Johannes Benninger

Acute hepatitis induced by greater celandine (Chelidonium majus)

The hepatotoxic potential of conventional drugs is well known, but herbal medicines are often assumed to be harmless. In the last 2 years, we have observed 10 cases of acute hepatitis induced by preparations of greater celandine (Chelidonium majus), which are frequently prescribed to treat gastric and biliary disorders. The course of hepatitis was mild to severe. Marked cholestasis was observed in 5 patients, but liver failure did not occur. Other possible causes of liver disease (viral, autoimmune, hereditary, alcohol, and secondary biliary) were excluded by laboratory tests and imaging procedures, and liver biopsy specimens were consistent with drug-induced damage. After discontinuation of greater celandine, rapid recovery was observed in all patients and liver enzyme levels returned to normal in 2-6 months. Unintentional rechallenge led to a second flare of hepatic inflammation in 1 patient. Greater celandine has to be added to the list of herbs capable of inducing acute (cholestatic) hepatitis. A significant proportion of unexplained cases of hepatitis may be caused by greater celandine.

Shockwave lithotripsy of salivary duct stones

Surgical extirpation of the affected gland has been necessary for cases of sialolithiasis in which the stone cannot be removed by dilatation or dissection of the salivary duct. The ability of the piezoelectric lithotripter to deliver shockwaves to a small focus makes extracorporeal shockwave lithotripsy of salivary gland stones potentially safe. Its safety and efficacy have been assessed in 51 patients with symptomatic solitary salivary stones that could not be removed by conservative measures. The stones had a median diameter of 8 (range 4-18) mm and were located in the submandibular gland in 69% of patients and in the parotid gland in 31%. A total of 72 shockwave treatment sessions (maximum 3 per patient) were given under continuous sonographic monitoring. In 45 patients (88%) complete fragmentation (fragments less than or equal to 3 mm) of the concrements was achieved. No patient needed anaesthesia, sedatives, or analgesics. The only untoward effects were localised petechial haemorrhages after 10 (13%) out of 72 treatments and transient swelling of the gland immediately after delivery of shockwave in 2/72 (3%) sessions. 20 weeks after the first session 90% (46/51) of patients were free of discomfort, and 53% (27/51) were stone free. Stone-clearance rate was higher among patients with stones in the parotid gland (81%) than among those with stones of the submandibular gland (40%). Auxiliary measures such as dilatation or dissection of the salivary duct were required only in patients with stones in the submandibular gland (20%). No long-term damage to the treated salivary gland or to adjacent tissue structures was noted during the median follow-up of 9 (1-24) months. Extracorporeal piezoelectric shockwave therapy seems likely to be safe, comfortable, and effective minimally-invasive, non-surgical treatment for salivary stones.

Pancreatic duct stones in chronic pancreatitis: Criteria for treatment intensity and success☆

BACKGROUND The aim of the study was to evaluate interventional endoscopic management of pancreatic duct stones in patients with chronic pancreatitis by describing therapeutic methods and defining factors that predict technical success. METHODS Records were retrospectively analyzed for 125 patients with symptoms caused by chronic pancreatitis with pancreatic duct stones (single 43, multiple 82) treated by interventional endoscopy, including extracorporeal shockwave lithotripsy. RESULTS Technical success was achieved in 85% of patients (11 patients by mechanical lithotripsy, 114 by piezoelectric extracorporeal shockwave lithotripsy). There were no serious complications from lithotripsy. Univariate analysis disclosed a statistically significant association between treatment success and patient age as well as prepapillary location of stones. A greater therapeutic effort was necessary in patients with stones located in the tail of the pancreas, 2 or more stones, a stone 12 mm or more in diameter, or who have had a longer duration (>8 years) of the disease. However, with exception of the last parameter, correction for multiple testing of data removed statistical significance. CONCLUSIONS Extracorporeal shockwave lithotripsy enhances endoscopic measures for treatment of pancreatic duct stones when mechanical lithotripsy fails. Middle-aged patients in the early stages of chronic pancreatitis with stones in a prepapillary location proved to be the best candidates for successful treatment. Unfavorable patient-related or morphologic factors can be compensated for through more intense efforts at therapy.

