Short-term bisphosphonate therapy could ameliorate osteonecrosis: a complication in childhood hematologic malignancies.

Osteonecrosis (ON) is a critical complication in the treatment of childhood leukemia and lymphoma. It particularly affects survivors of acute lymphoblastic leukemia and non-Hodgkin lymphoma reflecting the cumulative exposure to glucocorticosteroid therapy. ON is often multiarticular and bilateral, specially affecting weight-bearing joints. A conventional approach suggests a surgical intervention even if pharmacological options have also recently been investigated. We reported two cases of long time steroid-treated patients who underwent Bone Marrow Transplantation (BMT) for hematological disease. Both patients developed femoral head osteonecrosis (ON) that was diagnosed by magnetic resonance imaging (MRI) and the ON was also accompanied with pain and a limp. Despite of the conventional strategies of therapy, we successfully started a short-term treatment with bisphosphonates in order to decrease the pain and the risk of fracture.

Sonographic assessment of clubfoot.

PURPOSE: This study was performed to develop a standardized methodology for the sonographic assessment of clubfoot at birth and at the end of both conservative treatment and surgical correction. METHODS: Forty-two congenital clubfeet and 42 normal feet were examined sonographically in the position of spontaneous alignment and during passive manual correction. Scans along 4 planes provided information relevant to the assessment: sagittal posterior, sagittal anterior, coronal lateral, and transverse. RESULTS: Sagittal posterior sonograms demonstrated the progressive gain of dorsiflexion ability during the different steps of treatment for clubfoot. Sagittal anterior sonograms could not demonstrate the normal alignment of the navicular in clubfeet because of the bone's medial displacement. On transverse sonograms, the talar head and the medially displaced navicular may lie on the same plane, depending on the severity of the deformity. Coronal lateral sonograms provided for estimation of the relationships between the calcaneus and cuboid, which were described by the calcaneal-cuboid angle. CONCLUSIONS: Sonography is a promising technique for assessment and monitoring of clubfoot during treatment. The method described here yields accurate and reproducible information about the anatomy of the nonossified clubfoot, helping the orthopedic team decide on appropriate treatment steps.

Tetralogy of Fallot with absent pulmonary valve: a case complicated by bilateral relapsing pneumothorax.

We report a case of a neonate with tetralogy of Fallot with aneurysmal dilatation of the pulmonary artery, complicated by bilateral relapsing pneumothorax. The relapsing air leak made it necessary to place up to five chest drains and to switch from conventional ventilation to high frequency ventilation. In the course of 30 days, all drains were removed. Once other anatomical and functional malformations of the respiratory system had been appropriately excluded and reasonable haemodynamic stability had been achieved, the patient underwent successful radical corrective heart surgery in hypothermia and cardioplegia. We emphasize the advantage of resolving respiratory failure preoperatively to guarantee the success of corrective heart surgery and treatment of other surgically severe cases.

Is the tricuspid position suitable for testing replacement bioprosthetic valves in the sheep model?

BACKGROUND AND AIM OF THE STUDY: Glutaraldehyde may promote calcification in xenograft tissue by the action of toxic aldehyde group residues involved in the cross-link process. Post-fixation treatment with homocysteic acid (HA) neutralizes this toxicity by bonding aldehyde groups, and enhances biocompatibility on the basis of strongly electronegative sulfonic groups. Previous studies in a rat subcutaneous model showed significant long-term mitigation of mineralization of glutaraldehyde-fixed pericardium treated with HA. This study aimed to assess the anticalcific efficacy of HA in a valvular implant in growing sheep, and establish if the tricuspid position is suitable for testing replacement bioprosthetic valves. METHODS: Eleven stented 25 mm Pericarbon bioprostheses (seven HA-treated, four standard) were implanted in the tricuspid position of growing sheep. Infective endocarditis occurred in four prostheses. Among the remaining seven, three (two HA-treated, one standard) were explanted at 91 days (mid-term), and four (two HA-treated, two standard) at 140-141 days (long-term). All explants were studied by gross, X-ray, light, transmission and scanning electron microscopy, as well as by atomic absorption spectroscopy. RESULTS: No histological and ultrastructural difference in tissue preservation were observed between HA-treated and standard Pericarbon bioprostheses, either in the mid or long term. The mean calcium content of mid-term HA-treated explants was 9.55 mg/g compared with 16.26 mg/g in mid-term standard explants. Only one late standard explant failed as a result of severe stenosis caused by massive dystrophic calcification. Among four late explants, two showed significant increase in mineralization (HA-treated, 87.45 mg/g; standard, 181.20 mg/g), while two showed calcium contents similar to those in mid-term explants (HA-treated, 11.96 mg/g; standard, 17.32 mg/g). CONCLUSION: Post-fixation treatment with HA preserves structural properties after tricuspid implantation in growing sheep. The tricuspid implant in the sheep model failed to reproduce remarkable accelerated progressive calcification in all xenografts so as to demonstrate a significant difference between HA and standard explants. The tricuspid position for testing replacement bioprosthetic valves should be abandoned, and investigations repeated with the prosthesis in the mitral position.

