RESUMEN
OBJECTIVES: Alpha-mannosidosis is a rare genetic lysosomal storage condition leading to the systemic buildup of oligomannoside. Clinical presentation and associated conditions, as well as the full extent of histopathologic changes associated with this disease process, are not fully understood. CASE PRESENTATION: We present the case of an 8-year-1-month old patient with persistent anemia and who was initially diagnosed with Celiac disease before ultimately being diagnosed with alpha-mannosidosis. As part of his diagnostic work-up, duodenal and bone marrow biopsies were examined by pathology. Duodenal biopsies showed foamy plasma cells expanding the lamina propria which triggered a workup for a genetic storage disease; features suggestive of Celiac disease which resolved on gluten-free diet were also noted by pathology. Bone marrow analysis via electron microscopy showed cytoplasmic granules and inclusions in multiple immune cell lines. CONCLUSIONS: Alpha-mannosidosis can occur with Celiac disease and milder forms may only be suspected from incidental pathology findings. The ultrastructural bone marrow findings from this case, the first to be reported from human, show numerous disease-associated changes in multiple immune cell lines whose contribution to disease-associated immunodeficiency is unclear.
Asunto(s)
Enfermedad Celíaca , Enfermedades por Almacenamiento Lisosomal , alfa-Manosidosis , Humanos , Lactante , alfa-Manosidosis/diagnóstico , alfa-Manosidosis/complicaciones , alfa-Manosidosis/genética , Microscopía , Enfermedad Celíaca/complicaciones , Enfermedades por Almacenamiento Lisosomal/diagnósticoRESUMEN
BACKGROUND AND PURPOSE: Capsaicin-mediated modulation of taste nerve responses is thought to be produced indirectly by the actions of neuropeptides, for example, CGRP and substance P (SP), on taste cells implying they play a role in taste sensitivity. During the processing of gustatory information in taste buds, CGRP shapes peripheral taste signals via serotonergic signalling. The underlying assumption has been that SP exerts its effects on taste transmitter secretion in taste buds of mice. EXPERIMENTAL APPROACH: To test this assumption, we investigated the net effect of SP on taste-evoked ATP secretion from mouse taste buds, using functional calcium imaging with CHO cells expressing high-affinity transmitter receptors as cellular biosensors. KEY RESULTS: Our results showed that SP elicited PLC activation-dependent intracellular Ca2+ transients in taste cells via neurokinin 1 receptors, most likely on glutamate-aspartate transporter-expressing Type I cells. Furthermore, SP caused Type I cells to secrete GABA. CONCLUSION AND IMPLICATIONS: Combined with the recent findings that GABA depresses taste-evoked ATP secretion, the current results indicate that SP elicited secretion of GABA, which provided negative feedback onto Type II (receptor) cells to reduce taste-evoked ATP secretion. These findings are consistent with a role for SP as an inhibitory transmitter that shapes the peripheral taste signals, via GABAergic signalling, during the processing of gustatory information in taste buds. Notably, the results suggest that SP is intimately associated with GABA in mammalian taste signal processing and demonstrate an unanticipated route for sensory information flow within the taste bud.
Asunto(s)
Sustancia P/fisiología , Papilas Gustativas/fisiología , Ácido gamma-Aminobutírico/fisiología , Adenosina Trifosfato/fisiología , Animales , Células CHO , Calcio/fisiología , Cricetulus , Masculino , Ratones Endogámicos C57BL , Gusto/fisiologíaRESUMEN
BACKGROUND AND PURPOSE: Imiquimod is an immunomodulator approved for the treatment of basal cell carcinoma and has adverse side effects, including taste disturbances. Paracrine transmission, representing cell-cell communication within taste buds, has the potential to shape the final signals that taste buds transmit to the brain. Here, we tested the underlying assumption that imiquimod modifies taste transmitter secretion in taste buds of mice. EXPERIMENTAL APPROACH: Taste buds were isolated from C57BL/6J mice. The effects of imiquimod on transmitter release in taste buds were measured using calcium imaging with cellular biosensors, and examining the net effect of imiquimod on taste-evoked ATP secretion from mouse taste buds. KEY RESULTS: Up to 72% of presynaptic (Type III) taste cells responded to 100 µM imiquimod with an increase in intracellular Ca2+ concentrations. These Ca2+ responses were inhibited by thapsigargin, an inhibitor of the sarco/endoplasmic reticulum Ca2+ -ATPase, and by U73122, a PLC inhibitor, suggesting that the Ca2+ mobilization elicited by imiquimod was dependent on release from internal Ca2+ stores. Moreover, combining studies of Ca2+ imaging with cellular biosensors showed that imiquimod evoked secretion of 5-HT, which then provided negative feedback onto receptor (Type II) cells to reduce taste-evoked ATP secretion. CONCLUSION AND IMPLICATIONS: Our results provide evidence that there is a subset of taste cells equipped with a range of intracellular mechanisms that respond to imiquimod. The findings are also consistent with a role of imiquimod as an immune response modifier, which shapes peripheral taste responses via 5-HT signalling.
