Role of plasma exchange in autoimmune hyperthyroidism complicated by severe tiamazol-induced cholestatic jaundice.

Therapeutic plasma exchange (TPE) is an alternative treatment for hyperthyroidism, resulting in a rapid decline in plasma thyroid hormones and anti-thyroid antibodies. TPE has also been used both in primary liver disease and in drug-induced cholestasis. Data on thyrotoxic patients with severe hepatic complications are scarce. Cholestasis induced by imidazol-derived anti-thyroid drugs is extremely rare. The use of TPE for treating this complication was not previously reported. We report the experience of one such patient with a favorable response to TPE. A 45-year-old male patient with Graves' disease, presented with severe jaundice and extremely high serum bilirubin levels due to hepatotoxicity induced by tiamazol. Through extensive investigation primary liver disease, including viral, metabolic, neoplastic and autoimmune disease, as a cause of cholestasis were all ruled out. The patient underwent total of 6 TPEs which in combination with low dose of glucocorticoids and standard supportive measures, resulted in normalization of thyroid hormones and normal liver function tests. TPE provided a safe, rapid and effective treatment of severe drug-induced cholestasis and auto immune hyperthyroidism. From this case we conclude that TPE should be considered as a valuable alternative therapeutic option in thyrotoxic patients with severe complications. Guidelines and indication criteria for TPE treatment in patients with hyperthyroidism are still lacking.

Long-term outcome in Serbian patients with Wilson disease.

BACKGROUND AND PURPOSE: To investigate survival rates, prognostic factors, and causes of death in Wilson disease (WD). METHODS: In the years 1980-2007, a cohort of 142 patients with WD was prospectively registered (54 presented with neurologic symptoms, 49 with hepatic symptoms, 33 had mixed form, and data were missing for six patients). The duration of follow-up for patients alive was 11.1 +/- 8.8 years. RESULTS: After initiation of treatment (d-penicillamine and zinc salts), 79% of patients had a stable or improved course of disease. Despite early diagnosis and appropriate therapy, 15 patients still had a relentlessly progressive course. Thirty patients died. The cumulative probability of survival in a 15-year period for the whole group was 76.7 +/- 4.9%. Better prognosis of WD was associated with male sex, younger age at onset, neurologic form of the disease, and treatment continuity. Causes of death were predominantly related to hepatic failure (16 patients), but also suicide (four patients) and cancer (three patients). CONCLUSION: Despite the relatively early diagnosis and treatment of our patients with WD, mortality was still considerably high.

[Endoscopic ultrasonography in choledocholithiasis].

Diagnosis of choledocholithiasis is still difficult to establish and presents a great challenge in gastroenterology and surgery of biliary tract, since it requires expensive and sophisticated examining techniques. 10 to 15% of patients with symptomatic cholelithiasis were presented with choledocholithiasis as well. By EUS is possible to establish a diagnosis of choledocholithiasis with accuracy of 90 to 100% and precisely estimate dimensions of revealed stones. The main purpose of this survey is to present a great importance and many advantages of EUS as a contemporary diagnostic method. All patients were examined by Olympus equipment for endoscopic ultrasound with radial probe working with the frequency of 7,5 and 12 MHz at the Department for Endoscopic Ultrasound of the Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia. They were previously diagnosed with choledocholithiasis by ERCP method. We examined 16 patients, which were selected by estimated risk for cholelithiasis. We have tried to evaluate the importance of diameter of choledochus, defined by common ultrasonography, as well as values of alkaline phosphatase and serum ?GT. We defined 3 groups of patients: group no.1, with 2 patients presented with a low risk for choledocholithiasis; group no.2, with 6 patients with a moderate risk for choledocholithiasis, and group no.3, with 8 patients presented with significant risk for cholelithiasis. According to obtained results, EUS presents the most effective method for detecting of choledocholithiasis, which is sometimes even more efficient than ERCP. After choledocholithiasis is previously revealed by EUS, it is much easier to decide if some invasive method such as EPT or precut papillotomy has to be used. EUS is always recommended as a diagnostic method when it is necessary to avoid some expected complications, such as pancreatitis.

[The role of endoscopic ultrasonography in diagnostic and estimation of common bile duct carcinoma invasion].

