Effectiveness of oral litholysis therapy for improving glucose intolerance and malnutrition in patients with poor results following endoscopic therapy and extracorporeal shock wave lithotripsy for calcified pancreatic stones

Abstract

We report a case of pancreatolithiasis in which glucose intolerance and malnutrition were significantly improved after starting oral litholysis therapy (OLT) with use of trimethadione. A 43-year-old female with multiple calcified stones in the main and peripheral pancreatic ducts had experienced recurrent and severe attacks of pain for 7 years (from 21 to28 years of age). Impaired glucose tolerance was first noted at the age of 32 years. We started OLT after interventional endoscopic therapy combined with extracorporeal shock wave lithotripsy failed because of kink and stenosis of the main pancreatic duct (MPD). Over the next 9 years, a significant decrease in total pancreatic calcified stone volume was shown by computer analysis of follow-up computed tomography images. Larger stones completely disappeared without attacks of pain. In addition, both glucose intolerance and insulin secretion were significantly ameliorated, followed by improvement of malnutrition. OLT may induce intraductal decompression by dissolving stones in the peripheral ducts as well as the MPD, with resulting preservation of endocrine function and improvement of malnutrition. Since the present results were obtained in a single case, further clinical trials are necessary to evaluate the value of performing OLT under various conditions to eliminate stones.

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

“…Endoscopic therapy aims to eliminate as many stones as possible from the ducts and ultimately improves the outflow of pancreatic juice. On the other hand, dimethadione shrinks and disintegrates stones, leading to smooth clearance of stones from the ducts [18,19]. These overlapping mechanisms of action appear to have played roles in the representative cases of patients 1 and 2 who underwent ESWL and endoscopic therapy prior to or during OLT, implying the usefulness of litholytic therapy combined with ESWL and endoscopic therapy.…”

“…Based on the results obtained using experimental models of obstructive pancreatitis [23,24], dissolution of pancreatic stones may prevent elevated pancreatic intraductal pressure, avoid the progressive destruction of the islets of Langerhans, and preserve pancreatic endocrine function. Recently, Ashizawa et al [19] provided more precise evidence for the therapeutic effect of OLT on pancreatic endocrine function by calculating the total calcified stone volume using computer analysis of follow-up CT images and a follow-up 75-g oral glucose tolerance test.…”

“…Of these patients who discontinued OLT, 4 showed definite litholysis, 4 showed partial litholysis, and 2 showed no litholysis. The interim progress of 2 patients, who were different from those presented in the previous section, has already been described elsewhere [18,19].…”

“…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].…”

Citric Acid Loaded Hydrogel-Coated Stent for Dissolving Pancreatic Duct Calculi

“…Trimethadione is a common antiepileptic agent that causes significant damage to the liver and kidney and is converted to dimethadione by metabolic Gels 2024, 10, 125 2 of 14 demethylation in the human liver. Dimethadione is a lipid-soluble weak organic acid that diffuses rapidly to alkaline fluid compartments and dissolves pancreatic stones by releasing protons in pancreatic juice [11]. There are few drugs and medical management can be taken into consideration for patients who have poor compliance with other treatment methods [4].…”