Digoxin biotransformation

Serum digoxin and metabolites were assayed in plasma and urine by HPLC in 10 dialysis-dependent patients with end-stage renal failure (group I) and in five patients with comparatively normal renal function (group II) after ingestion of 150 muCi 3H-digoxin-12 alpha. Thirteen patients were on maintenance digoxin therapy and were at steady state. Metabolites found regularly but usually in small amounts, were 3 beta-digoxigenin and its mono- and bis-digitoxosides, and 3-keto and 3 alpha(epi)-digoxigenin. Quantitatively the most abundant metabolites were polar and averaged 26% (7 to 76) of the radioactivity in plasma 6 hr after drug, and 60% (11 to 88) for digoxin for all 15 patients. Neither values between group I and II for the polar metabolites nor digoxin differed significantly. The metabolites reacted with antibody to digoxin to varying degrees and may make up an important component of the serum digoxin concentration when determined by standard radioimmunoassay. In some patients, digoxin undergoes extensive biotransformation, mainly, we suggest by hydrolysis, oxidation, epimerization, and conjugation to polar end-metabolites.     

Synchronous adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma in a single stomach

BACKGROUND: Synchronous gastric adenocarcinoma and primary gastric mucosa-associated lymphoid tissue (MALT) lymphoma are rare, and the characteristics of these tumors are still unclear. METHODS: Histology of endoscopic and surgical specimens of 6012 gastric adenocarcinoma and 25 primary gastric MALT lymphoma cases were reviewed. RESULTS: Five cases of synchronous tumors were found among 25 primary gastric MALT lymphoma patients (20.0%) and among 6012 gastric adenocarcinoma patients (8.3%). Helicobacter pylori was detected only in two cases (40.0%) of these five synchronous cases. In only one case, two types of malignant cells were mingled each other as a colliding tumor. In other four cases, two pathologies coexisted separately. These two types of malignant tumors were not distinguished by endoscopic or gross findings. CONCLUSIONS: Although gastric adenocarcinoma coexists with MALT lymphoma at a relatively high frequency, synchronous carcinoma can be misinterpreted as a multifocal separated lesion of MALT lymphoma owing to their macroscopic resemblance. Therefore, gastric MALT lymphoma patients should be carefully examined by endoscopy, and any suspicious area must be biopsied considering the possibility of coexisting adenocarcinoma. In addition, etiologies other than H. pylori should be considered in these synchronous tumors.     

A case of successful treatment using "wrapping therapy" for huge hepatocellular carcinoma

This case is about a male in his 50's. In May 2004, he consulted a nearby doctor with abdominal pain and was pointed out a huge mass in the liver. He was diagnosed as hepatocellular carcinoma over 10 cm in diameter with chronic hepatitis type B. Because the tumor concurred with intra-hepatic metastasis along with lymph node metastasis, we planned transhepatic arterial embolization (TAE) as a first choice of treatment and performed twice. However, because of the tail inside part of the tumor was supplied from the gastroduodenal artery (GDA) and right gastroepiploic artery (RGEA) which were nutrient arteries, an effective TAE was impossible. The enhancement lesion that seemed viable was shown by enhanced CT. Therefore, a wrapping therapy (surgical decollateralization+silicon membrane sheeting) was performed under laparotomy for the purpose of cutting off blood supply to the part of the viable lesion in August of the same year. The tail inside part of the tumor that seemed viable fell into necrosis by wrapping alone, and the serum PIVKA-II level decreased within normal limit. As of ten months after the treatment, the patient is still alive without aggravation.     

A case report of complete obstruction of the left main bronchus caused by recurrent esophageal carcinoma with pulmonary embolism of right lung after surgery for esophageal cancer

A 54-year-old woman complained of dyspnea, due to complete obstruction of the left main bronchus caused by recurrent esophageal carcinoma, was transferred to our department about two months after curative resection (with preoperative chemotherapy for T4 cancer) in July 2004. She suddenly developed a severe shortness of breath with anxiety, and arterial blood gas analysis revealed a PaO2 of 25 mmHg (FiO2 1.0). The presence of pulmonary embolism was diagnosed by pulmonary perfusion scintigraphy. Thrombolytic therapy with urokinase was started to keep the air way. Fogarty catheter and bronchoscopic Nd-YAG laser treatment was performed. After that, an expandable metallic stent (EMS) was placed at the site of obstruction without any troubles, and there was a striking improvement in her condition of respiration and atelectasis. The radiation therapy was initiated and completed safely. The tumor lesion had disappeared on CT scan after the radiation therapy (a total dose of 50 Gy). We experienced a case that could be rescued from an advanced respiratory failure caused by one side air way obstruction and another side's blood circulation disorder.     

Tumor suppressive role of a 2.4 Mb 9q33-q34 critical region and DEC1 in esophageal squamous cell carcinoma

The key genes involved in the development of esophageal squamous cell carcinoma (ESCC) remain to be elucidated. Previous studies indicate extensive genomic alterations occur on chromosome 9 in ESCC. Using a monochromosome transfer approach, this study provides functional evidence and narrows down the critical region (CR) responsible for chromosome 9 tumor suppressing activity to a 2.4 Mb region mapping to 9q33-q34 between markers D9S1798 and D9S61. Interestingly, a high prevalence of allelic loss in this CR is also observed in primary ESCC tumors by microsatellite typing. Allelic loss is found in 30/34 (88%) tumors and the loss of heterozygosity (LOH) frequency ranges from 67 to 86%. Absent to low expression of a 9q32 candidate tumor suppressor gene (TSG), DEC1 (deleted in esophageal cancer 1), is detected in four Asian ESCC cell lines. Stably expressing DEC1 transfectants provide functional evidence for inhibition of tumor growth in nude mice and DEC1 expression is decreased in tumor segregants arising after long-term selection in vivo. There is 74% LOH in the DEC1 region of ESCC primary tumors. This study provides the first functional evidence for the presence of critical tumor suppressive regions on 9q33-q34. DEC1 is a candidate TSG that may be involved in ESCC development.