Piezoelectric lithotripsy: Stone disintegration and follow-up results in patients with symptomatic gallbladder stones

One hundred symptomatic patients with radiolucent gallbladder stones were treated with a new piezoelectric lithotripter and oral chemolitholytic agents. Stone disintegration was achieved in 99 of these patients (99%) with a mean (+/- SD) maximum fragment size of 5.1 +/- 4.1 mm. Significant differences were found when the mean (+/- SD) fragment sizes of single stones less than or equal to 20 mm (4.2 +/- 2.5 mm) were compared with those of single stones greater than 20 mm (5.8 +/- 3.4 mm; P less than 0.05) and multiple stones (6.2 +/- 3.8 mm; P less than 0.05), respectively. None of the patients required anesthesia, analgesics, or sedatives before or during the treatment. The stone-free rates for all patients followed up for up to 4-12 months (mean +/- SD, 10.7 +/- 2.9 months) were 18% (1 month), 25% (2 months), 38% (4 months), 52% (8 months), and 67% (12 months). Partly significant differences were obtained in stone-free rates for single stones (less than or equal to 20 mm) compared with larger stones (greater than 20 mm) and multiple stones (P less than 0.05), respectively. Serious adverse reactions (i.e., cholestasis and pancreatitis) were observed in only 3 patients (3%). These conditions were induced by fragment impaction in the common bile duct. In 2 of these patients, endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy was required. It is concluded that piezoelectrically generated shock waves are suitable for the effective and safe disintegration of gallbladder stones in humans. The anesthesia-free and analgesia-free shock-wave application opens up the possibility to perform biliary lithotripsy as an outpatient procedure. The stone-free rate achieved in combination with oral bile acids is most promising for single stones (less than or equal to 20 mm).

Evaluation of sensitivity and inter- and intra-observer variability in the detection of intestinal metaplasia and dysplasia in Barrett's esophagus with enhanced magnification endoscopy

Objective. Magnification endoscopy with acetic acid or dye for diagnosis of Barretts esophagus is presently undergoing clinical evaluation. Current studies report good accuracy in predicting specialized intestinal metaplasia. To date, however, there is no definitive information on the inter- and intra-observer variability of these methods applied to the diagnosis of normal and dysplastic Barretts mucosa. Material and methods. Sixty patients with endoscopically suspected Barretts esophagus were investigated prospectively with the zoom endoscope after contrast enhancement of the mucosa with 1.5% acetic acid. Two hundred and twenty-three enlarged and histologically investigated areas of gastric, cardiac, normal and dysplastic Barretts mucosa were photodocumented and in randomized sequence presented to 4 endoscopists in a blinded manner (2 with and 2 without experience of zoom endoscopy for evaluation). The reference for the first evaluation (A1) was standard endoscopic photographs of the respective, histologically confirmed mucosal entity. In a second evaluation (A2), the pictures were again interpreted by the same blinded investigators, but this time a modified pit-pattern classification as proposed by Sharma et al. was employed as the evaluation reference. Results. The diagnostic sensitivity for specialized intestinal metaplasia and dysplasia in Barretts esophagus calculated for the A1 evaluation ranged – investigator dependently – from 54.9% to 80.7% and for A2 from 42.2% to 81.5%. The inter- and intra-observer variability for the evaluation procedure A1 and A2 was high (all kappa values <0.4). In particular, the inexperienced investigators demonstrated high intra-observer variability and low sensitivity in comparison with the experienced investigators. Conclusions. The diagnosis of Barretts mucosa using enhanced magnification endoscopy after acetic acid instillation is associated with a high level of interobserver variability. One reason is a frequent mismatch between cardiac mucosa and non-dysplastic Barretts mucosa.

Extracorporeal shockwave lithotripsy of gallstones in cystic duct remnants and Mirizzi syndrome

BACKGROUND Although the efficacy of extracorporeal shockwave lithotripsy for treatment of bile duct calculi is established, there are few studies of the value of extracorporeal shockwave lithotripsy for cystic duct remnant stones and for Mirizzi syndrome. METHODS Patients who required extracorporeal shockwave lithotripsy for cystic duct stones were identified in a cohort of 239 patients with bile duct stones treated by extracorporeal shockwave lithotripsy between January 1989 and December 2001 at a single institution. The medical records of these patients were reviewed. Follow-up information was obtained by telephone contact. OBSERVATIONS Six women (age range 19-85 years) underwent extracorporeal shockwave lithotripsy for cystic duct stones after failure of endoscopic treatment measures. Three of the patients presented with retained cystic duct remnant calculi (one also had Mirizzi syndrome type I), and 3 presented with Mirizzi syndrome type I. The stones were fragmented successfully by extracorporeal shockwave lithotripsy in all patients; the fragments were extracted endoscopically in 5 patients. Endoscopy plus extracorporeal shockwave lithotripsy was definitive treatment for all patients except one who subsequently underwent cholecystectomy. CONCLUSIONS Gallstones in a cystic duct remnant and in Mirizzi syndrome can be successfully treated by extracorporeal shockwave lithotripsy in conjunction with endoscopic measures. Extracorporeal shockwave lithotripsy is especially useful when surgery is contraindicated.

Ten years experience with piezoelectric extracorporeal shockwave lithotripsy of gallbladder stones.

