Metástasis en región maxilofacial de carcinoma renal: serie de casos / Renal Cell Carcinoma metastases in the maxillofacial area: Case series

El carcinoma renal es un tumor de evolución imprevisible. A veces las metástasis son el debut de la enfermedad, mientras que en otras, éstas se manifiestan años tras el tratamiento del primario. Se presentan 4 casos clínicos de metástasis atípicas de carcinoma renal en región de cabeza y cuello: glándula parótida, hueso mandibular, encía adherida molar y espacio masticador. Se revisa la fisiopatología, clínica, histología y manejo del cáncer renal metastásico en esas localizaciones

Renal cell carcinoma is an unpredictable malignancy. Sometimes, metastases are the disease debut. On the other hand, metastases could present years after treatment of the primary tumor. Four clinical cases of atypical metastases in the head and neck location are presented: parotid gland, mandibular bone, attached molar gingiva and masticator space. Physiopathology, clinics, histology and management of metastatic renal cell carcinoma at those anatomical regions are reviewed

Factors limiting the species richness of bees in Saharan Africa.

There is a severe shortage of knowledge of bee biogeography. Some former studies have highlighted a link between bee diversity and xeric ecosystems, but we know practically nothing of the macro-ecological factors driving bee diversity. The present study aims to analyse the main macro-ecological factors driving bee species-richness in the Saharan region. Our dataset includes 25,000+ records for localities in Africa, between 37 degrees and 10 degrees N. Maps and GIS were used to get a first overview of the distribution of the studied taxa. Partial least squares analysis (PLS) was used to study the impact of a set of ecological factors on the bee species richness (SR). The mapping highlighted the clustering of the highest bee SR values in some parts of the Saharan area (e.g. Maghreb, western Africa). In Central Sahara, there is an obvious topological coincidence of the high SR, the local mountain chains and the inland waters. The PLS helped to quantify the relationships between bee SR and a set of eco-climatic variables. It also highlighted a residual variance not explained by the considered descriptors. Our results recover the tight link between bee SR and xeric ecosystems. They also suggest that, within these ecosystems, bee SR is driven by an optimum of the energy-water balance (on which adjustment is allowed by the above gradients).

Keeping data continuous when analyzing the prognostic impact of a tumor marker: an example with cathepsin D in breast cancer.

The prognostic value of cathepsin D has been recently recognized, but as many quantitative tumor markers, its clinical use remains unclear partly because of methodological issues in defining cut-off values. Guidelines have been proposed for analyzing quantitative prognostic factors, underlining the need for keeping data continuous, instead of categorizing them. Flexible approaches, parametric and non-parametric, have been proposed in order to improve the knowledge of the functional form relating a continuous factor to the risk. We studied the prognostic value of cathepsin D in a retrospective hospital cohort of 771 patients with breast cancer, and focused our overall survival analysis, based on the Cox regression, on two flexible approaches: smoothing splines and fractional polynomials. We also determined a cut-off value from the maximum likelihood estimate of a threshold model. These different approaches complemented each other for (1) identifying the functional form relating cathepsin D to the risk, and obtaining a cut-off value and (2) optimizing the adjustment for complex covariate like age at diagnosis in the final multivariate Cox model. We found a significant increase in the death rate, reaching 70% with a doubling of the level of cathepsin D, after the threshold of 37.5 pmol mg(-1). The proper prognostic impact of this marker could be confirmed and a methodology providing appropriate ways to use markers in clinical practice was proposed.

Assessment of tumour response to chemotherapy for metastatic colorectal cancer: accuracy of the RECIST criteria.

