De novo malignancies in liver transplantation.
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Biomedical subjects
Publications and source records attributed to F Pons.
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INTRODUCTION: Although chronic renal dysfunction (CRD) is a common complication among patients undergoing liver transplantation (OLT) its prevalence, risk factors, and impact on outcome have not been well defined. We aimed to assess the incidence of CRD, its associated risk factors and its impact on outcome. PATIENTS AND METHODS: The cohort of 289 consecutive adult first liver transplant patients with posttransplant follow-up longer than 6 months received cyclosporine in 230 patients (153 oil-based and 81 microemulsion formulation), tacrolimus in 55. CRD was defined as serum creatinine levels greater than 1.3 mg/dL for more than 6 months. RESULTS: After a mean follow-up of 67 months, 138 patients (47.8%) displayed CRD. The prevalence of CRD was 30.9%, 41.5%, and 38.9% at 1, 5, and 13 years after OLT, respectively. Twelve patients (4.1%) developed end-stage renal failure. Male gender, older recipient age, pretransplant renal dysfunction and hyperuricemia, posttransplant in-hospital renal dysfunction and hyperuricemia, and renal dysfunction during the first 6 months after OLT were each significantly associated with the development of CRD. Survival was significantly lower (63%) among liver transplant patients with CRD than those without this complication (71%, P=.024). CONCLUSIONS: CRD is an important cause of morbidity after OLT, although end-stage renal disease is infrequent. Because early renal dysfunction is associated with the development of CRD, and decreased long-term patient survival, efforts should be made to avoid early renal dysfunction after liver transplantation.
Water-in-fluorocarbon reverse emulsions and microemulsions stabilized by semi-fluorinated amphiphiles derived from the dimorpholinophosphate polar head group, C(n)F(2n+1)(CH(2))(m)OP(O)[N(CH(2)CH(2))(2)O](2) (FnHmDMP), are being investigated as new delivery systems for drugs or genetic materials into the lung. Since information related to the toxicity of fluorinated surfactants is still very limited, we evaluated herein the cytotoxicity of a series of FnHmDMP (n=4, 6, 8 and 10 and m=2, 5, and 11). Both solutions of FnHmDMP in fluorocarbons, and reverse water-in-fluorocarbon emulsions stabilized by FnHmDMP were assessed in order to determine the relation between surfactant structure and cell toxicity, and select the most innocuous emulsifier. A first short-term evaluation on mouse fibroblasts using a viability/cytotoxicity assay indicated that amphiphiles (in solution) with a chain length longer than C12 exhibit less toxicity than amphiphiles with shorter chain. Moreover cytotoxicity decreased also with length of the fluorinated segment. The protective effect of the fluorinated chain was strongly supported by the fact that the hydrogenated analog, C(15)H(31)OP(O)[N(CH(2)CH(2))(2)O](2) (H15DMP), was highly toxic. Qualitative evaluation on human lung epithelial cells (HLEC) using a colorimetric method (Mayer's hematoxylin) confirmed that amphiphiles (in solution) with longer chain were the least cytotoxic. The protective effect of the fluorinated chain appeared, however, to be significant only at low amphiphile concentrations (0.1% w/v). In contrast, at higher concentrations (1% and 5% w/v), the total chain length was the determining factor. Quantitative evaluation of the least cytotoxic amphiphiles using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method then showed that F10H11DMP (in solution) was harmless until its solubility limit (1% w/v); cell growth was even enhanced due to improved oxygenation provided by the fluorocarbon phase. F8H11DMP exhibited some cytotoxicity at both 1% and 5% w/v, but the toxicity appeared to level off with concentration. Reverse water-in-perfluorooctyl bromide (PFOB) emulsions stabilized by either F10H11DMP or F8H11DMP were found to be non-cytotoxic. In conclusion, the present evaluation indicates that the cytotoxicity of FnHmDMP depends on both total and fluorinated amphiphile chain length, and leads us to select F8H11DMP and F10H11DMP as the less cytotoxic amphiphiles among a series of FnHmDMP compounds. Furthermore, water-in-fluorocarbon emulsions stabilized with F8H11DMP and F10H11DMP appeared to be non-cytotoxic towards HLEC in culture.
