Dietary Melatonin and Glycine Decrease Tumor Growth through Antiangiogenic Activity in Experimental Colorectal Liver Metastasis

Despite multimodal treatment strategies, clinical outcomes of advanced stage colorectal cancer (CRC) patients remain poor. Neoadjuvant/adjuvant chemotherapy efficacy is limited due to chemoresistance, toxicity, and negative side effects. Since both melatonin and glycine have anti-cancer activities without relevant side effects, this study was designed to investigate their combined effects in experimental CRC liver metastases. CRC metastasis with CC531 cells were induced in male Wistar rats. Melatonin and glycine alone or their combination were supplemented for 14 days (n = 100). Blood parameters, a micro-computed tomography scan (tumor volume over time), and immunohistochemistry for Ki67 and CD31 expression in tumor tissue were compared between groups. Melatonin and glycine alone significantly reduced the tumor volume by 63.2% (p = 0.002) and 43% (p = 0.044) over time, respectively, while tumor volume increased by 8.7% in the controls. Moreover, treatment with melatonin and glycine alone reduced the tumor proliferation index. Most interestingly, the combination therapy did not have any influence on the above-mentioned tumor parameters. The leukocyte count was significantly increased with melatonin at the end of the experiment (p = 0.012) which was due to a high lymphocytes count. Tumor microvascular density was significantly reduced in all treatment groups. The results of this study suggest an inhibitory function for melatonin and glycine alone in the case of CRC liver metastasis growth by acting as natural antiangiogenic molecules, followed by angiogenesis-dependent cancer proliferation and immunomodulation.     

The relationship between the supply of cardiac catheterization laboratories, cardiologists and the use of invasive cardiac procedures in northern New England

OBJECTIVES: Utilization rates of coronary angiography and cardiac revascularization have been found to vary between areas. This study addresses the relationship between resource supply and procedure rates. METHODS: We compared the association of per capita catheterization laboratories, per capita cardiologists and multi-provider markets (where more than one hospital offers coronary angiography services) with the utilization rates for angiography and cardiac revascularization in northern New England, USA. Administrative data were used to capture invasive cardiac procedures. Small area analyses were used to create coronary angiography service areas. Linear regression methods were used to measure associations between the resource supply and utilization rates. RESULTS: Variation in the use of invasive cardiac procedures was strongly associated with the population-based availability of catheterization facilities and multi-provider markets and unrelated to cardiologist supply or need (as reflected in the hospitalization rates for myocardial infarction). In the multivariate model, an increase of 1 catheterization laboratory per 100,000 population was associated with an increase in the angiography rate of 1.62 per 1000 population; those service areas with multi-provider markets were associated with an additional increase in the angiography rate of 1.27 per 1000 population (R2 = 0.84, P = 0.0006). There was a moderately strong relationship between the catheterization laboratories per capita and the revascularization rates (R2 = 0.43, P = 0.029). Angiography rates were highly associated with cardiac revascularization rates: an increase in the angiography rate of 1 per 1000 population was associated with a 0.46 per 1000 increase in the cardiac revascularization rate (R2 = 0.85, P = 0.0001). CONCLUSIONS: Our work suggests that current efforts to address variation in cardiac procedures through activities such as appropriateness criteria, guidelines and utilization review are misdirected and should be redirected towards capacity, in this case the supply of catheterization facilities.     

Surgical treatment of non-malignant laryngotracheal stenosis

The objectives of this study were the following: (1) to analyze the results of surgical treatment of non-malignant subglottic laryngeal and tracheal stenosis, (2) to evaluate the feasibility and technical aspects of the video mediastinoscopy for the mobilization of the mediastinal trachea, (3) to evaluate the influence of the early internal condition of the anastomosis on the development of restenosis. From 1996 up to 2013, 75 patients aged 11–78 years underwent surgery for post-intubation/tracheostomy (71 patients), post-traumatic (3 patients), and idiopathic (1 patient) subglottic laryngeal and tracheal stenosis. Twenty-three (30.7 %) patients with subglottic laryngeal and upper tracheal stenosis underwent cricotracheal resection and thyrotracheal anastomosis (group A), while 52 (69.3 %) patients with tracheal stenosis underwent tracheal resection and cricotracheal or tracheotracheal anastomosis (group B). The length of the resected segment in patients of groups A and B was 28–55 (42 ± 11) mm and 18–65 (36 ± 14) mm, respectively, (p = 0.22). Perioperative complications within 30 days occurred in eight (34.8 %) patients of group A, and in six (11.5 %) patients of group B (p = 0.04). There was one intraoperative and one postoperative death on the third day due to heart failure. The excellent results were achieved in 63 (86.3 %), satisfactory in 8 (11.0 %), and unsatisfactory in 2 (2.7 %) patients. The incidence rate of perioperative complications is related to the location of the stenosis and the type of the resection and anastomosis. Video mediastinoscopy simplifies the mobilization of the mediastinal trachea, which allows for carrying out the anastomosis with minimal tension. Early internal abnormalities of the anastomosis predict its restenosis.     