Is surgical treatment of lipoblastoma always necessary?

Lipoblastoma is an uncommon, benign mesenchymal tumor with an excellent prognosis despite its potential to local invasion and rapid growth. However, in the literature, a spontaneous resolution has never been reported, and, consequently, the need for a complete surgical excision has never been questioned. The authors report a case of a 2-day-old boy with congenital diffuse lipoblastoma in the left thigh, which forced us to withhold from surgical treatment to avoid the risk of mutilation in a patient so young. The lesion was followed-up by imaging, and a complete spontaneous resolution of the diffuse lipoblastoma was shown by magnetic resonance imaging (MRI) at 1-year follow-up. In the literature, a complete surgical excision is recommended. The results of this case suggest that a "wait and see" approach is justified at least in infants with huge invasive lesions requiring a mutilating excision.

Testicular cystic dysplasia: evaluation of 3 new cases treated without surgery.

PURPOSE: We describe 3 cases of testicular cystic dysplasia that were diagnosed only by sonography to avoid an invasive approach. MATERIALS AND METHODS: Three patients 5, 8 and 12 years old, respectively, had increased testicular volume and/or intermittent pain. Sonographic examination of the testis by high frequency (7.5 mHz.) probes showed the typical onset of testicular cystic dysplasia, characterized by several small focal or diffuse intraparenchymal cystic formations. RESULTS: Biopsy or orchiectomy was not considered. At 16, 18 and 24 months of followup, respectively, testicular pain was absent in our 3 cases and sonographic findings were unchanged. CONCLUSIONS: Clinical and sonographic followup is considered sufficient to evaluate possible changes in the clinical course of this pathological condition which, although benign, still remains to be defined.

Detoxified glutaraldehyde cross-linked pericardium: tissue preservation and mineralization mitigation in a subcutaneous rat model.

BACKGROUND AND AIM OF THE STUDY: Glutaraldehyde is considered a promoter of calcification by the action of toxic aldehyde group residuals from cross-linking. Post-fixation treatment with homocysteic acid (HA), besides bonding aldehyde groups and neutralizing toxicity, should enhance biocompatibility due to the strongly electronegative sulfonic group. The aim of this investigation was to evaluate HA efficacy on tissue preservation and dystrophic calcification mitigation in glutaraldehyde cross-linked bovine pericardium (BP) using a subcutaneous rat model. METHODS: Four samples of BP, two with glutaraldehyde-HA and two with glutaraldehyde treatment, were implanted in each of 24 male Sprague-Dawley rats. Three rats were killed at 14 days, eight at 28 days, eight at 56 days and five at 84 days. Unimplanted glutaraldehyde-HA- and glutaraldehyde-treated samples served as controls. All samples were studied by gross examination, mammography, light transmission and scanning electron microscopy, and atomic absorption spectroscopy. The nature of mineralization was investigated by coupling techniques of scanning electron microscopy, electron microprobe analysis and X-ray powder diffraction. RESULTS: No histological and ultrastructural differences were found between glutaraldehyde-HA- and glutaraldehyde-treated BP, whether implanted or unimplanted. In both groups, calcification progressed with time, but significantly less after glutaraldehyde-HA treatment than after glutaraldehyde alone and at all time intervals (14.63 +/- 21.34 versus 43.17 +/- 15.99 at 28 days, p = 0.003; 56.42 +/- 40.20 versus 90.59 +/- 32.90 at 56 days, p = 0.008; 91.68 +/- 67.68 versus 156.23 +/- 17.85 at 84 days, p = 0.01). Differences were evident by mammography and histology (von Kossa stain). Electron microprobe analysis in both groups showed the composition of calcified nuclei to be calcium phosphate, stoichiometrically close to apatite (Ca5(PO4)3(OH)). The occurrence of crystallized apatite was supported by X-ray powder diffraction findings, the amount of crystallized apatite being higher in glutaraldehyde-treated samples. CONCLUSIONS: Post-fixation treatment with HA preserves BP structural properties and significantly mitigates mineralization of long-term subcutaneous implants.