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In the congenital malformations of the front chest wall showing depression or protrusion, the cardiorespiratory disorders are inconstant and often not linked with the distortion. On the other hand psychoaffective repercussions are major in adolescents and young adults justifying recourse to surgery with morphological and aesthetic aiming. The authors present the technique of modelling sternochondroplasty by raising with osteosynthesis by slide fastener-handle of Martin-Borrelly, applied to the correction of congenital malformation of the front chest wall in young adult, both of protrusion (pectus carinatum), of thoraxes in funnel (pectus excavatum) types or of mixed types (pectus arcuatum). This surgical replanning intervention is carried out by under-mammary way and aims at reestablishing a normal anatomy of the front chest wall. It leads to a genuine wide sternochondrocostal volet, which is stabilised by a specific, multipurpose, adaptable and reliable osteosynthesis equipment. The results obtained on a series of 14 cases are good or excellent in 86% of the cases and stable over time in the absence of major complications. A good cooperation of the patient is essential to obtain a good result in particular via the continuation of musculation exercises after assembly consolidation, possibly associated with remote mammary plastic surgery in the event of hypoplasia or of associated mammary agenesia.
The adequate care of thoracic ballistic traumatisms implies a good preliminary knowledge of wounding agents, and of the principles governing lesion-based ballistic, in particular the role played by the meeting with an obstacle which modifies the ballistic behaviour of the projectile, with worsened wounding effects. Authors describe the principal types of involved projectiles and their wound profile applied to the thorax, while stressing the need to treat systematically the wound and not the weapon, and on the importance of the choice of the surgical exploration way of these lesions, which conditions, as from the initial stage, the later choices of the parietal closure and rebuilding methods. The importance of parietal disrepair is therefore an essential decisional factor in the assumption of responsibility and the definition of the therapeutic strategy of these casualties.
99mTc-Sestamibi identifies the presence of hyperfunctioning autonomous parathyroid glands in patients with secondary hyperparathyroidism (SHP). The objectives of this study were: (i) to evaluate the interdependence between biochemical markers of SHP and 99mTc-Sestamibi uptake; and (ii) to determine whether 99mTc-Sestamibi uptake could be efficiently predicted by any combination of the former variables. Double-phase parathyroid 99mTc-Sestamibi uptake and total serum calcium, phosphorus, intact parathormone, 25-OH vitamin D and 1,25(OH) vitamin D determinations were performed simultaneously in 74 patients (36 female, 38 male) with SHP. Planar images of the neck and upper thorax were obtained in anterior view, 15 min (early phase) and 120 min (delayed phase) after the injection of 740 MBq of 99mTc-Sestamibi. In each patient, a final parathyroid/thyroid (P/T) activity index was obtained by adding the results of the P/T index of all parathyroid lesions. There was a significant correlation between intact parathormone levels and delayed 99mTc-Sestamibi uptake ( r=0.656; P<0.01). Of all the variables, intact parathormone was the only significant predictor of delayed 99Tc-Sestamibi uptake ( r=0.487; P<0.001). Calcium, phosphorus, vitamin D metabolites, age, gender, time spent on haemodialysis and cause of chronic renal failure displayed no significant correlation with 99mTc-Sestamibi uptake. It can be concluded that 99mTc-Sestamibi uptake is a potential predictor of parathyroid function in SHP patients. Hence, 99mTc-Sestamibi scintigraphy could be useful to assess parathyroid function and in the clinical follow-up of these patients.
The major factor influencing scintigraphic detection of abnormal parathyroid glands seems to be their size. However, false-negative results have been reported in large glands while some very small adenomas have been identified. Other factors can influence 99mTc-MIBI and 99mTc-Tetrofosmin uptake and therefore the accurate detection of hyperfunctioning glands depends also on these. Increases in both perfusion and functional activity and targeting of abundant mitochondria-rich oxyphil cells seem to be relevant mechanisms of uptake. A relationship has been observed between the intensity of focal uptake in the parathyroid glands and the cell cycle phases for patients with secondary hyperparathyroidism. Higher uptake grades correlated with the active growing phase, showing that scintigraphy accurately reflects the functional status of the hyperplastic parathyroid glands. Serum calcium levels may modify radiotracer kinetics by influencing the membrane potential. In addition, P-glycoprotein or multidrug resistance (MDR) associated protein expression may play an important role in the false-negative results of parathyroid scintigraphy. If the lipophilic cationic radiotracers used in parathyroid scintigraphy are transported by the same mechanism as the anticancer drugs, they will be quickly eliminated from the parathyroid glands containing P-glycoprotein or MDR-related protein expression and the uptake in images will be negative. In parathyroid glands with no P-glycoprotein or MDR-related protein expression, the radiotracers remain in the cells, making it easier to detect them by scintigraphy.