Asunto(s)
Aminoquinolinas/farmacología , Calcio/metabolismo , Serotonina/metabolismo , Papilas Gustativas/efectos de los fármacos , Adenosina Trifosfato/antagonistas & inhibidores , Adenosina Trifosfato/metabolismo , Animales , Técnicas Biosensibles , Imiquimod , Masculino , Ratones , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacos , Papilas Gustativas/metabolismoRESUMEN
Immunoelectron microscopy revealed that peripheral afferent nerve fibers innervating taste buds contain calcitonin gene-related peptide (CGRP), which may be as an efferent transmitter released from peripheral axon terminals. In this report, we determined the targets of CGRP within taste buds and studied what effect CGRP exerts on taste bud function. We isolated mouse taste buds and taste cells, conducted functional imaging using Fura-2, and used cellular biosensors to monitor taste-evoked transmitter release. The findings showed that a subset of Presynaptic (Type III) taste cells (53%) responded to 0.1 µm CGRP with an increase in intracellular Ca(2+). In contrast, Receptor (Type II) taste cells rarely (4%) responded to 0.1 µm CGRP. Using pharmacological tools, the actions of CGRP were probed and elucidated by the CGRP receptor antagonist CGRP(8-37). We demonstrated that this effect of CGRP was dependent on phospholipase C activation and was prevented by the inhibitor U73122. Moreover, applying CGRP caused taste buds to secrete serotonin (5-HT), a Presynaptic (Type III) cell transmitter, but not ATP, a Receptor (Type II) cell transmitter. Further, our previous studies showed that 5-HT released from Presynaptic (Type III) cells provides negative paracrine feedback onto Receptor (Type II) cells by activating 5-HT1A receptors, and reducing ATP secretion. Our data showed that CGRP-evoked 5-HT release reduced taste-evoked ATP secretion. The findings are consistent with a role for CGRP as an inhibitory transmitter that shapes peripheral taste signals via serotonergic signaling during processing gustatory information in taste buds. SIGNIFICANCE STATEMENT: The taste sensation is initiated with a highly complex set of interactions between a variety of cells located within the taste buds before signal propagation to the brain. Afferent signals from the oral cavity are carried to the brain in chemosensory fibers that contribute to chemesthesis, the general chemical sensitivity of the mucus membranes in the oronasal cavities and being perceived as pungency, irritation, or heat. This is a study of a fundamental question in neurobiology: how are signals processed in sensory end organs, taste buds? More specifically, taste-modifying interactions, via transmitters, between gustatory and chemosensory afferents inside taste buds will help explain how a coherent output is formed before being transmitted to the brain.
Asunto(s)
Adenosina Trifosfato/metabolismo , Péptido Relacionado con Gen de Calcitonina/fisiología , Papilas Gustativas/metabolismo , Vías Aferentes/fisiología , Secuencia de Aminoácidos , Animales , Células CHO , Péptido Relacionado con Gen de Calcitonina/farmacología , Señalización del Calcio , Cricetinae , Cricetulus , Estrenos/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Comunicación Paracrina , Pirrolidinonas/farmacología , Receptores de Péptido Relacionado con el Gen de Calcitonina/fisiología , Receptores Presinapticos/fisiología , Serotonina/metabolismo , Papilas Gustativas/efectos de los fármacosRESUMEN
The permeability of tight junctions to horseradish peroxidase (HRP) and the freeze-fracture appearance of junctional structures were investigated in the von Ebner's gland of gerbils. In the tracing study, HRP was either administered topically on the dorsal surface of tongues or injected subepithelially into the connective tissue of vallate papillae for 5-30 min. Lingual tissues containing the von Ebner's gland were sectioned and examined by light and electron microscopy. In von Ebner's glands, the reaction product for HRP was found in the intercellular and interstitial spaces, whereas HRP appeared to penetrate the tight junctions and the reaction product was localized in the lumina of serous acini. In contrast, the staining for HRP that delineated the boundary of epithelial cells was frequently observed in the superficial layers of the lingual epithelium but not the underlying tissues while applying HRP topically. Freeze-fracture replicas of acinar cells revealed that the tight junction had a depth of 0.815 ± 0.023 µm, and 4-6 parallel strands on the protoplasmic fracture face, with a branching network of joining strands with interruptions, interconnections and high linear strand density apically, and corresponding grooves on the extracellular face. Quantitative analyses showed a greater number of strands (7.217 ± 0.326) in gerbils compared to those of acinar cells (3.86 ± 0.22) in mice. These results demonstrate that the tight junctions in the gerbil von Ebner's gland is permeable, and that specific species differences in tight junction structures may be associated with the mechanism for survival in an extremely dry environment.