Evaluation of tumour size modifications in response to treatment is a critical issue in the management of advanced malignancies. In 1981, the World Health Organization (WHO) established guidelines for tumour response assessment. These WHO1981 criteria were recently simplified in a revised version, named RECIST (Response Evaluation Criteria in Solid Tumours), which uses unidimensional instead of bidimensional measurements, a reduced number of measured lesions, withdrawal of the progression criteria based on isolated increase of a single lesion, and different shrinkage threshold for definitions of tumour response and progression. In order to validate these new guidelines, we have compared results obtained with both classifications in a prospective series of 91 patients receiving chemotherapy for metastatic colorectal cancer. Data from iterative tomographic measurements were fully recorded and reviewed by an expert panel. The overall response and progression rates according to the WHO1981 criteria were 19% and 58%, respectively. Using RECIST criteria, 16 patients were reclassified in a more favourable subgroup, the overall response rate being 28% and the progression rate 45% (non-weighted kappa concordance test 0.72). When isolated increase of a single measurable lesion is not taken into account for progression with the WHO1981 criteria, only 7 patients were reclassified and the kappa test was satisfying, i.e. > or =0.75, for the whole population as well as for each of the responding and progressive subgroups. Since it provides concordant results with a simplified method, the use of RECIST criteria is recommended for evaluation of treatment efficacy in clinical trials and routine practice.

Primary thyroid lymphoma is a heterogeneous disease.

We retrospectively analyzed 26 patients with thyroid lymphoma (TL). Patients were mostly females, with a median age of 59 yr, presenting a rapidly growing nodular goiter with or without cervical adenopathy, without symptoms related to lymphoma for 81% and hypothyroidism in 61%. A previous history of Hashimoto thyroiditis was observed in 11 patients. Six different subtypes of lymphoma were observed: 13 of 26 (50%) had diffuse large B cell lymphoma, 6 (23%) mucosa- associated lymphoid tissue (MALT) lymphoma, 3 (12%) had follicular lymphoma, 2 (7%) had Hodgkin's disease, 1 (4%) had small lymphocytic lymphoma, and 1 (4%) had Burkitt's lymphoma. Diffuse large B cell lymphoma patients presented a compressive multinodular goiter, cervical adenopathy (66%), disseminated disease (50%), and poor performance status, with a poor prognosis (5-yr survival at 44%) despite a treatment based on a multidrug regimen. MALT lymphoma arose in patients with previous history of Hashimoto disease, was localized in all but 1, and was biologically associated with hypothyroidism and a high level of serum antithyroid antibodies. With total thyroidectomy, prognosis was good (5-yr survival at 100%). We did not find any routine clinical or biological parameters that could predict the evolution from Hashimoto's thyroiditis to MALT lymphoma. In conclusion, we confirmed the histological heterogeneity of TL corresponding to different clinical presentations and different prognoses.

Physical and biological dosimetry in patients undergoing radiosynoviorthesis with erbium-169 and rhenium-186.

Physical and biological dosimetry were investigated in 45 rheumatoid arthritis patients treated by radiosynoviorthesis (RSO) with 186Re-sulphide (medium-sized joints) and 169Er-citrate (digital joints). Biological dosimetry involved scoring dicentrics in lymphocytes, cultured from blood samples withdrawn just before and 6 h, 24 h and 7 days after treatment. Physical methods included repeated blood sample counts and scintigraphy data. For erbium-169 (pure beta emitter), only bremsstrahlung could be measured and solely in the injection area. For rhenium-186 (both beta and gamma emitter), whole body scans and static images of joints and locoregional lymph nodes were performed. Dosimetry calculations were in accordance with the MIRDOSE 3 software and tables. For erbium-169 (21 patients), either metacarpophalangeal (30 MBq) or proximal interphalangeal (20 MBq) joints of the hands were treated (one joint per patient); 18 patients (out of 21) were interpretable for biological dosimetry, 10 (out of 11) for physical dosimetry and six (out of 10) for both. For rhenium-186, 23 wrists, nine elbows, three shoulders and two ankles were injected in 24 patients, with a maximum of three joints per patient (70 MBq per joint); 20 patients (out of 24) and 10 (out of 10) were interpretable for biological and physical dosimetry, respectively, and eight (out of 10) for both methods. Erbium-169 biological dosimetry was negative in all interpretable patients, and physical dosimetry gave a blood dose of 15 +/- 29 microGy and an effective dose lower than 1 mSv/30 MBq. For rhenium-186, biological results were negative in 16 patients (out of 20), but showed a blood irradiation around 200 mGy in the last four. A significant cumulative increase of dicentrics 7 days after injection (16/10,000 instead of 5/10,000 prior to treatment; p < 0.04) was also noted. Gamma counts gave a blood dose of 23.9 +/- 19.8 mGy/70 MBq and the effective dose was found to be 26.7 +/- 5.1 mGy/70 MBq, i.e. about 380 microGy.MBq-1. Erbium-169 RSO is very safe from both physical and biological dosimetry standpoints. Rhenium-186 leak is greater, as demonstrated by the higher blood activity and the measurable, although limited, dicentrics induction in blood lymphocytes. However, the effective dose remains moderate, i.e. 30 times lower than in 131I therapy in benign thyroid diseases.

