Prognostic value of estrogen receptor and Ki-67 index after neoadjuvant chemotherapy in locally advanced breast cancer expressing high levels of proliferation at diagnosis.

PURPOSE: Breast cancers expressing high levels of Ki-67, a nuclear marker of cell proliferation, are associated with worse outcome. Recent data from neoadjuvant studies indicate that a single measurement of the nuclear proliferation marker Ki-67 in breast carcinoma during neoadjuvant therapy is strongly predictive of long-term outcome. Secondly, recent literature data indicate that prognostic evaluation with Ki-67 may be better after pre-surgical therapy. A retrospective study from a prospectively maintained clinical database to compare the predictive and prognostic significance of biological markers, assessed before and after neoadjuvant chemotherapy, in locally advanced breast cancer, was performed. PATIENTS AND METHODS: The following parameters were considered before and after chemotherapy for their relationship with treatment response and disease-free survival in 64 patients with locally advanced breast cancer: clinical stage, clinical and pathological lymph node involvement, Ki-67, estrogen receptor (ER), progesterone receptor (Pgr), Her2, tumor grade, clinical response, type of surgery performed, and number of chemotherapy cycles administered. The expression of Ki-67 was assessed using immunohistochemistry in pre-therapy tru-cut and post-therapy surgical excision specimens after neoadjuvant chemotherapy; only patients with breast tumors expressing high baseline Ki-67 (≥ 15%) were included in the analysis. In addition, the correlation between pre-chemotherapy biological markers and clinical and pathological response was reported. RESULTS: Post-chemotherapy Ki-67 proliferation index decrease, pre-chemotherapy ER expression and post-chemotherapy ER expression were the only significant prognostic factors adversely influencing disease-free survival in univariate analysis. Her2 overexpression was the only factor to impact on the clinical response. CONCLUSIONS: Post-treatment Ki-67 and ER status were predictors of outcome for patients with locally advanced breast cancer and a high pre-chemotherapy proliferation index.

Effects of rationalizing drug treatment of patients with epilepsy and mental retardation.

Eighty patients with epilepsy and mental retardation were observed for a mean period of 12.5 months to assess the effects of 'rationalisation' of their drug treatment on both epilepsy and behaviour. Anticonvulsant drugs were modified to provide the best seizure control with the lowest toxicity, and psychotropic drugs also were monitored and modified if necessary to obtain the best results. At the end of the follow-up period the number of anti-epileptic drugs had fallen from 1.84 to 1.05 per patient. On admission to the study 47 patients were being treated with 85 psychotropic drugs: at the end of the follow-up 44 patients were taking 63 drugs. Seizures were significantly reduced in 16 of 39 patients with unsatisfactory control on admission to the study. Among 41 patients with initial satisfactory control, only 16 had relapse of seizures. Behavior did not change significantly.

[Neurologic diseases, mental retardation and reduction in work capacity]. / Malattie neurologiche, ritardo mentale e riduzione della capacità di lavoro.

The reduction of working ability, because of disease, was considered in 1,053 subjects. 21 groups of maladies were found; the neurological disease and mental retardation (MR) caused various degrees of working inability in 416 subjects, i.e. in the 39.51% of the examined population; orthopaedic changes affected the 15.57% of the patients; psychic disorders determined some inability in 8.93% of the persons. The subjects unable to work receive, by Law, an economic help. This study was limited to neurological patients and to subjects mentally retarded. The working ability was reduced by 5 types of disturbances: neuromotor pathology, mental retardation, mental deterioration and dementia, epilepsy, other neurological diseases. The neuromotor pathology affected 163 subjects; the types of symptomatology: hemiplegia; it was found in 71 patients; 62 times it was the result of cerebrovascular disease; in 4 patients it was caused by a hypoxic-ischaemic pre-perinatal encephalopathy. 43 patients affected by cerebrovascular disease lost their personal autonomy, i.e. they could no longer do the activities of daily living (ADL); 7 patients lost their working ability; 12 subjects kept some ability to work. The hemiplegias which struck after 50 years of age were caused by cerebrovascular disease; paraplegia: 28 paraplegic patients have been seen; the aetiology was: poliomyelitis in 8 subjects; MS in 5 patients; ALS in 2 patients; in 13 patients the aetiology was unknown. 6 patients resulted unable to work; 8 persons kept some working ability; 14 patients lost the ability to do the ADL; tetraplegia, or double/bilateral hemiplegia, was found in 20 patients; the aetiology: poliomyelitis in 4 patients; pre-perinatal hypoxic ischaemic encephalopathy in 4 patients; 3 patients of MS; lesion of the cervical spinal cord because of breech delivery in 2 patients; the aetiology was not known in 7 persons. The ability to do the ADL was lost in 17 patients; 3 subjects kept some working ability. Double or bilateral hemiplegia (Little disease) was the model of neuromotor deficit subsequent natal encephalopathy (Infantile Cerebral Palsy, PCI); brachial plexus paralysis was only found from obstetrical (i.e. natal) origin; poliomyelitis and PKU resulted prevented as of 10 years. Mental Retardation (MR) was considered a borderline pathology between neurology and psychiatry; it included 162 subjects: in patients with severe MR a pre-perinatal hypoxic-ischaemic encephalopathy was found in 40.4% of the cases; in patients affected by moderate or light MR the same encephalopathy was found in the 11.3% of the subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

Intractable epilepsies. An open trial with Clobazam.

Clobazam was used as an added treatment in 28 patients with intractable epilepsies: 26 subjects had associated handicaps. A good response was observed during the first two-three months of Clobazam treatment: the reduction in seizure frequency of 73% for partial seizures and 62% for GTCs. A tolerance to Clobazam treatment was observed after the third month of treatment: at the end of the sixth month, the seizure frequency was reduced to 36% for partial seizures and 39% for GTCs. Out of 28 patients 4 were seizure free at the end of the sixth month; we have not found any specific characteristic in these patients. The AA. suggest the possibility of an intermittent use of Clobazam for this type of patients.