[TACE: therapy of the HCC before liver transplantation--experiences]. / TACE: Therapie des HCC vor Lebertransplantation -- Erfahrungen.

PURPOSE: Analysis of the course of disease in patients with histologically proven HCC before and after orthotopic liver transplantation (LTx) who received transarterial chemoembolization (TACE). MATERIAL AND METHODS: Thirty-five of a total collective of 363 patients with histologically proven HCC underwent LTx. Before LTx, all patients were treated with sequential TACE. According to treatment pattern, TACE should be performed every 6 weeks, using a suspension consisting of max. 10 mg Mitomycin C as well as 10 - 30 ml iodized oil (Lipiodol). Patients were classified according to the Milano criteria. Criteria were called exceeded if the tumor size was > 5 cm and/or > 3 tumors larger than 3 cm were found. Therapy success and liver function were examined by means of spiral CT and laboratory controls. Investigation parameters included the number of tumor knots as well as the maximum tumor size. Additionally, the Lipiodol accumulation, the patency of the portal vein and the occurrence of complications were checked. RESULTS: Altogether, 184 TACE procedures were accomplished (5.3 +/- 3.3, range 1 - 14). The waiting period up to the transplantation amounted to 366 +/- 255 days (range 44 - 1137). The average number of tumor knots for each patient was 3.1 +/- 2.2 before and 2.9 +/- 2.2 after TACE (p = 0.887). The average tumor size was 4.2 +/- 2.5 before and 2.8 +/- 1.4 after TACE. The Milano criteria to LTx crossed 17/35 patients. Patients with exceeded Milan criteria showed a highly significant size reduction of the tumor after TACE (p = 0.001); in 9/17 cases the transplantation criteria were secondarily fulfilled through downstaging. A successful LTx was accomplished in 35/35 cases. Follow up after LTx was 769 +/- 509 days. The tumor recurrence in patients with exceeded vs. fulfilled transplantation criteria was 11.1 % vs. 11.8 % (p = 0.99). The recurrence free survival was 93.3 %, 82.5 % and 82.5 % at 1, 3 and 5 years, respectively. There were no relevant differences between patients with exceeded vs. fulfilled transplantation criteria (p = 0.99). CONCLUSION: The sequential TACE is an effective method for the therapy of the HCC before LTx in selected patients. A relevant downsizing could be achieved by TACE in patients with advanced HCC. Patients with larger tumors showed a significantly stronger size reduction after TACE. The recurrence rate and the survival rate for patients with advanced or small tumors do not differ.

The need for more accurate and timely diagnosis in Fanconi anemia: a report from the International Fanconi Anemia Registry.

OBJECTIVE: The objective of this study was to address the need for early diagnosis of Fanconi anemia (FA), an autosomal recessive chromosomal instability syndrome characterized by a unique cellular hypersensitivity to DNA cross-linking agents, such as diepoxybutane, and by a high risk of malignancies. METHODS: We analyzed data from 370 FA patients enrolled in the American Registry of the International FA Registry. Of these individuals, 220 had congenital malformations; the rest were ascertained based on hematologic abnormalities only or on clinical evaluation and screening following the diagnosis of an affected family member. The probands noted to have congenital malformations at the time of diagnosis were classified into two groups on the basis of their clinical presentation: (1) patients manifesting both congenital malformations and hematologic abnormalities (159 individuals); (2) patients manifesting congenital malformations only (61 individuals). RESULTS: The mean age of diagnosis was 6.6 years and 1.1 years for Groups 1 and 2, respectively. Thus, the majority of FA patients with congenital malformations were not diagnosed until after the onset of hematologic abnormalities. We also report central nervous system, gastrointestinal, and skeletal malformations which previously have not been included as part of the FA phenotype. Our review of the patients enrolled in the International FA Registry indicates that the FA phenotype is more variable than recognized previously. CONCLUSIONS: Testing for sensitivity to diepoxybutane to rule out a diagnosis of FA needs to be applied more widely in patients with congenital malformations. All siblings of affected probands also should have testing, because a lack of concordance of phenotype in affected siblings makes clinical diagnosis unreliable even within sibships. A more timely diagnosis of FA in the preanemic phase is needed to implement appropriate therapy and to enable parents to make informed reproductive decisions.

[Evaluation of percutaneous vertebroplasty in osteoporotic vertebral fractures using a combination of CT fluoroscopy and conventional lateral fluoroscopy]. / Perkutane Vertebroplastie osteoporosebedingter Wirbelkörperfrakturen: Erfahrungen mit der CT-Fluoroskopie.

