CUSHING'S SYNDROME, A RISK FACTOR FOR VENOUS THROMBOEMBOLISM IS A CANDIDATE FOR GUIDELINES.

OBJECTIVES: The present paper aims to review important contemporary information about VTE risk in endogenous and exogenous CS, as a substantial discrepancy exists between the results of a recent meta-analysis confirming the increased risk for VTE and the absence of CS in VTE guidelines. METHODS: An extensive search of relevant databases (e.g. PubMed, Google Scholar, and Scopus) was performed in order to establish the interconnectedness of the following terms: Cushing's syndrome, venous thromboembolism, deep vein thrombosis, pulmonary embolism. RESULTS: The analysis demonstrated that patients with CS have about ten times the risk for VTE, particularly during the first year following the diagnosis of CS. Oral glucocorticoid users (with iatrogenic CS) have a 3-fold increase in risk of VTE in comparison with non-users. The most recent 2019 meta-analysis encompassed 7142 patients with endogenous CS (including Cushing's disease) undergoing transsphenoidal surgery or adrenalectomy, and their risk of unprovoked VTE was almost 18 times higher in comparison with a healthy population. CONCLUSION: Over the past 50 years considerable evidence of increased VTE risk in CS has been accumulated. It pertains to both endogenous and exogenous type of CS and has been confirmed in the vast majority, if not all the available studies, including meta-analyses. Nevertheless, official CS guidelines make no mention of CS as a VTE risk factor, even though it is important that not only physicians who treat CS, but also physicians who manage patients with suspected VTE be aware of increased VTE risk.

Diaphragmatic breathing exercises and pelvic floor retraining in children with dysfunctional voiding.

BACKGROUND: Dysfunctional voiding (DV) in neurologically normal children is characterized by involuntary intermittent contractions of either the striated muscle in external urethral sphincter, or the pelvic floor during voiding. Urinary incontinence, pelvic holding maneuvers, voiding difficulties, urinary tract infections (UTIs), constipation and vesicoureteral reflux are highly associated with DV. AIM: To investigate the role of abdominal and pelvic floor muscle (PFM) retraining in children with DV. DESIGN: Prospective clinical controlled study SETTING: Outpatient clinical facility POPULATION: Forty-three children, 5-13 years of age, with dysfunctional voiding METHODS: In addition to standard urotherapy (education, timed voiding, adequate fluid intake, voiding posture and pattern, constipation management and hygiene issues), children were assigned abdominal and PFM retraining. Diaphragmatic breathing exercises were done in lying and sitting positions, for the purpose of achieving abdominal muscle relaxation. PFM retraining consisted of low-level three-second contractions followed by thirty-second relaxation periods. Selected children received pharmacotherapy (anticholinergics or desmopressin). Recurrent symptomatic UTIs were treated with antibiotic prophylaxis. Uroflowmetry with PFM electromyography and ultrasound residual urine volumes were obtained before and at the end of the 12-month treatment period. Clinical manifestations and uroflowmetry parameters were analysed before and after the therapy. RESULTS: After one year of therapy, urinary incontinence was cured in 20 out of 24 patients (83%), nocturnal enuresis in 12 out of 19 children (63%), while 13 out of 19 children (68%) were UTI free. All 15 patients recovered from constipation. Post-treatment uroflowmetry parameters showed significant improvements and a bell-shaped curve was observed in 36 out of 43 children. CONCLUSION: In combination with standard urotherapy, abdominal and pelvic floor muscle retraining is beneficial for curing urinary incontinence, nocturnal enuresis and UTIs in children with DV, as well as for normalizing urinary function. Further trials are needed to define the most effective treatment program which would result in the best treatment outcome. CLINICAL REHABILITATION IMPACT: To improve clinical and objective treatment outcome in dysfunctional voiders. Diaphragmatic breathing and pelvic floor muscle exercises are simple and easy to learn and could be assigned to children aged 5 or older. As they do not require special equipment, they can be performed at all health care levels.

