Fractal dimension of trabecular bone: comparison of three histomorphometric computed techniques for measuring the architectural two-dimensional complexity.

Trabecular bone has been reported as having two-dimensional (2-D) fractal characteristics at the histological level, a finding correlated with biomechanical properties. However, several fractal dimensions (D) are known and computational ways to obtain them vary considerably. This study compared three algorithms on the same series of bone biopsies, to obtain the Kolmogorov, Minkowski-Bouligand, and mass-radius fractal dimensions. The relationships with histomorphometric descriptors of the 2-D trabecular architecture were investigated. Bone biopsies were obtained from 148 osteoporotic male patients. Bone volume (BV/TV), trabecular characteristics (Tb.N, Tb.Sp, Tb.Th), strut analysis, star volumes (marrow spaces and trabeculae), inter-connectivity index, and Euler-Poincaré number were computed. The box-counting method was used to obtain the Kolmogorov dimension (D(k)), the dilatation method for the Minkowski-Bouligand dimension (D(MB)), and the sandbox for the mass-radius dimension (D(MR)) and lacunarity (L). Logarithmic relationships were observed between BV/TV and the fractal dimensions. The best correlation was obtained with D(MR) and the lowest with D(MB). Lacunarity was correlated with descriptors of the marrow cavities (ICI, star volume, Tb.Sp). Linear relationships were observed among the three fractal techniques which appeared highly correlated. A cluster analysis of all histomorphometric parameters provided a tree with three groups of descriptors: for trabeculae (Tb.Th, strut); for marrow cavities (Euler, ICI, Tb.Sp, star volume, L); and for the complexity of the network (Tb.N and the three D's). A sole fractal dimension cannot be used instead of the classic 2-D descriptors of architecture; D rather reflects the complexity of branching trabeculae. Computation time is also an important determinant when choosing one of these methods.

[Pelvic lymph node invasion in cancer of the uterine cervix]. / L'envahissement ganglionnaire pelvien dans les cancers du col utérin.

Pelvic lymph node invasion is an important prognostic factor for cervical cancer. It is generally accepted that iliac lymph nodes must be treated systematically, but the extent of lymph node dissections is open to discussion. One hundred and eighty two cases of cervical cancer with lymph node invasion were treated at the Institut Curie between 1960 and 1988, by colpohysterectomy with lymph node dissection (168 cases) combined with preoperative brachytherapy and, in some cases, pre- and/or postoperative radiotherapy; in 14 cases, only an exploratory operation was performed. External iliac lymph node invasion was found in 95% of cases, situated in the middle and internal chains. Common iliac lymph node invasion was found in 24% of cases, but was only exceptionally isolated (3%). It is therefore possible, by means of well defined, localized external iliac dissection, with frozen section histological examination, to determine the exact lymph node status. Lumboaortic lymph node invasion was found in 8.2% of cases. The overall survival rate was 49% at 5 years and 40.5% at 10 years. Factors which influence survival are: the cervical volume (p = 0.015), the unilateral or bilateral nature of invasion (p = 0.0015), the number of lymph nodes invaded (two or more than two) (p = 0.0001), capsular rupture (p = 0.0008), lymph node adhesions other than venous (p = 0.0002), common iliac invasion (p = 0.0001). On Cox's model, the principal factors were the number of lymph nodes invaded, adhesion other than venous, common iliac invasion; on the other hand, venous adhesion does not modify the prognosis. The five-year survival rates following external iliac dissections and complete pelvic dissections were not significantly different. Finally, postoperative radiotherapy ensured a higher five-year survival rate than preoperative radiotherapy, but the cervical volume was greater and primary invasion was more frequent in these cases. Postoperative radiotherapy of 15 grays after preoperative radiotherapy did not appear to modify the survival and therefore appears to be useless.

Phenotypic and functional analysis of tumour-infiltrating lymphocytes from patients with melanoma and other metastatic cancers.

