Suicide attempt by an overdose of sitagliptin, an oral hypoglycemic agent: a case report and a review of the literature.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a newer class of oral hypoglycemic agents for the management of diabetes that elevate the plasma concentration of active glucagon-like peptide-1 via inhibition of DPP-4. They effectively lower not only glycosylated hemoglobin levels, but also fasting and postprandial plasma glucose levels. Patients with diabetes occasionally consume an overdose of oral hypoglycemic agents in suicide attempts: the prevalence of depression is high in patients with diabetes, and depression is a strong risk factor for suicide. We encountered an 86-year-old woman with type 2 diabetes and depression, who was transferred to the emergency room 4h after ingestion of 1,700 mg of the DPP-4 inhibitor sitagliptin (1,700 mg is 17 times greater than the approved maximum dose). Upon arrival, she was fully conscious, plasma glucose was 124 mg/dL, and serum immunoreactive insulin level was 5.81 µU/mL. Thereafter, the plasma concentration of sitagliptin rose to 3,793 nM, which is 4.5 times higher than the value found under regular treatment with the maximum dose. The patient did not suffer from hypoglycemia, suggesting that a single oral overdose of sitagliptin is unlikely to cause hypoglycemia. A literature review of oral anti-diabetic agents revealed that overdose of biguanides is occasionally fatal when immediate intensive care is not provided. In summary, sitagliptin is a good treatment option for diabetic elderly patients or patients with psychiatric disorders who are suicidal and do not require insulin.

Percutaneous transretroperitoneal direct approach to occlude a major shunt in a patient with extrahepatic portal-systemic encephalopathy.

A 73-year-old woman had sudden dystrophy and amnesia in our hospital. Her serum ammonia level was high. Marked collateral vessels from the splenic vein to the left renal vein around the spleen were seen on a computed tomography (CT) scan with contrast enhancement. An abdominal angiogram showed that the direction of the splenic vein was hepatofugal on superior mesenteric arterial portography, with a marked splenorenal shunt on splenic arterial portography. Hepatic encephalopathy due to a marked extrahepatic portal-systemic shunt was diagnosed. Transjugular retrograde obliteration (TJO) was attempted, but the catheter and guide wire could not selectively approach the splenorenal shunt because of many outflow routes. We punctured the vessels from the left side of the back under ultrasonographic guidance. We injected microcoils and ethanolamine oleate to completely obliterate the shunt. Marked collateral vessels showed no venous flow on a CT scan after treatment. The serum ammonia level was in the normal range. There has been no recanalization of the shunt vessels for 4 years after treatment. Hepatic encephalopathy has not recurred, and no other collateral vessels have developed. To our knowledge, this is the first report to document the use of a percutaneous transretroperitoneal direct approach to occlude a major shunt in a patient with extrahepatic portal-systemic encephalopathy.

In vivo metabolic activity of CYP2C19 and CYP3A in relation to CYP2C19 genetic polymorphism in chronic liver disease.

To study whether chronic liver disease (CLD) and genetic polymorphism affect the hepatic activity of cytochrome P450 (CYP) isoforms, we compared in vivo CYP2C19 and CYP3A activities using 3-hour omeprazole hydroxylation index (plasma concentration ratio of omeprazole to its 5-hydroxylated metabolite; a higher index indicates lower CYP2C19 activity) and partial formation clearance of cortisol to 6beta-hydroxycortisol (CL(cortisol-->6beta-HC)) in 31 CLD patients (9 with chronic hepatitis; 22 with cirrhosis comprising 20 Child-Pugh type A, 1 type B, and 1 type C) and 30 healthy subjects with different CYP2C19 genotypes. The mean (+/-SEM) omeprazole hydroxylation index in CLD patients with homozygous extensive metabolizer (EM) genotype (*1/*1, n = 8), heterozyous EM (*1/*2, n = 11; *1/*3, n = 6) genotypes and poor metabolizer (PM) genotypes (*2/*2, n = 3; *3/*3, n = 3) were 17.15 +/- 2.12, 20.02 +/- 2.63, and 26.04 +/- 3.15, respectively, which were significantly higher compared with control subjects with the corresponding CYP2C19 genotypes (0.81 +/- 0.09, 1.55 +/- 0.20, and 15.5 +/- 1.52). CLD patients with PM genotype had significantly (P < .05) higher omeprazole hydroxylation indexes than did those with homozygous EM genotype, and those with heterozygous EM genotypes had intermediate values. The mean CL(cortisol-->6beta-HC) decreased significantly (P < .001) in CLD patients compared with control subjects (1.19 +/- 0.12 versus 2.26 +/- 0.24 mL/min). Multiple regression analysis showed that CLD, serum albumin level, and CYP2C19 genotype correlated significantly (P < .05) with the omeprazole hydroxylation index, whereas no significant correlation was observed between CL(cortisol-->6beta-HC) and other variables, except CLD. Because CLD and genetic polymorphism of CYP2C19 act additively to reduce CYP2C19 activity, genotyping these patients may be of value in averting adverse reactions of drugs that depend on CYP2C19 for elimination.