Non-invasive imaging methods in the evaluation of chemotherapy response in malignant tumours are currently being explored. Standard Nuclear Medicine procedures seem to offer the clinician a promising tool in the management of those oncologic patients, who might benefit from chemotherapy. Early studies focused on the relationship between radionuclides used in tumour diagnosis and factors associated with multidrug resistance (MDR). The tumour expression of P-glycoprotein (Pgp) and multidrug resistance-related protein-1 expression (MRP) have been suggested as important factors in the failure of chemotherapy. Most studies found an association between Pgp levels and (99m)Tc-sestamibi ((99m)Tc-MIBI) or (99m)Tc-Tetrofosmin uptake ((99m)Tc-TF). Currently investigations in nuclear medicine oncology are focusing on the potential role of radionuclide imaging in the assessment of chemotherapy. Recent papers discuss the usefulness of radionuclides as (99m)Tc-MIBI and (99m)Tc-TF as non-invasive procedures to predict and to monitor therapy response in patients affected by malignant tumours treatable using chemotherapy. This chapter will review the latest development in (99m)Tc-TF, giving an overview of recent investigations carried out using this radiotracer in therapy oncology, with emphasis on its potential role as predictor of tumour response.
AIM: To evaluate the usefulness of immunoscintigraphy with an anti-CEA monoclonal antibody fragment labelled with (99m)Tc for early detection of colorectal recurrence in patients with rising serum CEA levels. METHODS: Fifty-one consecutive patients (27 women, 24 men) with colorectal cancer (mean age 68.9+/-10.2 years) and rising CEA levels (16.2+/-18.2 ng/ml) were prospectively studied. Two immunoscintigraphy studies were performed in 8 patients (n=59). Immunoscintigraphy was performed after i.v. injection of 925 MBq of anti-CEA monoclonal antibody. Planar images of the thorax, abdomen and pelvis, as well as SPECT of the abdomen and pelvis were obtained at 4 and 24 hours after injection. In all cases an abdominal CT scan was previously performed. Findings were validated by histopathological analysis (28 cases) or by imaging and clinical follow-up of at least 6 months following the immunoscintigraphy (31 cases). RESULTS: Forty-one patients did not show recurrence during follow-up. We found 18 cases with confirmed diagnosis of extrahepatic abdominal or pelvic diseases, 11 cases with liver metastases, 9 in the thorax and 2 in the bone. In patients with pelvic and extrahepatic abdominal disease, immunoscintigraphy was positive in 18 cases (14 true positive, 4 false positive). From the 14 true positive only 7 cases had been detected by CT. Immunoscintigraphy was negative in the remaining 41 cases (37 true negative, 4 false negative). Therefore, the sensitivity and specificity for immunoscintigraphy in extrahepatic abdominal and pelvic disease were 78% and 90%, respectively. CT results showed a lower sensitivity of 61% (p<0.05) and specificity of 83%. Liver metastases were detected by CT in 9 cases, but only 2 of these were identified using immunoscintigraphy. CONCLUSION: Scintigraphy with anti-CEA monoclonal antibody fragment labelled with (99m)Tc is superior to CT for the detection of pelvic and extrahepatic abdominal recurrence of colorectal cancer, while CT is more sensitive in the detection of liver and lung metastases. Immunoscintigraphy has a limited usefulness in the detection of distant metastases, but it may be helpful in the diagnosis of suspected colorectal recurrence in patients with non-conclusive CT findings, when FDG-PET is not available.
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OBJECTIVES: To report on the value of diagnostic videothoracoscopy in patients with possible penetrating cardiac wounds. METHODS: Thirteen patients admitted over a 4 year period with hemodynamic stability and a penetrating injury in cardiac proximity had exploratory videothoracoscopy. All data related to those patients were retrospectively reviewed. RESULTS: Eighty-five percent of patients had videothoracoscopy within 8 h of trauma. In most cases (eight of 13), operations were performed on patients in the supine position with the chest slightly rotated. Nine patients had a left hemothorax, five had pulmonary lacerations and five had a bleeding parietal vessel. Pericardial exploration was achieved either by direct vision (nine patients), or by the performance of a pericardial window (four patients). Acute hemopericardium related to a cardiac wound was diagnosed in two patients. Procedures included evacuation of clotted hemothorax (six patients), stapling of pulmonary laceration (four patients), and electrocoagulation of bleeding parietal vessel (four patients). Four patients required conversion to thoracotomy: two for repair of a cardiac wound, one for adequate exposure of the pericardium and one for ligation of a bleeding intercostal artery. The mean operative time was 37+/-23 min. Two patients experienced postoperative complications (coagulopathy, subcutaneous emphysema) and the in-hospital mortality was 0%. The mean hospital stay was 10+/-4 days. CONCLUSIONS: In the hands of an experienced surgeon, videothoracoscopy may represent a valid alternative to subxiphoid pericardial window in patients with hemodynamic stability and a suspected cardiac wound. Videothoracoscopy can rule out a cardiac injury and allows for the performance of associated procedures such as diaphragm assessment/repair, evacuation of clotted hemothorax, hemostasis of parietal vessels or pulmonary laceration and removal of projectiles.