Thirty tumour specimens, among which were 17 melanomas, were cultured with recombinant interleukin-2 (IL-2) in order to produce tumour-infiltrating lymphocytes (TIL). In the melanomas, three categories of TIL were characterised. The first, containing mostly CD3+ and CD8+ cells, lysed only autologous tumour cells; the second, containing mostly CD3+ and CD4+ cells, lysed both autologous tumour cells and allogeneic cells lines; the third, with mixed phenotype although cytotoxic for K562 targets, did not kill melanoma cells. The optimal conditions for a good development of TIL were established: we found that the lymph node or cutaneous origin of the tumour was unimportant, a 2 h enzymatic treatment was optimum and that TIL grew well in AIM V serum free medium. Therefore the easiness and the reproducibility of the TIL cultures from melanoma tumour samples allows the rapid development of therapeutic trials in metastatic melanoma.

[Conservative surgery after radiotherapy with preoperative doses in the treatment of breast cancer]. / Chirurgie conservatrice après radiothérapie à doses pré-opératoires dans le traitement des cancers du sein.

Radiotherapy as primary treatment is one of the means of increasing the rate of conservative treatment in patients with a breast tumour more than 3 cm in diameter. Between 1980 and 1986, 232 patients were treated in the Curie Institute by irradiation followed by conservative surgery for T2NO or T2N1a tumours wider than 3 cm, which accounted for 66 percent of the cases; 126 of these 232 tumours were located in the upper and outer quadrant. Axillary dissection was combined with tumoral excision in 63 percent of the cases. Conservative surgery was performed in patients who, after preoperative irradiation (50 Gy), had a persistent tumour less than 3 cm in diameter. Tumorectomy was complete in 96 percent of the cases, and the operative specimen was sterilized in 20 percent. The mean follow-up period was 46 months. The overall survival rate was 83 percent at 5 years (91 percent for T2NON1a). No local recurrence was observed in 92 percent of the patients at 3 years and 87 percent at 5 years. Nine percent of these women developed lymphoedema of the upper limb. The cosmetic result was good in 70 percent of the cases, fair in 25 percent and poor in 5 percent. The survival rate being the same with this treatment as with mastectomy, and the local recurrence rate being relatively low (13 percent at 5 years), we feel authorized to suggest that this post-radiotherapy conservative surgery should be used, at least in women with T2NON1a breast cancer.

[Lymphoceles and peritonization following lymphadenectomy for cancer of the uterus]. / Lymphocèles et péritonisation après lymphadénectomies pour cancers de l'utérus.

Pelvic lymphocysts following lymphadenectomy in the management of cervical and corporeal uterine carcinoma are recorded in one third of the cases and require surgery in 2-3% of cases. In order to prevent these lymphocysts, peritoneal suturing in front of the lymph node dissection area was progressively abandoned in order to allow peritoneal resorption of the lymph. A retrospective study analysed 226 iliac lymphadenectomies between 1982-1986 for uterine cancer treated at the Institut Curie. 220 patients received peritoneal suturing, while 46 patients were not sutured. The incidence of lymphocysts was respectively 35.9% and 17.4%. The difference is statistically significant (p = 0.01). The "no suture" technique lowered the incidence and the severity of lymphocysts. No side effect of the "no suture" technique was recorded. Multivariate analysis demonstrated that lymphocysts were significantly related to the side of the cancer in the cervix (p = 0.0001), to the preventive use of heparin (p = 0.0025) and to suturing the peritoneum with suction drainage (p = 0.004). We conclude that after pelvic lymphadenectomy the "no suture" technique for the peritoneum reduces the incidence of lymphocysts in the majority of patients.

[Conservative surgery after preoperative radiotherapy in the treatment of breast cancer. Indications and results]. / La chirurgie conservatrice après radiothérapie à doses préopératoires dans le traitement des cancers du sein. Indications et résultats.

From 1969 to 1983, 122 patients with unifocal breast cancer, equal or more than 3 centimeters in diameter, NON1a or N1b, were treated at the Institut Curie with conservative surgery after pre-operative external irradiation. Among them were 68% T2NON1a, and 26% N1b (with 21% T2N1b); 80% of the tumors were located in the upper part of the breast. Initial radiotherapy with a moderate dose (50 to 55 Gy for the breast and the lower axillary area) was followed 6 weeks later by a lumpectomy either alone (42 cases) or associated to an axillary node resection (80 cases). Five year survival rate with non evident disease T2NON1a cases is 79%, similar to the radical surgery rate in this group. We noted 8% local recurrences with no axillary recurrences. Post operative courses were a little more troubled than with initial lumpectomy. We noted 8% of upper limb oedema, only in patients who received both radiotherapy and surgery in the axilla. Cosmetic results are good in 65% of the cases, while they are good in 80% for initial lumpectomy. So this therapeutic method gives satisfactory results, but we need more cases with a longer follow-up to draw definitive conclusions.