Pathology of the Pericarbon bovine pericardial xenograft implanted in humans.

BACKGROUND AND AIMS OF THE STUDY: Pericarbon is a new-generation bovine pericardial bioprosthesis designed to withstand mechanical wear. Following optimal in vitro testing and animal experiments, clinical trials were initiated in many European centers and explants sent to our department for pathological evaluation. This included gross, radiographic, histologic and ultrastructural investigations. METHODS: Between 1986 and 1996, 24 bioprostheses (eight aortic, 11 mitral, two mitro-aortic, one tricuspid) were collected from 22 patients (10 males and 12 females; mean age 57.0 +/- 18.9 years) either at autopsy (nine) or reoperation (15). RESULTS: Ten bioprostheses explanted < 2 months after surgery were either normal or failed because of surgical problems or non-structural causes. Among the other 14 bioprostheses (mean placement 41.9 +/- 23.6 months; range: 7 to 90 months), structural deterioration occurred in seven and was due to dystrophic calcification with stenosis in five (three aortic, two mitral), mixed lesion in one (mitral), and incompetence in one by calcium-related commissural tear (mitral). At the ultrastructural level, calcification was detected either on cell debris or upon collagen fibers. No bioprosthesis failed because of fibrous tissue overgrowth. Of the remaining seven bioprostheses, vegetative endocarditis occurred in two, thrombosis in one, and aseptic paravalvular leak in one; whereas three showed no signs of dysfunction. CONCLUSIONS: This pathologic experience with the Pericarbon valve showed calcification to be the main cause of late structural failure, causing mainly cusp stiffness and bioprosthesis stenosis. Tissue rupture or abrupt dysfunction never occurred. Thus, prevention of mineralization remains the main challenge.

Fetal gallstones: sonographic and clinical observations.

Fetal gallstones were visualized sonographically in two cases at 30 and 37 weeks' gestation; follow-up scans at 2 and 3 months, respectively, disclosed their spontaneous resolution. The hypotheses advanced to explain the formation of echogenic material in the fetal gallbladder are reviewed, and the clinical utility of postnatal long-term sonographic follow-up is stressed.

Non-furosemide-related renal calcifications in premature infants with bronchopulmonary dysplasia.

Renal calcification is a known complication of long-term furosemide therapy in infants with bronchopulmonary dysplasia (BPD). In a prospective study the clinical course and long-term renal sequelae of renal calcifications of 19 consecutive premature neonates (birthweight < 1250 g) with bronchopulmonary dysplasia who did not receive furosemide were examined. Infants were divided into two different groups on the basis of ultrasound evidence of renal calcifications (RC group) or absence of renal calcifications (NRC group). Serial examinations, performed at the age of 1, 2, 3, 6, 9 and 12 months, showed that 12 infants at the mean age of 68.5 +/- 12.8 days of life had renal calcifications (63%), and 3 of them had nephrolithiasis; 8 had bilateral renal calcifications. Among the 9 survivors, 2 had chronic renal calcifications at the age of 9 months; however, all normalized at the age of 12 months. Twelve infants received hydrochlorothiazide and spironolactone (63%), 17 had prolonged courses of xanthines and dexamethasone (89.5%), while furosemide was not part of the routine pharmacological administration. Statistical analysis showed that birthweight, gestational age, Apgar score and length of parenteral nutrition were comparable in the RC and NRC group infants. Mean serum creatinine, creatinine clearance, fractional sodium excretion and urinary calcium excretion values during the 12-month study period were comparable in the RC and NRC groups. Mechanical ventilation and hospital stay length were instead associated with renal calcification occurrence. The strongest indicator of renal calcification risk for this high-risk population is the severity of the unresolved acute lung disease, where different facets of respiratory management, other than the addition of furosemide, represent sufficient stimuli and renal injury to potentiate stone formation.

