Prospective multicentre clinical study on inter- and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori.

OBJECTIVES: We report on a large prospective, multicentre clinical investigation on inter- and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori. METHODS: Therapy-naive patients (n = 2004) who had undergone routine diagnostic gastroscopy were prospectively included from all geographic regions of Austria. Gastric biopsy samples were collected separately from antrum and corpus. Samples were analysed by histopathology and real-time PCR for genotypic resistance to clarithromycin and quinolones. Clinical and demographic information was analysed in relation to resistance patterns. RESULTS: H. pylori infection was detected in 514 (26%) of 2004 patients by histopathology and confirmed in 465 (90%) of 514 patients by real-time PCR. PCR results were discordant for antrum and corpus in 27 (5%) of 514 patients, indicating inhomogeneous infections. Clarithromycin resistance rates were 17% (77/448) and 19% (84/455), and quinolone resistance rates were 12% (37/310) and 10% (32/334) in antrum and corpus samples, respectively. Combination of test results per patient yielded resistance rates of 21% (98/465) and 13% (50/383) for clarithromycin and quinolones, respectively. Overall, infection with both sensitive and resistant H. pylori was detected in 65 (14%) of 465 patients. CONCLUSIONS: Anatomically inhomogeneous infection with different, multiple H. pylori strains is common. Prospective clinical study design, collection of samples from multiple sites and microbiologic methods that allow the detection of coinfections are mandatory for collection of reliable data on antimicrobial resistance patterns in representative patient populations. (ClinicalTrials.gov identifier: NCT02925091).

[The history of prostate cancer from the beginning to DaVinci]. / Die Geschichte der Prostatektomie - Von den Anfängen bis DaVinci.

For hardly any other organ can the development of medicine and technical advances in the last 150 years be so clearly illustrated as for the prostate. The history of radical prostatectomy was initially characterised by the problems in approaching this relatively difficulty accessible organ. In 1867, Theodor Billroth in Vienna performed the first partial prostatectomy via a perineal access. In 1904, Hugh Hampton Young and William Stewart Halsted at the Johns Hopkins Hospital in Baltimore / USA carried out the first successful extracapsular perineal prostatectomy and opened up a new era. In Germany, Prof. Friedrich Voelcker in Halle in 1924 developed the so-called ischiorectal prostatectomy. But it was left to Terence Millin to publish in 1945 the first series of retropubic prostatectomies. In 1952, the sacroperineal approach according to Thiermann and the sacral prostatectomy according to were introduced. Finally, in 1991 another new era in prostate surgery started with the first laparoscopic prostatectomy. This development peaked in 2011 with the presentation of the laparoscopic DaVinci prostatectomy by Binder. Originally a stepchild of urological surgery that was to be avoided whenever possible due to the fear of serious complications, the prostate has progressed in the course of time to an obscure object of lust. The stepchild has become the favorite child.

Results of a new method to stop acute bleeding from esophageal varices: implantation of a self-expanding stent.

BACKGROUND: Acute bleeding from nontreated esophageal varices is associated with a mortality rate of 30% to 50%. Various pharmacologic and interventional methods to stop acute bleeding are available. However, for 10% to 20% of patients, therapy fails to stop the bleeding. This study aimed to assess the SX-ELLA Stent Danis Set (which has a self-expanding metal stent) instead of a balloon probe for compression of esophageal varices. METHODS: Using a multidisciplinary approach, a self-expanding stent was placed in 39 patients between January 2003 and August 2007. For 34 of these patients with ongoing bleeding from esophageal varices, stent implantation was performed with the SX-ELLA Stent Danis Set, and the patients were included in this study. For all these patients, common methods failed to stop hemorrhage. With the SX-ELLA Stent Danis Set, the stent was implanted with a positioning balloon that enabled delivery without X-ray control. After implantation of the stent, its position was controlled by endoscopy and computed tomography (CT) scan. RESULTS: For all 34 patients, the implantation of the esophageal stent succeeded in stopping ongoing bleeding. No stent-related complications occurred during or after stent implantation. No bleeding recurrence was observed during the stent implantation (median time, 5 days; range 1-14 days). For all the patients, the stent could be extracted by endoscopy without any complications using an extractor. Nine patients died of hepatic failure within 30 days after the procedure. No rebleeding occurred. CONCLUSIONS: The use of a self-expanding stent to stop acute bleeding from esophageal varices is a new therapeutic method. The authors' initial experience, which involved no method-related mortality or complications, is encouraging. More data are necessary to confirm their results.

