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ABSTRACT: Traditionally, physicians have believed that limb-salvage surgery has functional and cosmetic advantages over amputation, yet the literature is equivocal. Therefore, we sought to compare the psychosocial and functional outcomes in osteosarcoma survivors after limb-salvage surgery and amputation. We hypothesized there to be neither psychosocial nor functional outcome differences between groups.
Participants received treatment of extremity osteosarcoma, had received their cancer diagnosis at least 2 years prior, and were at least 16 years old. A comprehensive set of validated psychosocial and functional measures was used to assess outcome.
Fifty-seven patients participated in this study (33 who underwent limb-salvage surgery and 24 who underwent amputation). Participants had gone 12-24 years since diagnosis and were 16-52 years old at study participation. We used multiple linear regression models to examine differences in quality of life, body image, self-esteem, and social support between the two groups and found no differences. Lower limb function was a significant predictor of quality of life (P < 0.001), whereas surgery type did not impact this relationship. Body image was rated significantly worse by those who underwent late amputation, amputation after failed limb salvage, than by those who did not.
Participants with more functional lower limbs had better quality of life than did those with less functional lower limbs regardless of whether they underwent amputation or limb-salvage surgery.
Pediatric Blood & Cancer 02/2010; 54(7):990-9. · 1.89 Impact Factor
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ABSTRACT: Osteosarcoma derives from primitive bone-forming mesenchymal cells and is the most common primary bone malignancy. The incidence rates and 95% confidence intervals of osteosarcoma for all races and both sexes are 4.0 (3.5-4.6) for the range 0-14 years and 5.0 (4.6-5.6) for the range 0-19 years per year per million persons. Among childhood cancers, osteosarcoma occurs eighth in general incidence and in the following order: leukemia (30%), brain and other nervous system cancers (22.3%), neuroblastoma (7.3%), Wilms tumor (5.6%), Non-Hodgkin lymphoma (4.5%), rhabdomyosarcoma (3.1%), retinoblastoma (2.8%), osteosarcoma (2.4%), and Ewing sarcoma (1.4%). The incidence rates of childhood and adolescent osteosarcoma with 95% confidence intervals areas follows: Blacks, 6.8/year/million; Hispanics, 6.5/year/million; and Caucasians, 4.6/year/million. Osteosarcoma has a bimodal age distribution, having the first peak during adolescence and the second peak in older adulthood. The first peak is in the 10-14-year-old age group, coinciding with the pubertal growth spurt. This suggests a close relationship between the adolescent growth spurt and osteosarcoma. The second osteosarcoma peak is in adults older than 65 years of age; it is more likely to represent a second malignancy, frequently related to Paget's disease. The incidence of osteosarcoma has always been considered to be higher in males than in females, occurring at a rate of 5.4 per million persons per year in males vs. 4.0 per million in females, with a higher incidence in blacks (6.8 per million persons per year) and Hispanics (6.5 per million), than in whites (4.6 per million). Osteosarcoma commonly occurs in the long bones of the extremities near the metaphyseal growth plates. The most common sites are the femur (42%, with 75% of tumors in the distal femur), the tibia (19%, with 80% of tumors in the proximal tibia), and the humerus (10%, with 90% of tumors in the proximal humerus). Other likely locations are the skull or jaw (8%) and the pelvis (8%). Cancer deaths due to bone and joint malignant neoplasms represent 8.9% of all childhood and adolescent cancer deaths. Death rates for osteosarcoma have been declining by about 1.3% per year. The overall 5-year survival rate for osteosarcoma is 68%, without significant gender difference. The age of the patient is correlated with the survival, with the poorest survival among older patients. Complete surgical excision is important to ensure an optimum outcome. Tumor staging, presence of metastases, local recurrence, chemotherapy regimen, anatomic location, size of the tumor, and percentage of tumor cells destroyed after neoadjuvant chemotherapy have effects on the outcome.