Asunto(s)
Peroxidasa de Rábano Silvestre/análisis , Permeabilidad , Uniones Estrechas/fisiología , Uniones Estrechas/ultraestructura , Glándulas de von Ebner/fisiología , Glándulas de von Ebner/ultraestructura , Animales , Microscopía por Crioelectrón , Gerbillinae , Histocitoquímica , Microscopía Electrónica de TransmisiónRESUMEN
AIM: Recommended initial treatment for mixed urinary incontinence involves behavioral therapy, and drug and pelvic floor muscle exercises. Our objective is to evaluate the outcome of these conservative treatments in our patients with mixed urinary incontinence. METHODS: A retrospective review was conducted in patients with mixed urinary incontinence who were offered sequential conservative treatment modalities comprised of medication and physiotherapy. Outcome was defined as a score of 1 or less for questions 2 and 3 on the six-item Urodynamic Distress Inventory (UDI-6) and seven-item Incontinence Impact Questionnaire, in addition to clinical symptomatic improvement with no urgency, urge incontinence and voiding frequency of less than eight times per 24 h on a 3-day bladder diary after treatment. Treatment outcome of patients opting for medication plus physiotherapy (M + P) were analyzed against patients preferring medication only (M). RESULTS: Sixty-two mixed urinary incontinent patients received an initial treatment with conservative measures with mean follow-up of 14 months. A total of 61.2% (30/49) and 56.3% (9/13) subjects had improved symptoms in the M + P and M group, respectively. There was significant improvement in UDI-6 total score in the M + P group after conservative treatment, despite no significant difference when compared to the M group. Only 6.45% required subsequent anti-incontinence surgery after conservative treatment, amongst whom only half showed improvement after the surgery. CONCLUSION: Combined treatment with medication and physiotherapy is highly recommended for patients with mixed urinary incontinence. Conservative measures should still precede any surgical intervention. Further studies are needed to evaluate the long-term efficacy.
Asunto(s)
Antimutagênicos/uso terapéutico , Terapia Cognitivo-Conductual , Terapia por Ejercicio , Incontinencia Urinaria de Esfuerzo/terapia , Incontinencia Urinaria de Urgencia/terapia , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Humanos , Persona de Mediana Edad , Diafragma Pélvico/fisiopatología , Estudios Retrospectivos , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
OBJECTIVES: To investigate the discriminative ability and diagnostic accuracy of the Timed Up and Go Test (TUG) as a clinical screening instrument for identifying older people at risk of falling. DESIGN: Systematic literature review and meta-analysis. SETTING AND PARTICIPANTS: People aged 60 and older living independently or in institutional settings. MEASUREMENTS: Studies were identified with searches of the PubMed, EMBASE, CINAHL, and Cochrane CENTRAL data bases. Retrospective and prospective cohort studies comparing times to complete any version of the TUG of fallers and non-fallers were included. RESULTS: Fifty-three studies with 12,832 participants met the inclusion criteria. The pooled mean difference between fallers and non-fallers depended on the functional status of the cohort investigated: 0.63 seconds (95% confidence (CI) = 0.14-1.12 seconds) for high-functioning to 3.59 seconds (95% CI = 2.18-4.99 seconds) for those in institutional settings. The majority of studies did not retain TUG scores in multivariate analysis. Derived cut-points varied greatly between studies, and with the exception of a few small studies, diagnostic accuracy was poor to moderate. CONCLUSION: The findings suggest that the TUG is not useful for discriminating fallers from non-fallers in healthy, high-functioning older people but is of more value in less-healthy, lower-functioning older people. Overall, the predictive ability and diagnostic accuracy of the TUG are at best moderate. No cut-point can be recommended. Quick, multifactorial fall risk screens should be considered to provide additional information for identifying older people at risk of falls.