Endoscopically assisted percutaneous transesophageal gastrotubing: a retrospective pilot study.

BACKGROUND: Percutaneous transesophageal gastrotubing (PTEG) was developed as an alternative route to access the gastrointestinal tract when percutaneous endoscopic gastrostomy is contraindicated. PTEG was originally performed without endoscopy. However, endoscopy may enhance safety. MATERIALS AND METHODS: A percutaneous rupture-free balloon is inserted under ultrasonographic control into an upper esophageal puncture site with a specialized needle. A guidewire is inserted through the needle into the rupture-free balloon, followed by a dilator and sheath. A placement tube is then inserted through the sheath. PTEG was performed in 85 patients (56 men and 29 women, mean age 70.5 years), 30 under fluoroscopic guidance and 55 under endoscopic guidance. These groups were subdivided into the nutrition subgroup (fluoroscopy, 20 patients; endoscopy, 23) and the decompression subgroup (fluoroscopy, 10 patients; endoscopy, 32) according to the purpose of PTEG. RESULTS: Nine (30%) of the 30 patients in the fluoroscopy group required endoscopic assistance to complete the procedure. None of the patients in the endoscopy group required fluoroscopy (P<0.05). The overall complication rate of PTEG was 16.4%. Complication rates in the nutrition and decompression subgroups were, respectively, 20.0 and 20.0% in the fluoroscopy group and 17.4 and 12.5% in the endoscopy group (NS). No patient required surgery or died because of the procedure. Survival rates did not differ significantly between the groups. CONCLUSION: Endoscopically assisted PTEG is a feasible, safe, and useful procedure. The use of endoscopy enhances visual information, may increase the safety of the procedure, and allows better confirmation of each step involved, without radiation exposure.

Genetic polymorphisms of cytochrome P450 in patients with hepatitis C virus-associated hepatocellular carcinoma.

BACKGROUND: The carcinogenic process can be modulated by exposure to endogenous or environmental substance(s) acting as carcinogens or protocarcinogens. Polymorphic enzymes of cytochrome P450 (CYP) that play a role in detoxication/toxication of such substances via metabolization may account for the interpatient variability of clinical course in cancers such as hepatocellular carcinoma (HCC). Many CYP genetic polymorphisms, which may change enzyme activity, are known to exist in Japanese. The aim of the present study was to compare the frequencies of CYP polymorphisms between hepatitis C virus (HCV)-related HCC patients and healthy subjects. METHODS: Seven mutant alleles and related genotypes of CYP in 44 HCV-positive HCC patients were chosen as follows: *1C heterozygous, *1C homozygous and *1F homozygous for CYP1A2, *4A homozygous for CYP2A6, *2A or *3 heterozygous, *2A or *3 homozygous and *2A and *3 heterozygous for CYP2C19, and *10/*5 homozygous for CYP2D6. These mutant alleles have been reported to change the CYP enzyme activity in Japanese. The frequencies of the mutant alleles and genotypes were then compared with those reported in healthy Japanese. RESULTS AND CONCLUSION: There is no statistically significant difference in genetic mutant alleles between the two groups, except for the genotype of CYP2A6*4A homozygous. The frequency of this genotype in the HCC patients (0.144) is significantly higher than that in healthy Japanese (0.034; P < 0.05; odds ratio 3.36). The clinical significance related to HCC is unknown. Further evaluation of CYP2A6*4A (deletion type) in HCV-related HCC patients is required.

Complete regression of esophageal cancer with concomitant liver metastasis achieved by concurrent chemoradiation therapy.

We report a patient with esophageal cancer with concomitant liver metastasis in whom complete response was achieved by chemoradiation therapy. A 66-year-old man was diagnosed as having stage IVB esophageal cancer with synchronous metastasis in the liver and cardiac lymph node, and concurrent chemoradiation therapy was started. The chemotherapy, consisting of 5-fluorouracil (300 mg/body per day, continuous infusion) and low-dose cisplatin (5 mg/body per day on 1-5 days every week), was performed for 7 weeks. In addition, radiation therapy (2 Gy/day on 1-5 days every week) was employed for both the local and the metastatic lesions, along with the chemotherapy. Throughout the course of this therapy, the patient did not experience severe toxicity, and this chemoradiation therapy resulted in complete regression of both the local and the metastatic diseases. Subsequently, he was followed-up as an outpatient without any maintenance therapy, and he has been free of disease for 38 months after completion of the therapy. This concurrent chemoradiation therapy may be effective for esophageal cancer even with visceral metastasis.