Clearance of technetium-99m-DTPA in pulmonary sarcoidosis

Background. The aim of this study was to explore the possible association of the lung clearance of 99mTc- DTPA scan with HRCT lung abnormalities and with the pulmonary function tests [PFTs] in patients with sarcoidosis. Methods. We studied prospectively 15 patients [5 males, 10 females] of median age 46yr [range 27-67] with histologically proved sarcoidosis. HRCT scoring included the sum of the severity and extent of lymph node enlargement and parenchymal involvement. Results. The mean DTPA clearance half-time [τ 1/2 <40 min] was found [mean [SD]] 38.3+4.5min. The lymph node enlargement was found 34% and the parenchymal involvement 12%. DTPA clearance was negatively correlated with the parenchymal involvement [r= -0.651, p=0.009]. The HRCT parenchymal abnormalities were found significantly correlated with PFTs [FVC [r= -0.65, p=0.008] and TLCO [r= -0.76, p=0.02]. Conclusions. Our data suggest a moderate association between 99mTc-DTPA scan and HRCT in pulmonary sarcoidosis. However, further studies in large scale of sarcoid patients are needed to clarify the role of this novel methodology in the evaluation and follow-up of this disorder

Comparison of DC Bead-irinotecan and DC Bead-topotecan drug eluting beads for use in locoregional drug delivery to treat pancreatic cancer

DC Bead is a drug delivery embolisation system that can be loaded with doxorubicin or irinotecan for the treatment of a variety of liver cancers. In this study we demonstrate that the topoisomerase I inhibitor topotecan hydrochloride can be successfully loaded into the DC Bead sulfonate-modified polyvinyl alcohol hydrogel matrix, resulting in a sustained-release drug eluting bead (DEBTOP) useful for therapeutic purposes. The in vitro drug loading capacity, elution characteristics and the effects on mechanical properties of the beads are described with reference to our previous work with irinotecan hydrochloride (DEBIRI). Results showed that drug loading was faster when the solution was agitated compared to static loading and a maximum loading of ca. 40–45 mg topotecan in 1 ml hydrated beads was achievable. Loading the drug into the beads altered the size, compressibility moduli and colour of the bead. Elution was shown to be reliant on the presence of ions to perform the necessary exchange with the electrostatically bound topotecan molecules. Topotecan was shown by MTS assay to have an IC50 for human pancreatic adenocarcinoma cells (PSN-1) of 0.22 and 0.27 lM compared to 28.1 and 19.2 lM for irinotecan at 48 and 72 h, respectively. The cytotoxic efficacy of DEBTOP on PSN-1 was compared to DEBIRI. DEPTOP loaded at 6 & 30 mg ml-1, like its free drug form, was shown to be more potent than DEBIRI of comparable doses at 24, 48 & 72 h using a slightly modified MTS assay. Using a PSN-1 mouse xenograft model, DEBIRI doses of 3.3–6.6 mg were shown to be well tolerated (even with repeat administration) and effective in reducing the tumour size. DEBTOP however, was lethal after 6 days at doses of 0.83–1.2 mg but demonstrated reasonable efficacy and tolerability (again with repeat injection possible) at 0.2–0.4 mg doses. Care must therefore be taken when selecting the dose of topotecan to be loaded into DC Bead given its greater potency and potential toxicity

Co-existence of a giant splenic hemangioma and multiple hepatic hemangiomas and the potential association with the use of oral contraceptives: a case report

<p>Abstract</p> <p>Introduction</p> <p>Hepatic and splenic hemangiomas are common benign tumors that mainly affect female patients. Giant splenic hemangiomas are extremely rare, especially when correlated with multiple hepatic hemangiomas. Pathogenetic mechanisms between hemangiomas and oral contraceptives, as well as therapeutic approaches, are analyzed in this case report, in particular for the management of synchronous splenic and hepatic hemangiomas.</p> <p>Case presentation</p> <p>We report here a 42-year-old woman with a giant splenic hemangioma, multiple hepatic hemangiomas and a history of oral estrogen intake for many years. At first it was difficult to determine the organ from which the giant hemangioma originated. Angiography proved extremely helpful in tracing its origin in the spleen. Hematomas in the giant hemangioma posed a significant threat of rupture and catastrophic hemorrhage. We left the small hepatic hemangiomas in place, and removed the spleen along with the giant splenic hemangioma.</p> <p>Conclusion</p> <p>Diagnostic pitfalls in the determination of the origin of this giant hemangioma, attribution of its origin to the spleen angiographically, the unusual co-existence of the giant splenic hemangioma with multiple hepatic ones, and the potential threat of rupture of the giant hemangioma are some of the highlights of this case report. Estrogen administration represents a pathogenic factor that has been associated with hemangiomas in solid organs of the abdominal cavity. The therapeutic dilemma between resection and embolization of giant hemangiomas is another point of discussion in this case report. Splenectomy for the giant splenic hemangioma eliminates the risk of rupture and malignant degeneration, whereas observation for the small hepatic ones (<4 cm) was the preferable therapeutic strategy in our patient.</p