Tissue extraction procedures for investigation of urokinase plasminogen activator (uPA) and its inhibitors PAI-1 and PAI-2 in human breast carcinomas.

Urokinase type plasminogen activator (uPA) and its inhibitors, plasminogen activator inhibitor type I (PAI-1) and type II (PAI-2), are supposed to be involved in the expression of the invasive and metastatic phenotype of cancer cells. However, clinical investigations on the prognostic significance of their levels in tumor tissue are difficult to realize because of the absence of a convenient method of measurement of these parameters. The aim of the present investigation was to set up a method allowing the measurement of these enzymes and of sex steroid receptor status in appropriate subcellular fraction(s) in conditions easily reproducible in routine. We found that a tissue homogenate prepared according to the method recommended [5] for current measurement of sex steroid receptors is appropriate for further distinct preparations. One aliquot is used for cytosol preparation; another can be treated by 2% Triton X-100 (vol/vol) and provide an extract containing the totality of uPA and PAI-1. The advantage of this procedure is that appropriate subcellular fractions can be derived from a unique homogenization step. Total uPA and PAI-1 are measured in a Triton extract with good performance as compared to previous investigations [4]. PAI-2 is measured in the same cytosol fraction used for sex steroid receptors and other parameters. Because of its simplicity and its high reliability, this method could be a useful tool in the investigation of uPA family proteases and analysis of their prognostic significance in early breast tumors.

Viral inactivation of human bone tissue using supercritical fluid extraction.

A new bone tissue process using supercritical carbon dioxide fluid extraction (SFE) has been evaluated for its ability to inactivate or eliminate viruses. Four viruses, human immunodeficiency virus type 1 (HIV-1), Sindbis virus, polio Sabin type I virus, and pseudorabies virus (PRV), were exposed to four different processing steps. In addition to supercritical CO2, hydrogen peroxide, sodium hydroxide, and ethanol treatments were evaluated. The mean cumulated reduction factors (log10) for the four viruses exposed to these four steps were > 14.2 for HIV-1, > 18.2 for Sindbis virus, > 24.4 for poliovirus, and > 17.6 for PRV. The mean reduction factors obtained by the supercritical fluid extraction alone were > 4.0, > 4.3, > 6.6, and > 4.0, respectively. These results demonstrate that the SFE process is effective in inactivating viruses on human femoral heads, and provides a level of inactivation similar to that obtained by traditional cleaning methods. It is proposed that CO2 SFE be incorporated as a routine step in the processing of bone allografts for transplantation either to replace or supplement existing procedures.

Prognostic significance of TNF alpha and its p55 soluble receptor in malignant lymphomas.

