Selectivity of the photosensitiser Tookad® for photodynamic therapy evaluated in the Syrian golden hamster cheek pouch tumour model

The response to photodynamic therapy (PDT) with the photosensitiser (PS) Tookad was measured in the Syrian hamster cheek pouch model on normal mucosae and chemically induced squamous cell carcinoma. This PS is a palladium-bacteriopheophorbide presenting absorption peaks at 538 and 762 nm. The light dose, drug dose and drug injection-light irradiation times (DLI), ranging between 100 and 300 J cm(-2), 1-5 mg kg(-1) and 10-240 min respectively, were varied and the response to PDT was analysed by staging the macroscopic response and by the histological examination of the sections of the irradiated cheek pouch. A fast time decay of the tissular response with drug dose of 1-5 mg kg(-1) was observed for DLI ranging from 10 to 240 min and for light doses of 100-300 J cm(-2) delivered at a light dose rate of 150 mW cm(-2). A significantly higher level of tissular response was observed for squamous cell carcinoma compared to normal tissue. Nevertheless, the threshold level of the drug-light dose for a detectable response was not significantly different in the tumoral vs normal tissue. The highest response at the shortest DLIs and the absence of measurable response at DLI larger than 240 min at light dose of 300 J cm(-2) and drug dose of 5 mg kg(-1) reveals the predominantly vascular effect of Tookad. This observation suggests that Tookad could be effective in PDT of vascularised lesions

Uptake and localisation of mTHPC (Foscan®) and its14C-labelled form in normal and tumour tissues of the hamster squamous cell carcinoma model: a comparative study

The aim of this study was to evaluate the pharmacokinetics of meta(tetrahydroxyphenyl)chlorin (mTHPC) on different tissues of interest in a hamster tumour model and to confirm our earlier animal studies on semi-quantitative fluorescence microscopy. The results obtained by three different evaluation methods were compared: in vivo spectrofluorometry, ex vivo fluorescence microscopy and chemical extraction of 14C-labelled mTHPC. Following intracardiac injection of 0.5 mg kg−1 mTHPC, groups of five tumour-bearing animals were used for in situ light-induced fluorescence spectroscopy. Afterwards, the biopsies were taken and snap frozen for fluorescence microscopy. The presence of radioactivity in serum and tissues was determined after chemical digestion in scintillation fluid using a scintillation counter. For each analysed tissue, a good correlation was observed between the three evaluation methods. The highest fluorescence intensity and quantities of mTHPC were observed between 12 and 24 h in liver, kidney, serum, vascular endothelium and advanced neoplasia. The majority of mTHPC was found at around 48 h in smooth muscle and at 96 h in healthy cheek pouch mucosa and early malignant lesions. The lowest level of mTHPC was noted in striated muscle at all times. No selectivity in dye localisation was observed between early squamous cell carcinoma and healthy mucosa. Soon after the injection, a significant selectivity was noted for advanced squamous cell carcinoma as compared to healthy cheek pouch mucosa or striated muscle. A significant difference in mTHPC localisation and quantity was also observed between striated and smooth muscle during the first 48 h following the injection. Finally, this study demonstrated the usefulness of non-invasive in situ spectroscopic measurements to be performed systematically prior to photodynamic therapy as a real-time monitoring for each treated patient in order to individualise and adapt the light dosimetry and avoid over or under treatments

Wavelength-dependent effect of tetra(m-hydroxyphenyl) chlorin for photodynamic therapy in an "early" squamous cell carcinoma model

The purpose of the present study was to correlate the wavelength of the irradiation source with the phototoxic activity of tetra(m-hydroxyphenyl)chlorin (mTHPC) in healthy and neoplastic mucosae. The hamster tumour model for early squamous cell carcinoma was used in these experiments. In vitro and in vivo studies have shown that mTHPC absorbs significantly at 652 nm (1, 2). This wavelength is used currently in clinical mTHPC photodynamic therapy (PDT) trials. In order to study the wavelength dependence of the phototoxic effect on normal and tumour tissues, irradiation tests were performed 4 days after injection of 0.5mg kg-1 mTHPC. An argon-ion pumped dye laser was used as the light source. The light dose of 12 J cm-2 was delivered at a light dose rate of 150 mW cm-2. The wavelength was varied between 642.5 and 665 nm at 2.5-nm increments. The PDT damage was evaluated in serial Haematoxylin and Eosin stained sections using a tissue-damage scale. Light between 647.5 and 652.5 nm induced the highest damage to both the healthy and tumour mucosae. At wavelengths equal to or below 645 nm, and equal to or above 655 nm, tissue damage decreased. Wavelengths below 642 nm and above 660 nm did not induce any visible tissue damage. These results suggest that the in vivo optimal wavelength range for PDT with mTHPC is between 647 and 652 nm. This information is essential for selecting an appropriate light source