Cancer treatment and research 01/2010; 152:3-13.
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ABSTRACT: Studies to determine the etiology of osteosarcoma involve epidemiologic and environmental factors and genetic impairments. Factors related to patient characteristics include age, gender, ethnicity, growth and height, genetic and familial factors, and preexisting bone abnormalities. Rapidly proliferating cells may be particularly susceptible to oncogenic agents and mitotic errors which lead to neoplastic transformation. Genetic aberrations that accompany osteosarcoma have received increasing recognition as an important factor in its etiology. Osteosarcoma tumor cells exhibit karyotypes with a high degree of complexity which has made it difficult to determine whether any recurrent chromosomal aberrations characterize osteosarcoma. Although extremely rare, osteosarcoma has occasionally been observed in several members of the same family. No other clinical abnormalities in the proband or the affected members were reported. Pathologic examination of the tumors revealed no unusual features. Genetic testing was not available in most of these reports. The patients generally responded to conventional therapy. A genetic predisposition to osteosarcoma is found in patients with hereditary retinoblastoma, characterized by mutation of the retinoblastoma gene RB1 on chromosome 13q14. The Rothmund-Thomson syndrome is an autosomal recessive disorder with a heterogeneous clinical profile. Patients may have a few or multiple clinical features including skin rash, small stature, skeletal dysplasias, sparse or absent scalp hair, eyebrows or eyelashes, juvenile cataracts, and gastrointestinal disturbance including chronic emesis and diarrhea; its molecular basis is the mutation in the RECQL4 gene in a subset of cases. The Li-Fraumeni syndrome is an autosomal dominant disorder characterized by a high risk of developing osteosarcoma and has been found in up to 3% of children with osteosarcoma. It is associated with a germline mutation of the p53, a suppressor gene. The following three criteria must be met for a diagnosis of Li-Fraumeni syndrome: (1) A proband diagnosed with sarcoma when younger than 45 years; (2) A first-degree relative with any cancer diagnosed when younger than 45 years; (3) Another first- or second-degree relative of the same genetic lineage with any cancer diagnosed when younger than 45 years or sarcoma diagnosed at any age. A second recessive p53 oncogene on chromosome 17p13.1 may also play a role in the development and progression of osteosarcoma. Osteosarcoma has also been associated with solitary or multiple osteochondroma, solitary enchondroma or enchondromatosis (Ollier's disease), multiple hereditary exostoses, fibrous dysplasia, chronic osteomyelitis, sites of bone infarcts, sites of metallic prostheses and sites of prior internal fixation. Ionizing radiation is a well-documented etiologic factor. Osteosarcoma has also been associated with the use of intravenous radium and Thorotrast. Exposure to alkylating agents may also contribute to its development ,and it is apparently independent of the administration of radiotherapy.
Cancer treatment and research 01/2010; 152:15-32.
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ABSTRACT: As the number of osteosarcoma survivors increases, the impact of quality of life and function needs to be addressed. Limb salvage is the preferred treatment when patients have treatment options; yet, the questionable long-term durability and complications of prostheses, combined with ambiguous function, leave some doubt regarding the best clinical and surgical options. Comparisons between limb salvage patients, amputees and controls also require further investigation. Amputation would leave the patients with a lifelong requirement for an external prosthetic leg associated with an overall limited walking distance. While artificial limbs are much more sophisticated than those used in the past, phantom limb sensations remain a substantial and unpredictable problem in the amputee. Complications such as stump overgrowth, bleeding, and infection, also require further elucidation. Limb salvage surgery using endoprosthesis, allografts or reconstruction is performed in approximately 85% of patients affected by osteosarcoma located in the middle and/or distal femur. One drawback in limb-salvage surgery in the long-term survivor is that endoprostheses have a limited life span with long-term prosthetic failure. The inherent high rate of reoperation remains a serious problem. Replacing a damaged, infected or severely worn-out arthroplastic joint or its intramedullary stem is difficult, especially in the long-stem cemented endoprostheses used in the 1980s. Limb lengthening procedures in patients who have not reached maturity must also be addressed. Periprosthetic infections, compared to other indications for joint reconstruction, were found to be more frequent in patients treated for neoplastic conditions and their outcome can be devastating, resulting in total loss of joint function, amputation, and systemic complications. Quality of life in terms of function, psychological outcome and endpoint achievements such as marriage and employment apparently do not differ significantly between amputee and nonamputee osteosarcoma survivors. Amputee patients nonetheless appear to have made satisfactory adjustments to their deficits with or without a functional external prosthesis. It also appeared that amputee patients had a similar psychological and quality of life outcome as limb salvage patients. There was no evidence of excessive anxiety or depression or deficits in self-esteem compared with the normal population or matched controls. A number of long-term survivors also achieved high ranking in the professional and commercial work place. These positive aspects should be recognized and emphasized to patients and their parents when discussing the outcome.
