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.     

Intravenous immunoglobulin induction treatment in flow cytometry cross-match-positive kidney transplant recipients

Many recent studies have demonstrated increased acute humoral, cellular, subclinical, or chronic rejection, and decreased allograft survival in flow cytometry cross-match-positive kidney transplant recipients. The use of newer techniques and more sensitive of enzyme-linked immunosorbent assay (ELISA) or Flow Beads (microparticle based methods), donor-specific anti-human leukocyte antigen (HLA) antibodies have been detected in these immunologically high-risk patients. Intravenous immunoglobulin (IVIG) has immunomodulatory effects and has been demonstrated to downregulate anti-HLA antibodies in highly sensitized dialysis patients awaiting transplantation. Our initial studies demonstrate that IVIG induction treatment is promising in flow cytometry cross-match-positive kidney transplant recipients, and thus, those patients should not be excluded from receiving transplantation despite a positive flow cytometry cross match. Further studies with long-term follow-up are required to determine the effective dose and duration of IVIG treatment, and additional studies are needed to determine the most accurate tests for risk stratification.     

How much Reliable Is Alvarado Scoring System in Reducing Negative Appendectomy?

There is still an ongoing debate, especially regarding early diagnosis of acute appendicitis. Early surgery leads to inadequate evaluation of acute abdominal pain and negative appendectomy, whereas delayed surgery leads to appendicitis perforation complications. The diagnosis of this condition is considerably difficult, especially due to subtle early symptoms and clinical condition. The aim of the present study was to identify whether the Alvarado scoring system could reduce the incidence of negative appendectomy in patients who will undergo surgery for acute appendicitis. Patients who underwent surgery with acute appendicitis prediagnosis were retrospectively classified as negative appendectomies (group A) and positive appendectomies (group B) according to histological diagnosis. All groups were evaluated for age, gender, Alvarado scores, and parameters. Two hundred eighty-one patients were included in the study. Group A contained 71 (25.3 %) patients, and group B contained 210 (74.7 %) patients. There was a significant difference in WBC, left shift, rebound, and change of pain localization between the groups (p?=?0.002, p?<?0.001, p?<?0.001, and p?=?0.023, respectively). Alvarado scores were significantly different between the groups (p?<?0.001). In logistic model examination, the major factor was the Alvarado score (7 or above) and the minor factor was spreading pain. The Alvarado scoring system can be used to reduce negative appendectomy in patients who will undergo surgery with acute appendicitis.     

The role of surface ECG and transthoracic echocardiography for predicting postoperative atrial fibrillation after coronary artery bypass surgery

OBJECTIVE: To evaluate the roles of surface electrocardiogram (ECG) and transthoracic echocardiography (ECHO) for prediction of atrial fibrillation (AF) after coronary artery bypass grafting (CABG). METHODS: This study was conducted from 2002-2004 at the Cardiovascular Department of Hacettepe University, Ankara, Turkey. Seventy consecutive patients were enrolled in this study that underwent elective CABG. A 12-lead ECG was recorded one day before cardiac surgery and was repeated during the 5 days after CABG. P-wave dispersion (PWD) was defined as the difference between maximum and minimum P-wave duration. Differences in P-wave duration were compared between the pre- and postoperative 12-lead ECG measurements. RESULTS: Postoperative AF developed in 17 (24%) cases of 70 patients. The PWD was found to be significantly higher in patients with AF preoperatively (60+/-19 versus 47+/-13, p=0.003), postoperative first day (56+/-12 versus 44+/-11, p<0.002) and fifth day (51+/-29 versus 41+/-11, p<0.001). Patients with AF were significantly older, the mean age of the AF group was (68+/-7) years and of the sinus rhythm (SR) group was (59+/-10 years) (p<0.001). The AF group had left ventricular systolic dysfunction (56+/-13% versus 56+/-8%, p=0.042, preoperatively; 49+/-8% versus 60+/-10%, p=0.001, postoperatively) and a larger left atrium (46+/-5 versus 39+/-5 mm, p<0.001, preoperatively and 44+/-7 versus 39+/-5 mm, p=0.046, postoperatively) than the SR group. CONCLUSION: This prospective study demonstrated that PWD on surface ECG and additional echocardiographic parameters are simple and reliable indexes to predict the development of AF after CABG.     

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.     

When COVID‐19 delays the management of an urgent heart condition: A rare case of a spontaneous dissection of two coronary arteries

Some severe life‐threatening conditions could be misdiagnosed during the current COVID‐19 pandemic.