Dissolution of pancreatic stones by oral trimethadione in patients with chronic calcific pancreatitis

Abstract

The effect of oral dissolution therapy for pancreatic stones was evaluated in patients with chronic calcific pancreatitis. The anti-epileptic agent trimethadione was given orally to 30 outpatients at a dose of 0.9-1.5 g daily. On plain X-ray films and CT scans of the abdomen, pancreatic stones began to be dissolved around 8 months of treatment, and diminished in size and number or disappeared in 21 patients (70%) during the mean follow-up period of 32 months. The effect of trimethadione treatment on dissolution of stones was not closely related to the aetiology of the disease, distribution and size of stones, previous history of surgical interventions, or the degree of pancreatic dysfunctions. In three patients who stopped this medication of their own accord, pancreatic stones re-increased or reappeared about 6 months later. During trimethadione treatment, impaired exocrine pancreatic function returned to normal in four of nine patients examined, and diabetes mellitus was well controlled by either diet therapy alone or oral hypoglycaemic agents in eight of 10 patients who did not need insulin before trimethadione treatment. Complete relief of pain was noted in 73% of patients during the treatment. Overall gains and no change in bodyweight were observed in 83% of patients. Mild photophobia was the most common side effect, but could be easily overcome by wearing sunglasses. No severe side effects were observed in the liver, kidney, blood or the eyeground. Pancreatic stones in 30 patients not treated with trimethadione neither disappeared nor diminished spontaneously. Trimethadione treatment may be a useful tool for chemical dissolution of pancreatic stones.

Oral Litholysis in Patients with Chronic Calcific Pancreatitis Unresponsive to or Ineligible for Extracorporeal Shock Wave Lithotripsy and Endoscopic Therapy

“…In agreement, litholysis was only achieved in patients with good adherence. In the present and previous studies [17], there was no case in which litholytic therapy had to be discontinued because of adverse effects of trimethadione. The concomitant mechanisms of action of multiple procedures should also be considered in terms of treatment success.…”

“…Two-thirds of the patients had alcoholrelated chronic pancreatitis, and the remaining patients had idiopathic pancreatitis. Plain X-ray film and/or computed tomography (CT) scans of the upper abdomen showed that the distribution of the stones was diffuse in 80%, and the size of the stones [17] was small and mixed (large and small) in 94%.…”

“…The extent of litholysis during treatment was defined relative to the size and number of pancreatic stones at baseline. Litholysis was considered definite if the number or size of the pancreatic stones decreased by ≥50%, partial if the number or size of the pancreatic stones decreased by <50%, or none, when litholysis had not occurred [17]. Changes in the pancreatic and biliary ducts were evaluated using magnetic resonance cholangiopancreatography or endoscopic retrograde cholangiopancreatography (ERCP).…”

“…Eligibility for OLT was based on previously described criteria [17], with few modifications. Specifically, patients were considered eligible for OLT if they: (1) desired to undergo OLT; (2) were deemed capable of personal care or stated they were to the attending physician; (3) did not have a serious disorder of the liver, kidneys, blood, eyes, or skin; (4) did not have malignancy or findings that were suspicious for malignancy; (5) were not pregnant and did not intend to become pregnant during treatment (female patients); (6) did not have glucose tolerance abnormalities or had sufficient control of blood glucose levels if such abnormalities existed; and (7) were not hypersensitive to trimethadione.…”

“…Oral litholysis using a dimethadione precursor, trimethadione, was previously developed and shown to have efficacy for CCP as a noninvasive oral litholytic therapy (OLT) [17][18][19].…”