In 93 newly diagnosed lymphoma patients, tumor necrosis factor alpha (TNF alpha) and its p55 soluble receptor (p55-sR), were prospectively determined in plasma by IRMA and ELISA methods respectively. These 93 patients included 31 patients with low grade lymphoma, 55 with intermediate or high grade lymphoma and 7 with Hodgkin's disease. Median TNF alpha plasma values were 20 pg/mL (range 5-380 pg/mL) in patients versus 7 pg/mL (range 4-9 pg/mL) in healthy control subjects. Presence of TNF alpha level equal or greater than 20 pg/mL was significantly associated with elevated LDH level, serum beta 2-microglobulin level > or = 3 mg/L, hemoglobin < or = 12 g/dL, Ann Arbor stage III or IV disease, and with bulky tumor. High level of TNF alpha was also associated, although less strongly, with B symptoms, poor performance status, and serum albumin < or = 35 g/L, yet it was not associated with change in acute phase protein levels. Levels of p55-sR were also markedly elevated in these lymphoma patients (median of 3.5 ng/mL, range 0.8-18.8 ng/mL) versus 1.45 ng/mL in control subjects (range 1.1-2.3 ng/mL). Level of p55-sR equal or greater than 3.5 ng/mL was significantly associated with poor performance status, B symptoms, beta 2-microglobulin levels > or = 3 mg/L, serum albumin < or = 35 g/L, C-reactive protein > 6 mg/L, hemoglobin < or = 12 g/dL, and bulky tumor. In the whole group of 93 patients, both high TNF alpha and p55-sR levels strongly predicted short freedom from progression and overall survival. This study suggests that elevated TNF alpha and p55-sR plasma levels have a high correlation with other adverse prognostic factors in lymphoma patients and predict their poor outcome.

Cytokine and hormonal changes after cholecystectomy. Effect of ibuprofen pretreatment.

OBJECTIVE: Surgical stress induces hormonal and cytokine responses proportional to the extent of the injury. Therefore, the authors assessed the effect of ibuprofen pretreatment on metabolic and hormonal changes after surgery. SUMMARY BACKGROUND DATA: Postoperative administration of cyclo-oxygenase inhibitor reduces cytokine production and nitrogen losses. METHODS: The authors studied the plasma hormones and metabolic and cytokines changes after perioperative ibuprofen administration in 22 patients undergoing cholecystectomy under inhalational anesthesia. Suppositories containing ibuprofen (500 mg) or placebo were administered 12 and 2 hours before surgery, and every 8 hours until the third postoperative day. Blood samples were collected 24 and 2 hours before surgery and 2, 4, 6, 24, 48, and 72 hours after surgery for glucose, C-reactive protein, leukocytes, adrenocorticotropic hormone (ACTH), cortisol, tumor necrosis factor, and interleukin-1 and interleukin-6 determinations. RESULTS: In both groups, plasma cortisol levels remained elevated for 3 days, whereas plasma ACTH levels returned to the basal level at day 1. The ACTH (p < 0.01), cortisol (p < 0.01), and glucose changes (p < 0.001) were smaller in the ibuprofen group and their duration was shorter. The interleukin-6 levels increased gradually after skin incision until the sixth hour and were significantly lower (p < 0.05) in the ibuprofen group. CONCLUSION: Ibuprofen pretreatment in perioperative course is able to reduce the endocrine response and cytokine release. Therefore, ibuprofen may be useful in decreasing the stress response in severely surgical patients.

Elevated circulating levels of TNFalpha and its p55 soluble receptor are associated with an adverse prognosis in lymphoma patients.