The use of self-expanding metal stents to treat acute esophageal variceal bleeding.

BACKGROUND AND STUDY AIMS: Acute variceal bleeding is a life-threatening complication of liver cirrhosis. Essential factors for survival after variceal bleeding are the rapidity and efficacy of initial primary hemostasis. Endoscopic and vasoactive therapy is the gold standard in the management of acute variceal hemorrhage. The primary aim of this study was to evaluate the use of self-expandable metallic stents to arrest uncontrollable acute variceal bleeding. PATIENTS AND METHODS: Between November 2002 and May 2005, esophageal stents were implanted in 20 patients (18 men, two women; mean age 52, range 27-87) with massive ongoing bleeding from esophageal varices, as an alternative treatment to balloon tamponade. The patients had not been successfully managed with prior pharmacologic or endoscopic therapy. They had had one to five previous bleeding episodes (mean 2.4). Eight of the patients were in Child-Pugh grade B and 12 in grade C. A new type of stent with special introducers was developed that allowed placement without radiographic assistance. RESULTS: The stents were successfully placed in all of the patients and were left in place for 2-14 days. Bleeding from the esophageal varices ceased immediately after implantation of the stent in all cases. While the stent was in place, further diagnostic steps were carried out to optimize management of the patients' illness and portal hypertension. No recurrent bleeding, morbidity, or mortality occurred during treatment with the esophageal stent. All of the stents were extracted without any complications after definitive treatment had been started. CONCLUSIONS: In this pilot study, the new method of implantation of an esophageal stent was found to be a safe and effective treatment for massive bleeding from esophageal varices in patients with liver cirrhosis. These initial clinical results will of course have to be confirmed in comparative studies including a large number of patients.

Laparoscopic azygoportal disconnection procedure with a bipolar feedback controlled sealing system in a porcine model.

BACKGROUND: To examine the feasibility of a new, minimally invasive procedure for the devascularization of the proximal stomach and distal esophagus to prevent recurrent variceal bleeding in portal hypertension in a new animal model. MATERIAL AND METHODS: Portal hypertension was created by laparoscopic clip ligation of the portal vein on 20 pigs. After 2 weeks the azygoportal disconnection procedure was performed with the LigaSure-ATLAS instrument. RESULTS: There were 16 pigs out of 20 that survived both operations. Two died during introduction of anesthesia, one because of a cardiac arrest (second operation). One pig died resulting from necrosis of the gastric and esophageal wall. Autopsy (2 weeks later) showed that there was a complete arterial devascularization. At autopsy, none of the remaining 16 pigs had esophageal varices or necrosis of the stomach or esophagus. CONCLUSION: Laparoscopic azygoportal disconnection is a less invasive method for the prevention of rebleeding and seems to be safely performed with the LigaSure-ATLAS instrument.

[Congo red-negative light chain disease with intractable diarrhea]. / Kongorotnegative Leichtkettenerkrankung mit intraktablen Durchfällen.

A 56-year-old man was admitted due to chronic diarrhea with progressive weight loss (30 kg within 1 year). All results of medical investigations were normal. The suspected diagnosis of a neuroendocrinological neoplasm could not be established; there was also no evidence for a lymphoma or amyloidosis. Chronic diarrhea and weight loss persisted over the ensuing weeks. Additionally, impairment of renal function and heart insufficiency with consecutive pericardial effusion as well as peripheral facial paralysis and peripheral neuropathy could be observed. Six months after hospital admission, the patient died due to progressive multiple organ failure. Postmortem examination revealed normal bone marrow. Only with additional immunohistochemical investigations of all organs could the diagnosis of a systemic Congo red-negative light chain disease be established.

