Efficacy of repeat hepatic resection for recurrent hepatocellular carcinomas

Background: This study evaluated the efficacy of repeat hepatic resection for recurrent hepatocellular carcinoma (HCC) and the clinicopathological factors influencing overall survival after resection. Methods: From 1992 to 2005, 231 patients underwent curative hepatic resection for HCC at Yokohama City University, Japan. Of these, 105 patients developed intrahepatic recurrence, and 24 repeat hepatectomies were performed for recurrent HCC. Survival data were analysed, and prognostic factors for repeat hepatic resection were determined. Results: The overall cumulative 1‐, 3‐ and 5‐year survival rates and the median survival time of the patients after initial hepatic resection (n= 231) did not differ from those of the patients after repeat hepatic resection (n= 24), with values of 91.3, 70.2 and 49.1%, and 57 months, versus 91.7, 73.1 and 50.9%, and 61.5 months, respectively (P= 0.875). The operative time and blood loss in patients who underwent repeat hepatic resection did not differ from those who underwent primary resection. Multivariate analysis identified portal invasion at the first hepatic resection and a disease‐free interval of ≤1.5 years after primary hepatic resection as independent risk factors for survival after repeat hepatic resection. The 12 patients who did not show either of the two prognostic factors had 3‐ and 5‐year survival rates of 91.7 and 68.8%, respectively, after repeat hepatic resection. Conclusions: Our findings suggest repeat hepatic resection as the treatment of choice for recurrent HCC patients without portal invasion at the first resection whose recurrence develops after a disease‐free interval of >1.5 years since the previous surgery.     

The impact of advanced age on hepatic resection of colorectal liver metastases

BACKGROUND: The aim of this study was to evaluate the impact of patient age on surgical therapy for colorectal liver metastases. STUDY DESIGN: Between 1992 and 2004, 212 consecutive patients underwent potentially curative hepatic resection. Sixty-two patients were 70 years or older at the time of resection (older group) and 150 patients were less than 70 years at the time of resection (younger group). RESULTS: A proportion of older patients had a history of severe cardiopulmonary disease (32.3%) and respiratory insufficiency (6.5%). Intraoperative variables, such as resected liver volume, operation time, estimated blood loss, and blood transfusion, were not notably different between older and younger patients. Postoperative complications after resection occurred in 19.7% of older patients and at a similar rate (23.3%) in the younger group. Resection mortality was 0% in older patients and 0.49% in younger patients. The 5-year survival rates of older and younger patients were 34.1% and 53.1%, respectively. Compared with younger patients, the overall survival rate of older patients was markedly lower (p<0.01). CONCLUSIONS: Advanced chronologic age cannot be regarded as a medical contraindication for hepatic resection of colorectal liver metastases in patients who are more than 70 years of age.     

The effect of fibroblast growth factor-2 on autologous osteochondral transplantation

In this study, we performed a mechanical analysis of the effect of fibroblast growth factor-2 (FGF-2) on autologous osteochondral transplantation in a rabbit model. A full-thickness cartilage defect (diameter: 5 mm; depth: 5 mm) made in the right femoral condyle was treated with osteochondral transplantation using an osteochondral plug (diameter: 6 mm; depth: 5 mm) taken from the left femoral condyle. The animals were divided into three groups: Group I, the defect was filled with 0.1 ml of gelatin hydrogel containing 1 microg of FGF-2; Group II, the defect was filled with 0.1 ml of gelatin hydrogel only; Group III, the defect was left untreated. Thereafter, osteochondral plugs were transplanted and the transplanted osteochondral grafts were evaluated mechanically and histologically at postoperative weeks 1, 3, 8 and 12. The structural property of the osteochondral graft was significantly greater in Group I than in Groups II and III at postoperative week 3. Histological analysis at 3 weeks revealed a tendency towards increased subchondral bone trabeculae in Group I compared with the other groups. Autologous osteochondral grafts transplanted with gelatin hydrogel containing FGF-2 acquired adequate stiffness at an early postoperative phase.     

Equal sensitivity of early and late scans after injection of FDG for the detection of Alzheimer pattern: an analysis of 3D PET data from J-ADNI, a multi-center study

Objective

To determine the optimal accumulation time for three-dimensional positron emission tomography (3D-PET) with ¹⁸F-2-fluoro-2-deoxy-d-glucose (¹⁸F-FDG) to detect the brain uptake pattern typical of Alzheimer’s disease (AD).

