Genetic evolution of breast cancers III: Age-dependent variations in the correlations between biological indicators of prognosis

The influence of age on the occurrence of phenotypic features of prognostic significance was studied in relation to the DNA index values, measured on DNA histograms from a series of 1019 breast cancer patients. Globally, the distributions of all parameters showed variations with age, the most prominent being the decreases in the percentage of estrogen receptor-negative and high proliferative activity cases with increasing age. When analyzed according to the DNA index classes, all parameters were found to some extent linked with the stage of genetic evolution. However, the associations varied with age, defining two extreme groups. The younger patients (less than 40 years) presented a more complete acquisition of the aggressive phenotype and near-triploid tumors from this group were very frequently steroid hormone receptor-negative, high proliferation, and grade III. By contrast, near-triploid tumors in patients above 65 presented relatively frequently as receptor-positive, low proliferative activity, and even grade I. The correlation of the proliferative status with steroid hormone receptor content led to similar conclusions, high proliferation being more strongly correlated with the absence of estrogen and progesterone receptors in younger patients. Interestingly, the association between high proliferation and negative progesterone receptors was much weaker in patients above 55. Our results suggest that the currently established biological prognostic factors, including DNA profile, steroid hormone receptors, and histopathological grade, show patterns of association which vary with age. Of these, only progesterone receptor could be influenced by menopausal status. These findings have to be taken into consideration for future prognostic factor-related treatment decisions, but also for future methodological improvements of multivariate survival analyses.     

A Clinical Screening Cooperative Group phase II evaluation of lobaplatin (ASTA D-19466) in advanced head and neck cancer

Summary We evaluated the efficacy and tolerability of lobaplatin, a new platinum compound, given at the dose of 50 mg/m² by i.v. bolus every 4 weeks, in 49 patients with advanced and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). One complete and 2 partial responses were observed in 43 eligible patients for an overall response rate of 7% (95% confidence interval: 1–19%). The duration of responses was 11, 16 and 32 weeks. Toxicities of WHO grade 3 were hematologic: thrombocytopenia in 26%, granulocytopenia in 12% and anemia in 12% of patients. There was no therapy-related death. Nausea/vomiting, diarrhoea and paresthesia were mild and rare. In conclusion, lobaplatin was well tolerated, but its efficacy in advanced SCCHN at the presented dose and schedule, was marginal.     

Antiamphiphysin antibodies are associated with various paraneoplastic neurological syndromes and tumors

BACKGROUND: Antiamphiphysin antibodies react with a 128-kd protein found in synaptic vesicles.They were first described in patients with paraneoplastic stiff-man syndrome and breast cancer, but studies suggest that they can also occur in patients with other tumors and neurological disorders. OBJECTIVE: To determine if antiamphiphysin antibodies are associated with various paraneoplastic neurological syndromes and tumors. PATIENTS AND METHODS: Of 2800 serum samples tested by routine immunohistochemical procedures on sections of paraformaldehyde-fixed rat brain for the detection of autoantibodies associated with paraneoplastic neurological syndromes, 5 were selected because of labeling suggestive of antiamphiphysin antibodies and subsequently confirmed by the results of Western blot analysis using recombinant amphiphysin protein. Controls consisted of 40 patients with various nonparaneoplastic neurological diseases; 101 patients with cancer but without paraneoplastic neurological syndrome; 9 patients with small cell lung cancer, anti-Hu antibodies, and paraneoplastic neurological syndrome; 3 patients with M2-type antimitochondrial antibodies but no neurological disorder; and 30 normal subjects. RESULTS: Of the 5 patients with antiamphiphysin antibodies, patient 1 had sensory neuronopathy, encephalomyelitis, and breast cancer; patient 2 had limbic encephalitis, and small cell lung cancer was detected in the mediastinum after 24 months of follow-up; patient 3 had encephalomyelitis and ovarian carcinoma; and patients 4 and 5 had Lambert-Eaton myasthenic syndrome and small cell lung cancer (patient 4 subsequently developed cerebellar degeneration). None of the 5 had stiffness. Two patients (Nos. 2 and 4) had antimitochondrial antibodies. The two patients (Nos. 4 and 5) with Lambert-Eaton myasthenic syndrome had antibodies directed against the voltage-gated calcium channel, and patient 2 subsequently developed anti-Hu antibodies. In the controls, antiamphiphysin antibodies were detected by Western blot analysis in 3 of 8 patients with anti-Hu antibodies, but in none of the other groups. CONCLUSIONS: These data indicate that antiamphiphysin antibodies are not specific for one type of tumor or one neurological syndrome and can be associated with other neural and nonneural antibodies. The simultaneous association of several antibodies in some patients suggests multimodal autoantibody production.     