The main purpose of this survey is to present the importance of EUS in establishing a diagnosis of tumor of the choledochus. It is also important to emphasize that EUS is the most suitable diagnostic method for determination of tumor invasion to choledochus, i.e. to determine TN patient status and to predict if tumor could be successfully resected. The author would like to present his own experience in using of EUS as a contemporary method for establishing a diagnosis and effective treatment of patients with tumor of choledochus. All patients were examined by Olympus equipment for endoscopic ultrasound with radial probe working with the frequency of 7,5 and 12 MHz at the Department for Endoscopic Ultrasound of the Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia. All examined patients were subjected to surgical exploration after that. Therefore it was possible to compare preoperative estimation of tumor invasion with a final result obtained by surgical exploration. Five patients were diagnosed with tumor of choledochus localized at the distal part of choledochus. TN status of examined patients was specified by standard criteria. Estimated TN status for two patients was defined as T2N1a and T2N0, which indicate the possibility of excessive surgical treatment, what was confirmed by surgical exploration as well. A small number of patients was not possible to use for statistical evaluation. Our conclusion is that EUS presents the most effective method to estimate a degree of tumor invasion to choledochus, since it provides an accurate definition of TN patient status and predicts if tumor could be successfully resected.

[Endoscopic ultrasonography in pancreatic carcinoma].

Even though pancreatic cancer is not such a common diagnosis, its treatment is very expensive and it has a great economic impact to the health system. 5-year survival rates after excessive surgical treatment is only 5%, which imposes more careful selection of patients that have to be surgically treated. According to experience from some medical centers all over the world, EUS is considered as a high sensitive diagnostic method for establishing a diagnosis of pancreatic cancer and evaluation of TNM staging. The main purpose of this survey is to present our experience in using of EUS as a diagnostic method in establishing a diagnosis of pancreatic cancer, as well as to evaluate how reliable this method is in preoperative evaluation if tumor could be successfully resected. We examined the group of 63 patients with pancreatic cancer, which were surgically explored after EUS examination. We wanted to compare TNM status before and after the surgical treatment. All patients were examined by Olympus equipment for endoscopic ultrasound with radial probe working with the frequency of 7,5 and 12 MHz at the Department for Endoscopic Ultrasound of the Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia. Evaluation of pancreatic tumor extension to local organs (pancreas, duodenum, choledochus, stomach, colon and large veins) was performed for all patients. All regional lymph nodes were also explored. Due to low penetration ability of the probe working with the frequency of 7.5 MHz, EUS is not a suitable method for evaluation of M stage (figure 8,9). Patients were divided in different groups, specified by TNM status. For 10 patients resection was estimated as a probably successful solution, but only 8 of them was surgically treated. According to this, our estimation was 79.7% accurate, which is in accordance to results obtained from other medical centers all over the world.

[Endoscopic ultrasound (EUS) in initial assessment and follow-up of patients with MALT lymphoma treated drug therapy].

BACKGROUND: Endoscopic ultrasonography (EUS) is an important tool for diagnosis and pretreatment staging of primary gastric lymphoma. The aim of the study was to evaluate the diagnostic importance of endosonography (EUS) in gastric lymphoma; to assess the depth of tumoral infiltration in low-grade gastric lymphoma of mucosa-associated lymphoid tissue (MALT) and to assess EUS response to medical treatment (Cyclophosphamid/Mabtera and/or anti-Helicobacter pylori therapy). METHODS: 26 patients with MALT gastric lymphoma were investigated by EUS. Six of them were evaluated after the eradication of Helicobacter pylori infection and 20 after and during the cyclophosphamide/Mabtera and anti H. pylori treatment. EUS staging was compared with histopathology. Tumours were staged according to the 2000 TNM and modified Ann Arbor classification. RESULTS: Six patients were treated with anti - Helicobacter pylori eradication therapy. Full regression of lymphoma was observed in 2 of 6 (33.3%) patients, which was endoscopicaly and histologicaly proved. EUS correlated with histology in all (6/6). In 20 patients treated with cyclophosphamide/Mabtera therapy, EUS revealed regression of lymphoma in 14 cases. Positive correlation with histology was found in 11 patients (11/14; 78%). The initial EUS showed an increased wall thickness more than 5mm in 24 of 26 patients (92%). The thickening was predominantly of mucosa and submucosa and in 11 patients extended the muscularis propria. After the therapy, the gastric wall thickening returned to normal in 14 patients, however, 3 of them still had positive histology findings. In 2 cases, during the follow-up, the EUS showed remained thickening of gastric wall, whereas biopsies were negative. Six months later histology revealed progressive low-grade MALT lymphoma in this cases. CONCLUSION: EUS appears to be a sensitive procedure for initial staging and assessment of treatment response and long-term follow up in patients with gastric lymphoma. The importance of EUS lies in abbility to detect relapse early, too.