Estimation of the relative liver perfusion using two methods of radionuclide angiography in the patients with hemodynamic disorders in the portal system.

The aim of this study is the assessment of the relative arterial and venous contribution to the total liver blood flow (hepatic perfusion index-HPI), with two methods (S1 and S2), and estimation of their value. With this correction, HPI nonsignificantly increases (p>0.05) in all the groups of patients, with a very high correlation between the HPI (S1) and HPI (S2) values (p<0.01). In comparison to the portal perfusion in controls, values were significantly (p<0.01) lower in chronic active hepatitis and liver cirrhosis and differed between themselves (p<0.01). In the groups of cirrhotic patients with esophageal varices, sclerosated esophageal varices, recanalized umbilical vein, portal thrombosis and cavernous portal vein, portal perfusion was lower (p<0.01) than in controls, chronic active hepatitis and liver cirrhosis without collaterals. Both angioscintigraphic methods are useful for the estimation of the disturbances in the portal system. Because of the more exact estimation of the liver perfusion, S2 is recommended.

Radioimmunoscintigraphy of colorectal carcinomas with three different radiopharmaceuticals.

The aim of the study was evaluation of the clinical reliability of the immunoscintigraphy for the detection of metastases and recurrences of colorectal carcinomas using three different radiopharmaceutical substances. With IMACIS 1, the number of true negative findings (TN) was 4/7 and true positive (TP) 3/7, while in one patient, the results of immunoscintigraphy significantly influenced the therapeutical management. With INDIMACIS 19-9, there were 2/8 TN and 6/8 TP. In three patients, immunoscintigraphy results influenced patient further management. With ONCOSCINT in 2 patients findings were TN, in one FN and in one FP. In 3 patients, immunoscintigraphy influenced the management of the patient. Other imaging methods (CT, US, MRI) have advantage in detection of liver metastases, while immunoscintigraphy is more specific for the assessment of reccurences of the abdominal tumors. Thus immunoscintigraphy should be applied in patients with suggested recurrences and inconclusive outcome of routine diagnostic workup.

Extracorporeal shock wave lithotripsy in the management of pediatric urolithiasis.

The main objective of this paper was to evaluate the efficacy and safety of the management of pediatric urolithiasis by extracorporeal shock wave lithotripsy (ESWL). Between November 1988 and July 2000, 165 renal stones, 53 ureteral stones, and 5 bladder stones were treated in 126 pediatric patients using Siemens Lithostar lithotriptor. The ESWL treatments ranging from 1 to 7 were needed per patient (mean: 2.1). One ESWL session was performed for 49.6% of stones, two for 24.6%, three for 13.0 %, four for 5.6% and > 4 for 8.2%. The success rate for renal stone units (asymptomatic fragments less than 4 mm) was 88.2%, stone-free rate was 49.0%. The stone-free rate for ureteral stone units was 87.5%, but was 75% for bladder stones. The overall results of ESWL treatment in 126 children was satisfactory: the success rate was 90.5%, stone-free rate was 51.6%, residual fragments > 4 mm were 9.5%. General anesthesia was required in 65 children (136 treatments) under the age of 10, and only in 18 children (40 treatments) in the age 11-14. Auxiliary procedures, such as double J stent and percutaneous nephrostomy (PCN) were used in 19 and 7 patients, respectively. Perirenal hematoma in one patient and hematomas in enteric wall in another one patient were the only major complications managed conservatively without consequences. Low energy lithotripsy with the Siemens Lithostar in our series of pediatric patients was safe and relatively effective.

Detection of gastrointestinal and abdominal infections by 99mTc-ciprofloxacin.

