Strong Correlation of Basement Membrane Degradation With P53 Inactivation and/or MDM2 Overexpression in Superficial Urothelial Carcinomas

Purposes

We investigated the relationships between the degradation of basement membrane underlying superficial urothelial carcinomas, including carcinoma in situ and the functional p53 loss caused by inactivation of p53 and the overexpression of mdm2 oncoprotein.

Materials and Methods

Nuclear accumulations of p53 and mdm2 were examined immunohistochemically for 60 transitional cell carcinomas (primary lesions) and 13 accompanying (concomitant) carcinoma in situ lesions. Degradation of the basement membrane was defined as the reduction or total loss of type IV collagen expression. Whether there was up-regulation of MMP-1, MMP-2, and MMP-9 was analyzed immunohistochemically.

Results

The frequency of the degradation of basement membrane underlying grade 1 pTa tumors was 0%, grade 2-3 pTa tumors 57.1%, and primary CIS lesions 83.3%. Nuclear over-accumulation of p53 was found in 48.3% and of mdm2 in 23.3% of the primary tumors. In pTa-pT1 carcinomas, nuclear staining of p53, mdm2, or both was highly correlated with degradation of the basement membrane underlying carcinomas (p = 0.00002). In the CIS lesions, the association of p53 nuclear staining with the destruction of type IV collagen expression was of borderline significance (p = 0.03). When mdm2 overexpression was considered as a molecular abnormality together with p53 inactivation, the correlation with the degradation of the basement membrane was highly significant (p = 0.00006). Moreover, the functional p53 loss was strongly associated with the up-regulation of matrix metalloproteinases (MMPs) (p = 0.0005). This finding was well correlated with the strong association of basement membrane degradation with up-regulation of MMPs (p = 0.000004).

Conclusions

Degradation of basement membranes underlying superficial carcinomas or CIS of the urothelium was significantly related to p53 inactivation, mdm2 overexpression, or both. The expression status of mdm2 should provide better information about the progression of superficial urothelial carcinomas than the status of p53 alone.     

DNA ploidy analyses in 218 consecutive Pakistani breast cancer patients: Does it add anything?

An analysis was made to evaluate the significance of DNA ploidy in the biology and prognosis of breast carcinoma. This was done by estimating the correlation of DNA ploidy with other established prognostic markers of breast cancer, namely tumor size, tumor grade, lymph node metastasis and S-phase fraction. From 1995 up to year 2000 ploidy analysis was performed on 218 consecutive cases of infiltrating breast carcinoma by flow cytometry using formalin fixed paraffin embedded material. From the laboratory record, data regarding other pathological variables was retrieved. No correlation could be found between DNA ploidy and tumor grade, nor could there be found a correlation with tumor size. For lymph node metastasis there was a significant difference between the proportion of aneuploids and diploids having metastasis in more than 4 lymph nodes. However, no significant difference was found in axillary lymph node positive and negative groups when number of positive lymph nodes was not taken into account. The mean value of S-phase fraction for the aneuploids and the diploids was also insignificantly different. In conclusion DNA ploidy alone did not add much to predict tumor behaviour in terms of known pathologic variables.     

Serum paraoxonase-1 activities and oxidative status in patients with plaque-type psoriasis with/without metabolic syndrome

Objective: Psoriasis is a chronic immune‐mediated inflammatory skin disease associated with metabolic syndrome, which is made up of a cluster of disorders, including obesity, diabetes mellitus, dyslipidemia, and cardiovascular disease. The aim of this study was to investigate serum paraoxonase‐1 activities and oxidative status parameters in patients with plaque‐type psoriasis with or without metabolic syndrome. Methods: In this study, patients with plaque‐type psoriasis with (n=25) or without (n=27) metabolic syndrome, according to the criteria of the International Diabetes Federation (IDF), were matched for age and sex to an equally sized control group (n=25). Results: In patients without metabolic syndrome, serum paraoxonase and arylesterase activities showed mean decreases of 29 and 6%, respectively, whereas in patients with metabolic syndrome, the mean decreases in the enzymes' activities were 35 and 11%, respectively, compared with those in the control group. Serum total antioxidant capacity and total oxidant status were not statistically significant in any of the three groups. Multiple linear regression analysis revealed that HDL cholesterol and log‐transformed triglyceride were independent variables for serum arylesterase activity and that fasting glucose and diastolic blood pressure were independent variables for serum paraoxonase activity. Conclusions: These results suggest that according to the criteria of the IDF, the significant decrease observed in serum paraoxonase activity was independent of the metabolic syndrome in patients with mild‐to‐moderate plaque‐type psoriasis, whereas the significant decrease in serum arylesterase activity was associated with the metabolic syndrome. J. Clin. Lab. Anal. 25:289–295, 2011. © 2011 Wiley‐Liss, Inc.     

Comparison of Early and Late Changes in Immunoglobulins and Acute Phase Reactants after Laparoscopic Adjustable Gastric Banding in Patients with Morbid Obesity

Background

There are differences in the levels of inflammation mediators, lipids, and formed elements of the blood in morbidly obese patients compared with individuals of normal weight. In the current study, the change in these parameters was determined in patients who achieved weight loss by undergoing laparoscopic adjustable gastric banding (LAGB) by comparing preoperative, and early (3 months) and late (12 months) postoperative values.