Regulation of CD23 expression by Notch2 in B-cell chronic lymphocytic leukemia.

The original observation that sera from patients with chronic B-cell lymphocytic leukemia (B-CLL) contain high amounts of soluble CD23 (sCD23), which reflect disease activity and tumor load has been confirmed by numerous reports and serial determinations of sCD23 are now recognized as important indicators of disease progression. The reason why the leukemic cells over express CD23 and subsequently release large quantities of sCD23 as compared to healthy persons or patients with other lymphoproliferative disorders is still not clear. However, progress has been made in understanding the mechanism leading to the upregulation of CD23 in the leukemic cells. Following is an update on clinical data and a short review on the potential functions of CD23 as well as its regulation by Notch2 in B-CLL.

Induction of apoptosis by proteasome inhibitors in B-CLL cells is associated with downregulation of CD23 and inactivation of Notch2.

Recently, proteasome inhibitors (PI) have attracted interest as novel anticancer agents in B-cell chronic lymphocytic leukemia (B-CLL). A prominent feature of B-CLL cells is the high expression of CD23, which is closely related to cell survival and is regulated by Notch2. Since several components of the Notch signaling cascade are tightly regulated by proteasomal degradation, we studied the effect of PI on Notch2 activity and CD23 expression. Exposure of B-CLL cells to PI led to induction of apoptosis, a time- and dose-dependent downregulation of CD23 expression and a decline in DNA binding of transcriptionally active Notch2. In contrast, the transcription factor NF-AT and its putative target gene CD5, which is highly expressed in B-CLL cells, were unaffected. When the late phase of PI-induced apoptosis was arrested by inhibition of caspase 3, the reduction of Notch2 activity was still observed, indicating that reduction of active Notch2 took place already during an earlier phase of apoptosis. Enforced expression of constitutively active Notch2 decreased PI-mediated apoptosis in a human B-cell line. These data indicate that downregulation of CD23 and loss of Notch2 activity are early steps in PI-induced apoptosis of B-CLL lymphocytes and may be part of the full apoptotic response.

Novel technique of laparoscopic azygoportal disconnection for treatment of esophageal varicosis: preliminary experience with five patients.

BACKGROUND: Liver cirrhosis leads frequently to the development of ascites and a formation of varicose veins in the esophagus. The latter presents increased mortality risk. Recently, significant progress in laparoscopic technology enabled devascularization of the proximal stomach in a less invasive way. The results experienced by five patients are presented. METHODS: Laparoscopic azygoportal disconnection was performed by means of novel technique (Danis procedure) in five men with esophagus varices bleeding (2nd to 11th events) and liver cirrhosis stage Child-Pugh B and C. This procedure was performed after all other methods had either failed to prevent recurrent bleeding or were refused by the patient. Five ports were positioned on the upper abdominal wall. The veins in the lesser omentum were divided by means of the LigaSure-Atlas device. The stomach coronary vein was visualized, and all the proximal branches toward the esophagus as well as the short gastric vessels were divided. The diaphragm hiatus was opened, and the distal esophagus was dissected. The paraesophageal venous collaterals also were divided, and the remaining varicose veins of the esophagus were interrupted by transmural stitching. RESULTS: All the patients survived the minimally invasive procedure. Two of them died 9 and 16 months after surgery, respectively, because of liver insufficiency. No bleeding event from varicose veins in the esophagus occurred postoperatively. CONCLUSION: Laparoscopic azygoportal disconnection is a less invasive method for prevention of rebleeding from varicose veins in the esophagus. Further studies are necessary to confirm these preliminary results.

Recurrent hyperparathyroidism after total parathyroidectomy due to multiple ectopic parathyroid glands in a patient with long-term haemodialysis.

