Long-term health-related quality of life after minimally invasive surgery for diverticular disease.

BACKGROUND AND AIMS: The aim of this multicentric study was to evaluate the disease specific and the generic quality of life in patients affected by colonic diverticular disease (DD) who had undergone minimally invasive or open colonic resection or who had been treated with medical therapy in the long-term follow-up. PATIENTS AND METHODS: Seventy-one consecutive patients admitted to the departments of surgery of Padova and Arzignano Hospitals for DD were interviewed: 22 underwent minimally invasive colonic resection, 24 had open resection, and 25 had only medical therapy. The interview focused on disease specific and generic quality of life, body image, and disease activity. RESULTS: Padova Inflammatory Bowel Disease Quality of Life (PIBDQL) was validated for the use in DD patients. PIBDQL scores were significantly worse in all patients with DD than those obtained by healthy subjects and it correlated with the symptoms score. The generic quality of life seemed similar in patients who had minimally invasive colonic resection compared with healthy subjects. Body Image Questionnaire scores correlated inversely with the presence of a stoma. CONCLUSIONS: Disease activity resulted as the only independent predictor of the disease-specific quality of life. In fact, DD affected bowel function and quality of life of patients in the long-term follow-up regardless of the type of therapy adopted. The presence of a stoma affected the patients' body image.

Tumour-localizing and -photosensitising properties of meso-tetra(4-nido-carboranylphenyl)porphyrin (H2TCP).

A water-soluble meso-substituted porphyrin (H(2)TCP) bearing 36 boron atoms, which appeared to be an efficient photodynamic sensitiser (singlet oxygen quantum yield=0.44), was studied for its accumulation by murine melanotic melanoma cells (B16F1). The amount of H(2)TCP in the cells increased with the porphyrin dose in the incubation medium up to, and at least, 100 microM concentrations with no significant cytotoxic effect in the dark. Moreover, the H(2)TCP uptake increased with the incubation time reaching a plateau value corresponding with the recovery of 0.4 nmol of H(2)TCP per mg of cell proteins after 24h incubation. Fluorescence microscopy observations showed that the porphyrin was largely localized intracellularly, exhibiting a discrete distribution in the cytoplasm with a pattern which was closely similar to that observed for the endosomal probe Lucifer yellow. The photosensitising efficiency of the H(2)TCP toward B16F1 cells was studied for different irradiation (1-15 min) and incubation (1-24 h) times. Nearly complete (>95%) cell mortality was obtained upon incubation with 20 microM H(2)TCP and 10 min irradiation with red light (600-700 nm, 20 mW/cm(2)). The porphyrin was also accumulated in appreciable amounts by the tumour tissue after intravenous injection to C57BL/6 mice bearing a subcutaneously transplanted melanotic melanoma. Maximum accumulation in the tumour was achieved by administration of H(2)TCP dissolved in the ternary mixture 20% dimethylsulfoxide (DMSO)-30% polyethyleneglycol (PEG 400)-50% water. Thus, this porphyrin could act as both a photodynamic therapy agent and a radiosensitising agent for boron neutron capture therapy.

A novel 10B-enriched carboranyl-containing phthalocyanine as a radio- and photo-sensitising agent for boron neutron capture therapy and photodynamic therapy of tumours: in vitro and in vivo studies.

The synthesis of a Zn(ii)-phthalocyanine derivative bearing four 10B-enriched o-carboranyl units (10B-ZnB4Pc) and its natural isotopic abundance analogue (ZnB4Pc) in the peripheral positions of the tetraazaisoindole macrocycle is presented. The photophysical properties of ZnB4Pc, as tested against model biological systems, were found to be similar with those typical of other photodynamically active porphyrin-type photosensitisers, including a singlet oxygen quantum yield of 0.67. The carboranyl-carrying phthalocyanine was efficiently accumulated by B16F1 melanotic melanoma cells in vitro, appeared to be partitioned in at least some subcellular organelles and, upon red light irradiation, induced extensive cell mortality. Moreover, ZnB4Pc, once i.v.-injected to C57BL/6 mice bearing a subcutaneously transplanted pigmented melanoma, photosensitised an important tumour response, provided that the irradiation at 600-700 nm was performed 3 h after the phthalocyanine administration, when appreciable concentrations of ZnB4Pc were still present in the serum. Analogously, irradiation of the 10B-ZnB4Pc-loaded pigmented melanoma with thermal neutrons 24 h after injection led to a 4 day delay in tumour growth as compared with control untreated mice. These results open the possibility to use one chemical compound as both a photosensitising and a radiosensitising agent for the treatment of tumours by the combined application of photodynamic therapy and boron neutron capture therapy.

Meso-substituted tetra-cationic porphyrins photosensitize the death of human fibrosarcoma cells via lysosomal targeting.

In this paper we present a study on the intracellular localisation and the efficiency of cell photoinactivation of a series of derivatives of 5,10,15,20-tetrakis-(4-N-methylpyridyl)-porphine (C1), whose degree of lipophilicity was varied through replacement of one methyl group with an alkyl chain of various length. Human HT1080 fibrosarcoma cells exposed to the various C1 derivatives (0.25 microM) for 24 h and irradiated with increasing doses of red-light (0.45-27 J/cm2) were inactivated with different efficiencies. The efficiency of cell photoinactivation increased with the increasing length of the hydrocarbon tail and lipophilicity and correlated with the efficiency of the porphyrin accumulation into the cells. Despite the presence of positive charges, these porphyrins did localise rather selectively in lysosomes while mitochondrial localisation was not evident, as demonstrated by fluorescence microscopy studies. Studies on isolated mitochondria provided evidence that the porphyrin uptake and distribution in these organelles were not modulated by the transmembrane potential but were exclusively controlled by partitioning phenomena which might have prevented mitochondria localization in whole cells. Our findings demonstrated that these porphyrins entered the cells through the endocytotic pathway and were transported to lysosomes whose pH increased rapidly upon irradiation. Lysosomal damage did not cause any intracellular redistribution of the porphyrin and represented the primary event causing cell death, very likely via necrosis.