BACKGROUND/AIMS: The aim of the study is detection and evaluation of the abdominal and gastrointestinal infective foci using 99mTc-ciprofloxacin (Laboratory for radioactive isotopes, Vinca). METHODOLOGY: In total 21 patients with clinical suspicion on abdominal or gastrointestinal infection were investigated. In all the patients, planar liver/spleen scintigraphy was performed. Ciprofloxacin chloride (3.5 mg) was mixed with 555 MBq of 99mTc in 3 mL of physiological solution and incubated for 20 min. After slow i.v. injection in a cubital vein, dynamic acquisition (1 f/min) was performed during the first 60 min in the position of interest, followed by static acquisition (500,000 imp) anterior and posterior view, abdomen and pelvis after 1 h and 4 h in all patients. When necessary, additional scintigrams were acquired after 24 h. In all the patients with negative or equivocal findings of planar scintigraphy, emission computerized tomography (SPECT) was performed (60 positions, 6 degrees). Interpretation was made by three independent observers. Additional data were provided using clinical findings, ultrasonography, computed tomography and magnetic resonance imaging, laboratory analyses, and surgical or microbiological confirmation of infection. RESULTS: There were eleven true-positive findings, seven true negative, two were false negative while one was false positive due to intestinal obstruction. Sensitivity was 79%, specificity 91%, positive predictive value 92%, negative predictive value 77%, accuracy 84%. CONCLUSIONS: According to our results, scintigraphy with radiolabeled ciprofloxacin is a useful method for detection and assessment of exact localization of abdominal and gastrointestinal infections.

[Radionuclide detection of Helicobacter pylori infection].

The aim is the assessment of the HP infection in stomach using breath test and comparison to other diagnostic methods, as well as following up the effect of therapy. In 83 patients with digestive discomfort rapid urease test, histology and breath test were performed, while in 25 patients with proven HP infection the effect of therapy was followed up using breath test and clinical findings. For rapid urease test and histology, samples were taken from antral mucosa. Breath test was performed after per oral administration of the capsule of 14C- urea (37 kBq) (Izotop, Hungary and Laboratory for radioactive isotopes, Vinca) which, in the presence of Helicobacter pylori breaks up to 14CO2 and NH3. Radioactivity was measured by beta counter in the exhaled air fasting and 30 minutes after ingestion of the capsule. According to our results, the rise of activity over 100% was considered positive. From 83 patients, 58 were breath test was positive, 24 negative and one equivocal. Fast urease test was in 54 positive, in 29 negative while histology was in 57 postitive and 26 negative. Findings of the breath and urease tests were in accordance in 93% patients while breath test and histology in 98% patients. During follow up of the therapeutic effects, breath test and clinical findings were in accordance in 98% patients. Breath test can be useful in diagnosis but is a method of choice in following up the patients after therapy for H. pylori infection, because it is non-invasive, fast and precise.

Radioimmunodetection of colorectal carcinoma.

BACKGROUND/AIMS: The aim of the study is detection of the recurrences and metastases of colorectal carcinomas using 111In-labeled antibodies B72.3. METHODOLOGY: Fourteen patients underwent planar immunoscintigraphy and/or tomoscintigraphy. RESULTS: With tomography in comparison to planar scintigraphy, we can access better distinction of tumor and estimation of its size. Other imaging methods (computed tomography, ultrasonography) have an advantage in detection of liver metastases, while immunoscintigraphy is more specific for the assessment of malignant abdominal tumors and extrahepatic metastases. CONCLUSIONS: The first results point out that Oncoscint CR-103 can be useful in diagnosis of recurrences and metastases of colorectal carcinoma, viability assessment after radiotherapy and in the choice of the adequate surgical treatment in dependence of the spread of the disease.

[Indium 111-labeled antibodies in the detection of colorectal carcinoma]. / (111)In obelezena antitela u otkrivanju kolorektalnog karcinoma.