Asunto(s)
Accidentes por Caídas/prevención & control , Accidentes por Caídas/estadística & datos numéricos , Actividades Cotidianas , Aptitud , Evaluación Geriátrica/métodos , Anciano , Prueba de Esfuerzo/métodos , Humanos , Equilibrio Postural , Factores de RiesgoAsunto(s)
Enfermedad de Crohn/diagnóstico , Deficiencia de Mevalonato Quinasa/diagnóstico , Displasia Septo-Óptica/diagnóstico , Dolor Abdominal/etiología , Niño , Enfermedad de Crohn/complicaciones , Fiebre/etiología , Humanos , Hiperbilirrubinemia/etiología , Hipoglucemia/etiología , Hipotermia/etiología , Lactante , Ganglios Linfáticos/patología , Masculino , Deficiencia de Mevalonato Quinasa/complicaciones , Calambre Muscular/etiología , Cuello , Displasia Septo-Óptica/complicaciones , Espasmo/etiología , Pérdida de PesoRESUMEN
BACKGROUND: Misunderstanding between clinicians and patients may lead to medication-related errors and poor clinical outcomes, particularly in anticoagulant care. METHODS: One hundred forty-seven chronic warfarin users were randomized to receive a visual medication schedule at each visit, along with brief counseling, versus standard care, and followed for 90 days. At baseline, patient and clinician reports of the prescribed warfarin regimen were recorded to identify patients as "discordant" versus "concordant" to determine whether the effect of the intervention varied with clinician-patient discordance. RESULTS: At baseline, clinician-patient warfarin regimen discordance was common in intervention and control groups (38% versus 42%). Intervention subjects achieved anticoagulation control more rapidly than control subjects (median 28 versus 42 days; hazard ratio [HR], 1.43; confidence interval [CI], 1.00, 2.06). The benefit of the intervention was significant among subjects with baseline regimen discordance (median, 28 versus 49 days; HR, 1.92; CI, 1.08, 3.39) but not among subjects with baseline concordance (median 28 versus 35 days; HR, 1.14; CI, 0.71,1.83). DISCUSSION: Among patients in poor anticoagulant control whose understanding of their warfarin regimen is discordant with their providers', a visual medication schedule, combined with brief counseling, reduced time to anticoagulation control. The study suggests a simple strategy to enhance medication safety and efficacy for at-risk patients.
Asunto(s)
Anticoagulantes/administración & dosificación , Consejo , Cooperación del Paciente , Autoadministración , Warfarina/administración & dosificación , Anciano , Anticoagulantes/uso terapéutico , Continuidad de la Atención al Paciente , Esquema de Medicación , Femenino , Hospitales Generales , Humanos , Masculino , Persona de Mediana Edad , Servicio Ambulatorio en Hospital , San Francisco , Interfaz Usuario-Computador , Percepción Visual , Warfarina/uso terapéuticoRESUMEN
CONTEXT: Lipochoristomas (lipomatous choristomas) are rare tumors of the acoustic nerve (cranial nerve VIII/vestibulocochlear nerve) within the internal acoustic canal and sometimes the cerebellopontine angle, and are histogenetically believed to be congenital malformations. Their clinically indolent behavior has recently prompted a more conservative management protocol in a quest for maximal nerve/hearing preservation. This approach contrasts sharply with that for the common internal acoustic canal/cerebellopontine angle tumors, the neuroepithelial neoplasms (acoustic schwannomas and meningiomas), which behave more aggressively and have more prominent clinical manifestations. Owing to their rarity, the clinicopathologic features of cranial nerve VIII lipochoristomas have been obtained mainly through case reports. OBJECTIVE: We present the clinicopathologic features of 11 cases of lipochoristomas of cranial nerve VIII. DESIGN: The 11 cases were documented between 1992 and 2003. We performed complete clinical reviews with histologic, histochemical, and immunohistochemical analyses of formalin-fixed, paraffin-embedded tumor samples. RESULTS: The patients were 8 men and 3 women with hearing loss of the right ear (5 patients) or the left ear (6 patients). No patient had bilateral tumors. All lipochoristomas histologically possessed mature adipose tissue admixed with varied amounts of mature fibrous tissue, tortuous thick-walled vessels, smooth muscle bundles, and skeletal muscle fibers, the latter verified with immunohistochemistry. CONCLUSIONS: The histomorphologic and immunophenotypic evidence showed that these tumors are better characterized as choristomas than as simple "lipomas," as they have been labeled in the past. Their overall nonaggressive clinical nature in addition to the characteristic radiologic and histomorphologic findings are important clinicopathologic features for the pathologist to recognize and differentiate, especially during frozen section evaluations, in order to direct the neurosurgeon to a more appropriate conservative therapeutic intervention.