Background A critical review of the experience with extracorporeal shockwave lithotripsy (ESWL) of gallbladder stones is needed to clarify whether this method should continue to be applied to patients. Methods Patients with symptomatic gallbladder stones were treated by piezoelectric ESWL according to a prospective protocol between 1988 and 1997. ESWL treatment was limited to a maximum of three (solitary stones <20 mm diameter) to five sessions (larger solitary or multiple stones) and 3000 pulses per session. Univariate and multivariate analyses of pretreatment and treatment variables were performed to investigate their impact on fragmentation efficacy and stone clearance. A tree-based analysis was used to identify prognostically homogenous subgroups of individuals with maximum benefit from ESWL. Results Four hundred and eight patients, 76% female and 24% male, with a mean age of 46 (SD, 13) years, were selected for evaluation. Cox regression analysis identified three pretreatment variables with significant prognostic impact: (1) number of gallstones >1 (relative risk, 2.6 (95% CI, 1.9–3.5)), (2) size of stones >17 mm (1.7 (1.4–2.2)), and (3) computed tomography (CT) density of stones >55 Hounsfield units (H) (1.4 (1.1–1.8)). According to tree-based analysis, the stone clearance rate after 1 year was 85% (95% CI, 75–91%) for solitary stones <16 mm, 79% (70–86%) for solitary stones ≥16 mm with a CT density <84 H, 45% (32–55%) for solitary stones ≥16 mm with a CT density ≥84 H, and 42% (30–51%) for multiple stones. Five years after stone clearance, recurrence occurred in 43% of patients (95% CI, 39–47%). Conclusions ESWL treatment showed an acceptable stone clearance in the case of small solitary gallbladder stones (<16 mm) or larger solitary stones with a CT density <84 H, but a very low success rate in the case of multiple stones. The poor long-term success, however, is an important argument against the use of ESWL of gallbladder stones.

Rezidivierende Fieberschübe mit abdominellen Schmerzen und Emesis

ZusammenfassungEin 34-jähriger türkischer Patient wurde wiederholt mit der Diagnose „akuter Schub einer chronischen Pankreatitis“ aufgenommen. Klinisch imponierten abdominelle Schmerzen mit Fieber bis 39,2°C und Erbrechen. Laborchemisch zeigten sich erhöhte Entzündungsparameter und leicht erhöhte Pankreasenzyme. Der Patient erholte sich unter Nulldiät und Schmerzmedikation in wenigen Tagen spontan von seinen Beschwerden. Bei entsprechender Symptomatik und ethnischer Zugehörigkeit ist unbedingt auch das Familiäre Mittelmeerfieber in die differenzialdiagnostische Überlegung einzubeziehen und ggf. eine Therapie mit Colchizin durchzuführen, auch wenn gentechnische Analysen nicht die typischen Mutationen aufzeigen können. Eine rechtzeitige und konsequente Therapie kann die drohende Amyloidnephropathie weitgehend verhindern.AbstractA 34 year-old Turkish patient was admitted to hospital several times with the same symptoms of abdominal pain, fever up to 39.2°C and vomiting. The diagnosis always was an acute attack of chronic pancreatitis. The inflammation scores in the blood were high and he had a moderate increase in pancreatic enzymes. He always got well in a few days on a strict diet and regime of analgesics. Taking these symptoms and his ethnic affiliation into consideration, differential diagnosis should include familial Mediterranean fever (FMF). Therapy with colchicine should be initiated even if genetic testing does not reveal the mutation characteristics for FMF. Immediate and consistent therapy helps to avoid amyloid nephropathy as the most dangerous complication of this disease.

Extrakorporale piezoelektrische Stoßwellenlithotripsie

Im Jahre 1985 wurde die erste erfolgreiche Behandlung von Gallenblasensteinen durch extrakorporale, elektrohydraulisch generierte Stoswellen durchgefuhrt [9]. Aufgrund der technischen Weiterentwicklung stehen heute 3 unterschiedliche Prinzipien der Stoswellenerzeugung zur Verfugung (elektrohydraulisch, elektromagnetisch und piezoelektrisch). Beim piezoelektrischen System werden die Stoswellen durch einen selbstfokussierenden Schallstrahler erzeugt, der mosaikartig aus mehreren 1000 Keramikteilchen aufgebaut ist, die durch einen Spannungsimpuls schlagartig in Schwingung versetzt werden. Die entstehende hochenergetische Druckwelle (= Stoswelle) wird uber entgastes Wasser fortgeleitet und in den Korper eingekoppelt. Die konkave Kalottenform des Schallwandlers ermoglicht die direkte Fokussierung der Stoswelle im Brennpunkt. Die Ortung erfolgt uber je einen der 2 in der Langsachse des Schallstrahlers eingebauten Ultraschallscanner (Abb. 1).