Patient and tumour biology predict survival beyond the Milan criteria in liver transplantation for hepatocellular carcinoma

Background

Patients with hepatocellular carcinoma (HCC) beyond the Milan criteria are not considered for liver transplantation (LT) in many centres; however, LT may be the only treatment able to achieve long-term survival in patients with unresectable HCC. The aim of this study was to assess the role of recipient age and tumour biology expressed by the DNA index in the selection of HCC patients for LT.

Patients

Clinicopathological data of 364 patients with HCC who underwent LT between 1989 and 2010 were evaluated. Overall survival (OS) was analysed by patient age, tumour burden based on Milan criteria and the DNA index.

Results

After a median follow-up time of 78 months, the median survival was 100 months. Factors associated with OS on univariate analysis included Milan criteria, patient age, hepatitis C infection, alpha-fetoprotein (AFP) level, the DNA index, number of HCC, diameter of HCC, bilobar HCC, microvascular tumour invasion and tumour grading. On multivariate analysis, HCC beyond Milan criteria and the DNA index >1.5 independently predicted a worse OS. When stratifying patients by both age and Milan criteria, patients ≤60 years with HCC beyond Milan criteria had an OS comparable to that of patients >60 years within Milan criteria (10-year OS: 33% versus 37%, P = 0.08). Patients ≤60 years with HCC beyond Milan criteria but a favourable DNA index ≤1.5 achieved excellent long-term outcomes, comparable with those of patients within Milan criteria.

Conclusions

Patients ≤60 years may undergo LT for HCC with favourable outcomes independently of their tumour burden. Additional assessment of tumour biology, e.g. using the DNA index, especially in this subgroup of patients can support the selection of LT candidates who may derive the most long-term survival benefit, even if Milan criteria are not fulfilled.     

Efficacy and cost effectiveness of harmonic scalpel compared with electrocautery in posterior instrumentation of the spine

Different methods to reduce blood loss during spinal surgery have been described already. Although the use of the harmonic scalpel (HS), an ultrasonically activated coagulator, has been described in endoscopic spinal surgery, its efficacy in posterior instrumentation of the spine remains unclear. The aim of this study was to determine if blood loss was lower using the HS than electrocauterization (EC) and to evaluate the cost effectiveness of the HS in reducing the need for transfusion in patients undergoing posterior instrumentation of the spine. The two groups were matched in a blinded manner, without knowledge of blood loss and were similar with respect to mean age, diagnosis and operation data. All instrumentations were done by the same surgeon. After matching was completed (HS group n=50, EC group n=50) blood loss and overall costs for blood products were analyzed by independent observers. The following were significantly lower with the HS than with EC: (1) blood loss (1106±985 ml vs 2176±1764 ml, P<0.001), (2) frequency of cell saver use (13 vs 28 patients, P=0.001), (3) average cost of blood products (€72 vs €219, P<0.001), (4) predonation of autologous fresh frozen plasma (2.58±2.78 vs 4.5±2.2 U, P=0.002) and red blood cells (0.38±0.75 vs 0.88±1.1 U, P=0.009). The overall costs, including the costs for the HS, remained neutral. The use of the HS in posterior spinal surgery leads to significantly lower blood loss, and less need for and cost of blood products, compared to EC in cases with major anticipated blood loss.No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this article.     

24‐h storage of pig livers in UW,HTK, hydroxyethyl starch,and saline solution: is microdialysis an appropriate method for the continuous graft monitoring during preservation?

Recent studies demonstrate the feasibility of microdialysis to monitor metabolism in ischemic livers. Whether these parameters correlate with markers of liver cell integrity in an experimental model using pig livers and different preservation solutions was an aim of this study. Pig livers were flushed with either 4 degrees C Histidine-Typtophan-Ketoglutarate solution (HTK) (Custodiol), University of Wisconsin solution (ViaSpan), and hydroxyethyl starch, or 12 degrees C saline solution. After 24-h storage, the livers were rinsed with saline to measure liver enzymes and lactate from the effluate. Utilizing microdialysis, intraparenchymal lactate, pyruvate, glucose, and glycerol was monitored. Tissue biopsies were taken for histological examinations. Cold preservation resulted in a decrease of metabolic activity measured by intrahepatic glucose, lactate, and pyruvate levels, as well as lactate in the effluate, independently of the solution used. Of particular interest, glycerol levels partially reflected the extent of hepatocellular damage and liver enzyme release. Glycerol levels partially discriminated preservation of different quality and were in accordance to histological findings and liver enzyme release. Lactate, pyruvate, and glucose levels were not appropriate as markers during cold storage. Whether or not glycerol monitoring could represent an additional and rational complementation to the current practice of macroscopic, microscopic and donor evaluation has to be clarified by further studies.     