PURPOSE: Evaluation of vertebroplasty using a combination of CT-fluoroscopy and conventional lateral fluoroscopy in patients with osteoporotic vertebral fractures. MATERIALS AND METHODS: Fifty-eight patients (23male, 35 women, age 69.7 +/- 10.2 years) with painful osteoporotic vertebral fractures were treated with vertebroplasty in conscious sedation and local anesthesia. Spiral-CT with sagittal reconstructions of the respective vertebral bodies was used for classification of the fracture. The cannula was placed under CT-guidance in the ventral third of the respective vertebral bodies and cement instilled under CT fluoroscopy and lateral fluoroscopy. When cement migrated towards the vertebral canal, the injection was immediately stopped for 30 - 60 seconds. After polymerization in this location, the injection was continued until sufficient filling of the vertebra. Results were documented by spiral CT with sagittal reconstructions. RESULTS: A total of 123 vertebral bodies were treated, comprising 39 thoracic and 84 lumbar vertebral bodies, with a mean of 2.1 +/- 1.3 (range 1 to 6) vertebral bodies in each patient and a maximum of 3 vertebral bodies per session. All interventions were successfully completed in conscious sedation and local anesthesia. A mean volume of 5.9 +/- 0.6 ml (range 2 to 14 ml) cement was applied for each vertebra, with 79.7 % of procedures performed using a unilateral access. To achieve a sufficient cement deposit, a bilateral access was used in 20.3 %. The dorsal wall of the vertebra was included in 23.6 % of the fractures. In one case, cement migration into the spinal canal was detected, reducing the diameter of the canal by 30 %. In two other cases, cement leakage was seen at the puncture site of the vertebra (one intercostotransversally in the 10 (th) thoracic vertebra and one dorsolaterally in the 1 (st) lumbar vertebra) with retrograde cement migration through the neuroforamen into the epidural space. In one of these cases, the cannulation of the vertebra had been changed before cement application resulting in a hole in the dorsolateral vertebral wall. However, all patients were discharged without evidence of neurologic complications. Multiplanar reconstructions of CT scans were used for the detection of extraosseous cement leaks: The incidence of extraosseous cement leaks was 4.1 % in epidural veins, 6.5 % in paravertebral vessels (6 veins, 2 arteries), and 17.9 and 11.4 %, respectively, for upper or lower end plates. At discharge, 25 patients (43.1 %) were free of pain and 28 (48.3 %) significantly improved with a considerable reduction of analgetic drugs. Significant complaints persisted in 5 patients (8.6 %) with concomitant degenerative disease in four and vasculitis in one case. CONCLUSION: Percutaneous vertebroplasty is effective for stabilization and pain management of osteoporotic vertebral fractures. The procedure can be safely performed in conscious sedation and local anesthesia. Compared to conventional fluoroscopy alone, CT fluoroscopy provides an excellent additional monitoring of the procedure and probably contributes to the safety of the procedure.

[Micronodular sonographic pattern of the spleen: a frequent finding in children and adolescents]. / Feinnoduläres Milzparenchym, ein häufiger sonografischer Befund bei Kindern und Jugendlichen.

UNLABELLED: In textbooks about abdominal sonography, the parenchyma of the spleen is described as homogeneous. However, using high-frequency probes, sonography of the spleen in children often reveals a micronodular pattern. AIM: To investigate the prevalence of a micronodular pattern in the pediatric spleen and to evaluate possible correlations to clinical parameters. METHODS: In 106 non-selected children (54 males, 52 females, mean age 7 years 10 months), the spleen was examined with a 17 MHz probe. Simultaneously the size of the spleen was measured, and other parameters such as leukocyte and thrombocyte counts were recorded. The pattern of the spleen was estimated using a four-step scale. 0: homogeneous tissue without micronodular components, 1: faint micronodular pattern/barely perceptible, 2 and 3: micronodular pattern clearly visible of moderate (2) or strong intensity (3). RESULTS: In 33 children a homogenous pattern was found (31.1 %) and in 48 children (45.3 %) a micronodular pattern of the spleen was clearly visible. A statistical correlation to spleen size or leukocyte or thrombocyte count or CRP could not be proven. 52 % of children with an enlarged spleen had a micronodular pattern, as well as 66.7 % of children with leukocytosis, 44.7 % of children with increased CRP, and 54.5 % of children with thrombocytosis. However, there was a strong statistical correlation to the age of the children with a maximum at the age of 1 to 5 years. CONCLUSION: A micronodular pattern of the spleen is frequent in children, even without clinical signs of infection. It is important to be aware of this finding and not to confuse it with pathological changes.

Why the Kantian ideal survives medical learning curves, and why it matters.

The "Kantian ideal" is often misunderstood as invoking individual autonomy rather than rational self legislation. Le Morvan and Stock's otherwise insightful discussion of "Medical learning curves and the Kantian ideal"--for example--draws the mistaken inference that that ideal is inconsistent with the realities of medical practice. But it is not. Rationally to be a patient entails accepting its necessary conditions.

The kidney trade: or, the customer is always wrong.