The significance of hepatopulmonary syndrome in liver transplantation.

The objective of the study is to determine the diagnostic role of pulmonary functional tests and perfusion pulmonary scintigraphy for quantifying the oxygenation and vascular abnormality in patients with liver cirrhosis. The prospective study included 70 patients with liver cirrhosis. Arterial blood gases analysis were performed in both supine and sitting positions while inhaling room air, and 15 minutes after exposure of hyperoxic mixture. Perfusion pulmonary scintigraphy using albumin macroagregate labelled with radioactive technetium (99mTc-MAA) was performed for the visualisation of intrapulmonary vascular dilatation. The diagnosis of hepatopulmonary syndrome was made in 10 (14.3%) patients. The patients with hepatopulmonary syndrome had severe hypoxemia (Pa,O2 7.41 +/- 1.81 kPa), and poor response to 100% oxygen inhalation (Pa,O2 21.07 +/- 14.41 kPa) and higher alveolo-arterial gradient (5.73 +/- 2.65 kPa). Radioisotope marker 99mTc-MAA skipped intrapulmonary circulation in all patients with HPS and in no one without pulmonary vascular dilatations. The combined approach of 100% inspired oxygen and perfusion pulmonary scintigraphy may identify early oxygenation disorders and alter the priority for liver transplantation, especially in view of potential syndrome resolution.

[Partial resection of the spleen in the treatment of benign and traumatic lesions]. / Parcijalna resekcija slezine u lecenju benignih i traumatskih lezija.

It has been thought that the spleen is an organ without important functions, until recently. That is, why splenectomy has been the procedure of choice in a treatment of splenic diseases. Even now, when we know the functional [figure: see text] importance of the spleen, splenectomy is performed frequently, regardless of its complications. The need of spleen functions salvage, favours partial resection of the spleen as competitive in a treatment of its traumatic and benign lesions. Improvement in diagnostic procedures, surgical techniques, transfusiology and postoperative treatment, will promote it as a treatment of choice. The authors of this study have experience with 17 partial resections of the spleen for traumatic, 11 for benign lesions of the spleen, and one ectopic spleen with hypersplenism, without mortality and with insignificant complications.

[Partial resection of the spleen and spleno-renal shunt in the treatment of portal hypertension with splenomegaly and hypersplenism]. / Parcijalna resekcija slezine i spleno-renalni sant u lecenju portne hipertenzije sa splenomegalijom i hipersplenizmom.

Some of serious hepatic diseases with cirrhosis may be complicated by portal hypertension, splenomegaly and hypersplenism. Splenomegaly inhibits regenerative processes of the liver, and also intensifies sequestration of the cellular components of blood up to hypersplenism. Cytopenia caused by hypersplenism is aggravated by negative hepatic influence on bone marrow activity-hemathopoesis, and also by recurrent bleeding from oesophageal varices, and from the other site of gastrointestinal tract. This circle of pathologic conditions may be interrupted only by liver transplantation, until which patients are jeopardized by acute bleeding and chronic anemia. Partial resection of the spleen and splenorenal shunt may correct portal hypertension and hypersplenism, prevent gastrointestinal bleeding, and alleviate hepatic regenerative processes inhibition. In this study, 51 patients with partial resection of the spleen and splenorenal shunt, were analyzed.

[Personal experience in embolization of liver hemangiomas]. / Nase iskustvo u embolizaciji hemangioma jetre.