The aim of the study is detection of the recurrences and metastases of colorectal carcinomas using (111)In labelled antibodies B72.3 in 14 patients. With tomography, we can access better distinction of tumour in comparison to other structures and estimation of its size. Other imaging methods (CT, US) have advantage in detection of liver metastases, while immunoscintigraphy is more specific for the assessment of malignant abdominal tumours and extrahepatic metastases. The first results point out that Oncoscint CR-103 can be useful in diagnosis of recurrences and metastases of colorectal carcinoma, viability assessment after radiotherapy and in the choice of the adequate surgical treatment in dependence of the spread of the disease.

[Detection of abdominal infections using radio-labeled antibiotics]. / Otkrivanje infekcija u abdomenu primenom radioobelezenog antibiotika.

The aim of the study is detection of the abdominal infective foci using 99mTc-ciprofloxacin, radiopharmaceutical supposed to distinguish inflammation from infection. Twenty-one patient was investigated. There were 11 true positive findings, 7 true negative, two were false negative, while 1 was false positive. Sensitivity of the method was 79% and specificity 91%. According to our results, scintigraphy with infection is a useful method for detection and assessment of exact localization of deep seated bacterial infections, which might be useful for (differential) diagnosis, surgical treatment in due time as well as monitoring of the treatment of conservative therapy.

Long-term functional outcome of kidneys in children with urolithiasis after ESWL treatment.

The aim of this study was to determine the long-term functional outcome of kidneys in children with urolithiasis treated by means of extracorporeal shock wave lithotripsy (ESWL). The effectiveness and safety of this method in the management of pediatric urinary stone disease was also studied. This prospective study enrolled 84 children, 33 boys (age: 9.1 +/- 3.8 yrs) and 51 girls (age: 9.6 +/- 3.9 yrs), with urolithiasis who were treated using a second-generation "Siemens" Lithostar lithotriptor, in the period between 1988 and 1998. Dynamic kidney scintigraphy using (99 m)Tc-DTPA was done prior to, immediately following ESWL treatment, three months later, and again after an observation period of 12 - 67 months (38 +/- 13 months). Immediate fragmentation rate was 90 %, while the calculus clearance rate was 61 %. Glomerular filtration rate (GFR), measured by clearance of (99 m)Tc-DTPA, immediately after an ESWL treatment of 107 +/- 6 ml/min was significantly lower compared to the pretreatment value of 118 +/- 7 ml/min, but returned three months later to 121 +/- 6 ml/min, and to 131 +/- 10 ml/min at the end of the observation period. A separate analysis was performed on three groups of patients treated by ESWL: with acute calculous disease, chronic calculous disease, and chronic calculous with partial stasis. ESWL treatment in children with acute obstruction was associated with an immediate increase in GFR; however, in chronic calculous disease a decrease in GFR was found. A return of GFR to the pretreatment level was observed at the three-month control in these patients. In patients with acute stone obstruction, at 3 and 12 - 67 months after ESWL treatment, GFR of the treated kidney was found to be significantly increased compared to the pretreatment level. In contrast, in children with chronic calculous disease this increase was modest. This study has demonstrated ESWL to be an effective treatment option for urinary calculi management, which can be safely performed in a pediatric population without long-term effects on the growing kidneys.

ESWL in the treatment of stone in child with horseshoe kidney.

We report a case of struvite calculi in the child with horseshoe kidney treated by extracorporeal shock wave lithotripsy (ESWL). Complete stone clearance was obtained after 3 sessions using Siemens Lithostar Lithotriptor.

Combined treatment of immobilization staghorn stones in 14-year old boy.

We report a combined urologic treatment of bilateral staghorn stones, developed in a boy after prolonged immobilization for limb fractures. He underwent percutaneous nephrostolithotomy (PCNL) on the left side, and after three months pyelolithotomy and nephrolithotomy for stasis in the right kidney, followed by ESWL for residual calculus in the left ureter. He becomes stone free, with apparently normal kidney function.

[Evaluation of enterogastric reflux in relation to functional status of the gallbladder]. / Procena enterogastricnog refluksa u odnosu na funkcionalno stanje zucne kese.