Lipid Nanocapsules Loaded with Rhenium-188 Reduce Tumor Progression in a Rat Hepatocellular Carcinoma Model

International audienceBACKGROUND: Due to their nanometric scale (50 nm) along with their biomimetic properties, lipid nanocapsules loaded with Rhenium-188 (LNC(188)Re-SSS) constitute a promising radiopharmaceutical carrier for hepatocellular carcinoma treatment as its size may improve tumor penetration in comparison with microspheres devices. This study was conducted to confirm the feasibility and to assess the efficacy of internal radiation with LNC(188)Re-SSS in a chemically induced hepatocellular carcinoma rat model. METHODOLOGY/PRINCIPAL FINDINGS: Animals were treated with an injection of LNC(188)Re-SSS (80 MBq or 120 MBq). The treated animals (80 MBq, n = 12; 120 MBq, n = 11) were compared with sham (n = 12), blank LNC (n = 7) and (188)Re-perrhenate (n = 4) animals. The evaluation criteria included rat survival, tumor volume assessment, and vascular endothelial growth factor quantification. Following treatment with LNC(188)Re-SSS (80 MBq) therapeutic efficiency was demonstrated by an increase in the median survival from 54 to 107% compared with control groups with up to 7 long-term survivors in the LNC(188)Re-SSS group. Decreased vascular endothelial growth factor expression in the treated rats could indicate alterations in the angiogenesis process. CONCLUSIONS/SIGNIFICANCE: Overall, these results demonstrate that internal radiation with LNC(188)Re-SSS is a promising new strategy for hepatocellular carcinoma treatment

Emergent Orthotopic Liver Transplantation for Hemorrhage from a Giant Cavernous Hepatic Hemangioma: Case Report and Review

IntroductionCavernous hemangiomas represent the most common benign primary hepatic neoplasm, often being incidentally detected. Although the majority of hepatic hemangiomas remain asymptomatic, symptomatic hepatic hemangiomas can present with abdominal pain, hemorrhage, biliary compression, or a consumptive coagulopathy. The optimal surgical management of symptomatic hepatic hemangiomas remains controversial, with resection, enucleation, and both deceased donor and living donor liver transplantation having been reported.Case reportWe report the case of a patient found to have a unique syndrome of multiorgan cavernous hemangiomatosis involving the liver, lung, omentum, and spleen without cutaneous involvement. Sixteen years following her initial diagnosis, the patient suffered from intra-abdominal hemorrhage due to her giant cavernous hepatic hemangioma. Evidence of continued bleeding, in the setting of Kasabach-Merritt Syndrome and worsening abdominal compartment syndrome, prompted MELD exemption listing. The patient subsequently underwent emergent liver transplantation without complication.ConclusionAlthough cavernous hemangiomas represent the most common benign primary hepatic neoplasm, hepatic hemangioma rupture remains a rare presentation in these patients. Management at a center with expertise in liver transplantation is warranted for those patients presenting with worsening DIC or hemorrhage, given the potential for rapid clinical decompensation

Clearance of technetium-99m-DTPA and HRCT findings in the evaluation of patients with Idiopathic Pulmonary Fibrosis