Cancer treatment and research 01/2010; 152:421-36.
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ABSTRACT: Recent anatomo-pathological studies have revealed a frequent associated hypoplasia of both arcuate nucleus and lungs in stillbirths. The purpose of this study is to analyze the lung and brainstem development in sudden unexplained perinatal death and sudden infant death syndrome (SIDS). A total of 51 cases were investigated. A complete autopsy was performed in each case. Anatomo-pathologic examination of the central autonomic nervous system included an in-depth study on histological serial sections of the brains where the main structures participating in control of the vital functions are located. The stage of lung development was evaluated by macroscopic and microscopic criteria. In 52.9% of cases, a pulmonary hypoplasia was detected. The pulmonary hypoplasia was significantly more frequent in the SIDS group compared to the sudden perinatal unexplained death groups (p < 0.05). In 72.5% of cases, histological examination of the brainstem on serial sections showed hypodevelopment of the brainstem nuclei, particularly hypoplasia, of the arcuate nucleus (60.8%). In 47.1% of cases, pulmonary hypoplasia was associated with brainstem hypodevelopment.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 05/2009; 454(4):451-6. · 2.49 Impact Factor
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Europace 03/2009; 11(3):395. · 1.98 Impact Factor
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ABSTRACT: The sudden unexpected death of a person believed healthy has occasionally been followed by a detailed postmortem examination that revealed no cause of death except for the unexpected presence of a medullary brain lesion. Our review of all available cases of sudden unexpected death related to medullary brain lesions (SUD-MBL) revealed the absence of any specific constellation of ante-mortem disease characteristics, together with the finding that major motor and sensory pathways were grossly preserved in most cases. The wide variety in ages of the victims, and in specific types of tissue pathology affecting the medulla, makes this illness extremely difficult to anticipate when the medullary lesions are not otherwise known to exist during life. SUD-MBL may be a specific clinico-neuropathologic disease entity, having significant importance for forensic investigators trying to establish the cause of sudden unexpected death in a victim of any age. Because victims often harbor their medullary lesions for days or weeks before SUD-MBL, clinical physicians as well need to consider the possibility of medullary brain involvement by any disease process, neurologic or systemic, while managing their patients.
The American journal of forensic medicine and pathology: official publication of the National Association of Medical Examiners 01/2009; 29(4):371-4. · 0.71 Impact Factor
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ABSTRACT: A 13-year-old white boy died suddenly and unexpectedly while playing soccer. This case acquires a unique interest because of the coincidence of sudden unexpected death in a 13-year-old boy, anomalous origin of the left coronary artery from the right aortic sinus of Valsalva, anomalous location of the right coronary ostium within proper aortic sinus of Valsalva, hyperacute myocardial infarction, and myocardial fibrosis. The authors are convinced that the cardiovascular evaluation of young athletes needs to be focused on the identification of individuals at high risk of sudden cardiac arrest, paying attention to suggestive symptoms and to a family history of sudden death due to cardiac arrest, particularly at an early age. In addition, enquiry should be made into the concomitant presence of a smoking habit or of passive smoke exposure.