We report the rare case of a recurrent hyperparathyroidism after total parathyreoidectomy due to multiple ectopic glands in a patient on long-term haemodialysis. In a today 47 years old man with membranoproliferative glomerulonephritis intermittent haemodialysis therapy was started in 1975. In 1982 an advanced secondary hyperparathyroidism with a parathormone (PTH) level > 500 pg/l was diagnosed; later on PTH concentration increased to 2,550 pg/ml. In 1987 total parathyroidectomy with parathyroid autograft into the left forearm was performed. After parathyroidectomy the PTH level fell to 150 pg/ml. In 1993 PTH concentration increased again to 1,750 pg/ml. There was no evidence for recurrent parathyroid glands in the neck or forearm. Therefore, we investigated the substernal region by 99mTc-tetrofosmin scintigraphy and magnetic resonance imaging. Both investigations showed evidence for two ectopic parathyroid glands in the anterior mediastinum. In June 1999 in an open thoracic surgical procedure only the greater parathyroid gland in the anterior mediastinum was isolated, but a second gland was detected in the posterior mediastinum. Both parathyroid glands were resected (histologically hyperplastic parathyroid gland tissue). After surgery the PTH level decreased to 340 pg/ml, but later on PTH increased again to > 1,000 pg/ml in January 2001. A control 99mTc-tetrofosmin scan showed evidence for a third ectopic parathyroid gland in the anterior mediastinum. Recurrent secondary hyperparathyroidism can rarely be caused by recurrent ectopic parathyroid glands in the mediastinum.

The incidence of thrombovenous and thromboembolic complications in kidney transplant patients with recurrent glomerulonephritis is dependent on the occurrence of severe proteinuria.

BACKGROUND: Patients with recurrent glomerulonephritis (RG) after kidney transplantation are at high risk for thromboembolic events but it is unclear when the risk begins to increase. PATIENTS AND METHODS: We evaluated the risk for thrombovenous and thromboembolic complications in relation to the occurrence of severe proteinuria (> or = 2 g protein in 24-hour urine) in 15 renal allograft recipients with biopsy-proven RG, who had received 20 allografts RG. The total period of observation was 53 (10-91) months. The post-transplant period before the occurrence of severe proteinuria lasted 18 (1-34) months and the subsequent proteinuric period until the end of the study, 35 (9-85) months. RESULTS: The monthly incidence of thrombovenous and thromboembolic complications was only 1/18 in the first period before and in contrast, 11/35 in the subsequent period after the occurrence of severe proteinuria. The mean urinary protein excretion increased from 0.4 +/- 0.1 g/day immediately after transplantation to 6.1 +/- 4.8 g/day at the end of the study (p < 0.001). During the same period there was a 1.2-fold increase of fibrinogen (from 366 +/- 88 to 442 +/- 120 mg/dl, p < 0.025) and a 1.2-fold decrease of antithrombin III (from 110 +/- 12 to 92 +/- 12%, p < 0.001). All thrombotic complications occurred in 6 patients with 9 grafts; at the end of the study this group showed higher fibrinogen concentrations (454 +/- 155 versus 433 +/- 89 mg/dl, NS) m and lower antithrombin III levels (88 +/- 11 versus 97 +/- 11%, p < 0.05) than the group without thrombotic complications. CONCLUSION: In kidney transplant patients with RG a high risk for thrombovenous and thromboembolic complications can be obs- served after the occurrence of severe proteinuria; this can mainly be explained by high fibrinogen and low antithrombin III levels. Anticoagulation therapy should be started in patients with RG immediately after the occurrence of severe proteinuria.

Reconstitution of endogenous interferon a by recombinant interferon in hairy cell leukemia.