Increased postoperative peritoneal adhesion formation after the treatment of experimental peritonitis with chlorhexidine

Background and aims Chlorhexidine is known as a substance that produces adhesions. However, in an experimental model of peritoneal injury, lavage with chlorhexidine and saline solutions produced a similar number of adhesions. This study was designed to test the hypothesis that chlorhexidine gluconate 0.05% solution used for the treatment of peritonitis increases formation of postoperative peritoneal adhesions as compared to standard lavage with saline solution.Material and methods Forty Wistar rats were randomly allocated to gastric or faecal peritonitis groups. In each group rats were further randomly subdivided into saline or chlorhexidine peritoneal lavage groups. After 30 days the rats were killed and intraperitoneal adhesions were evaluated by adhesion score and grading.Results Adhesion scores were statistically significantly different between saline and chlorhexidine groups in both gastric and faecal peritonitis models. In the faecal peritonitis chlorhexidine group a 20% small bowel intussusception rate was observed, while there were no such complications in the other study groups. The conglomerate of organs formed by dense adhesions was present in 60% of cases when gastric peritonitis was lavaged by chlorhexidine and in only 10% when saline solution was used (P<0.05). Neither chlorhexidine nor saline solutions have caused such dense adhesions in faecal peritonitis.Conclusion Peritoneal lavage with chlorhexidine gluconate 0.05% solution in the treatment of experimental peritonitis results in increased adhesion formation.     

Spinal hernia tissue autofluorescence spectrum

The laser intervertebral disc decompression may provide appropriate relief in properly selected patients with contained disc herniations. The present investigation aims to characterise intervertebral disc material by autofluorescence induced by laser light. Degeneration of the intervertebral disc is associated with progressive biochemical changes in disc material. Percutaneous laser disc decompression has become rather popular for the treatment of lumbar disc herniation, but there are problems in the selection of patients. For this purpose, recognition of the disc composition is necessary. We propose a new type of spectroscopic investigation. It is advantageous to the characterization of intervertebral disc material. Intervertebral disc specimens were removed during open surgery from different disc locations. Preoperative patients’ MRI was evaluated using the Pfirrmann disc degeneration and Komori scale for migrating of herniated nucleus pulposus. Adjacent slices of stained disc sections were evaluated by histology/histochemistry and autofluorescence spectra. Comparison of the MRI, spectral, histological and histochemical data was performed. The MRI Komori scale correlated with the histology Boos degeneration index. In the histochemistry, collagens other than collagens I and II of the disc were distinguished with best positive correlation coefficient (0.829) and best negative one (?0.904) of proteoglycans of sequester to Boos index. A correlation of the IV Gaussian component of the hernia spectra with the Boos index was established. The Gaussian component correlation with different collagen types and proteoglycan was determined for the disc and sequester. “Autofluorescence-based diagnosis” refers to the evaluation of disc degeneration by histological and histochemical evaluation; it can provide additional data on the degeneration of an intervertebral disc.     

Malignancies after kidney transplantation: 3 clinical case reports

Post-transplant malignancies present an aggressive course and are a significant cause of morbidity and mortality. Tumours of viral ethiology have the greatest risk in renal transplant recipients. Oncogenic effect of immunosuppressive therapy is another major risk factor of post-transplant malignancy. We report cases of three different types of malignancies developed after kidney transplantation: non-Hodgkin’s lymphoma, Kaposi’s sarcoma and germ cell testicular cancer (nonseminoma).