The American journal of forensic medicine and pathology: official publication of the National Association of Medical Examiners 01/2009; 29(4):337-9. · 0.71 Impact Factor
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Archives of neurology 09/2008; 65(8):1135-6; author reply 1136. · 6.31 Impact Factor
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ABSTRACT: The purpose of this study was to describe cases presenting with fibromuscular hyperplasia of the pulmonary arteries that could belong to the group of sudden infant death syndrome (SIDS) and sudden unexpected perinatal death "gray zone" or borderline cases.
In a total of 12 cases, eight females and four males, ranging in age from 39 gestational weeks to 93 postnatal days, dying suddenly and unexpectedly, a fibromuscular hyperplasia of the pulmonary artery was detected. Postmortem examinations were requested with a clinical SIDS or sudden unexpected perinatal death. A complete autopsy was performed, including close examination of the brainstem and cardiac conduction system.
Histological examination showed the presence of various degrees of fibromuscular hyperplasia with fibrosis of the right (six cases), left (five cases) or both (one case) pulmonary arteries.
In our cases, fibromuscular hyperplasia of the pulmonary artery alone might or might not have accounted for the sudden deaths, if it had not been for the concomitant presence of hypoplasia of the arcuate nucleus in the brainstem and/or cardiac conduction system abnormalities. Therefore, they were classified as SIDS/sudden unexpected perinatal death gray zone or borderline cases. Necropsy studies of sudden infant and perinatal death should always include an accurate gross and histological examination of the pulmonary arteries, as well as of the brainstem and cardiac conduction system.
Cardiovascular pathology: the official journal of the Society for Cardiovascular Pathology 09/2008; 18(4):223-30. · 1.63 Impact Factor
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ABSTRACT: Because the fetal origin of coronary artery lesions is controversial, early atherosclerotic coronary artery lesions in late fetal stillborns and infants, as well as the possible atherogenic role of maternal cigarette smoking, were studied.
Twenty-two fetal death and 36 sudden infant death syndrome victims were examined by autopsy. In 28 of 58 cases, the mothers were smokers. Serially cut sections of coronary arteries were stained for light microscopy and immunotypified for CD68, CD34, alpha-smooth muscle actin, proliferating cell nuclear antigen, c-fos and apoptosis.
Multifocal coronary lesions were detected in 10 of 12 fetuses and in 15 of 16 infants whose mothers smoked. Arterial lesions in infants with nonsmoking mothers were observed in only five cases (two of 10 fetuses and three of 20 infants) (P<0.001). Alterations ranged from focal areas with mild myointimal thickening in prenatal life to early soft plaques in infants. Smooth muscle cells infiltrated into the subendothelium. These early lesions demonstrated c-fos gene activation in the smooth muscle cells of the media, and in some of these, positivity for apoptosis was observed, suggesting that c-fos overexpression may promote proliferation, as evidenced by proliferating cell nuclear antigen-positive cells.
Early intimal alterations of the coronary arteries are detectable in the prenatal and infancy period, and may be significantly associated with maternal smoking.
