Tolerability and efficacy of pegylated consensus interferon-α in the treatment of chronic hepatitis C.

This study aimed to explore and evaluate the tolerability and antiviral activity of pegylated recombinant human consensus interferon-α (PEG-CIFN) in adults with hepatitis C virus (HCV) infection. A total of 48 adult subjects chronically infected with HCV were divided into five groups, which were treated separately with PEG-CIFN 1.0 µg/kg (n=10), 1.5 µg/kg (n=10), 2.0 µg/kg (n=9) or 3.0 µg/kg (n=10), or pegylated IFN α-2a (Pegasys) 180 µg (n=9) as controls. Symptoms were observed and laboratory results collected to monitor adverse reactions, adjust drug dosage and evaluate tolerability. The thrombocytopenic effects in all PEG-CIFN dose groups were less than that of pegylated IFN α-2a (at week 14, P<0.05). The rapid virologic response of the PEG-CIFN 1.5, 2.0 and 3.0 µg/kg groups and the pegylated IFN α-2a group were significantly higher than that of the PEG-CIFN 1.0 µg/kg group (P<0.05). Patients who had HCV genotype 1b infections had relatively high responses. The early virologic response of the PEG-CIFN 1.0, 1.5 and 2.0 µg/kg groups and the pegylated IFN α-2a group were 30, 90, 88.8 and 88.8% respectively. PEG-CIFN is well tolerated, and was found to have dose-dependent effectiveness in subjects with chronic hepatitis C. Virological response rates between PEG-CIFN 1.5 or 2.0 µg/kg, and pegylated IFNα-2a were similar, and not significantly different. It is concluded that 1.5 µg/kg PEG-CIFN may be the clinically recommended dose. PEG-CIFN is superior to pegylated IFN α-2a in maintaining platelet levels.

Pharmacokinetics and safety profiles of novel diethylstilbestrol orally dissolving film in comparison with diethylstilbestrol capsules in healthy Chinese male subjects.

OBJECTIVE: We compared the pharmacokinetic (PK) profiles of diethylstilbestrol orally dissolving film (DES ODF) and DES-capsule as well as assessing the safety, local tolerability, taste, and disintegration time of DES ODF. MATERIALS AND METHODS: Twelve healthy male volunteers receiving a single administration of 2.0 mg of DES ODF or DES-capsule were included in the study. The tolerability, taste, and time to dissolution of DES ODF were assessed after dosing. Safety assessments included adverse events, hematology and biochemistry tests, urinalysis, vital signs, and electrocardiography. RESULTS: The PK parameters of DES ODF were all greater than those of DEScapsule. The Cmax values were 5.64 ± 1.1 and 3.4 ± 1.93 ng/mL for DES ODF and DES-capsule, respectively. Assessment of bioequivalence was based on the 90% CIs of the treatment ratios of the log-transformed Cmax, AUC0-t, and AUC0-∞ (DES ODF to DES-capsule), with the mean values being 1.93 (141 - 264), 1.24 (98 - 156), and 1.59 (121 - 207), respectively, indicating that DES ODF had a significantly high bioavailability. The mean DES ODF disintegration time was 14 ± 5 minutes. DES ODF was well tolerated and no serious adverse events or clinically relevant changes were observed. CONCLUSIONS: The DES ODF is well tolerated and better absorbed in comparison with DES-capsule.

[Extended hepatic pedicle occlusion in major hepatectomy for primary liver cancer].

