Thiopurine maintenance therapy for ulcerative colitis: the clinical significance of monitoring 6-thioguanine nucleotide.

BACKGROUND: 6-Mercaptopurine (6-MP) is an effective maintenance medication in patients with ulcerative colitis (UC), but toxic effects like myelosuppression limit its clinical benefit. In the blood, 6-thioguanine (6-TGN) is formed from 6-MP and mediates the therapeutic efficacy and most of the toxicities of 6-MP. The level of 6-TGN depends on the activity of thiopurine methyltransferase (TPMT), inherited as 1 of its 3 polymorphic forms with low, moderate, or normal/high activity. Accordingly, the 6-MP dose needs to be pharmacogenetically guided. METHODS: Patients with quiescent UC received 6-MP as maintenance therapy and 6-TGN was assayed as its concentrations in red blood cells (RBCs) done by high-performance liquid chromatography. In a preliminary investigation, 30 mg/day 6-MP (n = 50) was given orally over 12 weeks to determine the time course of blood 6-TGN level. Then 257 patients were given 6-MP at 15-80 mg/day in a stepwise manner based on RBC 6-TGN, white blood cell count, and body weight to monitor 6-MP efficacy and safety profiles. RESULTS: At 30 mg/day 6-MP, RBC 6-TGN peaked over 4-8 weeks. In the main dosing study, the mean RBC 6-TGN level in patients who remained in remission during the 1-year observation time (n = 151) was 322.3 +/- 119.5 pmole/8 x 10(8) RBC versus 204.8 +/- 78.7 pmole/8 x 10(8) RBC in patients (n = 19) who relapsed (P < 0.001). Bone marrow suppression was seen almost exclusively at high 6-TGN concentration ranges. Further, a regression plot showed an inverse relationship between 6-TGN levels in RBC and TPMT enzyme activity. CONCLUSIONS: By regularly measuring RBC 6-TGN in patients with quiescent UC receiving 6-MP as maintenance therapy, we could monitor bone marrow suppression as well as other toxic side effects. Potentially, this strategy should enable physicians to avoid thiopurine-related adverse effects and identify individuals who may benefit most from 6-MP maintenance therapy.

Long-term prognosis of patients after endoscopic sphincterotomy for choledocholithiasis.

INTRODUCTION: The aims of the present study were to clarify the long-term prognosis of endoscopic sphincterotomy (EST) for choledocholithiasis and to evaluate the need for cholecystectomy after EST. METHODS: Between 1993 and 2007, 262 patients who underwent successful EST for choledocholithiasis were followed up for more than 6 months). Eighteen patients had previously undergone cholecystectomy (Group A), 129 had a calculous gallbladder (GB) and underwent cholecystectomy after EST (Group B), 46 had a calculous GB in situ (Group C), and 69 had an acalculous GB in situ (Group D). Late complications, including recurrence of choledocholithiasis, acute cholecystitis and biliary carcinoma, were evaluated. RESULTS: Of the 262 patients, late complications occurred in 34 patients (13.0%) and recurrence of choledocholithiasis occurred in 29 patients (11.1%). The rate of late complications was higher in Group C (23.9%) than in Group B (7.8%) (P < 0.001). The rate of recurrent choledocholithiasis was higher in Group C (17.4%) than in Group B (7.8%) (P < 0.05). Univariate analysis indicated that pneumobilia after EST was associated with the recurrence of choledocholithiasis (P < 0.001). Acute cholecystitis occurred in eight (7.0%) of 115 patients with intact GB. A gallbladder carcinoma was found after EST. Late complications were not serious and endoscopically or surgically manageable. CONCLUSIONS: EST for choledocholithiasis is safe and effective. Cholecystectomy after EST is recommended in patients with calculous GB, but is not necessary in patients with acalculous GB. Pneumobilia was associated with the recurrence of choledocholithiasis.

[Case of pancreatic mucosa-associated lymphoid tissue (MALT) lymphoma].

A 77-year-old woman underwent abdominal ultrasonic diagnosis in a screening test for diabetes mellitus. A 65 x 45 mm tumor with low echo level was revealed and located from the uncinate process of the pancreas to the body. Contrast-enhanced computed tomography demonstrated the pancreas had a low density area in the arterial phase and a comparable area in the equilibrium phase, compared with the parenchyma of the normal pancreas. Gallium-scintigraphy showed strong accumulation, consistent with the tumor. Mucosa-associated lymphoid tissue (MALT) lymphoma was diagnosed by endosonography-guided fine-needle aspiration biopsy (EUS-FNAB). Complete remission was achieved after radiation therapy.

[Retroperitoneal fibrosis and Castleman disease in two patients with high IgG4 levels].

With the cumulative increase in the number of autoimmune pancreatitis cases, the disease is now widely accepted as a symptom of IgG4-related systemic disease. We recently experienced two cases of retroperitoneal fibrosis and Castleman disease presenting high IgG4 levels without evident pancreatic lesions. Both patients were successfully treated with steroid therapy. It is necessary to acknowledge that retroperitoneal fibrosis and Castleman disease, with or without pancreatic lesions, may have aspects of IgG4-related systemic disease and that the measurement of serum IgG4 and tissue immunostaining for IgG4 should be considered for diagnosing and treating the conditions.

[A case of colonic obstruction due to post-operative stenosis of the colon and multiple enteroliths].

An 81-year-old man who had under gone two abdominal surgeries and temporary colostomy 30 years previously was admitted due to lower abdominal pain and vomiting. An abdominal X-ray film and abdominal CT scan showed intestinal distension and multiple calcareous deposits in the colon. Gastrografin enema examination revealed smooth stenosis at the sigmoid colon and many additional defects. Endoscopy could not be performed due to the stenosis. He did not agree to surgery. Seven months later, he was admitted again, due to colonic obstruction. Surgery was performed which revealed colonic obstruction as the source of post-operative stenosis of the sigmoid colon and multiple enteroliths. The stones consisted of a core and a hull and contained ammonium magnesium phosphate.

[A case of Castlemans disease (plasma cell type) in which autoimmune pancreatitis developed 6 years later].

In 1998 a 74-year-old man, he had a medical checkup and mediastinal and hilar lymph node hyperplasia were discovered. Since the lymph nodes showed a tendency to increase in size, mediastinal lymph node biopsy was performed in the following year. Castlemans disease was diagnosed, and he was followed up. In 2005, autoimmune pancreatitis (AIP) developed. At this time, the mediastinal lymph node that had been biopsied was stained with anti-IgG4 antibody. Further examinations on pancreatic lesions associated with Castlemans disease and AIP are necessary in relation to IgG4-related systemic diseases.