Much of the opinion scandalized by recent reports of kidneys being sold for transplant is significantly inconsistent. The sale of kidneys is not substantially different from practices espoused, and indeed endorsed, by many of those who condemn the former. Our moral concern, I suggest, needs to focus on the customer's actions rather than the seller's; and on the implications for larger questions of the considerations to which this gives rise.

Buying human kidneys: autonomy, commodity and power.

Buttle's reply to my objections to buying kidneys is helpful but unconvincing in two respects. Doing something freely leaves quite open the possibility that one is thereby making a commodity of a person; and the effects of institutionalising such a practice is itself a matter for concern. And while his emphasis on 'power' is important, the concept is hardly less problematic than 'commodification'.

What would a socialist health service look like?

A socialist health service cannot be a socialist island in a sea of capitalism, as the record of the British National Health Service shows. Nonetheless, since health is a basic need, it can be a key component of the advocacy of socialism. I propose two central socialist principles. On the basis of these I suggest that a socialist health system would emphasise care rather than service; insist on democratic structures and control of resources; and require the prohibition of private medicine.

Hematologic abnormalities in Fanconi anemia: an International Fanconi Anemia Registry study.

We analyzed data from 388 subjects with Fanconi anemia reported to the International Fanconi Anemia Registry (IFAR). Of those, 332 developed hematologic abnormalities at a median age of 7 years (range, birth to 31 years). Actuarial risk of developing hematopoietic abnormalities was 98% (95% confidence interval, 93% to 99%) by 40 years of age. Common hematologic abnormalities were thrombocytopenia and pancytopenia. These were often associated with decreased bone marrow (BM) cellularity (75% of cases studied). Clonal cytogenetic abnormalities developed in 23 of 68 persons with BM failure who had adequate studies. Actuarial risk of clonal cytogenetic abnormalities during BM failure was 67% (47% to 87%) by 30 years of age. Fifty-nine subjects developed myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML). Actuarial risk of MDS or AML was 52% (37% to 67%) by 40 years of age. Risk was higher in persons with than in those without a prior clonal cytogenetic abnormality (3% [0% to 9%] v 35% [0% to 79%]; P = .006). One hundred twenty persons died of hematologic causes including BM failure, MDS or AML and treatment related complications. Actuarial risk of death from hematologic causes was 81% (67% to 90%) by 40 years of age.

Fanconi's anaemia and pregnancy.

We have identified six new cases of Fanconi's anaemia (FA) who had pregnancies, and reviewed 11 others from the literature. At least 110 FA females have reached 16 years of age or more, of whom 15% became pregnant. There were a total of 26 pregnancies, resulting in 19 births and 18 surviving children. Anaemia and/or thrombocytopenia worsened during pregnancy in 10 patients, but five subsequently improved: seven had no haematological problems. Seven of the FA patients who had pregnancies died subsequently from cancer, and two from thrombocytopenic bleeding 3 and 20 years later. There were no peripartum deaths. Pregnancy in FA is clearly possible, with increased risks that are manageable from both the haematological and the obstetric aspects.

Fanconi anemia: a model for genetic causes of abnormal brain development.

Fanconi anemia is an autosomal recessive disease resulting in bone-marrow failure, phenotypical abnormalities and predisposition to malignancy. The authors reviewed 257 clinical and neuropathology results from the International Fanconi Anemia Registry at The Rockefeller University. Two patients had hydrocephalus and ventriculoperitoneal shunts. Of 15 neuropathology reports, 10 found CNS abnormalities, with the most common--ventriculomegaly--seen in six, two of whom required shunts. Aqueductal stenosis, agenesis of the corpus callosum and septum pellucidum, and holoprosencephaly were found. The authors conclude that neurological derangements are probably more common in Fanconi anemia than previously recognised. Fanconi anemia cells in culture are highly sensitive to oxidative stress and alkylating agents; Fanconi anemia may provide a model for a genetic disorder potentially predisposing to environmental insults.

Fanconi anemia: evidence for linkage heterogeneity on chromosome 20q.

Fanconi anemia is a rare autosomal recessive disorder in which affected individuals are predisposed to acute myelogenous leukemia and other malignancies. We report the results of a genetic linkage study involving 34 families enrolled in the International Fanconi Anemia Registry. A significant lod score was obtained between D20S20, an anonymous DNA segment from chromosome 20q, and Fanconi anemia (Zmax 3.04, theta max = 0.12). However, six other anonymous DNA segments from chromosome 20q, including D20S19, which is highly polymorphic and tightly linked to D20S20, showed no or only weak evidence for linkage to Fanconi anemia. An admixture test revealed significant evidence for linkage heterogeneity (chi 2 = 6.10, P = 0.01) at the D20S19 locus. Lod scores suggestive of linkage between Fanconi anemia and this locus were obtained with two of the largest kindreds studied (lods = 2.6 and 2.1, at theta = 0.001). Thus, our data support the provisional assignment of a Fanconi anemia gene to chromosome 20q.