Superficial dysesthesias secondary to epidermoid cyst of the foot

This paper presents a case history of dysesthesias of the lateral branch of the superficial peroneal nerve secondary to compression by an epidermoid cyst in the foot of a 42-year-old patient.     

Long-term follow-ups in adult idiopathic necrosis of head of femur (author's transl)

28 patients were subjected to follow-up examination after having suffered for more than 10 years from idiopathic necrosis of head of femur. The high incidence of the bilateral affection of the hip joint as well as the occurrence of multiple osteonecroses are correlated with distrubances of lipid metabolism. Under conservative treatment the disease takes a progressive course, which, however, can remain subclinical for a long time. Good postoperative results can only be expected from intertrochanteric corrective osteotomy which often leads to a regeneration of the head of femur. Caution is recommended before confirming the indication for athrodesis or total endoprothesis because of the risk of disturbances of consolidation or loosening of the implant.     

An integrated analysis of five double-blind, randomized controlled trials evaluating the safety and efficacy of a hyaluronan product for intra-articular injection in osteoarthritis of the knee

OBJECTIVE: Five double-blind, randomized, saline-controlled trials (RCTs) were included in the United States marketing application for an intra-articular hyaluronan (IA-HA) product for the treatment of osteoarthritis (OA) of the knee. We report an integrated analysis of the primary Case Report Form (CRF) data from these trials. METHOD: Trials were similar in design, patient population and outcome measures - all included the Lequèsne Algofunctional Index (LI), a validated composite index of pain and function, evaluating treatment over 3 months. Individual patient data were pooled; a repeated measures analysis of covariance was performed in the intent-to-treat (ITT) population. Analyses utilized both fixed and random effects models. Safety data from the five RCTs were summarized. RESULTS: A total of 1155 patients with radiologically confirmed knee OA were enrolled: 619 received three or five IA-HA injections; 536 received "placebo" saline injections. In the active and control groups, mean ages were 61.8 and 61.4 years; 62.4% and 58.8% were women; baseline total Lequèsne scores 11.03 and 11.30, respectively. Integrated analysis of the pooled data set found a statistically significant reduction (P < 0.001) in total Lequèsne score with hyaluronan (HA) (-2.68) vs placebo (-2.00); estimated difference -0.68 (95% CI: -0.56 to -0.79), effect size 0.20. Additional modeling approaches confirmed robustness of the analyses. CONCLUSIONS: This integrated analysis demonstrates that multiple design factors influence the results of RCTs assessing efficacy of intra-articular (IA) therapies, and that integrated analyses based on primary data differ from meta-analyses using transformed data.     

Impact of organ preservation using HTK for graft flush and subsequent storage in UW in rat kidney transplantation

BACKGROUND: In kidney transplantation, preservation has a significant influence on organ function. Since previous reports have indicated a benefit of combining histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) solution, we evaluated the effects of initial flush with low viscosity HTK, followed by storage in UW. MATERIAL AND METHODS: Kidneys from inbred Lewis rats were procured using HTK or UW for initially perfusion and re-flushed after 30 min with either solution. In a third group, after perfusion with HTK, organs were re-flushed with UW. Organs were stored for 16-24 h (4 degrees C). Study parameters were high-energy phosphates, histology, apoptosis, recipient survival and urine excretion of 15-F2t -isoprostanes (oxidative stress marker). RESULTS: Prior to transplantation, tissue ATP/ADP concentrations were: HTK/UW > UW-only > HTK-only. In transplanted kidneys, histological damage was highest after preservation in HTK-only. Twenty-four hours after transplantation (24 h cold ischemia time - CIT), cleaved-PARP was most abundant using UW-only. 16 h of CIT resulted in higher urine concentrations of isoprostanes in the order HTK-only (368 +/- 308) > UW-only (157 +/- 105) > HTK/UW (67 +/- 26), and was lower in HTK/UW after 24 h of CIT (146 +/- 38) vs. UW-only (507 +/- 33 pg/mg creatinine). Survival (24 h CIT) was significantly reduced, and percentage of initial non-functioning (INF) kidneys highest in HTK-only (2.6 +/- 0.3 days, 100%), compared to UW-only (13 +/- 4.4 days, 75%) and HTK/UW (18.5 +/- 4.6 days, 33%). CONCLUSIONS: In long-term preservation, UW is superior over HTK. However, our results indicate that perfusion with HTK prior to storage in UW may improve the results of UW alone which is reflected by better survival, lower rate of INF, higher cellular energy conservation and a decrease of free radicals.