Ultrasonographic evaluation of superficial lymph node metastases in melanoma.

The aims of the present work were to assess the diagnostic accuracy of ultrasonographic evaluation of superficial lymph nodes in patients with cutaneous melanoma and to describe the sonographic characteristics which permit early detection of neoplastic nodal involvement. Eighty-seven patients (89 lymph node sites) were studied for approximately a 3-year period, with a minimal surveillance time of 1 year. The ultrasonographic imaging equipment utilized were a 10 MHz scanner with a mechanical and one with 10 MHz electronic linear probe. The characteristics considered indicative of possible metastatic involvement were: round shape (short to long axis ratio > 0.5), no central hilus, nodular areas within the lymph node, sinuosity of the lymph node edges and lymph node with regular morphology and echostructure but with maximum diameter greater than 3 cm. Generally inguinal and axillary lymph nodes are larger than cervical ones. Of the 89 sites explored, 32 were considered 'suspect'. All 32 of these were subjected to cytology using ultrasound-guided, fine needle aspiration. The remaining 56 came in for a periodic control examination during a year. Thirteen of the 32 'suspect' lymph nodes proved positive at the pathologic examination. Two patients whose ultrasound diagnosis was negative developed metastases within 2 to 4 months (ultrasound false negatives). Our study indicates that there are sonographic features indicative of lymph node metastases from melanoma even in the early stages of the disease. Ultrasound scanning, therefore, is a useful diagnostic tool in the follow-up of melanoma patients, identifying which should be subjected to further testing with needle biopsy.

Is there a place for medical treatment in children with gallstones?

BACKGROUND: Medical treatment of gallstones with ursodeoxycholic acid (UDCA) or chenodeoxycholic acid (CDCA) has not been evaluated in children. AIM: The purpose of this study was to assess the effectiveness of UDCA in the treatment of gallstones in children. METHODS: UDCA was used to treat 15 patients, (7 boys and 8 girls; mean age, 7.8 years; range, 3 months to 15 years) for 1 year. All had radiolucent stones with a maximum diameter of 10 mm and a normally contractile gallbladder. RESULTS: The stones disappeared completely in two children but returned later. All symptomatic patients became symptom free. CONCLUSION: UDCA is ineffective in the treatment of gallstones in children except in terms of relieving symptoms while on treatment.

Low-profile porcine bioprosthesis (Liotta): pathologic findings and mode of failure in the long-term.

BACKGROUND AND AIMS OF THE STUDY: The Liotta low profile porcine bioprosthesis (LBP) was designed in order to minimize complications due to excessive protrusion of the stent prongs in the left ventricle. MATERIALS AND METHODS: From April 1984 to November 1993, 25 LBP surgical explants were available for pathology study, which included gross and X-ray evaluations. Reoperation was performed after a mean period of 95 +/- 25 months (range 46 to 143 months), in five males and 20 females (mean age at implantation 51.1 +/- 11.4 years). RESULTS: The cause of failure was stenosis due to cusp stiffness caused by dystrophic calcification in one and incompetence in 24 LBPs. In only one case was incompetence ascribable to endocarditis; in the remaining 23 the mechanism of regurgitation was due to commissural tearing (21 LBPs), commissural dehiscence (one LBP) and both tears and dehiscence (one LBP). Overall, 28 commissural tears were observed: 20 involved the right coronary cusp, eight the left coronary cusp, and none the non-coronary cusp. The anterior commissure was most frequently involved by tears (n = 17) followed by the right posterior (n = 9) and the left posterior (n = 2). Tears were calcium-related in all but two cases. Calcific deposits were observed in each explant, involving a total of 62 commissural attachments, 17 cusp bodies and five right muscular shelves. CONCLUSION: In conclusion, valve regurgitation is the usual mode of LBP failure in the mitral position; commissural tearing of the right coronary cusp was the most common cause of valve regurgitation, and occurred even in the presence of pin-point calcification. These pathologic findings seem to confirm that low profile design, which implies bulging of the right coronary cusp, entails the risk of increased stress at the commissures, accelerated calcification and tearing.