Asunto(s)
Neoplasias Cerebelosas/patología , Nervio Coclear/patología , Neoplasias de los Nervios Craneales/patología , Lipoma/patología , Adulto , Neoplasias Cerebelosas/complicaciones , Neoplasias Cerebelosas/diagnóstico por imagen , Ángulo Pontocerebeloso/diagnóstico por imagen , Ángulo Pontocerebeloso/patología , Nervio Coclear/diagnóstico por imagen , Nervio Coclear/cirugía , Neoplasias de los Nervios Craneales/complicaciones , Neoplasias de los Nervios Craneales/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Formaldehído/metabolismo , Pérdida Auditiva/etiología , Humanos , Inmunohistoquímica , Lipoma/complicaciones , Lipoma/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Adhesión en Parafina , Fijación del Tejido , Tomografía Computarizada por Rayos X/métodos , Nervio Vestibulococlear/diagnóstico por imagen , Nervio Vestibulococlear/patologíaRESUMEN
The ZZ variant of alpha(1)-antitrypsin deficiency (AATD) is well known to cause liver damage and cirrhosis in some affected children. Ubiquitin abnormality was recently shown to be significant in AATD in childhood cirrhosis. Molecular misreading (MM), defined as faulty transcription of genomic information from DNA into mRNA, as well as its translation into mutant proteins, has been documented in many pathologic processes where aggregation of abnormal proteins occurs. The misread protein, ubiquitin-B(+1) (UBB(+1)), was recently identified in the hallmarks of various neurological disorders. The objective of this study was to determine whether MM of ubiquitin occurs in AATD. Twelve explanted liver specimens from AATD-affected children with cirrhosis were retrieved from archival sources, along with 10 control liver specimens obtained from autopsies of age-matched children with no clinical, gross anatomic, or histologic evidence of liver disease. Double immunofluorescence studies using rabbit polyclonal antibodies against UBB(+1) and AAT were performed on consecutively sectioned tissue. UBB(+1) immunoreactivity was colocalized with AAT in all cirrhotic AATD livers. The control livers were consistently negative. Ubiquitin MM is prominent in AATD-affected cirrhotic livers. This indicates that for children with AATD and cirrhosis, ubiquitin MM is a necessary cofactor to the aggregation of mutant ZZ isoform of AATD.
Asunto(s)
Mutación del Sistema de Lectura , Cirrosis Hepática/metabolismo , Hígado/metabolismo , Ubiquitina/metabolismo , Deficiencia de alfa 1-Antitripsina/metabolismo , Adolescente , Niño , Preescolar , Femenino , Técnica del Anticuerpo Fluorescente , Homocigoto , Humanos , Hígado/patología , Cirrosis Hepática/genética , Cirrosis Hepática/patología , Masculino , Transcripción Genética , Ubiquitina/genética , Deficiencia de alfa 1-Antitripsina/genéticaRESUMEN
BACKGROUND: Lipoblastomas are rare tumors of embryonal fat that occur in infants and children. They are usually located in the extremities and trunk. Two cases in the parotid region have been described. A diagnosis on fine needle aspiration (FNA) specimens has been reported in six cases. CASE: Lipoblastoma of the parotid region occurred in a 6-year-old boy and was diagnosed by FNA. Cytology showed rare lipoblasts and hibernomalike cells in a myxoid background with spindle and stellate mesenchymal cells, mature adipose cells and plexiform capillaries. A 7.0-cm, well-circumscribed mass with lobulated adipose tissue and delicate fibrous bands was resected. Microscopically, it showed a lobulated myxoid stroma, many capillaries, mesenchymal cells, lipoblasts and mature adipose cells. CONCLUSION: Lipoblastoma has to be differentiated from myxoid and lipomatous soft tissue tumors, especially from myxoid liposarcoma, a malignancy that classically affects older individuals and shows pleomorphism, atypical lipoblasts and chromosome-12 translocation. A lipoblastoma diagnosis must be established only after careful consideration of all available clinical, radiologic, cytogenetic and morphologic data.