The Canadian journal of cardiology 02/2008; 24(2):137-41. · 3.36 Impact Factor
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ABSTRACT: In light of the growing information on the pathophysiology and clinical aspects of unexpected perinatal loss and sudden infant death syndrome (SIDS), a novel approach to the inherent problems by pathologists has become necessary. Herein, we propose an up-to-date protocol for accurate examination of the central autonomic nervous system and of the cardiac conduction system, which can encompass morphological and/or functional abnormalities of reliable epicritical value in unexplained perinatal loss and SIDS, particularly in those cases (still quite numerous) lacking adequate clinical documentation. Anatomo-pathologic examination of the central autonomic nervous system includes an in-depth study on histological serial sections of the brainstem, cerebellum, and spinal cord, where the main structures participating in control of the vital functions are located. For the histological study of the cardiac conductions system, serial sections were obtained from two blocks, including the sino-atrial node and the atrio-ventricular system, respectively. This type of updated investigation is yielding important arguments for a broader discussion of the pathogenesis of unexpected stillbirth, early neonatal death, and SIDS, besides allowing a more complete forensic-medical documentation of individual cases.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 02/2008; 452(1):19-25. · 2.49 Impact Factor
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ABSTRACT: We intended to evaluate the technique of treatment of complex fractures of the tibial plateau using external circular fixation combined with limited internal fixation, and to evaluate the treatment outcomes.
From 1992 to 2002, we treated 59 patients (40 men, 19 women) ranging in age from 23 to 63 years with the external circular fixation. All the cases were classified preoperatively as Schatzker types V, VI/Orthopedic Trauma Association 41-C1.3, C2.3, C3.1, C3.3. Five fractures were open. Three different strategies of treatment were used: (1) the frame is confined to the tibia when the external fixation is stable enough to allow knee bending; (2) the frame is extended onto the distal femur, with the proximal tibial ring located at the level of the tibial plateau when the joint surface is severely unstable; and (3) the frame is extended onto the distal femur, with the proximal tibial ring located more distally, bypassing the fracture, when the skin and soft tissue are compromised and within the fracture there is no bone suitable to place wires and pins for the external fixation construct.
The results were evaluated as excellent in 30 patients (50.85%), good in 27 patients (45.76%), fair in 1 patient (1.695%), and poor in another 1 (1.695%). The patients' satisfaction was significantly related with the functional results.
Our hybrid Ilizarov method combined with minimal internal fixation enables excellent to good results in most cases of complex tibial plateau fractures.
The Journal of trauma 12/2007; 63(5):1043-53. · 2.48 Impact Factor
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ABSTRACT: The present study was aimed to evaluate the possible presence of cytohistologic and/or biologic modifications of the human dentate-olivary complex in sudden unexplained perinatal and infant deaths.
We investigated the histologic morphology of the dentate and inferior olivary nuclei, the glial index, the c-fos and apoptotic immunopositivity, as well as the possible effects elicited by maternal cigarette smoking, in 44 cases of perinatal and infant death victims, aged from the 26th gestational week to 10 months of life.
We observed subtle alterations of both the medullary inferior olivary nucleus and of the cerebellar dentate nucleus, represented by a significant increase in the reactive astrocyte density and in the neuronal c-fos and apoptotic expression in unexplained death victims, compared with age-matched controls. These alterations were closely related to a maternal cigarette smoking habit.
We postulate that maternal smoking, besides inducing the previously demonstrated morpho-functional alterations of the autonomic central nervous system, could also exert an adverse influence on the dentate-olivary complex, leading to sudden death in vulnerable periods of perinatal development or early infancy.
Neurological Research 10/2007; 29(6):525-32. · 1.52 Impact Factor
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ABSTRACT: This article affirms the value of the application of the Ilizarov frame for gradual transport of the ipsilateral fibula to replace massive tibial bone loss following chronic refractory osteomyelitis.