Painless scrotal masses in the pediatric population: prevalence and age distribution of different pathological conditions--A 10 year retrospective multicenter study.

PURPOSE: In the pediatric population a broad spectrum of intrascrotal pathology ranging from congenital to neoplastic lesions present as a painless scrotal mass. The aim of our 10-year retrospective study was to review 71 pediatric cases of a painless scrotal mass to determine the overall and age specific prevalence of diseases manifesting as such masses. MATERIALS AND METHODS: From 1980-1991, 71 patients 1 day to 16 years old with a painless scrotal mass underwent evaluation using 7.5 or 10 MHz. ultrasound probes with transverse and longitudinal sections. RESULTS: The painless scrotal mass was testicular in 61 cases (86%, 28 neoplasms, 27 congenital malformations, and 6 posttraumatic/inflammatory lesions) and extratesticular in 10 (14%, 5 neoplasms, 2 hematoceles, 2 pachyvaginitis and 1 sebaceous cyst). Patient age distribution showed 2 peaks at 0 to 1-year and 13 to 14-year intervals. More than a third of the painless scrotal masses (24 cases) were found during the first year of life, predominantly congenital anomalies (in utero torsion) and neoplasia. A total of 45 patients (63%) underwent surgery (orchiectomy in 39 and conservative treatment in 6) and a pathognomonic echo pattern allowed nonsurgical treatment in 26 (37%). CONCLUSIONS: Testicular ultrasound proved to be highly reliable in differentiating intratesticular from extratesticular lesions but it demonstrated poor specificity because of extensive overlap between benign and malignant pathologies. Therefore, testicular ultrasound changed the management of a few select cases of a painless scrotal mass (epididymal cysts/spermatoceles and in utero torsion).

Nodular regenerative hyperplasia of the liver: description of two cases.

Nodular regenerative hyperplasia (NRH) of the liver is a condition of unknown origin, rarely occurring in children, usually accidentally discovered, described in association with a variety of clinical conditions and drugs. Confusion with other types of hepatic masses may pose a problem and for this reason NRH is considered a "tumor-like lesion." Histologically it consists of single or multiple regenerative foci. Hepatic failure and rupture of the liver have been rarely described as complications in adults, and not in children, and malignant transformation has not been demonstrated. Neither surgical removal nor other treatment is needed. These features are described as they were found in two patients we encountered.

[Imaging of the thymus gland in myasthenia gravis (computerized tomography and magnetic resonance)]. / L'imaging del timo nella miastenia grave (tomografia computerizzata e risonanza magnetica).

Since thymectomy is nearly always indicated as a possible treatment of myasthenia gravis, we examined with Magnetic Resonance (MRI) and Computed Tomography (CT) 22 patients (21-62 years old) to identify the best methodological approach. MR images were obtained with a 1.5 T superconducting unit with slice thickness ranging from 6 to 8 mm and an interslice gap of 0.6 and 0.8 mm. Spin-echo images were acquired with repetition time (TR) < 700 ms and echo time (TE) of 20 ms and T2-weighted images with TR > 1800 ms and TE of 80 ms. The sections were obtained, with cardiac gating, on transverse and sagittal planes. CT was performed with contiguous 5-mm slice thickness, after intravenous bolus injection of contrast medium. All the patients underwent surgery of anterior mediastinum and histologic diagnosis was made. Both CT and MRI correctly identified the patterns of normal thymus or hyperplasia not associated with gland enlargement, the only two cases of hyperplasia with thymic enlargement and clearly demonstrated thymomas. MRI appears to be more accurate in the evaluation of the relationship between thymus and contiguous structures. If pericardial infiltration is suspected, sagittal MR scans yield accurate information on tumor spread. We recommend MRI of anterior mediastinum to rule out the presence of a thymoma and the possible involvement of contiguous structures.

The aortic valve after heart transplantation.