Methods

Patients with mild AD or amnestic mild cognitive impairment (MCI) and normal control subjects were recruited in the Japanese Alzheimer’s disease neuroimaging initiative and examined with a PET scan during the 30–60 min after FDG injection. Three independent blinded experts interpreted the 30- to 60-min sum images, and images of patients with AD and MCI presenting AD patterns and normal subjects presenting normal patterns were used in the analysis. Early-scan (ES) and late-scan (LS) images were obtained from the data acquired at 30–35 min and 55–60 min after the injection, respectively. Separate target regions of interest (ROI) for ES and LS were defined as areas of significant reductions in the posterior cingulate and parietotemporal lobe in both hemispheres from the results of an initial cohort with 21 patients (AD 16, MCI 5) and 19 controls. A subsequent sample of 36 (AD 9, MCI 27) patients and 38 controls were used to compare the diagnostic capability of ES and LS using Z scores within the target ROI in individual statistical parametric mapping analysis.

Results

Compared to LS, ES showed lower activity in the frontal lobes and higher activity in the venous sinus than LS; however, the diagnostic capability of ES and LS did not significantly differ (sensitivity 0.97 and 0.97, specificity 0.82 and 0.84, area under the receiver-operating characteristic curve 0.96 and 0.97, respectively).

Conclusions

For a qualitative diagnosis of the AD pattern in 3D FDG-PET, results of ES were equivalent to those of LS. ES may be an option to shorten the entire PET procedure time, particularly in diagnosing early stages of AD.     

Feasibility of low-radiation-dose CT for abdominal examinations with hybrid iterative reconstruction algorithm: low-contrast phantom study

Our purpose in this study was to evaluate the image quality of low-radiation-dose CT using hybrid iterative reconstruction (HIR), and to compare the results with those of filtered back projection (FBP) at routine doses. We measured the mean values and standard deviation of the CT numbers within and outside a 15-mm low-contrast object cylinder at 1.0 % contrast level. The noise reduction levels of the HIR were 1 (weak) to 7 (strong). Visual inspection of the low-contrast detectability was done by six radiologic technologists. The low-contrast detectability of the cylinder at the 1.0 % contrast level with HIR at all mAs levels was equal to that obtained with FBP, and thus the use of HIR did not result in any improvement of low-contrast detectability.     

Imaging P-glycoprotein function in rats using [11C]-N-desmethyl-loperamide

Objective

One mechanism that may be responsible for drug resistance in epilepsy is the upregulation of P-glycoprotein (P-gp), a drug efflux pump, at the epileptogenic focus. In this study, we sought to evaluate the potential of a recently developed P-gp PET radiotracer, [¹¹C]N-desmethyl-loperamide ([¹¹C]dLop), for measuring P-gp function in the rat brain.

Methods

The precursor to [¹¹C]dLop was synthesized in two steps from commercially available starting materials and subsequently radiolabeled in one step using [¹¹C]methyl iodide. [¹¹C]dLop was then administered to two groups of rats, controls (n = 4) and those treated with a P-gp inhibitor (n = 8). Cyclosporin A (CsA, 50 mg/kg, n = 3) and tariquidar (TQ, 20 mg/kg, n = 5) were both used as P-gp inhibitors. MicroPET brain scans were performed for 120 min with arterial blood sampling. A one-tissue compartment model was used to estimate the distribution volume of radiotracer as the outcome measure of P-gp function.

Results

Plasma levels of parent [¹¹C]dLop decreased rapidly to <0.1 mean standardized uptake value (SUV) at 60 min. In controls, brain uptake of [¹¹C]dLop was very low (<0.1 mean SUV). In contrast, the mean SUVs were significantly higher in rats treated with CsA (0.51) or TQ (0.22). Estimation of distribution volumes was stable by 70 min. Estimated distribution volumes were significantly larger after P-gp inhibition (CsA = 7.3, TQ = 4.7) compared to controls (no inhibitor = 2.1).

Conclusions

The rat brain demonstrates significantly increased uptake of [¹¹C]dLop after P-gp inhibition. [¹¹C]dLop is a substrate of P-gp, and will serve as a promising radiotracer for studying P-gp function in the future.     