OBJECTIVE: To evaluate the influence of extended hepatic pedicle occlusion (HPO) on hepatic ischemic/reperfusion (I/R) injury and intraoperative blood loss in major hepatectomy for primary liver cancer (PLC). METHODS: Between June 2001 and December 2005, a total number of 843 patients with PLC had been operated on. Those whose hepatic pedicle were occluded continuously for or longer than 30 min during hepatectomy were retrospectively reviewed (continuous HPO group) and compared to the patients whose hepatic pedicle were occluded for the same length of time but intermittently (intermittent HPO group). The amount of intraoperative blood loss, the percentage of the patients who needed blood transfusion and postoperative liver biochemical tests were compared between the two groups. RESULTS: There were 35 cases in continuous HPO group and 38 cases in intermittent HPO group with occlusion time between 30 min and 45 min. The two groups were matched for underlying liver disease ,preoperative liver function, tumor size and location, major intrahepatic vessel involvements and the types and extensions of the hepatectomies. The mean intraoperative blood loss in continuous HPO group was significantly less than that in intermittent HPO group (660 ml vs. 1054 ml, P < 0.05); accordingly, the percentage of patients who need blood transfusion in continuous HPO group was significantly lower than that in intermittent HPO group (48.6% vs. 78.9%, P < 0.01). Patients in both of the groups were recovered smoothly after operation, with no occurrence of liver failure. CONCLUSIONS: The hepatic pedicle can be continuously occluded for 3045 min in cirrhotic patients with well compensated liver function, and when compared to routine intermittent HPO, continuous HPO significantly decreases the intraoperative blood loss and reduces the need for transfusion. Meanwhile it does not increase the hepatic I/R injury.

[Surgical resection of hepatic tumor in segment IXb by anterior transhepatic approach].

OBJECTIVE: To evaluate the feasibility and the effect of surgical resection of hepatic tumor originated from segment IXb. METHODS: The cases with hepatic tumors in segment IXb who had been operated on between March 2003 and January 2007 were retrospectively reviewed. RESULTS: A total of 15 tumors in segment IXb, including 13 primary liver cancers and 2 benign tumors with a mean diameter of (4.3 +/- 1.6) cm, were successfully resected by anterior transhepatic approach under sequential occlusions of portal tride and total hepatic vascularity or portal tride clamping only. There was no operative mortality,with a mean operative time of (190.3 +/- 37.6) min and a mean operative blood lose of (376.7 +/- 252.7) ml. All the patients had uneventful postoperative course except one who suffered from ascites and edema of the low body, which was successfully managed medically. The mean postoperative hospital stay was (13.3 +/- 6.0) d. During the follow-up of 1-47 months, two patients with benign tumor enjoyed a normal life. Among the 13 patients with primary live cancers, 1 patient died of recurrence, 2 patients remained alive with intrahepatic recurrence and 10 patients survived without any sign of relapse, with a median tumor-free survival time of 23.5 months. CONCLUSIONS: Surgical resection of hepatic tumor in segment IXb, despite their sophisticated anatomic position, is feasible in technique with high safety. The local resection can provide the patients with potential to cure.

[Surgical management of small intrahepatic lesions adjacent to the major vasculature].

OBJECTIVE: To assess the feasibility and the significance of surgical resection of small intrahepatic lesions adjacent to the major vasculature. METHODS: The results of treatment were retrospectively reviewed in 40 patients who received operation for intrahepatic lesions less than 3 cm in diameter between Jan. 2003 and Dec. 2005. The lesions were all adjacent to the major vasculature in the liver. RESULTS: In the 40 patients, a total of 44 small intrahepatic lesions were successfully resected with minimal morbidity and blood loss (mean 163 ml). A second lesion was found in 4 patients (10%) during intraoperative exploration. Histologically the lesion was malignant in 29 cases (including 4 cases with two lesions) and benign in 11 cases, with correct preoperative diagnosis in 62.5% of all cases. For 26 patients with hepatocellular carcinoma, the 1-, 2-, and 3-year postoperative survival rates were 90.1%, 83.2% and 64.7%, respectively, while the patients with benign lesions were cured with the operation. CONCLUSIONS: Surgical resection of small intrahepatic lesions adjacent to the major vasculature is demanding but feasible and with satisfying effect. The significance of surgical management of these small lesions is not only excising the lesions but also making definite diagnosis and finding new lesions in some patients.