Asunto(s)
Lipoma/patología , Neoplasias de la Parótida/patología , Biopsia con Aguja , Niño , Humanos , Lipoma/diagnóstico , Lipoma/cirugía , Masculino , Neoplasias de la Parótida/diagnóstico , Neoplasias de la Parótida/cirugíaRESUMEN
Rhabdomyomas are the most common primary cardiac tumors in children, and have been shown to undergo spontaneous regression. The aim of our study was to investigate morphologically and immunohistochemically some mechanisms that may explain this clinical phenomenon. Eleven tumors from three term newborn girls who had physical and radiographic features pathognomonic of tuberous sclerosis were evaluated. Control specimens were left and right heart sections from five autopsies of age- and sex-matched patients who died of causes unrelated to the cardiovascular system. The tumors had been surgically excised from various regions in the heart, and all had similar "typical" histology. Histomorphologic evaluation with von Kossa and alizarin-red stains and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) method were performed to evaluate cell calcifications, necrosis, and apoptosis. Ubiquitin immunohistochemical study was also conducted to evaluate intracytoplasmic protein degradation. In cardiac rhabdomyomas (CR), all myocytes with acidophilic cytoplasmic myofibrils showed strong intracytoplasmic ubiquitin immunoreactivity, compared with the occasional weak cytoplasmic and focal nuclear positivity in control heart sections. Calcified myocyte nuclei were commonly seen in CR tumoral and nontumoral rhabdomyocytes, whereas control nontumoral cardiac myocytes did not show any calcification. The incidence of TUNEL reactivity seen in CR (4.8 nuclei per 100 cardiac rhabdomyocyte nuclei) was higher than that seen in control heart sections (1.7 nuclei per 106 cardiac myocytes, P < 0.005). The data led us to conclude that the cytoplasmic contents in CR were degraded via the ubiquitin pathway, and from our observation of increased TUNEL positivity, the rate of cell death in CR appeared increased. These findings may explain, to some extent, the mechanism of tumor regression.
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Neoplasias Cardíacas/patología , Regresión Neoplásica Espontánea/patología , Rabdomiosarcoma/patología , Apoptosis , Calcinosis/metabolismo , Calcinosis/patología , Recuento de Células , Núcleo Celular/metabolismo , Núcleo Celular/patología , Femenino , Neoplasias Cardíacas/química , Neoplasias Cardíacas/cirugía , Humanos , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Recién Nacido , Rabdomiosarcoma/química , Rabdomiosarcoma/cirugía , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/patología , Ubiquitina/análisisRESUMEN
Operative manipulation during hepatic resection (HR) causes tumor cell shedding which is a factor in disease recurrence. Radiofrequency ablation (RFA) causes coagulative necrosis and was used to destroy the tumor before HR. We evaluated tumor necrosis and recurrence of hepatic malignancies treated by sequential RFA/HR. A retrospective review of patients treated with sequential RFA/HR from April 1999 to January 2002 was performed. A Radionics 500-kW RF generator was used to ablate lesions via H2O-cooled electrodes under ultrasound guidance. Segmental HR was performed after RFA. Resected specimens were reviewed with hematoxylin and eosin staining and for apoptosis. Patient follow-up ranged from 10 to 33 months with evaluation of salient clinical, radiologic, and laboratory parameters. Seven patients (four male and three female) ages 62.1 +/- 10.3 years had sequential RFA/HR. Four patients had hepatocellular carcinoma (HCC) and three had colorectal metastases (CRm). The tumors were unifocal right-lobe lesions measuring 4.1 +/- 0.9 cm with a resection margin of 0.4 to 2.5 cm. Extensive necrosis was noted but intact nests of tumor cells occurred in all specimens with minimal apoptosis. Three of seven patients (two HCC and one CRm) developed pulmonary metastases at 3 to 20 months with one HCC patient developing concurrent liver metastases. Two deaths occurred in the HCC group. Sequential RFA/HR may minimize local recurrence; however, the high incidence of pulmonary metastases raises concern of transvenous migration. The histologic findings demonstrate foci of intact tumor cells after RFA. Controlled study of additional patients with long-term follow-up is necessary to better understand these findings.