The Potential Role of TGFβ1, TGFβ2 and TGFβ3 Protein Expression in Colorectal Carcinomas

PURPOSE: This study investigates the expression of tumor growth factors TGFbeta1, TGFbeta2 and TGFbeta3 in tissue material from patients with colorectal carcinoma and evaluates their correlation with known prognostic markers and patient survival. PATIENTS AND METHODS: The study included 124 patients with colorectal carcinoma. According to the TNM classification of malignant tumors, 26 tumors were identified as being stage I, 30 stage II, 48 stage III, and 20 stage IV, whereas 106 tumors were low-grade and 18 high-grade malignancies. On paraffin sections, the streptavidin-biotin technique using antibodies against TGFbeta1, TGFbeta2 and TGFbeta3 was applied. Morphological and immunohistochemical results were correlated with clinicopathologic parameters. RESULTS: TGFbeta1 protein was expressed in 88 out of 124 (71%) carcinomas, whereas TGFbeta2 and TGFbeta3 proteins were detected in all tumors examined. Normal colonic mucosal epithelial cells expressed TGFbeta2 (significantly less as compared to neoplastic cells; p < 0.01) and TGFbeta3 (p > 0.05 compared to neoplastic cells), but not TGFbeta1. Statistical analysis revealed a higher expression of TGFbeta1 in low-grade carcinomas (p = 0.009) and a higher presence of TGFbeta2 in advanced tumors (p = 0.008). TGFbeta1 expression was related with increased disease-free and overall survival (p < 0.05 each). The presence of TGFbeta2 was correlated with worse prognosis (p < 0.05). Cox analysis revealed that besides tumor grade and stage, TGFbeta1 expression constituted an independent prognostic factor. CONCLUSION: This study shows that in adenocarcinomas of the colon, there is a differential expression of TGFbeta1, TGFbeta2 and TGF3. TGFbeta1 may be implicated in the pathogenesis of these tumors, since it is expressed only in neoplastic but not in normal cells. TGFbeta1 is related with an increased disease-free and overall survival and constitutes an independent prognostic factor. In advanced stages, TGFbeta2 seems to be involved in tumor progression and is related with worse prognosis.     

Progression of carotid atherosclerosis and the role of endothelin in diabetic patients.

An increased thickness of the carotid artery wall is thought to be a sign of early atherosclerosis. Since vascular endothelium is the site of formation of several substances, we have investigated the rate of progression of carotid atherosclerosis and the contribution of endothelin (ET-1), lipid peroxides [measured as thiobarbituric acid reacting species (TBARS)] and 6-keto-Prostaglandin-F1A (6-keto-PG-F1A) at baseline and after 30-months. Fifty patients with Type 2 diabetes without evidence of macroangiopathy, hypertension, proteinuria or proliferative retinopathy, and 27 healthy, non-diabetic persons were studied. Arterial wall thickness was measured as the mean of the maximum intimal-medial thickness (IMT) in 16 carotid segments by b-mode ultrasound. The IMT values was significantly increased in diabetic subjects (at baseline: 1110 +/- 310 microm, after 30 months: 1260 +/- 280 microm, p < 0.01), but not in control subjects (1100 +/- 280 microm, 1200 +/- 290 microm, respectively). At baseline time both groups had similar levels of ET-1, TBARS and 6-keto-PG-F1A. In 30-months follow-up, the ET-1 level 8.0 pmol/l (5.8-10.7) was significantly elevated in diabetic subjects, compared with the level at baseline time 7.43 pmol/l (4.8-11.1) p < 0.01. No significant differences were found in the other examined parameters in the studied groups. Although insulin levels remained unchanged in the two studied groups, in 30 months follow-up, the insulin level in the diabetic subjects, 92.4 +/- 35.1 pmol/l was significantly elevated compared with those of control subjects 76.0 +/- 31.0 pmol/l, p < 0.05. In conclusion, endothelis is the main associate of the change of IMT value over 30 months in diabetic patients, in whom the extent of atherosclerosis was significantly greater than in control subjects.     