The aim of the study was estimation of the relation between the gallbladder (GB) motility function and the presence and quantity of enterogastric reflux (EGR). We investigated 172 patients with: physiological GB function (filling and emptying)(FGB), impaired GB function (prolonged filling and ejection fraction < 45%) and afunctional gallbladder (AGB)(without visualization). The study was performed during 90 min (1 f/min) after i.v. application of 185 MB 99mTc-dietil IDA. After 30 min. test meal was given while at the end stomach was marked. According to the parameters from time activity curves over stomach and hepatobiliary system, the index of ERG was calculated, while GB filling and ejection fraction were estimated from the GB time/activity curve. We can conclude that EGR occurs more frequently in the patients with afunctional GB in comparison to those with functional and decreased motor function. Also, EGR quantity is in correlation with the impairment of the GB function.

Aortal aneurysm as a cause of ileus.

A 62-year-old patient presented with flatulence, abdominal distension and other symptoms of ileus. Roentgenographic finding found compression on duodenum. Blood pool scintigraphy ((99m)Tc erythrocytes) showed aortal aneurysm, while simultaneous gastric emptying study with liquid meal ((99m)Tc-S-colloid) showed dislocation of duodenum and compression from abdominal aortal aneurysm.

The predictive value of 131I-hippurate clearance in the prognosis of acute renal failure.

The aim of this investigation was to study the validity of the radionuclide methods in the estimation of kidney function, for prognosis and follow-up of acute renal failure (ARF). In thirty-one ARF patients, the evaluation of glomerular filtration rate (GFR) by 99mTc-DTPA clearance and effective renal plasma flow (ERPF) by 131 I-ortoiodohippurate (131I-OIH) clearance was performed within 7 days and after 6 months from ARF onset. All patients were divided in three groups according to 131I-OIH clearance values obtained within 7 days: group 1, under 150 mL/min; group 2, 150-250 mL/min; and group 3, over 250 mL/min. Seven days clearance values of both radiopharmaceuticals were found to be very low, however, GFR was found more severely impaired than ERPF. Clearance values obtained after 6 months demonstrated no recovery of renal function in the first group, partial recovery in the second and almost complete recovery in the third group. Patients with the lowest 131I-OIH clearance values at the ARF onset had no recovery of renal function, while in the other two groups recovery corresponded to initial 131I-OIH clearance values. In patients with ARF both, 99mTc-DTPA and 131I-OIH clearances were shown suitable for the follow up of renal function, however, only 131I-OIH clearance had a strong predictive prognostic value for renal function recovery in ARF.

Estimation of the enterogastric reflux by modified scintigraphic method.

BACKGROUND/AIMS: The aim of the study was to introduce the chosen and modified model of the nuclear medicine method for the detection and quantification of enterogastric reflux, as well as evaluation of its clinical validity. METHODOLOGY: The study was performed in 172 patients: with gastric and duodenal ulcer, after Billroth I and Billroth II gastrectomy, with gastroesophageal reflux, after cholecystectomy, with chronic cholecystitis and chronic duodenal disease. Acquisition was performed with a gamma camera, during 90 min after intravenous application of 185MBq 99mTc-Dietil IDA. Test meal was given in the 30th minute, while the gastric region was marked at the end of the study. On the basis of the radioactivity changes in the regions of the stomach and hepatobiliary system, the presence of enterogastric reflux was determined and its index calculated. RESULTS: In all the groups of patients, values were significantly higher than in the controls (P < 0.05). The most frequent occurrence and the largest quantity of reflux was present in patients after Billroth II gastrectomy with significantly different values from other groups of patients (P < 0.05). CONCLUSIONS: The obtained results approve clinical value of the chosen and modified scintigraphy of enterogastric reflux, as a non-invasive and physiological method, which provides exact data about its presence and quantity.

Extracorporeal shock wave lithotripsy monotherapy of 'stoned' internal ureteral stent in children. Case report.

