[Sternal metastasis disclosing hepatocarcinoma].
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Biomedical subjects
Publications and source records attributed to A Lortholary.
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Elderly patients are often considered as subjects at risk for bad tolerance to chemotherapy. They are therefore treated in a less aggressive way compared with younger women. In a retrospective study, we evaluated the dose-intensity of a chemotherapy for 15 patients older than 70 years of age, presenting an ovarian carcinoma. Median age was 73 years. All but one were classified in stage III-IV and only four were presented with a complete surgery or with a pathological residue < 2 cm. Six patients were considered as non operable. Performance status (PS) was in 11 cases equal to 0 or 1. The treatment associated from D1 to D4: carboplatine 75 mg/sqm/day, cyclophosphamide 250 mg/sqm/day, etoposide 50 mg/sqm/day for six cycles each over four weeks. We compared for each drug the delivered dose-intensity (DID) all along the six cycles to the forecast dose-intensity (FID). Except for the patients with a PS > or = 2, treated in first intention by a 2/3 dose, the DID/FID ratio was > 90%. It decreased between the 1st and 3rd cycles, then remained unchanged. Treatment was well tolerated by patients with a PS < 2 whose 4/11 have presented a grade III-IV hematologic toxicity. In return, despite the initial dose reduction, 3/4 patients with a PS > or = 2 had severe complications. There were no toxic deaths. Three patients only had a delay for reinduction. Three out of six non operables at first had a surgical second-look with possibility of residual masses cutting of (3 PRh). Four patients were alive in first CR at 18, 22, 23 and 28 months. Women older than 70 years with a good performance status presenting an ovarian carcinoma can be treated as younger women are. A chemotherapy using efficient drugs can be delivered with an acceptable toxicity and a high dose-intensity.
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PURPOSE: The platinum concentration in plasma was studied in 19 patients treated by 3 or 4 successive courses of chemotherapy including cisplatin for head and neck cancers. METHODS: Cisplatin was given i.v. daily at 25 mg/m2 by 1-h infusions for 4 days every 3 weeks. Total and ultrafiltrable platinum were measured in plasma using an inductively coupled plasma mass spectrometry (ICPMS) technique. RESULTS: A progressive accumulation of total platinum in plasma was observed with consecutive infusions. The mean (+/- SD) total plasma platinum level detected at the end of cisplatin infusion was 1134 +/- 234, 1407 +/- 268, and 1618 +/- 282 micrograms/l at the end of the first, second, and third courses, respectively. The minimal platinum concentration measured before the second and third courses also increased to 221 +/- 59 and 309 +/- 76 micrograms/l, respectively. The steady state was not reached before the third course. However, differences in the evolution of platinum plasma levels were found among the 19 patients. In 14 patients the pharmacokinetics of platinum was characterized by low initial levels, a progressive accumulation, and a long terminal half-life with a very late steady state. In 5 patients, the pharmacokinetic behavior of platinum was different: platinum levels were directly high, without progressive accumulation, the steady state being reached as early as the first course. Significant levels of ultrafiltrable platinum were found throughout the treatment, even during the intervals between courses with this very sensitive analytical method. A close equilibrium between ultrafiltrable and total platinum (ratio, 6%) persisted for as long as 3 weeks after cisplatin administration. DISCUSSION: These results underline the importance of individual differences in platinum metabolism. The relationship between total and ultrafiltrable platinum are discussed.
Hypercalcemia of malignancy is due either to local osteolysis at the site of bone metastases or to production by the malignancy of parathyroid hormone-related peptide, which shares some of the effects of parathyroid hormone. We used a radioimmunoassay (antiserum specific to the amino-terminus) to measure serum parathyroid hormone-related peptide levels in controls (n = 61), chronic renal failure patients (n = 10), patients with primary hyperparathyroidism (n = 19), cancer patients with (n = 35) or without (n = 57) hypercalcemia and/or bone metastases (n = 53 and n = 39, respectively), and patients with hematologic malignancies (n = 15). We set the upper limit of normal of the parathyroid hormone-related peptide assay at 2.7 pmol/L. The peptide was undetectable in two-thirds of healthy controls. Renal failure did not interfere with the assay. Eighteen of the 19 patients with primary hyperparathyroidism had normal levels. In contrast, 82% of patients with humoral hypercalcemia of malignancy (i.e., without detectable bone metastases) had increased levels; in this subgroup there was a significant inverse correlation between serum levels of the peptide and phosphorus. Elevation of parathyroid hormone-related peptide levels was less common among hypercalcemic patients with metastatic bone disease (38%). Four of the seven hypercalcemic patients with hematologic malignancies had elevated parathyroid hormone-related peptide levels. In our overall study population, serum calcium levels were weakly but significantly correlated with parathyroid hormone-related peptide levels. In conclusion, elevated parathyroid hormone-related peptide in a patient with hypercalcemia suggests a malignant disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Measurement of parathyroid hormone-related peptide (PTHrP) associated with that of parathyroid hormone, allows to establish, in most cases, diagnosis of hypercalcemia of malignancy and more exactly of patients with Malignancy Humoral Hypercalcemia (MHH). Because of the variety of molecular forms of PTHrP, linked to its catabolism, its immunoassay remains difficult. After a study evaluating the methodological reliability, we measured the contribution of PTHrP to the hypercalcemia by 2 assays: a N-terminal RIA and a 1-72 IRMA in samples from 47 control subjects, 10 patients with chronic renal failure (IRC), 13 patients with primary hyperparathyroidism (HPT), and 48 patients with solid tumors classified by their level of calcemia: 48 normocalcemia and 23 hypercalcemia. We noted a strong correlation (r = 0.92) between the two assays. They do not show increases in renal insufficiency; they have a good diagnostic discrimination between HPT, normal subjects and patients with MHH. Elevated levels of PTHrP are similar in both assays. However, IRMA appears to be more sensitive and more practical than RIA. Moreover, it shows the best correlation between serum calcium and phosphorus in patients with MHH.