Methods

The body mass index (BMI), weight, blood pressure, and waist circumference of 72 patients treated by LAGB procedures between September 2006 and February 2009 were measured and recorded. Pre- and postoperative 3- and 12-month C-reactive protein (CRP), immunoglobulin (Ig) G, IgA, IgM, fibrinogen (Fbg), complement components C3 and C4, total cholesterol, triglycerides, low-density lipoprotein-C and high-density lipoprotein-C levels, and leukocyte, neutrophil, lymphocyte, and platelet counts were also measured. Results were presented as mean?±?SD. The preoperative values were compared with the 3- and 12-month values. A p value?<?0.05 was considered statistically significant.

Results

BMI, weight, blood pressure, and waist circumference measurements were reduced at 3 and 12 months postoperatively compared with preoperative values (p?<?0.05). Among the inflammatory mediators, IgG, IgM, and Fbg were reduced to near-normal values, beginning in the early postoperative period (p?<?0.05). There was no significant reduction parallel to weight loss with respect to CRP, C3, C4, and IgA values at 3 months postoperatively (p?>?0.05). However, the 12-month values of these parameters were significantly reduced (p?<?0.05).

Conclusions

Morbid obesity leads to significant changes in the levels of inflammation mediators. While there is a significant reduction in some of these mediators accompanying slight weight loss in the early period following an LAGB procedure, significant changes occur in other mediators in the late period when there is a larger amount of weight loss.     

Pretransplant immunomodulation of highly sensitized small bowel transplant candidates with intravenous immune globulin

Presence of preformed lymphocytotoxic antibodies may represent a barrier to isolated intestinal transplantation (IITx). We developed an intravenous immunoglobulins (IVIg) based desensitization protocol for candidates with high panel-reactive antibodies (PRA). Six patients with a mean PRA of 72+/-22% were included in a four-level (L) protocol with escalating doses of IVIg (L1, L2), addition of mycophenolate mofetil (MMF) or plasmapheresis (L3); and anti-CD20 (Rituximab) (L4). Four of six candidates improved their PRAs (from a mean of 66.2% to 25.5%; P=0.01) and were successfully transplanted. At a mean follow-up of 8 months, number and severity of rejection episodes of protocol patients did not differ from patients with low PRA transplanted during the same period. These data support the use of IVIg to desensitize patients waiting for IITx. It increases the applicability of IITx, and reduces the waiting time and mortality on the waiting list with outcomes comparable to nonsensitized recipients.     

Childhood mediastinal masses in infants and children

We reviewed all cases of primary pediatric mediastinal masses diagnosed and treated over a 24-year period. In this study, out of 187 primary mediastinal mass cases diagnosed between 1980 and 2004 in Istanbul University Istanbul Faculty of Medicine, Cardiovascular Surgery Department, 37 pediatric primary mediastinal mass cases were retrospectively evaluated according to age, sex, symptoms, diagnostic procedure, anatomical location, surgical treatment, histopathological evaluation and postoperative adjuvant therapy. The patients ranged in age from 2 months to 15 years at the time of diagnosis, with a mean age of 8 years. There were 24 benign (64.8%) and 13 malignant (35.2%) tumors. The cases were lymphoma (27%), neurogenic tumors (21.6%), cystic lesions (18.9%), germ cell tumors (13.5%), thymic lesions (10.8%) and cardiac tumors (8.1%). Complete and partial resections of the tumor were the surgical procedures performed in 24 patients (64.8%) and 3 patients (8.1%), respectively. The three patients with a malignant tumor, in whom the entire mass could not be removed, received chemotherapy and radiation after surgery. In 10 patients with lymphoma, surgery was not a part of treatment and they received medical and radiation therapy after the establishment of the definitive diagnosis. All patients survived and were discharged from the hospital. Except for the cases with lyphoma, all patients are now free of recurrent disease. Compared to adults, children had more lymphomas and neurogenic tumors. Primary pediatric mediastinal malignancies are relatively common in infants and children. Lymphoma, neurogenic tumors and cystic lesions predominated. These differences between the age groups should also be considered when dealing with a mediastinal mass.     

Klippel-Trenaunay syndrome associated with polydactyly

Klippel-Trenaunay syndrome (KTS) manifests cutaneous vascular nevus, superficial venous varicosities, and hypertrophy of the affected limb. KTS may be associated with other developmental anomalies such as polydactyly, syndactyly, and macrocephaly. We present a case with KTS associated with polydactyly.     

Characteristics of pediatric urolithiasis in south-east Anatolia

BACKGROUND: Urolithiasis is endemic in Turkey and characteristics of urolithiasis vary in different regions of the world. The aim of the present study was to evaluate the etiological and clinical characteristics and course of pediatric urolithiasis in south-east Turkey. METHODS: The study population consisted of 81 children (52 girls) with urolithiasis at a mean age of 6.2 +/- 4.2 years who were followed up for 1-32 months. RESULTS: Metabolic disorders, anatomical defects and infection stones were found to be the etiological factor in 34.6, 29.6 and 22.2% of patients, respectively, while 13.6% of patients were considered idiopathic. Of all patients, 28.4% were admitted with acute renal failure (ARF) and 72.8% had urinary tract infection. Recurrence was seen in 19.8% of patients at presentation. The localization of the stone was found to be in the upper urinary tract, the lower urinary tract or both in 65.4, 14.8% and 17.3% of patients, respectively. Patients with multiple and bilateral stones had a higher risk for ARF than the others. The risk for chronic renal failure was significantly higher in children with multiple, bilateral or recurrent stones and with ARF at presentation. CONCLUSIONS: Early diagnosis and management of renal stones and urinary tract infections is necessary to prevent the development of ARF or chronic renal failure and to improve the quality of a patient's life.