INTRODUCTION: Cavernous haemangioma is the most often found benign liver tumour. Its size usually does not change, although there are cases in which it grows. Large haemangiomas can cause hepatomegaly, pain in the right subcostal area, and spontaneous ruptures. By modern diagnostic procedures they are detected more often and therefore gained more diagnostic importance. Cavernous haemangiomas, especially giant ones, can be treated surgically (enucleation or resection of a part of the liver), by embolization or by other procedures. The aim of the study was to determine the important role of embolization in the treatment of symptomatic haemangiomas with risk of rupture. MATERIAL AND METHODS: Over a period of 5 years, at the Department of Gastroenterology and Hepatology, haemangioma was discovered in 35 of 178 patients with focal liver lesions. Eighteen (51%) patients were males and 17 (49%) females. In 21 (60%) patients, the size of the tumour was 2-4 cm, in 10 (29%) 5-10 cm, and in 4 more than 10 cm. Ultrasonography, computerized tomography, celiacography, scintigraphy with blood pool and ultrasound guided liver biopsy were used to diagnose haemangiomas. Polyvinyl-alcohol (Ivalon) was used for embolization. Through femoral catheter truncus coeliacus was reached, a. hepatica was catheterized, contrast was injected, and then microembolization of peripheral branches was performed. In 10 patients, because of the size of haemangioma, symptoms or localization, and a high risk of bleeding, embolization was performed. Biochumoral parameters were analyzed on the first, the second and the seventh day after the intervention. Within the period of five years, control ultrasound examinations were performed in all patients, and results were compared. In 9 patients control liver scintigraphy with blood pool was carried out. RESULTS: Embolization was performed with polyvinyl-alcohol. During angiography which followed, avascular zones were seen. There was no statistically significant difference between biochumoral parameters before and after embolization. Five years after the embolization, a reduced size of haemangioma was found in 8 patients. The echosonographic appearance of the tumour was changed in almost all patients. All clinical symptoms disappeared. There was no bleeding. In 8 of 9 patients liver scintigraphy with blood pool was performed, and there were no "warm fields." DISCUSSION: Due to modern diagnostic procedures, haemangiomas are now more often detected. However, ultrasonography is not always specific in discovering haemangiomas. Liver scintigraphy does not always reveal the typical shape of these tumours. Every procedure has its advantages and disadvantages. Once haemangioma is detected, it is the question how to treat it. Experience of most hepatologists suggests that interventions should be performed only in case of symptomatic haemangiomas, progressively growing haemangiomas, and in case of the high risk of bleeding. Embolization of the hepatic artery, previously used only as the first part of surgical procedures is now used as the only procedure in the treatment of these tumours. Some authors reported pain and fever after this intervention, which were also noticed in our patients. The reported agranulomatous arteritis with eosinophilic infiltration was not found in our patients. There were no significant changes in biochumoral analysis; this finding confirmed that there was no necrosis around embolized haemangioma. On the basis of the follow-up of our patients we came to the conclusion that embolization of haemangioma, performed by an experienced radiologist, is a very useful procedure in the therapy of symptomatic haemangiomas and haemangiomas with a high risk of bleeding.

[Liver damage caused by sensitivity to anti-inflammatory agents]. / Ostecenja jetre izazvana senzibilizacijom na antiinflamacione lekove.

Nonsteroidal antiinflammatory drugs may cause hepatic sensibilization and impairment. The incidence of these changes is low and referential data are scarce and related mainly to reaction which clinically corresponds to hepatic or cholestatic reaction. We present a patient who is sensitive to Diclofenac and has hepatic granuloma which developed after the use of the drug. History, clinical presentation, laboratory results, US examination of the liver and pathohistologic analysis of the hepatic biopsy sample enabled us to diagnose hepatitis with granulomatous impairment. Improvement of symptoms and signs of the disease was spontaneous and without administration of glucocorticoid drugs.

[Leiomyoma of the esophagus. Case report]. / Leomiom jednjaka. Prikaz bolesnika.

Of all oesophageal tumours benign tumours account for less than 10%, of which 4% are leiomyomas. These tumours are most frequently asymptomatic, mostly localized in the lower oesophageal third. The most frequent symptoms, if any, are the following: dysphagia, unspecific retrostemal pain, heartburn, and occasionally, weight loss. Tumour enucleation is a therapy of choice in patients with oesophageal leiomyoma. In case of successful surgical removal, the prognosis is good and complains are practically eliminated. A male patient, aged 53, with paroxysmal tachycardia, in whom transhiatal enucleation was carried out in order to remove a large oesophageal leiomyoma after which cardiac complains were eliminated, is reported.