OBJECTIVE: To analyse the relation between airborne exposure to major rat allergen and to endotoxins in exclusively rat-exposed workers and the prevalence of rat-related symptoms and sensitization. METHODS: A total of 113 workers answered a standardized questionnaire on their atopy status, occupational exposure to rats, and possible work-related symptoms. Specific IgE against rat urinary proteins (RUP) was measured for 73 subjects. Individual airborne exposure to Rat n 1 and endotoxin were determined with static (n = 256) samplings. Rat n 1 was measured with enzyme-linked immunosorbent assay (ELISA) and endotoxin by the Limulus method. RESULTS: Forty-four of 113 subjects (38.9%) reported at least one rat-related symptom: asthma (4.4%), rhinitis (34%) and conjunctivitis (16%). Twelve per cent were sensitized to RUP (specific IgE > 0.35 KU/L). But only 30.8% of all symptomatic subjects were sensitized to rat allergens. Airborne Rat n 1 levels were not related to symptoms in workers. Symptomatic patients not sensitized to rats were exposed to higher endotoxin levels, but airborne exposure to endotoxins did not significantly protect against or increase sensitization to RUP or rat-related symptoms. CONCLUSION: Most symptomatic workers were not sensitized to rat allergen; but no significant relation between rat-related symptoms and endotoxin levels was found. This suggests that more studies are needed to determine causes other than rat allergens or endotoxins that may be responsible for symptoms in rat-exposed workers.
The aim of this study was to establish whether tumour uptake of 99mTc-MIBI can predict response to chemotherapy in patients with breast carcinoma. Forty women suffering from breast carcinoma confirmed by tumour biopsy were studied prospectively. Fifteen patients subsequently underwent surgery and 25 were candidates for neoadjuvant chemotherapy. Breast scintigraphy was performed and planar and tomographic views (single photon emission computed tomography (SPECT)) were obtained after injection of 740 MBq of 99mTc-MIBI. The tumoural uptake was quantified by computer analysis. P-glycoprotein was evaluated by immunohistochemistry only in operable patients. The response to chemotherapy was evaluated at 3 months upon completion of treatment. The results of this study showed no relationship between 99mTc-MIBI uptake and the histological type or tumour size. There was an inverse correlation with the degree of tumour differentiation (P<0.05). 99mTc-MIBI uptake in negative P-glycoprotein lesions (2.36+/-1.72) was higher than in positive P-glycoprotein lesions (1.53+/-1.29), although the difference was not statistically significant. Lesions which responded to chemotherapy (16) showed higher 99mTc-MIBI uptake (7.70+/-5.20) than non-responding lesions (nine) (2.21+/-1.0) (P<0.001). In conclusion, there is a correlation between 99mTc-MIBI uptake in breast cancer and response to chemotherapy. Furthermore, 99mTc-MIBI uptake may be influenced by other factors such as the degree of tumour differentiation or tumour P-glycoprotein levels.
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Although prostatitis is a common problem the diagnosis is still controversial despite the availability of a wide variety of diagnostic tools. In fact, there is still no accurate method of localizing the infected tissue. The aims of the present study were to assess whether 111In labelled leukocytes (ILLs) accumulated in the infected tissue of acute prostatitis and if such uptake responded to treatment. We prospectively studied 10 adult male patients who had community acquired prostatitis and compared them with six male patients who had urinary tract infections but without prostatitis. An initial urinary culture and two blood cultures were carried out for each patient. All patients were followed up for 8 weeks after therapy was completed. Pre- and post-treatment scintigraphies were performed. Before treatment, all patients with prostatitis showed uptake of ILLs in the prostate area. After the patients had completed treatment with antibiotics, the scintigraphy results showed no uptake in the prostate area in 9/10 patients. The remaining patient showed a marked decrease in the uptake of ILLs. None of the six patients with urinary tract infection showed ILL uptake in the prostate region. It is suggested that ILLs could be useful for detecting acute prostatitis, especially in clinically ambiguous patients with urological infections. Furthermore, scintigraphy with 111In labelled leukocytes could help to determine the most appropriate course of therapy.