A case of ESWL treatment, as monotherapy, of a 'stoned' ureteral stent in a 12-year-old boy was described. Two years previously, the patient had pyelolithotomy with staghorn stone removal, and double-J stent was left indwelling intraoperatively. The patient was lost for follow-up for 2 years, when he had multiple stone formation adherent to the whole length of the stent. Four ESWL sessions were required before the stent was freed for removal.

Radionuclide voiding pattern in children with unstable bladder.

BACKGROUND: The purpose of this study was to investigate bladder function parameters by means of quantitative radionuclide cystography (QRC) in anxious, irritable children with unstable bladder. METHODS: Quantitative radionuclide cystography was performed in 18 children aged between 8 and 12 years, without evidence of neurologic and nephrologic disorders. Findings were compared with those obtained in 10 healthy children aged between 7 and 10 years. The dynamics of the bladder emptying were studied after intravenous injection of 37 MBq/10 kg b.w. 99mTc-diethylenetriaminepentaacetic acid (DTPA) in the posterior views. Images of 90 frames every 2 sec. were stored in the 64 x 64 computer matrix during voiding. The patients voided into a container and the volumes were measured. RESULTS: The parameters evaluated were: functional bladder capacity (ml)--FBC, expected bladder capacity (ml)--EBC, percentage of EBC (%), voided urine volume (ml)--VV, residual urine (ml)--RU, voiding time (sec)--VT, average flow rate (ml/sec)--AFR and peak flow rate (ml/sec)--PFR. There was a statistically significant difference between controls and children with unstable bladder in the following parameters: FBC 288 +/- 33 vs. 244 +/- 27 ml (p < 0.001), % of EBC 99 +/- 6 vs. 82 +/- 6% (p < 0.0001), VV 265 +/- 37 vs. 202 +/- 35 ml (p < 0.0001), RU 22 +/- 11 vs. 48 +/- 19 ml (p < 0.007), AFR 13 +/- 5 ml/sec vs. 9 +/- 4 ml/sec. (p < 0.01) and PFR 19 +/- 2 vs. 13 +/- 3 ml/s (p < 0.0001), respectively. The VT obtained from the control group of 23 +/- 9 s did not differ significantly from the value of children with unstable bladder of 28 +/- 14 s. CONCLUSION: The results show that quantitative radionuclide cystography is a simple, noninvasive method, which allows a good separation of patients with unstable bladder from the children with normal voiding pattern.

Tissue polypeptide antigen and carcinoembryonic antigen lack diagnostic accuracy in urothelial carcinoma.

Carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) levels in serum and urine from 25 patients with bladder cancer and 42 patients with cancer of the renal pelvis/ureter have been evaluated as an aid for clinical diagnosis of urothelial cancer. The tumour CEA content varied markedly, from values obtained in normal urothelium up to 822 and 7306 ng/g wet tissue in cancer of the renal pelvis/ureter and bladder cancer, respectively. Serum and urine CEA levels were found not to correlate with the tumour CEA content. Serum CEA levels were found increased over 5 microg/L in up to 16% of bladder cancer patients, but only in 4.8% in renal pelvis/ureter cancer. Urine of cancer patients contained usually normal CEA levels. Increased serum TPA levels were found in 48% and 35.7% of patients with bladder cancer and cancer of renal pelvis/ureter, respectively. Urine TPA levels were significantly increased in both, patients with bladder cancer (p<0.001) and cancer of renal pelvis/ureter (p<0.01). The median values of urine TPA were 59, 1095 and 1325 U/L, in controls, patients with bladder cancer and cancer of renal pelvis/ureter, respectively. However, considering previously described increase of TPA in inflammatory diseases of urinary tract and in renal failure patients, results of urinary TPA obtained in the diagnostic workup of urothelial cancer should be cautiously interpreted. This study shows that serum and urine levels of CEA and TPA have no diagnostic accuracy required for clinical diagnosis of urothelial cancer.