Pharmacokinetic and toxicodynamic evaluation of 5-fluorouracil administration after major hepatectomy in a rat model

Cancer Chemotherapy and Pharmacology - Chemotherapy after hepatectomy for colorectal liver metastasis has not been established, due to the toxic side effects, which are likely related to impaired...     

A case of hepatitis C-associated osteosclerosis that was improved with the combination therapy of peginterferon alfa-2b and ribavirin

Hepatitis C-associated osteosclerosis (HCAO) is a rare disorder characterized by a marked increase in skeletal mass in patients who are infected with hepatitis C virus (HCV). The clinical presentation is an acquired deep bone pain with increased serum alkaline phosphatase (ALP) activity. We present a case of a patient with HCAO who was treated with antiviral therapy. A 42-year-old Japanese man presented with severe, stabbing pain in his lower limbs. He was diagnosed with hepatitis C secondary to intravenous drug use 20 years earlier. Serum biochemical studies revealed markedly elevated ALP activity and osteocalcin levels. Skeletal radiographs showed diffuse bony sclerosis with marked cortical thickening in the long bones. The bony findings and clinical symptoms were attributed to HCAO. The HCV RNA viral load was high and the genotype was 2a. The patient was treated with peginterferon alfa-2b and ribavirin for 24 weeks. After 24 weeks of the combination therapy, the patient had a sustained virological response and clinical remission of bone pain and a decrease in the level of serum ALP. In conclusion, HCAO was improved by the combination therapy of peginterferon alfa-2b and ribavirin when the patient achieved sustained virological response. It was confirmed that HCAO was one of the extrahepatic manifestations of HCV.     

Prognostic value of preoperative peripheral blood monocyte count in patients with hepatocellular carcinoma

BACKGROUND: The prognostic significance of the leukocyte subsets in peripheral blood has not yet been investigated in hepatocellular carcinoma patients. We sought to clarify the prognostic value of preoperative peripheral blood leukocyte subset counts, especially the absolute monocyte count, in HCC patients who have undergone hepatic resection. METHODS: We retrospectively examined the relation between the preoperative absolute number of peripheral monocytes and clinicopathologic factors or long-term prognosis in 198 patients with hepatocellular carcinoma who underwent curative resection. RESULTS: Univariate analysis indicated a significantly worse 5-year disease-free survival rate in patients with a peripheral blood monocyte count > 300/mm(3) (14.8%) than in patients with a count < or = 300/mm(3) (29.2%). There were no significant differences between patients in disease-free survival based on the lymphocyte or neutrophil count. According to multivariate analysis, preoperative peripheral blood monocyte count > 300/mm(3), alpha-fetoprotein level > 100 ng/mL, aspartate aminotransferase level > 100 IU/mL, and presence of microvascular invasion were independent risk factors for disease-free survival of less than 5 years. The peripheral blood monocyte count was higher in patients of male sex or those with a noncirrhotic liver, microvascular invasion, major hepatic resection, older age (>65 years), large tumor (> or =50 mm), or increased platelet count (>100,000/mm(3)) than in patients without these characteristics. CONCLUSIONS: Our findings indicate that the preoperative absolute count (>300/mm(3)) of peripheral blood monocytes may be related to tumor progression and that it is an independent risk factor for recurrence of hepatocellular carcinoma after resection. Postoperative adjuvant chemotherapy might be necessary in patients with elevation of the preoperative absolute count of peripheral blood monocytes.     

Duodenum-preserving head resection in chronic pancreatitis

A duodenum-preserving head resection was performed in 295 patients with chronic pancreatitis and an inflammatory mass in the head of the pancreas. Ninety-four percent of patients suffered severe pain syndrome, 48% had a common bile duct stenosis, 17% a vascular obstruction in the portal vein and splenic vein branches, and 6% had a severe stenosis of the duodenum. Surgical resection of the inflammatory mass in the head of the pancreas was indicated after a medical treatment of 4.1 years (median). Subtotal resection of the head of the pancreas, including the inflammatory mass, resulted in decompression of the narrowed common bile duct segment, decompression of the pancreatic main duct, and the relief of duodenum stenosis, as well as a relief of portal hypertension. The mean hospitalization time was 13 days, frequency of re-operation 5.8%, and hospital mortality 1.02%. Seventy-nine percent of patients experienced long-lasting pain relief and 11% reported a significant and long-lasting reduction of pain; late morbidity proved to be low. In comparison to the Whipple procedure the duodenum-preserving head resection has the advantage of preserving the stomach, duodenum and biliary tract.     

Factors Predicting Long-term Responses to Splenctomy in Patients with Idiopathic Thrombocytopenic Purpura

Background Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder for which appropriate diagnostic treatments are uncertain. The response to splenectomy varies from 60% to 90%, and the remaining patients relapse and require further treatment. Therefore, it is important to predict the outcome of splenectomy before and after surgery. The objective of this study was to evaluate the efficacy of splenectomy in patients diagnosed with ITP. Materials and Methods From 1988 to 2004, we splenectomized 32 patients with ITP; 17 underwent laparoscopic splenectomy (LS) and 15 underwent conventional open splenectomy (OS). For analysis, patients were separated retrospectively into two groups: the “responding group,” those who showed good outcomes with splenectomy, and the “non-responding group,” those who did not show good outcomes with splenectomy. Blood samples were examined before and immediately after surgery (day 0) and on postoperative days (POD) 1, 3, 5, and 7. Results The median follow-up was 8.3 years (range: 1–16 years). The overall 5- and 10-year survival rates after splenectomy were 96.9% (one death). The responding group included 24 patients (75%), and the non-responding group included 7 (21.9%). Platelet counts in the responding group increased gradually until POD 7, and although platelet counts in the non-responding group were almost constant until POD 5, they subsequently decreased until POD 7. Average platelet counts in the responding and non-responding groups were 269 and 124 × 10⁹/l on POD 7, respectively (P < 0.05). The pre- to post-surgery ratio of platelet counts were almost the same as the result of the actual data. Platelet counts during the long-term follow-up for the responding and non-responding groups were related to those noted on discharge. Conclusions A high platelet count on POD 7 was associated with a good response to splenectomy, but age at surgery, the time interval between diagnosis and splenectomy, and prior responses to corticosteroid were not. We suggest that long-term outcomes of splenectomy can easily be predicted by platelet counts on POD 7.