Second primary squamous cell carcinoma arising in cutaneous flap reconstructions of two head and neck cancer patients

Early complications of myocutaneous flap transfers following surgical eradication of head and neck tumors have been extensively described. However, knowledge concerning long-term complications of these techniques remains limited. We report the cases of two patients with a prior history of squamous cell carcinoma of the head and neck (HNSCC), who developed a second primary SCC on the cutaneous surface of their flaps, years after reconstruction. Interestingly, it seems that the well-known risk of a second primary SCC in patients with previous head and neck carcinoma also applies to foreign tissues implanted within the area at risk. Given the important expansion of these interventions, this type of complication may become more frequent in the future. Therefore, long-term follow-up of patients previously treated for HNSCC not only requires careful evaluation of the normal mucosa of the upper aero-digestive tract, but also of the cutaneous surface of the flap used for reconstruction

Tumeurs du hile hépatique [Tumours of the hepatic hilum]

Portant un intérêt particulier pour la pathologie hépatique, et après avoir collecté plus de 50'000 coupes histologiques, Gerald Klatskin décrit en 1965, pour la première fois, une famille particulière de tumeurs malignes des voies biliaires extra hépatiques, situées au niveau de la bifurcation du hile hépatique. Cette entité est connue aujourd'hui dans la littérature sous le nom de «tumeur de Klatskin» et correspond à un adénocarcinome de l'épithélium biliaire. Il s'agit d'une tumeur rare, représentant dans l'année 2000 moins de 0.5% des nouveaux cas de cancer aux Etats-Unis. Les autres tumeurs malignes intéressant la région péri-hilaire sont le cholangiocarcinome des voies biliaires intrahépatiques, l'adénocarcinome de la vésicule biliaire, ainsi que les tumeurs malignes primaires d'organes avoisinants, tels que carcinome hépatocellulaire et l'adénocarcinome de la tête du pancréas. On a rapporté également quelques rares cas de sarcome du hile hépatique (Soareset al., 1989), de néoplasies hématopoïétiques (Eliason et Grosso, 2001) et occasionnellement, des métastases à distance d'un site primaire (i.e. cancers coliques, gastriques, pancréatiques, prostatiques, pulmonaires ou mammaires). Les tumeurs bénignes comme le papillome (solitaire ou multiple, Fig. 1) ou le cystadénome, les pseudotumeurs inflammatoires (Sakaiet al., 2001), et les kystes ou pseudokystes de la voie biliaire principale (Seguchiet al., 2004) se présentent avec une Symptomatologie identique à celle observée dans les tumeurs malignes. Seules, les tumeurs du hile hépatique seront abordées dans cette revue. Les autres pathologies non-tumorales, telles que la cholangite sclérosante, la cholangite pyogénique récidivante, la lithiase biliaire (i.e. Syndrome de Mirizzi) ainsi que la sténose hilaire d'origine inflammatoire, traumatique ou iatrogène ne seront pas discutées ici. Il est toutefois important de savoir que 5 à 15% des patients opérés avec un diagnostic préopératoire de cancer du hile, présentent en effet une sténose inflammatoire pseudotumorale non-spécifique (Santoroet al., 2004). [Through his extensive interest in liver pathology, a collection of more than 50.000 histological slides, in concert with his keen interest in patients' histories, Gerald Klatskin identified and first described in 1965 a distinct family of malignant tumours located in the bifurcation of extrahepatic bile ducts in the liver hilum (Klatskin, 1965). These tumors, which today carry his name «Klatskin tumours», are mostly adenocarcinomas typically originating from the bile duct epithelium. These tumours are rare, accounting for less than one half percent of all new cancers in the United States in 2000. Other malignant tumours that affect the perihilar region of the liver include cholangiocarcinomas of the intrahepatic ductal system, adenocarcinomas of the gallbladder, as well as primary malignant tumours originating from adjacent organs, such as hepatocellular carcinomas, carcinomas of the pancreatic head, rare sarcomas (Soares et al., 1989) and hematopoietic malignancies (Eliason and Grosso, 2001). Finally, occasional metastases from distant sites are found (i.e. from carcinomas of the colon, the stomach, the pancreas, the prostate, the lungs, or the breasts, to name only the most frequent primary sites). In addition to these malignant tumours, several benign tumours and tumourlike lesions cause similar symptoms, such as epithelial precursor lesions of the large extrahepatic bile ducts (i.e. solitary or multiple papillomas and/or adenomas, (Fig. 1)), rare inflammatory pseudotumours (Sakai et al., 2001), as well as occasional cysts or pseudocysts of the major duct systems (Seguchi et al., 2004). Not included in this review are nontumorous causes of obstructive jaundice such as primary sclerosing cholangitis, recurrent pyogenic cholangitis, stone disease (i.e. Mirizzi syndrome), as well as traumatic, inflammatory, or iatrogenic strictures. Indeed, these latter benign pseudotumoral strictures of mostly unspecific or unknown etiology are found in 5 to 15 percent of tumours surgically resected from the hepatic hilum for biliary stenosis (reviewed in: Santoro et al., 2004).]]]> fre X263271148/163 <OAI-PMH xmlns="http://www.openarchives.org/OAI/2.0/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/ http://www.openarchives.org/OAI/2.0/OAI-PMH.xsd"> 2022-10-06T05:35:44Z http://serval.unil.ch/oaiprovider/ oai:serval.unil.ch:BIB_B2DC209EEBA0 2022-10-01T01:27:28Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_B2DC209EEBA0 Multicenter evaluation of the reproducibility of the proposed antifungal susceptibility testing method for fermentative yeasts of the Antifungal Susceptibility Testing Subcommittee of the European Committee on Antimicrobial Susceptibility Testing (AFST-EUCAST). info:doi:10.1046/j.1469-0691.2003.00592.x info:eu-repo/semantics/altIdentifier/doi/10.1046/j.1469-0691.2003.00592.x info:eu-repo/semantics/altIdentifier/pmid/12848721 Cuenca-Estrella, M. Moore, C.B. Barchiesi, F. Bille, J. Chryssanthou, E. Denning, D.W. Donnelly, J.P. Dromer, F. Dupont, B. Rex, J.H. Richardson, M.D. Sancak, B. Verweij, P.E. Rodríguez-Tudela, J.L. info:eu-repo/semantics/article article 2003-06 Clinical Microbiology and Infection, vol. 9, no. 6, pp. 467-474 info:eu-repo/semantics/altIdentifier/pissn/1198-743X <![CDATA[OBJECTIVE: To evaluate the intra- and inter-laboratory reproducibility of a new standard for susceptibility testing of fermentative yeasts. This standard is based on the M27-A procedure of the National Committee for Clinical Laboratory Standards (NCCLS), but incorporates several modifications, including spectrophotometric growth-dependent endpoint reading. METHODS: Nine laboratories participated in the study. Common material lots were used to test six Candida species (one each of C. albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei, and C. lusitaniae), and two quality control strains (C. krusei ATCC6258 and C. parapsilosis ATCC22019). Triplicate testing on three separate days was performed in microtiter format with RPMI-2% glucose, pH 7.0. Flucytosine, fluconazole and itraconazole were tested. In total, 3888 MIC values were included in the analyses. Reproducibility was calculated by means of agreement (percentage of MICs within one two-fold dilution of the mode) and intraclass correlation coefficient (ICC, maximum value of 1). RESULTS: The average intra-laboratory agreements were 99% and 96% after 24 h and 48 h of incubation, respectively, with ICCs of 0.98 and 0.97 (P &amp;lt; 0.05). Two strains exhibiting a trailing effect showed intra-laboratory agreement of 92% and ICCs of &amp;lt; 0.91 at 48 h. The inter-laboratory agreement was 94% and 88% after 24 h and 48 h, respectively, with ICCs of 0.93 and 0.91 (P &amp;lt; 0.05). Lower values of agreement and ICCs were obtained for strains exhibiting trailing after 48 h of incubation. Itraconazole yielded the lowest values of reproducibility. CONCLUSION: The new procedure of EUCAST for antifungal susceptibility testing is a reproducible method within and between laboratories and offers several advantages over the NCCLS approved method