[Echohistograms of circumscribed liver lesions]. / Ehohistogrami cirkumskriptnih lezija jetre.

The term focal liver changes usually applies to benign and malignant primary and secondary tumours. However, according to echotomographic findings, tumour-like diseases, such as focal nodular hyperplasia and diseases caused by bacteria, fungi, protozoa and parasites may also be included. Improvement in echotomographic technique and use of echohistogram have recently enabled provision of data determining the aetiology, i.e. pathohistological structure of changes with computerized analysis. The study included 178 patients with circumscribed liver lesions: thirty patients had primary carcinoma, 39 had secondary carcinoma, 41 had cystic disease, 35 hemangioma, 10 focal steatosis, 23 had other circumscribed lesions, as well as 175 subjects with healthy liver. The examinations were performed using the real-time ulstrasound apparatus (Toshiba SA 100 A). Echohistograms were obtained by placing certain amount of liver tissue onto X and Y axes, to be processed and graphically presented by the apparatus. X axis showed the number of particles (N) of liver tissue on certain surface, while Y axis showed the average value (M) and maximal value (Max) of particles. Analysis of echohistographic parameters evidenced the following: mean distribution values of M, Max and N differed in different pathological conditions (Tables 1 and 2). Correlation analysis of the studied parameters revealed different values among the studied groups of patients (Table 3, Figure 1). Analysis of echohistograms and their parameters revealed differences between the tissues of the "healthy" and "affected" liver which may be significant in diagnosis of circumscribed liver changes. N/Max:N/M ratio was higher in normal liver when compared to the studied groups of patients (except for N/M subration in focal changes). Our study, as well as the studies performed by aforementioned authors, evidenced close correlation of the appearance of echohistograms and parameter ratio with density, homogenicity and greatly with vascularization of the studied tissue. It has also been evidenced that the interrelations between the echosistographic parameters are in a complexly interwoven, and partly in aetiology, or it is better to say in relations between the healthy tissue and pathological liver changes. However, it must be concluded that the series of the described cases is small to enable establishment of diagnostic criteria exclusively based on echohistograms. Similar analysis of echohistograms in circumscribed liver diseases was not evidenced in the referential literature published so far. We consider the method useful and believe that the future development of computerized ultrasound extensions will enable differentiation of lesions.

[Idiopathic congestive splenomegaly--Banti's disease]. / Idiopatska kongestivna splenomegalija--Bantijeva bolest.

Banti's disease is a condition where congestive splenomegaly can be observed in the absence of intrahepatic or extrahepatic obstruction. The diagnosis is established by splenectomy, but it is necessary to exclude liver diseases or portal vein obstruction before surgery. The advanced stage of Banti's disease may be complicated by upper gastrointestinal haemorrhages; so splenectomy has both diagnostical and therapeutical benefits. Primary lesions of the small splenic arterioles are one of the offered explanations. A patient with no intrahepatic or extrahepatic obstruction, is described. We also excluded diseases which might be complicated by splenomegaly, part of them after splenectomy. Cytogenetics showed normal female pattern. The histologic examination revealed no liver disease, but the spleen was congestive with reduced lymphoid tissue. Immunohistologically, the reduced spleen white-pulp nodules were composed of polyclonal B-cells and T-cells in a normal distribution, discarding indolent lymphoprolipherative disorder. Over one year after splenectomy the patient had no trouble. In conclusion, we believe that Banti's disease is a condition clearly separated from Banti's syndrome. We also believe that splenectomy is the treatment of choice.

[Atrial natriuretic paptide in liver cirrhosis]. / Atrijumski natriuretski peptid u cirozi jetre.

Atrial natriuretic paptide (ANP) a potent hormone with important role in sodium homeostasis has been widely investigated in experimental and clinical hepatology during last years. High serum levels are found in decompensated liver cirrhosis, condition characterised with extremely low sodium urinary excretion. This paradoxal finding is poorly understood until nowdays. High tone of sympathetic nerve activity independently increase hormone secretion in cirrhosis. Refractory ascites, rare and discouraging complication of advanced cirrhosis, can be succesfully treated, in carefully selected patients, with repeated intravenous bolus or continous infusions of ANR Serum concentrations of ANP may be used as noninvasive marker of disease activity in compensated and decompensated patients. High levels in still compensated patients predict ascites formation in soon course.