertebral dysplasia were examined by light microscopy. Results The ear deformities included deformity of the auricle, atresia of the external auditory canal, and malformation of the tympanic cavity and ossicles. Abnormalities of the stria vascularis and the semicircular canals were also demonstrated. Further inner ear deformities were not identified in this case. Conclusion These histopathologic findings appear to confirm the conductive component of the congenital hearing deficit, but a sensorineural component could not be omitted. The ear alterations favor early developmental field defects. The causes of this condition are controversial. Recent results in genetic research pertaining to the MSX class genes permit better understanding of the variety, variability, and different degrees of severity of the anomalies described here.