Orthopedics 09/2007; 30(8):608-11. · 2.66 Impact Factor
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ABSTRACT: The aims of this study were to investigate in the human cerebellar cortex the structural and biological ontogenetic features, the possible presence of alterations in cases of sudden unexplained fetal and infant death, and the involvement of the maternal cigarette smoking in developmental abnormalities. We analyzed 52 brains of fetal and infant death victims, aged from the second gestational trimester to 12th postnatal month. In the cerebellar cortex we evaluated, besides the morphological aspects, the expression of several biomarkers implicated in proliferative processes (c-fos, proliferating cell nuclear antigen, and apoptosis) as well as the presence of the neurotransmitter somatostatin, which is strongly implicated in central nervous system differentiation, and of EN2 gene. The observed features of the cerebellar cortex, mainly confined to the transient external granular layer, were high proliferative activity and high expression of both somatostatin and EN2 gene in prenatal life and high apoptotic index after birth. In 41% of the sudden unexplained death victims, in the greater part with smoking mothers, we observed different biopathological alterations of the cerebellar cortex. Maternal smoking is increasingly being demonstrated to be one of the main contributors to developmental neurological alterations in the offspring.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 02/2007; 450(1):31-40. · 2.49 Impact Factor
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Cancer 01/2007; 107(12):2958-9; author reply 2959. · 4.77 Impact Factor
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ABSTRACT: Various risk factors have been postulated to be related to sudden infant death syndrome (SIDS). Despite its reduction, thanks to the "Back to Sleep" campaign, SIDS is still a major cause of infant mortality in the first year of life. The purpose of this study was to correlate the different risk factors with the autopsy results and thus to determine if one or more of these variables is really specific for SIDS. We collected 128 sudden infant death victims with clinical diagnosis of SIDS and performed a complete autopsy with in-depth histology on serial sections, particularly of the brainstem, in accordance with our necropsy protocol. Histopathologic and immunohistochemical examination of the central autonomic nervous system revealed, in 78 cases of the SIDS group, the following anomalies: hypodevelopment of the arcuate nucleus, somatostatin positive hypoglossus nucleus, tyrosine hydroxylase negativity in the locus coeruleus, gliosis, and hypoplasia of the hypoglossus nucleus. A significant relation was found between maternal smoke and brainstem alterations.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 01/2007; 449(6):697-706. · 2.49 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate if there is a difference in the rates of infection between Ilizarov wires and half-pins and between half-pins with threads outside and inside the skin in circular fixators modified by Catagni and Cattaneo.
Between May and December 2004, 218 patients with circular Ilizarov fixators for various orthopaedic indications who visited our Ilizarov clinic were subjected to a one-time evaluation of half-pins and wires.
A total of 1,093 half-pins were checked and 34 (3.11%) of these were infected (50% with threads outside and 50% with threads inside the skin). Among a total number of 951 wires (1,092 pin tracts) checked, 45 (4.73%) were infected.
We conclude that the circular Ilizarov fixation with conical half-pins and wires has similar rate of infection compared with conventional Ilizarov circular fixator. Moreover, there is no difference in infection rates between pins with threads inside the skin as compared to those with threads outside the skin.
The Journal of trauma 12/2006; 61(5):1186-91. · 2.48 Impact Factor
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ABSTRACT: The aim of this study was to investigate the histological and biological features of the human cerebellar cortex development and differentiation. We analyzed 52 brains of fetal and infant death victims, aged from 17 gestational weeks to 12th postnatal month. In particular, in the cerebellar cortex at different ages we evaluated, besides the structural aspects, the expression of several biomarkers implicated in proliferative processes (c-fos, PCNA and apoptosis). We observed morphological patterns progressively evolving every month, from the indefinite structure of the second gestational trimester to the four-layered structure (external granular layer, molecular layer, Purkinje cell layer, internal granular layer) of the late fetal cortex and subsequently to the three-layered postnatal definitive morphology, due to involution of the external granular layer. The evaluation of the biological features of the cerebellar cortex showed high proliferative activity mainly confined to the transient external granular layer in prenatal life, and high apoptotic index after birth. Thus, the histological examination, better with the support of biomarker investigations, allows with accuracy to describe the dynamic sequence of steps that occur in human cerebellar cortex development and to establish in each case the age, namely the pre- or postnatal month of life. Consequently, we can diagnose delayed or altered processes of differentiation during the development of the human cerebellar cortex.
International Journal of Developmental Neuroscience 11/2006; 24(6):365-71. · 2.42 Impact Factor
