Oval cell proliferation in cirrhosis in rats. An experimental study.

AIM: Oval cells are liver stem cells involved in liver regeneration following liver damage. Previous studies have shown that pretreatment with a hepatocyte inhibitor is required to allow full oval cell activation. This study investigates whether oval cells develop and proliferate in a model of experimental liver fibrosis without pretreatment with a known hepatocyte inhibitor. METHODS: The study comprised 66 male Wistar rats divided into two groups: A (n = 6): controls; and B (n = 60): CCl(4) injection (intraperitoneally 2 mL/kg bodyweight 1:1 volume in corn oil twice weekly). Rats were sacrificed at four, eight and 12 weeks. Liver tissues were evaluated for the degree of fibrosis (Masson's trichrome), cell proliferation (Ki67 antigen), expression of alpha-fetoprotein (AFP) mRNA (RT-PCR and in situ hybridization), AFP protein (Western blot) and cytokeratin-19. Cells with morphologic features of oval cells that were cytokeratin 19 (CK19)+ and AFP mRNA+ were scored in morphometric analysis. RESULTS: Oval cells were present in all 66 specimens; their percentage was higher in group B compared to group A (P < 0.001). AFP mRNA and protein expression increased as fibrosis advanced. Similarly, the numbers of CK19+, AFP mRNA+ and Ki67+ oval cells were higher in advanced fibrosis stages. CONCLUSION: This study demonstrates that oval cells develop and proliferate in a model of experimental liver fibrosis without pretreatment with a known hepatocytic inhibitor. However, further research is warranted in order to identify the exact molecular mechanisms involved in this process.

Tumoral and non-tumoral trachea stenoses: evaluation with three-dimensional CT and virtual bronchoscopy.

BACKGROUND: We evaluated the ability of 3D-CT and virtual bronchoscopy to estimate trachea stenosis in comparison to conventional axial CT and fiberoptic bronchoscopy, with a view to assist thoracic surgeons in depicting the anatomical characteristics of tracheal strictures. METHODS: Spiral CT was performed in 16 patients with suspected tracheal stenoses and in 5 normal subjects. Tracheal stenoses due to an endoluminal neoplasm were detected in 13 patients, whilst post-intubation tracheal stricture was observed in the other 3 patients. Multiplanar reformatting (MPR), volume rendering techniques (VRT) and virtual endoscopy (VE) for trachea evaluation were applied and findings were compared to axial CT and fiberoptic bronchoscopy. The accuracy of the procedure in describing the localization and degree of stenosis was tested by two radiologists in a blinded controlled trial. RESULTS: The imaging modalities tested showed the same stenoses as the ones detected by flexible bronchoscopy and achieved accurate and non-invasive morphological characterization of the strictures, as well as additional information about the extraluminal extent of the disease. No statistically significant difference was observed between the bronchoscopic findings and the results of axial CT estimations (P = 1.0). No statistically significant differences were observed between bronchoscopic findings and the MPR, VRT and VE image evaluations (P = 0.705, 0.414 and 0.414 respectively). CONCLUSION: CT and computed generated images may provide a high fidelity, noninvasive and reproducible evaluation of the trachea compared to bronchoscopy. They may play a role in assessment of airway patency distal to high-grade stenoses, and represent a reliable alternative method for patients not amenable to conventional bronchoscopy.

A novel study investigating the therapeutic outcome of patients with lytic, mixed and sclerotic bone metastases treated with combined radiotherapy and ibandronate.