Recombinant human IFN alpha (rhIFN-alpha) plays an important role in the treatment of hairy cell leukemia (HCL). However, the mechanisms leading to its beneficial effect are not completely clarified, and there is no information on IFN-alpha gene expression in this disease. Therefore, we investigated the pattern of IFN-alpha gene expression and protein production in HCL and their potential regulation by rhIFN-alpha. Blood samples from 10 patients with HCL and 8 healthy donors (HD) were investigated. Expression of IFN-alpha mRNA was assessed by reverse transcription-PCR analysis in peripheral blood mononuclear cells (PBMCs) under basal conditions and on induction with rhIFN-alpha and polyionosinic-polycytidylic acid [poly(I.C)]. IFN-alpha concentrations in plasma and culture supernatants were measured by immunoassays, and intracellular IFN-alpha was evaluated by fluorescence-activated cell sorting analysis. Results showed that, in contrast to blood samples from HDs, freshly isolated PBMCs from un treated HCL patients did not express IFN-alpha mRNA, whereas IFN-alpha transcripts were found in patients who were under rhIFN-alpha therapy Plasma of untreated patients contained no, or extremely low levels of IFN-alpha as compared with plasma of treated patients and HDs. Ex vivo treatment of PBMCs with rhIFN-alpha or poly(I.C) resulted in a remarkable up-regulation of IFN-alpha at the mRNA and protein level. In HCL, however the amounts of IFN-alpha protein remained less than in HD. Inhibition of IFN-alpha transcription was found after exposure of PBMCs to serum fron untreated patients. Finally, a reduced capacity to produce IFN-alpha was found within B- cell, T-cell, and monocyte compartments in HCL patients which could be enhanced by rhIFN-alpha. The results demonstrate the ability, of rhIFN-alpha to up-regulate the expression of IFN-alpha gene and protein production and suggest that priming the production of endogenous IFN-alpha is a critical step in the mechanism of action of rhIFN-alpha in HCL.

[Serum uric acid level in type 1 and type 2 diabetic patients]. / Serum-Harnsäurespiegel bei Typ-1- und Typ-2-Diabetikern.

In 50 type-1 and 50 type-2 diabetic patients serum uric acid levels were measured. Type-1 diabetics showed significantly lower serum uric acid levels in comparison to type-2 diabetics (p < 0.02). This significant difference has been observed in both women (p < 0.001) and men (p < 0.01). Serum uric acid level was lower in type-1 diabetics than in healthy controls but only in diabetic men the difference was statistically significant (p < 0.001). Male type-2 diabetic patients showed serum uric acid levels similar to the controls, but levels were higher in women with type-2 diabetes (p < 0.001). The results of this study show that in type-1 diabetic patients the serum uric acid levels are lower in normal (creatinine clearance > or = 80 ml/min) as well as in slightly decreased (creatinine clearance < 80 ml/min) glomerular filtration rate. But in type-2 diabetic patients the serum uric acid levels were significantly higher when glomerular filtration rate was below 80 ml/min in contrast to normal renal function (p < 0.05).

Effect of mild dietary protein restriction on urinary protein excretion in patients with renal transplant fibrosis.

In recent studies, it has been demonstrated that strict dietary protein restriction has a beneficial effect on renal transplant patients who show chronic rejection, or transplant fibrosis respectively; however, the protein intake in those investigations usually has been below 0.6 g/kg day, and such a strong restriction may be associated with both a negative nitrogen balance, and low patient compliance. Our study was therefore undertaken to investigate whether the same beneficial effect could be attained with a more moderate dietary protein restriction in renal transplant recipients. In a randomized cross-over study, 14 patients with biopsy-proven transplant fibrosis received a mildly protein restricted diet (0.7 g/kg/day), and a normal protein diet (1.2 g/kg/day) respectively during two 3-week periods. In the patients undergoing moderate protein restriction, a significant reduction in urinary albumin, and total protein excretion, as well as a decrease in albumin/creatinine ratio was observed at the end of the 3-week period when compared to the patients on normal protein diet (p < 0.05). The 51Cr-EDTA-clearance did not differ at the end of each of these dietary periods. In contrast to earlier studies with lower protein intake, the moderate protein restriction in our investigation was not associated with a decrease in serum proteins. In conclusion, a mildly restricted protein intake has also proved effective in significantly reducing the urinary protein excretion in patients with renal transplant fibrosis, yet, without causing decreasing serumprotein-concentrations, which are a sign for a negative nitrogen balance.