Percutaneous implantation sites were used by the same operator in 141 patients (87 females and 54 males) with usually metastatic cancer. A titanium Districath implantable chamber and a 1.1 mm inner diameter silicone catheter were used. Percutaneous venous access was via the subclavian vein in 139 cases (98.6%). Mandatory safety measures were emphasized. Insertion was complicated by puncture of the subclavian artery in 6 cases (4.2%). There were no case with abscess, disunion, infection or death due to the method. The chamber was removed in 7 cases due to: 3 ruptures of the catheter, 2 septicaemias, 1 rejection reaction and 1 psychological intolerance. In our series, percutaneous implantation via the subclavian vein has been a reliable and rapid technique with little morbidity.
Having found, in the same medical centre, an abnormally high (15%) frequency of bone metastases from colorectal carcinoma, the authors report a series of 8 cases and review what is now known of this reputed rare (4%) metastases. Their clinical and imaging features are not very different from secondary bone lesions of other origins. They usually appear approximately 5 years after the primary tumour has been diagnosed; and they are rarely isolated, being part of a diffuse metastatic disease; their prognosis is in fact conditioned by visceral metastases (liver, lung, peritoneum). Concerning treatment, pain relieving radiotherapy is crucial, as witnesses by the authors. Chemotherapy must always be prescribed for its proven effectiveness against visceral lesions. The other medicinal treatments (e.g. analgesics, bisphosphonates) are very useful. Surgery must be reserved to emergency situations (spinal cord compression) and to patients in good general condition. To our 8 patients these treatments brought comfort and increased survival. Survivals of at least 6 to 9 months were obtained, and one patient is still alive 14 months after the diagnosis of bone metastasis. These results compare favourably with the 4 months median survival observed in other series.
Although not rare, paraneoplastic syndromes develop in a minority of cancer patients. Their exact frequency seems to be underestimated. These syndromes are hereby described. Their clinical usefulness is of great importance: they can be the first sign of a malignancy and can be used as tumor markers. The diagnosis of paraneoplastic syndromes is often difficult. A "diagnosis score" is proposed in order to make the diagnosis easier.
Although not rare, paraneoplastic syndromes develop in a minority of cancer patients. Their exact frequency seems to be under estimated. These syndromes are hereby described. Their clinical usefulness is of great importance: they can be the first sign of a malignancy and can be used as tumor markers. The diagnosis of paraneoplastic syndromes is often difficult. A "diagnosis score" is proposed to establish this diagnosis easier.
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We report a case of severe hypercalcaemia in a 16-year-old patient, 24 weeks after immobilization for quadriplegia. The biochemical and histomorphometric parameters showed increased osteoclastic resorption and decreased osteoblastic formation. Hydration, chair sitting, salmon and porcine calcitonin, sodium etidronate were unable to normalize the hypercalcaemia. The new antiosteoclastic agent, 3-amino-1 hydroxypropylidene-1, 1-bisphosphonate (AHPrBP), was effective in normalizing serum calcium and biochemical parameters of osteoclastic activity within five days. Bone histomorphometry showed a marked reduction in osteoclastic activity after AHPrBP treatment, as well as a drastic depression of osteoblastic activity, presumably due to the reduction of bone turnover. This case represents to our knowledge, the first successful use of AHPrBP in the treatment of immobilization hypercalcaemia.
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Cutaneous neuroendocrine carcinoma (CNEC) is a rare tumour. We report the case of a 75-year old woman affected with a rapidly progressive CNEC of the right cheek which kept recurring despite surgical excision followed by radiotherapy. The clinical features of CNEC are not specific. The tumour is located in the dermis, and the tumoral cells (Merkel cells) have a monotonous appearance. Gould's classification of these carcinomas into three types has a prognostic value. Immunohistochemistry is a mandatory complement to light microscope examination. It is very difficult to distinguish between CNEC and metastasis from a visceral small cell carcinoma. Treatment consists of surgery combined with radiotherapy. Chemotherapy was very successful in our patient and should be considered in other cases.
Three-quarters of breast carcinomas at an advanced stage display metastases, usually of the osteolytic type. Osteolysis results from a predominant increase of osteoclastic activity stimulated by humoral or local factors secreted by cancerous cells. Bisphosphonates interfere with osteoclasts and therefore can reduce the osteolysis. These compounds act through three main mechanisms: physico-chemical inhibition of bone crystal, cytostatic effect on osteoclasts, and in the case of pamidronate, direct or indirect action on the mononucleate precursors of osteoclasts. Three bisphosphonates are now available: etidronate, clodronate and pamidronate. Ten published studies report on their use in breast carcinoma with osteolytic metastases, and without hypercalceamia. Four studies concern clodronate in 54 patients, and six studies concern pamidronate in 128 patients. Intravenous pamidronate seems to be the more effective of the two, with densification of the lytic areas in 25% of the cases. All studies mention a decrease of pain, risk of fracture, hypercalcaemia and new metastatic locations. Side-effects are minimal. Controlled studies are needed to confirm the position of bisphosphonates in the management of malignant osteolysis.
We report a case of aseptic meningoencephalitis induced by ibuprofen (Brufen) in a 24-year old unmarried woman with unrecognized systemic lupus erythematosus. The neurological manifestations induced by ibuprofen revealed the systemic disease. Clinicians confronted with aseptic meningitis or meningoencephalitis developed after treatment with a non-steroidal anti-inflammatory drug, notably ibuprofen, should investigate for systemic disease.