Radiographic findings of space-occupying lesions in sialo-CBCT of the major salivary glands.

OBJECTIVES: When performing CBCT sialography (sialo-CBCT), space-occupying lesions may be identified incidentally. The objective was to describe their radiologic-clinical-histopathologic correlations. METHOD AND MATERIALS: The archive of sialo-CBCT scans was retrospectively searched for suspected space-occupying lesions. Based on the scan and clinical-histopathologic data, the cases were divided into "pathologic" vs "normal," "intra-parenchymal" vs "extra-parenchymal," and "benign" vs "malignant." Two precalibrated, blinded radiologists performed a survey of the radiographic features of each scan. Cohen kappa, chi-square, Kruskal-Wallis, and Mann-Whitney tests assessed inter-observer agreement and radiologic-clinical-histopathologic correlations. RESULTS: In total, 27 (1.5%) suspected space-occupying lesions were found in 1,758 reports. Full follow-up data were available for 15 cases: four were "malignant," six were "benign," and the remaining five were "normal." Kappa showed substantial inter-observer agreement (0.8 to 1.0). Constant swelling correlated with "pathologic" cases (P = .003). Lesion diameter was greater in "pathologic" than "normal" (P < .001) cases, with a cut-off of 12.6 mm. Clinical and radiographic features were similar in "benign" and "malignant" lesions. "Intra-parenchymal" and "extra-parenchymal" space-occupying lesions correlated with "no-fill-region" (P = .01) and "main-duct-displacement" (P = .002), respectively. CONCLUSIONS: Suspected space-occupying lesions in sialo-CBCT with a diameter greater than 12.6 mm are likely to be "pathologic." No radiographic features were able to differentiate between "malignant" and "benign" space-occupying lesions.

Ex-vivo activation of a liposomal prodrug of mitomycin C by human tumors.

PURPOSE: To examine the ex- vivo ability of explanted human tumors and normal tissue to activate liposomal mitomycin C lipidic prodrug (MLP) by releasing the active free drug form, mitomycin C (MMC). METHODS: We tested conversion of MLP to MMC in an ex vivo assay using explanted tissues obtained during routine surgery to remove primary tumors or metastases. Tumor and adjacent normal tissue were obtained from freshly explanted tumors and were immediately deep frozen at - 70 °C. On test day, the fragments were thawed, homogenized and incubated in the presence of a fixed amount of liposomal MLP at 37 °C for 1 h. We measured MLP and its rate of conversion to MMC by HPLC. Controls included plasma, malignant effusions, red blood cells, tumor cell lines, mouse liver, and buffer with dithiothreitol, a potent reducing agent. RESULTS: Most patients tested (16/20) were diagnosed with colo-rectal carcinoma. The average fraction of MLP cleaved per 100-mg tumor tissue (21.1%, SEM = 1.8) was greater than per 100-mg normal tissue (16.6%, SEM = 1.3). When the tumor and normal tissue samples were paired by patient, the difference was statistically significant (p = 0.022, paired t test). Biological fluids did not activate liposomal MLP, while normal liver tissue strongly does. Interestingly, the omental fatty tissue also greatly activated MLP. CONCLUSIONS: Tumor tissue homogenates activate MLP with greater efficiency than the surrounding normal tissues, but far less than liver and adipose tissue. These observations demonstrate the bioavailability of liposomal MLP in human tumors, and its pharmacologic potential in cancer therapy.

Biocompatibility evaluation of crosslinked chitosan hydrogels after subcutaneous and intraperitoneal implantation in the rat.

The aim of the present study was to evaluate the toxicity of biodegradable hydrogels in the rat with a future aim of utilizing this hydrogel as a vehicle for brachytherapy delivery in cancer patients. Two types of chitosan hydrogels: fast degrading and slow degrading; were prepared and surgically implanted in rats. The adjacent tissue response to the gels after subcutaneous and intraperitoneal implantation was examined histologically and found to be identical to typical foreign body response and was milder than the response to absorbable surgical sutures (Vicril). Neither tissue damage nor gel fragments could be detected in distant organs (brain, heart, lungs, liver, spleen, kidney, and sternal bone marrow) after implantation of the hydrogels. The degradation mechanism of the gels was studied in vivo, and it was deduced that an oxidative process degraded the chitosan. Loading the hydrogels with a radioisotope (131I-norcholesterol) caused a severe tissue response and necrosis in adjacent tissues only at a distance of several microns. It is concluded that crosslinked chitosan implants could serve as alternative, biocompatible, and safe biodegradable devices for radioisotope delivery in brachytherapy for cancer.