Dose and image quality optimization in neonatal radiography

In a special care baby unit, neonates, mainly premature, encounter serious to life-threatening diseases, the timely diagnosis and treatment of which may require a large number of radiographs. Increased neonatal radiosensitivity and longer life expectancy increase the risk of radiation-induced cancer, which emphasizes the importance of minimizing dose while maintaining clinically satisfactory image quality. An optimization study on radiation dose and image quality in neonatal radiography is presented. Neonates were categorized into four groups depending on birthweight. For a total of 378 chest and chest-abdomen radiographs, exposure parameters were recorded. Entrance surface dose (ESD) was estimated and dose-area product (DAP) was measured. Image quality evaluation was performed by two observers and was based on the visibility of certain anatomical features and catheters placed during treatment using a five-grade scale. ESD values increased with neonatal weight and demonstrated wide variation (16.4-76.9 microGy, mean 38.2 microGy). A wide variation was also observed in DAP values (1.2-15.0 mGycm2, mean 7.2 mGycm2). Image quality evaluation revealed the feasibility of achieving a diagnostically satisfactory image (score >70%) using both low and high tube voltage techniques, with the latter resulting in reduced ESDs. The majority of estimated ESDs are in accordance with the reference level of 50 microGy recommended by the National Radiological Protection Board for neonatal radiography. The results suggest that the use of high tube voltage techniques could result in further reductions in neonatal dose, without image quality degradation, underlying the requirement for establishing standard examination protocols for neonatal radiography with respect to neonatal weight.     

External Beam Irradiation and Restenosis Following Femoral Stenting: Long-Term Results of a Prospective Randomized Study

Purpose To assess the long-term outcome of external beam irradiation (EBI) for the prevention of restenosis due to neointimal hyperplasia, following percutaneous transluminal angioplasty (PTA) and stenting of the superficial femoral artery. Methods Sixty consecutive patients with peripheral arterial disease, who were treated with “bail-out” stent implantation in the superficial femoral artery due to suboptimal PTA, were included in this study. Patients were randomly allocated into two groups, receiving either external beam irradiation (6 MV photons, total dose 24 Gy in a hypofractionated schedule) plus antiplatelet therapy (EBI group) or antiplatelet therapy alone (control group). Results No procedure-related complications occurred, and all patients of the EBI group received the full dose of 24 Gy. During the long-term follow-up, an overall statistically significant difference was demonstrated in favor of the EBI group patients, regarding both the in-stent (log-rank test, p = 0.0072) and the in-segment binary restenosis (log-rank test, p = 0.0103). The primary patency rates were also significantly better in the EBI group at specific time-points, such as in the first (74.2% vs 46.5%, p = 0.019), second (62.5% vs 33.8%, p = 0.020), and third (54.6% vs 29.0%, p = 0.039) year, respectively. Moreover, the overall clinically driven reintervention rate was significantly lower among patients of the irradiated group (log-rank test, p = 0.038). Conclusion Our long-term follow-up analysis revealed that EBI following femoral artery PTA and stenting significantly reduces restenosis and reintervention rates, while improving primary patency.     

Unilateral leg edema in a cirrhotic patient with tense ascites

TO THE EDITOR A 61 year old man with cirrhosis and hepatocellular carcinoma developed on the background of chronic hepatitis B was admitted because of acute and gradually intensified right thigh pain and swelling, which, within a few hours, was expanded to his right foot. The patient,due to ascites refractory to diuretics, was almost weekly subjected to large volume paracentesis of ascitic fluid for the last six months; meanwhile he has developed a left inguinal, a right femoral and an umbilical hernia. It should be noted that 48 h before admission, the patient was referred to the emergency room because of dyspnoea and 5 L of ascitic fluid were removed.     

A phantom-based evaluation of an exposure equalization technique in mammography

An anatomical filter based exposure equalization technique in mammography is evaluated quantitatively using a phantom. The evaluation is carried out by a comparative observer performance study, comparing the equalization technique with a conventional one based on visualization of low contrast, 6 mm circular details and high contrast, 0.5 mm and 0.25 mm small size details. These details are situated at the phantom edge, simulating the breast periphery. Visualization of these details is studied with respect to the parameters of tube voltage, optical density, detail location and phantom thickness. Phantom images are interpreted independently by three observers using a four-point grading scale. Use of the Wilcoxon signed ranks test for paired data shows statistically highly significant improvement (p < 0.0001) in the visualization of details for the equalization technique for all values of the parameters studied. The improvement is independent of tube voltage but dependent on optical density, detail location and phantom thickness. Optimal performance is obtained for detail location closer to the outer border of the simulated breast periphery and/or further away from the film, as well as for a greater phantom thickness simulating both thick and dense breast.     