Interim evidence of the renoprotective effect of the angiotensin II receptor antagonist losartan versus the calcium channel blocker amlodipine in patients with chronic kidney disease and hypertension: a report of the Japanese Losartan Therapy Intended for Global Renal Protection in Hypertensive Patients (JLIGHT) Study

Background. Insufficiency of renal function and high blood pressure influence each other and eventually result in life-threatening endstage renal disease. It has been proposed that proteinuria per se is a determinant of the progression of chronic kidney disease (CKD). The therapeutic strategy for patients with proteinuric CKD and hypertension should therefore be targeted with a view not merely toward blood pressure reduction but also toward renoprotection. Methods. We examined the effect of the angiotensin (AT)₁ receptor antagonist losartan and the calcium channel blocker amlodipine, throughout a period of 12 months, on reduction of blood pressure and renoprotection. This was done by assessing amounts of urinary protein excretion, serum creatinine (SCr), and creatinine clearance (CCr) in patients with hypertension (systolic blood pressure [SBP] 140mmHg or diastolic blood pressure [DBP] 90mmHg) and CKD (male, body weight [BW] 60kg: 1.5 SCr < 3.0mg/dl; female or male BW < 60kg: 1.3 SCr < 3.0mg/dl), manifesting proteinuria of 0.5g or more/day. Losartan was administered once daily at doses of 25 to 100mg/day, and amlodipine was given once daily at 2.5 to 5mg/day. No antihypertensive combination therapy was allowed during the first 3-month period. Results. A 3-month interim analysis revealed that, despite there being no difference in blood pressure between the two groups, there was a significant reduction in 24-h urinary protein excretion in the losartan group (n = 43), but there was no change in the amlodipine group (n = 43). Analysis of stratified subgroups with proteinuria of 2g or more/day and less than 2g/day showed that losartan lowered proteinuria by approximately 24% in both subgroups, while amlodipine lowered proteinuria by 10%, but only in the subgroup of less than 2g/day (NS). SCr and CCr did not change throughout the period of 3 months in either group. No severe or fatal adverse event was experienced in either group during the study period. Conclusions. Losartan appeared to be efficacious for renoprotection in patients with proteinuric CKD and hypertension, with the mechanism being independent of its antihypertensive action.     

Life-threatening veno-occlusive disease after living-related liver transplantation

Veno-occlusive disease (VOD) can develop in association with the administration of cytotoxic chemotherapeutic agents and irradiation. In solid-organ transplant settings, azathioprine has been implicated as a predisposing factor. VOD with fatal outcome occurred in a post liver-transplant recipient who had never been exposed to any agents that have the potential to induce VOD. At onset, the disease manifested clinically as gross ascites and progressive jaundice and was observed after clinically diagnosed acute graft rejection. The disease was confirmed by histologic examinations. Histologic studies of biopsy samples from this patient revealed that most small hepatic veins less than 300 microm in diameter were affected, exhibiting concentric intimal thickening with sparse inflammatory cells. A few of the hepatic veins exhibited active endotheliitis with occasional extension of inflammation to neighboring centrilobular areas. Despite intensified immunosuppression, the observed fibrous obliterative changes were irreversible. Although the cause of VOD in this patient is tentative, the damage to the endothelium, associated with acute rejection, is likely to be attributable. VOD deserves recognition as one of the causes for liver dysfunction and persistent ascites after liver transplantation.     

Risk factors for acute rejection in living donor liver transplantation

The influence of human leukocyte antigen (HLA) compatibility and lymphocytotoxic crossmatch on acute rejection in living donor liver transplantation (LDLT) has not been well examined. We analyzed 100 consecutive adult LDLT cases. The patient and graft survival rates and post-operative complications were assessed. The relation between the incidence of acute rejection and some clinical factors including HLA and lymphocytotoxic matching was also examined. Patients with HLA DR zero mismatching (p = 0.02) or negative T-lymphocytotoxic crossmatch (p = 0.04) had a significantly lower chance of rejection within 6 wk after LDLT. However the results had no influence on the patient survival. Our results demonstrate that in LDLT, a graft from an HLA-DR zero mismatching or negative T-lymphocytotoxic crossmatch might be advantageous because of the decreased probability of early acute rejection.