[D-penicillamine induced myasthenic syndromes in rheumatoid arthritis. Two cases (author's transl)]. / Syndromes myasthéniques induits par la D-pénicillamine au cours de la polyarthrite rhumatoïde. Deux observations.

The authors report on 2 personal cases, and review 48 published cases of myasthenia induced by D-penicillamine (D-P) treatment in patients with rheumatoid arthritis. The clinical symptoms were not different from those of myasthenia gravis, and no correlation could be found between the total cumulative dose of D-P and the onset on the myasthenic syndrome. In 71% of the patients the neurological deficiency regressed after D-P was withdrawn, but in some cases anticholinesterase treatment had to be continued and thymectomy was contemplated. The most remarkable biological abnormalities were anti-striational antibodies (found in 58% of the cases) and anti-acetylcholine receptors antibodies (found in 4 out of 7 patients tested). These findings are in favour of a genuine myasthenia and against a myasthenic syndrome due to neuro-muscular blockade. While the mechanisms underlying the emergence of these antibodies remains unknown, their presence throws new light on immunological disorders in rheumatoid arthritis.

[Ionized fluorine in the plasma and urine of subjects treated with organofluorine drugs prescribed in rheumatology]. / Fluor ionisé dans le plasma et dans les urines de sujets traités par des médicaments organofluorés prescrits en rhumatologie.

The elimination of ionized urinary fluorine was studied in groups of eight subjects treated during several days with niflumic acid, flufenamic acid, sulindac, antrafenine and floctafenine. Sulindac and floctafenine do not changes this elimination. After administration of niflumic acid, flufenamic and antrafenine, the urinary elimination of ionized fluorine increase in all the subjects. This increase is manifested from the start of treatment and persists for several days after it has been stopped. The administration of three drugs also results in an elevated level of ionized plasmic fluorine the duration of treatment. The results prove the existence in the human organism of a metabolic process capable of effecting the ionization of the organic fluor contained in the drugs studied. This biotransformation causes a fluorine impregnation of endogenous origin that is permanent and relatively stable, and whose consequences are examined (risk of fluorine osteosis and possibility of therapeutic application).

[Fluorine osteosis caused by a very long-term niflumic acid treatment in 2 cases of rheumatoid arthritis]. / Ostéose fluorée secondaire à un traitement très prolongé par l'acide niflumique dans deux cas de polyarthrite rhumatoïde.

An osteosclerosis opacifying the axial skeleton and affecting in particular all of the spine, was observed in two women aged 75 and 42 years who had been suffering from a rheumatoid arthritis developing between 15 and 26 years. It was traced to a chronic fluorine intoxication, stemming from the regular taking, for 10 years and 8 1/2 years, of a non cortisone, anti-inflammatory niflumic acid. This fluorine product has 3 atoms of fluor in its molecule (50.0 mg for a tablet of 250 mg). Its administration to control subjects proved the production of ionized fluor by way of the metabolism, and the accumulation of fluor in the organism. Rheumatoid polyarthritis and the prolonged corticotherapy (10 mg of prednisone per day for 21 years) cannot be dismissed as the origin of the severe demineralization of the limbs observed in the second patient, but the role of fluorine seems marked in the occurrence of this peripheral involvement with problems of mineralization and secondary hyperparathyroidisms. On the other hand, the absence of an intervertebral narrowing in the 2 patients, despite the very prolonged taking of cortisone (5 mg of prednisone per day for 15 years, for the 75-year-old patient) is perhaps a result of the fluorine.

[Vitamin-resistant osteomalacias of hepatic origin in the adult]. / Les ostéomalacies vitamino-résistantes d'origine hépatique de l'adulte.

The authors report two cases of vitamin resistant osteomalacia in an adult connected with an apparent inability of the liver to hydroxylate vitamin D. One of the cases showed a case of pseudo-hypo parathyroidism of type II, reversible by the administration of calcium. The other case demonstrated vertebral hyperossification. Treated with 25 hydroxycholecalciferol in physiological dosage an improvement in the clinical, biochemical and histological states resulted.