Dialysate magnesium level and blood pressure

BACKGROUND: We investigated the way dialysate magnesium (dMg) concentrations could affect blood pressure (BP) during hemodialysis (HD). METHODS: Eight HD patients underwent four midweek HD treatments consecutively, using, during each four-hour HD session, one of the following four dialysate formulations, in randomized order, which differed only with regard to dMg and dialysate calcium (dCa) concentrations (in mmol/L): 0.75 dMg, 1.75 dCa (group I); 0.25 dMg, 1.75 dCa (group II); 0.75 dMg, 1.25 dCa (group III); 0.25 dMg, 1.25 dCa (group IV). Before HD and at four 60-minute intervals during the HD sessions, BP and noninvasive measurements of cardiac index (CI) were obtained. Additionally, 14 HD patients were treated for four weeks with 0.5 mmol/L dMg, followed by four weeks with 0.25 mmol/L dMg, and another four weeks with 0.75 mmol/L dMg, in random order. In all treatments dCa was 1.25 mmol/L. BP and symptoms were recorded during each HD session. RESULTS: Mean arterial pressure (MAP) decreased to a significantly (P < 0.05) greater extent in group IV compared to the other groups. This substantial drop in MAP by 15.2% in group IV, paralleled by a 12.1% and 17% drop in CI and stroke index, respectively, was not seen in group II, despite comparable reductions in intradialytic serum Mg (sMg) of about 35% in both groups. In groups I and III, the increase in sMg by 2% did not compromise BP via vasodilatation. In the second study, treatment with 0.75 mmol/L dMg was superior to the other two treatments regarding intradialytic morbidity (P < 0.001) and BP stability (P < 0.05). CONCLUSION: We (1) identified a dialysis solution containing 0.25 mmol/L Mg and 1.25 mmol/L Ca as a major cause of intradialytic hypotension (IDH) due to an impairment of myocardial contractility, and (2) showed that increasing dMg level to 0.75 mmol/L could prevent IDH frequently seen with the use of 1.25 mmol/L dCa. Thus, manipulating dMg levels independently or in concert with dCa levels might have important implications with regard to dialysis tolerance.     

Ureteropelvic junction obstruction: an innovative approach combining metallic stenting and virtual endoscopy

PURPOSE: We report our experience with auto-expandable metallic stents for treating ureteropelvic junction obstruction. MATERIALS AND METHODS: We treated 4 patients with a mean age of 45 years who had ureteropelvic junction obstruction with placement of a self-expandable intraureteral metallic stent (Wallstent, Schneider, Zurich, Switzerland). All patients presented with recurrent ureteropelvic junction obstruction after open pyeloplasty. Excretory urography and 3-dimensional reconstruction computerized tomography were performed 1 and 6 months after stent insertion. Virtual endoscopy images were obtained at followup due to the need to define ureteral patency. RESULTS: Mean followup was 16 months (range 9 to 24). Wallstent placement was successful and immediate patency was achieved in all cases. During followup 3 patients required no further intervention and the stented ureteropelvic junction remained patent. In the remaining patient stricture recurred 2 months after initial stent insertion due to the ingrowth of scar tissue through the prosthesis. Additional intervention was deemed necessary after placing a longer 6 cm., completely coaxial overlapping metal stent. Virtual endoscopy and excretory urography findings concurred. Virtual endoscopy allows visualization of the stented ureteropelvic junction lumen cephalad and caudal to the prosthesis. It also enables easy navigation within the stent at different angles of view. CONCLUSIONS: The concept of applying metallic stents for ureteropelvic junction obstruction and adjacent adynamic ureteral segments combined with virtual endoscopy is strengthened by the results of this study.