[Surgical treatment for the giant hepatic carcinomas occupying the central part of the liver].

OBJECTIVE: To evaluate the techniques and the effects of surgical resection of giant hepatic carcinomas which occupied the central part of the liver. METHODS: A retrospective study was carried out of hepatectomies performed for central giant hepatic carcinomas. The hepatic tumors included in this study were hepatocellular carcinomas, cholangiocarcinomas and hepatic metastases which situated in the central part of the liver (segment IV, V, VIII, I) with a diameter of larger than 10 cm and involved hepatocaval confluence, retrohepatic inferior vena cava (IVC) as well as hepatic portal. RESULTS: A total of 40 central giant hepatic carcinomas were successfully resected, with a mean diameter of 13.6 cm (range 10.5-19.0 cm). The types of the hepatectomies conducted were as follows: extended mid-hepatectomy in 9 cases, atypical mid-hepatectomy in 13 cases, extended left hepatectomy in 13 cases, total caudatectomy plus extended left hepatectomy in 3 cases and extended right hepatectomy in 2 cases. The mean operation time was 197 min (range 90 - 380 min) and the mean intraoperative blood lose 1,596 ml (range 300-11,000 ml), with operative mortality and morbidity being 0 and 20%, respectively. The postoperative 1, 3 and 5 year survival rates for the patients were 88%, 56% and 28%, respectively. CONCLUSIONS: The hepatic carcinomas of central type, when larger than 10 cm in diameter, frequently involves all the hepatic portal, hepatocaval confluence and retrohepatic IVC. Surgical resection of this kind of tumor, though sophisticated in technique, is safe and effective and, therefore, the first choice of the treatments.

[Surgical treatment of hepatocellular carcinoma with tumor thrombus in the inferior vena cava].

OBJECTIVE: To clarify the proper surgical procedure of treating hepatocellular carcinoma (HCC) with a tumor thrombus in the inferior vena cava (IVC). METHODS: Four patients with HCC with a tumor thrombus in the IVC underwent hepatectomy and thrombectomy. Following hepatectomy, tumor thrombus was removed by incising the wall of the IVC in 3 patients and from the hepatic vein in one patient. The 3 patients underwent thrombectomy under either hepatic vascular exclusion (HVE) or Satinsky's vascular clamping. RESULTS: All the operations were successful without operative death and major complications. The postoperative course was uneventful in 3 patients and pleural effusion occurred in one patient who needed thoracentesis. Follow-up showed 3 patients died after 30, 10 and 14 months, respectively, and one patient is alive for 7 months. CONCLUSIONS: HCC with tumor thrombus in the IVC is operable and the proper procedure is hepatectomy plus thrombectomy.

Intermittent portal triad clamping in resection of liver tumors involving the hepatocaval confluence.

OBJECTIVE: To review our experience in and the results of resecting liver tumors involving the hepatocaval confluence under intermittent portal triad clamping (PTC). METHODS: Sixty-eight consecutive patients with liver tumors involving the hepatocaval confluence underwent hepatectomies with liver parenchymal transections under intermittent PTC. RESULTS: All the tumors were successfully resected under PTC, except for one in which the infrahepatic inferior vena cava was concomitantly occluded in addition to PTC. There was neither operative death nor uncontrollable massive bleeding or air embolism occurred in our patients. The bleedings from the main and short hepatic veins and right adrenal veins were properly managed during the operation, with a mean intraoperative blood loss of 1400 ml. Of the 68 tumors resected, 65 were hepatocellular carcinomas (HCC). Their 1-, 2-, 3- and 4-year survival rates were 64.11%, 52.82%, 44.90% and 36.98%, respectively, and the patients with HCC with capsules survived significantly longer than those with HCC without capsules. CONCLUSIONS: The liver tumors involving the hepatocaval confluence could be safely resected simply under PTC, without routine use of total hepatic vascular exclusion. As for HCCs in this area, the tumor with capsule is a better indicator for surgical resection than that without capsule.