Blue-violet excited autofluorescence spectroscopy and imaging of normal and cancerous human bronchial tissue after formalin fixation1

Autofluorescence (AF) imaging is a powerful tool for the detection of (pre-)neoplastic lesions in the bronchi. Several endoscopic imaging systems exploit the spectral and intensity contrast of AF between healthy and (pre-)neoplastic bronchial tissues, yet, the mechanisms underlying these contrasts are poorly understood. In this report, the effect of formalin fixation on the human bronchi AF, hence on the contrast, was studied by spectrofluorometric point measurements and DAFE (Diagnostic AutoFluorescence Endoscopy) broad field imaging. Generally, formalin-fixed samples have higher AF intensity than in vivo, whereas the emission spectral shape is similar. Additionally, the spectrofluorometric data showed a moderate decrease of the AF intensity on (pre-)neoplastic lesions relative to the healthy bronchial samples. However, this decrease was lower than that reported from in vivo measurements. Neither spectral measurements nor imaging revealed spectral contrast between healthy bronchial tissue and (pre-)neoplastic lesions in formalin. These results indicate that epithelial thickening and blood supply in the adjacent lamina propria are likely to play a key role in the generation of the AF contrast in bronchial tissues. Our results show that the AF contrast in bronchial tissues was significantly affected by standard, 10% buffered, formalin fixation. Therefore, these samples are not suited to AF contrast studie