BACKGROUND: Clearance of inhaled technetium-labeled diethylenetriamine pentaacetate ((99m)Tc-DTPA) is a marker of epithelial damage and an index of lung epithelial permeability. The aim of this study was to investigate the role of (99m)Tc-DTPA scan in patients with Idiopathic Pulmonary Fibrosis (IPF). Our hypothesis is that the rate of pulmonary (99m)Tc-DTPA clearance could be associated with extent of High Resolution Computed Tomography (HRCT) abnormalities, cell differential of bronchoalveolar lavage fluid (BALF) and pulmonary function tests (PFTs) in patients with IPF. METHODS: We studied prospectively 18 patients (14 male, 4 female) of median age 67yr (range 55–81) with histologically proven IPF. HRCT scoring included the mean values of extent of disease. Mean values of these percentages represented the Total Interstitial Disease Score (TID). DTPA clearance was analyzed according to a dynamic study using a Venticis II radioaerosol delivery system. RESULTS: The mean (SD) TID score was 36 ± 12%, 3 patients had mild, 11 moderate and 4 severe TID. Abnormal DTPA clearance half-time (t(1/2)<40 min) was found in 17/18 (94.5%) [mean (SD) 29.1 ± 8.6 min]. TID was weakly correlated with the DTPA clearance (r = -0.47, p = 0.048) and with % eosinophils (r = 0.475, p = 0.05). No correlation was found between TID score or DTPA and PFTs in IPF patients. CONCLUSION: Our data suggest that (99m)Tc-DTPA lung scan is not well associated with HRCT abnormalities, PFTs, and BALF cellularity in patients with IPF. Further studies in large scale of patients are needed to define the role of this technique in pulmonary fibrosis

Feasibility, safety and pharmacokinetic study of hepatic administration of drug-eluting beads loaded with irinotecan (DEBIRI) followed by intravenous administration of irinotecan in a porcine model

Irinotecan eluting embolization beads (DEBIRI) are currently being evaluated in the clinic for the treatment of colorectal cancer metastases to the liver. The aim of this study was to determine the safety and pharmacokinetics associated with two cycles of hepatic embolization using DEBIRI followed by intravenous administration of irinotecan. Pigs were embolized with DEBIRI (100–300 μm, 100 mg dose, n = 6) and blood samples taken over 24 h to determine plasma levels of irinotecan and SN-38 metabolite and for haematology and biochemistry. At 24 h an IV infusion of 250 mg/m2 of irinotecan was administered and the plasma levels taken again. This cycle was repeated 3 weeks later. A single animal was subjected to a more aggressive regimen of embolization with 200 mg bead dose and IV of 350 mg/m2 for two cycles. Three animals were sacrificed at 6 weeks and the remaining four (n = 3 standard dose, n = 1 high dose) animals at 12 weeks and detailed histopathology performed. All animals tolerated the treatments well, with only minor changes in haematological and biochemical parameters. There was no overlap in drug plasma levels observed from the bead and IV treatments when given 24 h apart and no difference between the pharmacokinetic profiles of the two cycles separated by 3 weeks. Irinotecan plasma AUC values were similar in both the embolization and IV arms of the study. Cmax values obtained during the IV arms of the study are approximately double that of the embolization arms whilst Tmax times are shorter in the IV arms, supporting extended release of drug from the beads. Bioavailability for bead-based delivery was double that for IV administration, which was attributed to reduced clearance of the drug when delivered by this route. No additive toxicity was observed as a consequence of the combined treatments. The combination of irinotecan delivery via drug eluting bead and IV was well-tolerated with no significant clinical effects. Pharmacokinetic analyses suggest the bioavailability from bead-based delivery of drug is double that of IV infusion, attributable to reduced drug clearance for the former.Andrew L. Lewis, Rachel R. Holden, S. Ting Chung, Peter Czuczman, Timothy Kuchel, John Finnie, Susan Porter, David Foste

Drug-eluting particles in the treatment of HCC: Chemoembolization with doxorubicin-loaded DC Bead™

The advantage of chemoembolization of the liver as an antineoplastic treatment for hepatocellular carcinoma is that it achieves high intratumoral concentrations of the chemotherapeutic agent locally that cannot be reached with systemic chemotherapy in nontoxic doses. However, chemotherapeutic release and local concentrations cannot be standardized by this technique. Drug-eluting beads have predictable pharmacokinetics and can achieve higher doses of the chemotherapeutic and prolonged contact time with cancer cells. The DC Bead™ is a drug-eluting bead that has proven favorable kinetics and clinical characteristics. This review describes the features of the DC Bead loaded with doxorubicin for the treatment of hepatocellular carcinoma. © 2008 Expert Reviews Ltd