In 88 newly diagnosed lymphoma patients, tumour necrosis factor alpha (TNFalpha) and soluble TNF type I receptor (p55-R-TNF) were prospectively determined in plasma by immunoradiometric assay (IRMA) and ELISA methods respectively. These 88 patients included 19 with centrocyto-centroblastic lymphoma, 13 patients with other low-grade lymphoma, and 56 with high-grade lymphoma. Median TNFalpha plasma values were 20 pg/ml (range 5-380 pg/ml) in patients versus 7 pg/ml (range 4-9 pg/ml) in 20 healthy control subjects. Presence of TNFalpha level > or = 20 pg/ml was significantly associated with elevated LDH level (P<0.0001), serum beta2-microglobulin level > or = 3 mg/l (P<0.0001), haemoglobin < or = 12 g/dl (P=0.0001), Ann Arbor stage III or IV disease (P<0.005), and with bulky tumour (P=0.01). High level of TNFalpha was also associated with B symptoms (P<0.005), poor performance status (P<0.05), and serum albumin < or = 35 g/l (P<0.05). Levels of p55-R-TNF were also markedly elevated in these lymphoma patients (median of 3.5 ng/ml, range 0.8-18.8 ng/ml) versus 1.45 ng/ml in control subjects (range 1.1-2.3 ng/ml). Level of p55-R-TNF > or = 3.5 ng/ml was significantly associated with poor performance status (P<0.0001), B symptoms (P<0.0001), beta2-microglobulin levels > or = 3 mg/l (P<0.0001), serum albumin < or = 35 g/l (P=0.0001), C-reactive protein > 6 mg/l (P=0.0003), elevated (>20 pg/ml) IL-6 level (P<0.005), haemoglobin < or = 12 g/dl (P<0.005), and bulky tumour (P<0.001). In the whole group of 88 patients, both high TNFalpha and p55-R-TNF levels strongly predicted short progression-free survival (P<0.005 for both variables) and overall survival (P<0.001 and P<0.001 respectively). In multivariate analyses the elevation of p55-R-TNF retained a higher significance over the other variables and therefore improved the predictive value of the International Prognostic Index. This study suggests that elevated TNF gamma and p55-R-TNF levels have high correlation with other adverse prognostic factors in lymphoma patients and may predict a poor outcome.

Indirect parameters of pancreatic function in cystic fibrosis (CF) during a controlled double-blind trial of pancreatic supplementation.

During two treatment periods (4 weeks each), serum immunoreactive trypsin (IRT), immunoreactive human lipase in stool (IRL), and chymotrypsin (CT) activity in stool were determined in 16 cystic fibrosis patients and compared with fecal fat excretion (72-h sampling). Fecal fat estimation revealed mild to severe steatorrhea in all 16 patients (X = 13.7 +/- 9.0 g/24 h) in at least one study period. Stool fat excretion was highest in underweight adolescents and adults. Comparison of IRT and IRL with stool fat values showed no significant statistical correlation. IRT values revealed an inverse exponential correlation with age, with a steep decline at the age of 5 years. CT levels were very high in 14 of our 16 patients during supplementation therapy, whereas 2 patients showed subnormal CT values. We conclude that since indirect parameters of pancreatic function do not correlate with stool fat excretion, stool fat remains the best indirect parameter for the assessment of pancreatic insufficiency in cystic fibrosis. Leaving pancreatic enzyme supplementation in cystic fibrosis patients on the basis of normal serum trypsin or fecal lipase values does not appear to be adequate.

A specific immunoradiometric assay of cationic trypsin(ogen) that does not recognize trypsin-alpha-1-proteinase inhibitor complex.

An immunoradiometric assay using two monoclonal antibodies directed to human trypsin 1 was developed for measuring trypsin(ogen) in biological fluids. The assay is different from other assays in that it is specific for cationic trypsinogen and does not recognize the alpha-1-proteinase inhibitor-trypsin complex. It can be used as a complement to classical immunoassays to characterize trypsinogen activation in pathological cases. The evaluation and the specificity of the assay are presented.

Description of a human papillary thyroid carcinoma cell line. Morphologic study and expression of tumoral markers.

BACKGROUND: The establishment of cell lines from thyroid carcinomas can provide an in vitro model of oncogenesis. B-CPAP is a new cell line that has been obtained from a differentiated papillary thyroid carcinoma. The data presented give a broader characterization and expression of tumoral markers of this cell line and identify the differentiated functions that are preserved. METHODS: An ultrastructural study was performed to confirm the thyroid nature of the new cell line. The cellular markers (thyroglobulin, S100, neuron-specific enolase [NSE]) and the oncogenes (mutated p53, H-ras, c-myc, PTC, trk) were studied by immunohistochemistry, Southern blot, or in situ hybridization. RESULTS: The cells were of a differentiated ultrastructural thyroid type. All of the cells proved immunoreactive with antibodies specific to thyroglobulin, S100 proteins, NSE, and mutant p53 protein. Mutations of H-ras, PTC, and trk were not observed. The c-myc gene was not amplified. CONCLUSIONS: The cell line described in these data provides a suitable model for the study of thyroid carcinogenesis, given that the cells present thyroid characteristics, and metabolic disorders not previously found in such cell lines. In addition, the coexpression of S100 proteins and mutant p53 proteins in the cells should permit the study of the interaction between these two proteins.