We studied the aortic root (wall, semilunar cusp, septal myocardium) in 37 patients (29 male and 8 female; mean age; 41 years) who died 2 to 4,380 days (mean, 398 days) after heart (n = 34) and heart-lung (n = 3) transplantation. The aim of the study was to assess tissue viability, graft-host biological interaction, and cusp mineralization with time. Study methods included gross inspection and photos of each specimen, microradiography, histology and immunohistochemistry, scanning and transmission electron microscopy, and atomic absorption spectroscopy. There were no cases of valve dysfunction; in particular, cusp tears or perforations never occurred. Only 1 valve, in place for 12 years, had a pin-point calcification visible to the naked eye. Optimal preservation of the tissue components (endothelium, fibroblasts, collagen and elastic fibers, proteoglycans, intrinsic nervous ganglia) was observed at both short and long term. Concomitant acute rejection of valve leaflets and myocardium was seen in 7, mild valve thickening in 14, myxoid degeneration in 4, and graft aortic atherosclerosis in 26. Mineralization was negligible and was not progressive with time. No linear correlation was found between mineralization and number of acute rejections. In conclusion, we observed optimal cusp viability and integrity even at long term, concomitant valve and myocardium rejection with no valvular sequelae, and negligible, non-progressive cusp calcification. Donor-recipient blood group matching, heart-beating donor, and chronic immunosuppression are the reasonable explanations of the optimal durability of the aortic valve after heart transplantation.

Diabetic fibrous breast disease: a clinical entity that mimics cancer.

Three typical cases of fibrous mastopathy associated with diabetes mellitus are described. The histological change is a connective-tissue overgrowth with vasculitis and some proliferation of duct epithelium. The clinical changes are indistinguishable by physical or radiographic findings from malignancy. In young patients with long-standing diabetes the presence of one or more suspicious clinical and imaging findings can suggest the presence of this lesion but a surgical biopsy or, at least, a close follow-up is required.

Hancock II porcine bioprosthesis: excellent durability at intermediate-term follow-up.

OBJECTIVES: This study aimed to assess the clinical performance and durability of a new generation of porcine valve, the Hancock II bioprosthesis, at intermediate-term follow-up. BACKGROUND: Standard porcine bioprostheses undergo progressive structural deterioration, mainly due to cusp and commissural calcification, affecting durability and requiring reoperation. The Hancock II bioprosthesis, which is currently undergoing clinical investigation, is made from a porcine aortic valve treated with a calcium-retarding agent (sodium dodecyl sulfate [T6]), which should delay onset of calcification and increase durability. METHODS: From May 1983 to December 1992, we used the Hancock II bioprothesis in aortic (59 patients), mitral (101 patients) and mitral-aortic (25 patients), valve replacement procedures. Postoperative follow-up ranged from 0.1 to 8.7 years (mean [+/- SD] 4.5 +/- 2.6 years) and was 100% complete. Freedom from major postoperative events was calculated at 7 years for patients with aortic valve replacement and at 8 years for those with mitral and mitral-aortic valve replacement. RESULTS: The actuarial survival rate was 48 +/- 10%, 76 +/- 3% and 63 +/- 6%; freedom from valve-related mortality was 91 +/- 4%, 94 +/- 2% and 89 +/- 6%; freedom from thromboembolism was 80 +/- 11%, 90 +/- 2% and 79 +/- 7%; and freedom from reoperation was 100%, 97 +/- 1% and 89 +/- 6% after aortic, mitral and mitral-aortic valve replacement, respectively. No structural valve deterioration occurred. CONCLUSIONS: At intermediate-term follow-up the Hancock II bioprosthesis showed excellent durability in all positions. However, the effectiveness of anticalcification treatment must be assessed with longer follow-up studies.

[Misdiagnosis of asthma. Two paradigmatic case reports]. / Diagnosi errata di asma bronchiale. Due casi paradigmatici.

We present two children, respectively five and six years old, misdiagnosed and treated as asthmatics in allergological centers. After admission to our department, endobronchial inflammatory pseudotumor and lung tuberculosis were diagnosed respectively. While endobronchial pseudotumor is rather rare, lung tuberculosis is a less rare diagnosis that must be considered in patients with a history of persistent and recurrent coughing with or without wheezing, especially when there is no family history of atopical diseases and skin allergic tests are negative, and the social and economic conditions at risk.