Crosslinked chitosan implants as potential degradable devices for brachytherapy: in vitro and in vivo analysis.

Compared with conventional external beam radiation, brachytherapy offers a superior therapeutic regimen. However, some major constraints are associated with its implementation, including the need of complicated procedures for device placement and removal. The purpose of this study was to examine whether crosslinked chitosan (Ct) implants could serve as potential biodegradable devices for brachytherapy. Ct was reacted with increasing amounts of glutaraldehyde to obtain hydrogels with different crosslinking densities, which were characterized chemically, thermally and mechanically. The effect of the dialysis medium conditions (ionic strength, osmolarity and pH) on the gel hydration and in vivo degradation was assessed. Two types of implants, slow and fast degrading gel (SDG and FDG, respectively), were prepared and implanted with or without Sudan Black (SB) in the rat. While SDG withstood for over a month, the FDG degraded within two weeks after implantation. The release kinetics of SB from the hydrogels verified their in vivo degradation properties. The incorporation of the radioactive compound (131)I-norcholesterol ((131)I-NC) into the SDG altered the degradation kinetics of the gel as reflected by the release kinetics of the radioactive marker. Eighty percent of (131)I-NC was released within a month after implantation, after which time, radioactivity was detected in the regional lymph nodes. Histological examination of the tissues surrounding the implants demonstrated negligible tissue response to the implants, when compared to biodegradable surgical sutures. It is concluded that hydrogels made of crosslinked Ct are potential novel, safe, degradable devices for brachytherapy.

Targeting normal and neoplastic tissues in the rat jejunum and colon with boronated, cationic acrylamide copolymers.

A series of boronated cationic copolymers, composed of different ratios of acrylamide, N-acryloyl-3-aminophenylboronic acid and N-acryloyl-diaminoethane (the cationic moiety), were prepared with the intention of localizing boron neutron capture therapy (BNCT) in experimentally induced polyps on the luminal side of the gut of the rat. The goals of this study were to: (a) test the effect of cationization of the boronated copolymers on their uptake by polyps and normal adjacent epithelium; (b) compare the whole rat body distribution of aminophenylboronic acid (APB) and polymeric APB after local application; (c) measure the effect of micro-environmental parameters such as pH, the presence of mucin and cations on the interaction between the APB-copolymers and the epithelium of the rat intestines. Direct analysis of tissue boron levels showed that polymeric APB-uptake was higher in the colonic polyps than in the surrounding normal tissues. Free APB, however, was found in similar quantities in both. When tested in the normal jejunum and colon of the rat, polymeric APB uptake was directly proportional to the molar content of the cationic monomer in the copolymers. The presence of magnesium ions, free boron cationic monomer and mucin interfered with this uptake in a concentration-dependent manner. The uptake was pH-independent at pH 5, 7 and 10. APB accumulation in the colon polyps was inversely proportional to the cationic monomer content in the copolymers, suggesting an increased amount of mucus around the polyps, which probably impeded the electrostatic attachment of the polymer to the malignant tissue. The use polymeric APB for targeting BNCT in perioperative treatment of colorectal carcinoma is suggested, especially in the cases of microscopic residual disease after curative resection.

Polystyrene microspheres as a specific marker for the diagnosis of aspiration in hamsters.

The diagnosis of recurrent aspiration in young children is problematic because there is no specific gold standard test to be used. In the present work, normal saline or a suspension of white polystyrene microspheres in normal saline was instilled into hamsters' trachea (n = 42), and bronchoalveolar lavage (BAL) cytology, microsphere index (total microspheres/100 macrophages), and lung histology were followed for 90 d. Naive animals (n = 6) had no tracheal instillation. On Days 1, 3, 10, 32, 60, and 90 after tracheal instillation, animals were killed (saline-instilled animals, n = 3; and microsphere-instilled animals, n = 4), and BAL was performed. There was a marked inflammatory response in BAL on Day 1 after tracheal instillation of saline or microsphere suspension. White microspheres were clearly identified within alveolar macrophages in all studied days. Microsphere numbers showed a 50% disappearance rate of 10 d. A mild peribronchial inflammation was noted in lung histology only on Day 1 after instillation. Microspheres were not detected in extrapulmonary organs. We conclude that polystyrene microspheres instilled in hamsters' trachea can be easily identified in BAL macrophages for as long as 3 mo and could potentially be used as a sensitive, specific, and stable marker for the diagnosis of aspiration.