Coagulation/fibrinolysis balance in septic shock related to cytokines and clinical state.

This study explored the relationship between cytokines (TNF, IL-1, IL-6), coagulation and fibrinolytic factors in the early stage of sepsis syndrome and the relation between these factors with the severity of inflammatory illness as measured by the Simplified Acute Physiology Score (SAPS). Twenty-one normal controls were compared to 34 patients divided into three categories ranging from uncomplicated postoperative patients, to patients with severe infectious conditions including septic shock. A major hemostatic imbalance was demonstrated with particularly marked reduction in fibrinolytic activity [drop of antithrombin III (ATIII) and protein C with an increase of plasminogen activator inhibitor (PAI-1) levels] which were directly correlated with the severity of the inflammatory state. Both ATIII and PAI-1 levels were correlated with the levels of TNF and IL-6 and the severity of illness as measured by SAPS. We established an index, ATIII/PAI-1 antigen that is significantly different among the four groups (p < 0.001) and strongly correlated with the SAPS (p < 0.001). As PAI-1 could be secreted not only by TNF activating endothelial cells but also by hepatocytes activated by insulinemia, treatment of sepsis with cytokine-specific agents might be of limited effect.

Cytokine production during intraperitoneal chemohyperthermia.

The aim of the present work is to investigate in vivo cytokine production during chemohyperthermia. 11 patients suffering from gastric adenocarcinoma (n = 6), ovarian adenocarcinoma (n = 4) or malignant mesothelioma (n = 1) were studied. Patients received 60 mg mitomycin or 100 mg cisplatin per square meter during 2 h in 6 liters of a heating solution (temperature 42 degrees C, flow rate 200 ml/min in a closed circuit) after previous surgical resection. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured at 0, 30, 45, 60 and 90 min, both in the blood stream and in the heating solution circulating intraperitoneally. We observed a slight increase in plasma IL-6 occurring as soon as 30 min, a dramatic rise in IL-6 in the heating solution. TNF-alpha values were only slightly augmented. In addition, the importance of various factors in the induction of IL-6 and TNF-alpha production during chemohyperthermia (temperature, mitomycin C, cisplatin) were studied using a whole blood ex vivo model.

Detection of RET oncogene activation in human papillary thyroid carcinomas by in situ hybridisation.

We have recently reported the activation of a new oncogene in human papillary thyroid carcinomas. This oncogene, named PTC, is a novel rearranged version of the ret proto-oncogene. In fact PTC is the product of the fusion of the tyrosine kinase domain of the ret proto-oncogene with the 5'-terminal region of another gene that we have named H4. The ret proto-oncogene shows a pattern of expression restricted to neuroendocrine tissue. Its fusion with H4 allows the expression of the activated form in thyroid papillary carcinomas. Therefore the detection of ret transcripts is a tool to investigate ret activation in thyroid neoplasms. Here we show the detection by in situ hybridisation, of activated ret transcripts in human thyroid papillary neoplasms that were positive for PTC activation by Southern blot analysis. We did not find any ret transcripts in papillary carcinomas negative for PTC activation, nor in normal thyroid and in non-papillary thyroid neoplasias.

Serum N terminal procollagen III fragment: a predictive marker of joint destruction in rheumatoid arthritis?

The level of the N terminal fragment of procollagen III (P3NP) levels of 100 consecutive patients affected by rheumatoid arthritis (RA) were evaluated in comparison with disease activity markers (erythrocytes sedimentation rate, C reactive protein), immunological status (rheumatoid factors, immune complexes) and joint destruction (assessed according to the Steinbrocker index). P3NP levels showed no significant relationship either to disease activity or to immunological status; however, a strong association was fond between X-ray grade and P3NP values. A two-year retrospective study of 32 patients belonging to the original 100 patient population allowed us to assign a predictive value for joint destruction to the P3NP level in the early stage of the disease.