PURPOSE: To investigate the therapeutic response of patients with different types of bone metastases treated with combined radiotherapy and bisphosphonates. PATIENTS AND METHODS: By using computed tomography 52 patients were grouped into groups of lytic, mixed and sclerotic bone lesions. All patients were treated with concomitant radiotherapy and ibandronate (10 monthly cycles) and underwent clinical and radiological evaluations prior to therapy and at 3, 6 and 10 months of follow up. RESULTS: At baseline there were statistically significant differences between the three groups for all the evaluated parameters. From 3 months onwards differences were leveled out. Statistically significant improvements were noted at all time points of evaluation for all groups in parameters such as pain (0-10), quality of life (QOL-physical functioning, 0-100) and Karnofsky performance status (KPS). The average pain score for the lytic group was reduced from 8.1 to 1.5 points at 3 months. The corresponding reductions for the mixed and sclerotic groups were from 6.2 to 0.5 and from 4.4 to 0.3 points respectively. Complete pain responses were >76.4% at all time points for all groups. Opioid consumption was also markedly reduced. Overall, the highest clinical response was noted for the lytic group, even though the mean values of pain, QOL and KPS were worse than those of the two other groups at all time points (apart from pain score at 10 months). The percentage of patients of the lytic group experiencing a complete pain response was the least of the three groups during follow up. At 10 months bone density was almost tripled for the lytic and almost doubled for the mixed group. CONCLUSIONS: Even though the therapeutic outcome for the three groups was similar, the degree of clinical response and reossification differed.

Clinical and radiological evaluation of patients with lytic, mixed and sclerotic bone metastases from solid tumors: is there a correlation between clinical status of patients and type of bone metastases?

PURPOSE: To investigate the association between the clinical status of patients with metastatic bone disease and the type of bone metastases. PATIENTS AND METHODS: 80 patients with skeletal metastases underwent both clinical and radiological assessments. Bone lesions were evaluated with computed tomography (CT), and patients were separated into three groups: lytic, mixed, sclerotic. Bone density of each lesion was measured in Hounsfield units (HU). RESULTS: Patients with osteolytic lesions had the highest mean pain score with 8.1 +/- 2.2 points, the least mean scores for quality of life (QoL) and performance status (PS) with 31.4 +/- 14.6 and 58.6 +/- 9.7 points respectively, the highest percentage and mean opioid consumption (100% and 220.9 mg of oral daily morphine equivalent respectively), and the least mean bone density (116.3 +/- 40.4 HU). On the contrary, the group with sclerotic metastases had the least mean pain score with 4.6 +/- 1.3 points, the highest mean scores of QoL and PS (61.1 +/- 15.5 and 66.6 +/- 10 points respectively), the least percentage and mean opioid requirement (55.5% and 170.6 mg respectively), and the highest mean bone density (444 +/- 86.6 HU). The differences between the three groups were statistically significant for all parameters evaluated, apart from performance status between the sclerotic and mixed groups. The correlation coefficients were statistically significant between all parameters investigated. Bone density had a strong negative correlation with pain. CONCLUSION: Our results show a clear correlation between the type of bone metastases and the clinical status of patients. Patients with excessive bone resorption suffer the most, and may be given priority in treatment. CT proved to be a practical and efficient method to investigate and classify metastatic bone lesions.

Combination ibandronate and radiotherapy for the treatment of bone metastases: clinical evaluation and radiologic assessment.

PURPOSE: Ibandronate is a single-nitrogen, noncyclic bisphosphonate with proven efficacy for reducing metastatic bone pain. In this study, we assessed the palliative effects of combined ibandronate and radiotherapy. METHODS AND MATERIALS: Forty-five patients with bone metastases from various solid tumors received external-beam radiotherapy, 30-40 Gy over 3-4.5, weeks combined with 10 cycles of monthly intravenous ibandronate, 6 mg. RESULTS: After combined therapy, mean bone pain scores (graded from 0 to 10) were reduced from 6.3 at baseline to 0.8 after 3 months, with further reductions at later time points (all p < 0.001). Opioid use decreased from 84% of patients at baseline (38/45) to 24% (11/45) at 3 months, with further subsequent reductions (all p < 0.001). Mean performance status and functioning scores also significantly improved. Bone density (assessed by computed tomography scan) increased by 20% vs. baseline at 3 months, 46% at 6 months, and 73% at 10 months (all p < 0.001). Lesion improvement was also demonstrated by magnetic resonance imaging. Treatment was well tolerated with no renal toxicity. CONCLUSIONS: In this pilot study, combined radiotherapy and ibandronate provided substantial bone pain relief and increased bone density. Computed tomography-based or magnetic resonance imaging-based evaluations offer objective methods for assessing therapeutic outcomes.