Wagner vitreoretinal degeneration with genetic linkage refinement on chromosome 5q13-q14

· Background: It has been previously described that Wagner disease is linked to chromosome 5q13-q14. This study was carried out to describe the ophthalmological aspects and report the results of genetic linkage analysis in a large pedigree affected by Wagner disease. · Methods: Fourty members of one same family agreed to be examined. · Results: Twenty patients presented vitreoretinal degeneration in both eyes without any extra-ocular abnormalities. In young patients, visual acuity was usually normal after correction of frequent mild myopia. Presenile cataracts progressed by the third decade and required removal for visual rehabilitation. The primary disorder involved an abnormal vitreous. A few avascular vitreous bands were usually the only optical feature in the mostly empty vitreous cavity. A circumferential vitreous condensation formed in contact with the retina on many spots. Less common retinal findings included retinal detachment, abnormal retinal pigmentation, progressive atrophy of the RPE simulating choroideremia and lattice degeneration. Genetic analysis revealed a highly significant linkage (lod score >5.0) between the disease and 10 markers of the chromosome 5q13-q14 region. Two recombination events allowed us to refine the linked interval to 20 cM between the D5S650 and D5S618 markers. · Conclusion: Ophthalmological aspects of Wagner’s disease appear to progress with age. Regular ophthalmological examination is important for detecting retinal abnormalities. The gene involved in Wagner’s disease lies in a 20 cM interval on chromosome 5q13-q14. Received: 30 June 1998 Revised version received: 5 October 1998 Accepted: 6 October 1998     

The diagnostic value of bone scintigraphy in patients with low back pain

Bone scintigraphy has been studied in two groups of patients presenting with low back pain. In one group of 38 patients suffering "nonspecific" back pain, bone scintigraphy and laboratory findings were negative in 24. There were abnormal laboratory findings in all of the remaining 14 and 7 had positive bone scans indicative of clinically significant disease. Selection of patients for bone scintigraphy in this group should therefore be influenced by abnormal laboratory findings and elevation of the erythrocyte sedimentation rate in particular. By comparison, the bone scans were reviewed from another group of patients suffering previously known malignancy. Out of 138 patients, nearly 40% showed a positive bone scan due to subsequently proven metastasis. Bone scintigraphy was positive in a further 14% as a result of osteoporotic rib fracture and vertebral body collapse. In half of these, it was not possible to exclude malignancy by scintigraphy. The present findings indicate that bone scintigraphy is not a useful procedure in patients with long-standing low back pain who have normal radiographs and normal laboratory findings.     

Sequential electrodiagnostic evaluation of diabetic neuropathy after combined pancreatic and renal transplantation

To asses the long-term evolution of diabetic polyneuropathy after a combined kidney-pancreas transplant, an electrophysiological study was performed in 20 diabetic patients before transplant, and 1 (n=18), 2 (n=16), 3 (n=10) and 4 years (n=5) at a later date. Motor and sensory scores were calculated for conduction velocity and amplitude to determine the physiopathological process. During evolution the scores were not found to be decreasing. Motor and sensory velocity scores were significantly improved (p<0.05) 1=" and=" 2=" years=" after=" the=" graft,=" when=" score=" values=" tended=" to=" stabilize.=" motor=" and=" sensory=" amplitude=" scores,=" which=" are=" more=" sensitive=" for=" axonal=" loss=" assessment=" were=" slightly=" but=" not=" significantly=">     

Surgical anatomy and anatomical surgery of the liver

The morphologic anatomy of the liver is described as 2 main and 2 accessory lobes. The more recent functional anatomy of the liver is based on the distribution of the portal pedicles and the location of the hepatic veins. The liver is divided into 4 sectors, some of them composed of 2 segments. In all, there are 8 segments. According to the anatomy, typical hepatectomies (or réglées) are those which are performed along anatomical scissurae. The 2 main technical conceptions of typical hepatectomies are those with preliminary vascular control (Lortat-Jacob's technique) and hepatectomies with primary parenchymatous transection (Ton That Tung's technique). A good knowledge of the anatomy of the liver is a prerequisite for anatomical surgery of this organ.

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Résumé L'anatomie morphologique du foie permet d'individualiser 2 lobes principaux et 2 lobes accessoires. L'anatomie fonctionnelle du foie, plus récemment décrite, est fondée sur la distribution des pédicules portaux et sur la localisation des veines sus-hépatiques. Le foie est divisé en 4 secteurs, eux-mÊmes composés en général de 2 segments. Au total, il y a 8 segments.Selon les données anatomiques, les hépatectomies typiques (ou réglées) sont celles qui sont réalisées le long des scissures anatomiques. Les deux conceptions principales des exérèses hépatiques typiques sont, du point de vue technique, les hépatectomies avec contrÔle vasculaire préalable (technique de Lortat-Jacob) et les hépatectomies avec abord transparenchymateux premier (technique de Ton That Tung). Une connaissance approfondie de l'anatomie du foie est une condition préalable à la réalisation d'une chirurgie anatomique de cet organe.

     

Comparative patterns of i-antigen expression, F-cell frequency and Hb A2 level in acute myeloid leukemia and in acute lymphoid leukemia

Hb F, Hb A₂ and i-antigen expression were investigated in adulthood acute leukemias. The study of i-antigen expression by immuno-agglutination and immunofluorescence showed that it is preferentially increased among AML patients. A similar result was obtained for F-cell frequency which was often increased in AML, while it was normal in ALL. Hb A₂ level was significantly lower in AML than in ALL. These differences between AML and ALL red cell patterns further suggest that the leukemic clone involves the erythroid lineage in AML but not in ALL.     

Idiopathic ocular neuromyotonia: a neurovascular compression syndrome?

Ocular neuromyotonia in the muscles innervated by the right oculomotor nerve was diagnosed in a patient without a history of radiation therapy. Electromyography of the levator palpebrae showed continuous motor unit activity. Brain MRI disclosed a close contact between the right third cranial nerve and a basilar artery dolichoectasia. The patient partly benefited from carbamazepine therapy. This unique finding suggests that neurovascular compression syndrome could be an hitherto unrecognised cause of ocular neuromyotonia.