Adverse effects of irreversible electroporation of malignant liver tumors under CT fluoroscopic guidance: a single-center experience

PURPOSE

We aimed to describe the frequency of adverse events after computed tomography (CT) fluoroscopy-guided irreversible electroporation (IRE) of malignant hepatic tumors and their risk factors.

METHODS

We retrospectively analyzed 85 IRE ablation procedures of 114 malignant liver tumors (52 primary and 62 secondary) not suitable for resection or thermal ablation in 56 patients (42 men and 14 women; median age, 61 years) with regard to mortality and treatment-related complications. Complications were evaluated according to the standardized grading system of the Society of Interventional Radiology. Factors influencing the occurrence of major and minor complications were investigated.

RESULTS

No IRE-related death occurred. Major complications occurred in 7.1% of IRE procedures (6/85), while minor complications occurred in 18.8% (16/85). The most frequent major complication was postablative abscess (4.7%, 4/85) which affected patients with bilioenteric anastomosis significantly more often than patients without this condition (43% vs. 1.3%, P = 0.010). Bilioenteric anastomosis was additionally identified as a risk factor for major complications in general (P = 0.002). Minor complications mainly consisted of hemorrhage and portal vein branch thrombosis.

CONCLUSION

The current study suggests that CT fluoroscopy-guided IRE ablation of malignant liver tumors may be a relatively low-risk procedure. However, patients with bilioenteric anastomosis seem to have an increased risk of postablative abscess formation.About 70% of hepatic metastases are nonresectable because of their anatomic location, the presence of comorbidities, or limited hepatic functional reserve (1). In these patients and in case of nonresectable primary liver tumors, percutaneous thermal ablation procedures, such as radiofrequency (RF) and microwave ablation, have become effective tools for treating hepatic malignancies (2–4). However, the effectiveness of RF and microwave treatment may be limited, either because of thermal damage to temperature-sensitive structures located in close proximity to the target tissue (5) or because of incomplete ablation of tumors adjacent to major hepatic vessels due to a phenomenon commonly termed “heat-sink effect” (6–10) which describes the loss of the applied thermal energy through the blood flow in those major vessels, whereby the effective energy application remains inadequate to ablate the target lesion.Irreversible electroporation (IRE) is a theoretically nonthermal ablation technique that delivers a series of high-voltage millisecond electrical pulses to the surrounding tissue, thus leading to irreversible disruption of the integrity of cell membranes and subsequent cell death by apoptosis (11–14). IRE may overcome the problems raised with thermal ablation: previous animal studies reported that bile ducts, blood vessels, nerves, and connective tissues are affected by IRE; however, regeneration is possible to some extent due to preservation of the tissue architecture (12, 13, 15–19). Moreover the feasibility of inducing cell death up to a vessel wall without any perivascular sparing was shown with IRE (12, 13, 18). The safety of IRE in the treatment of humans has been described (20). First reports have described potential complications after IRE, such as hemorrhage requiring blood transfusion (1.2%, two of 167 ablation procedures), portal vein thrombosis (3.2%, one of 31 ablation procedures), injury to bile ducts (1.8%, three of 167 ablation procedures), and infection (3.6%, six of 167 ablation procedures) (21, 22). However, few data are available for evaluating the potential risk factors associated with the occurrence of post-IRE complications.The purpose of this study was to review the frequency of mortality and morbidity after computed tomography (CT) fluoroscopy-guided liver IRE conducted at a single center and assess the factors influencing the occurrence of major complications.     

Effectivity of a T-cell-adapted induction therapy with anti-thymocyte globulin (Sangstat).

BACKGROUND: Cytolytic induction therapy with anti-thymocyte globulin (ATG) should induce effective immunosuppression, with a low rate of rejection in the initial phase after heart transplantation. Induction therapy with ATG allows post-operative renal recovery without the negative effects of highly nephrotoxic cyclosporine levels. An increased rate of infection is a common problem, however, and has been associated with "over-immunosuppression" early after transplantation. Therefore, we investigated whether reduced T-cell-adapted ATG induction therapy could be performed without increasing the risk of graft loss by rejection and whether reductions in infection rates and costs are possible. METHODS: Between March 1999 and December 2002, T-cell-adapted ATG induction therapy with ATG (Sangstat) (1.5 mg/kg) was given to 62 heart transplant recipients (study group) starting on post-operative Days 1 to 6. T-lymphocyte sub-populations were screened daily using flow cytometry. If total lymphocytes were <100/microl (reference 1,300 to 2,300/microl), T-helper lymphocytes (CD4+) <50/microl (reference >500/microl) and T-suppressor cells (CD8+) <50/microl (reference >300/microl), then no ATG was given. Further immunosuppression was continued with triple therapy consisting of methylprednisolone, azathioprine and cyclosporine. An historic group of heart transplant recipients given a full-dose ATG regimen for 8 days served as controls. These recipients were treated with ATG (Merieux 1.5 mg/kg) until reaching monoclonal cyclosporine levels of >300 mg/dl. Additional immunosuppressive treatment did not differ. Patients in both groups received systemic antibiotics (Imipenem) peri-operatively. Results of routine endomyocardial biopsies and rates of infections were examined. RESULTS: Study group patients were older (52 +/- 10 vs 49 +/- 14 years). In the study group, mean cumulative ATG dose was reduced significantly to 596 +/- 220 mg (p < 0.05) for 3.9 +/- 1.6 days compared with 1,159 +/- 376 mg for 6.9 +/- 1.1 days in the control group. The rate of cytomegalovirus (CMV) seroconversion was 23% in the study group compared with 13% in the control group. Rate of deep sternal infections was lower in the study group (1.6% vs 3.2%). The mean rejection rate in the first 3 months was 0.4 +/- 0.7 for the study patients (185 biopsies) vs 1.1 +/- 1.7 for controls (237 biopsies). All biopsies with ISHLT Grade >2 were treated successfully with 1,000 mg of methylprednisolone intravenously for 3 days. Both groups showed a similar 1-year survival rate (study 88%, control 89%). CONCLUSIONS: T-cell-adapted ATG induction therapy can be a helpful tool for individualized immunosuppression. It is not associated with an increased rate of rejection. Lower doses of immunosuppression help to minimize the rates of infection. In addition, cytolytic induction therapy combined with reduced ATG results in significant cost reduction.     

Good outcome after liver transplantation for ALD without a 6 months abstinence rule prior to transplantation including post‐transplant CDT monitoring for alcohol relapse assessment – a retrospective study

Alcoholic liver disease (ALD) is the second most common indication for liver transplantation (LT). The utility of fixed intervals of abstinence prior to listing is still a matter of discussion. Furthermore, post‐LT long‐term observation is challenging, and biomarkers as carbohydrate‐deficient transferrin (CDT) may help to identify alcohol relapse. We retrospectively analyzed data from patients receiving LT for ALD from 1996 to 2012. A defined period of alcohol abstinence prior to listing was not a precondition, and abstinence was evaluated using structured psychological interviews. A total of 382 patients received LT for ALD as main (n = 290) or secondary (n = 92) indication; median follow‐up was 73 months (0–213). One‐ and five‐year patient survival and graft survival rates were 82% and 69%, and 80% and 67%, respectively. A total of 62 patients (16%) experienced alcohol relapse. Alcohol relapse did not have a statistically significant effect on patient survival (P = 0.10). Post‐transplant CDT measurements showed a sensitivity and specificity of 84% and 85%, respectively. In conclusion, this large single‐center analysis showed good post‐transplant long‐term results in patients with ALD when applying structured psychological interviews before listing. Relapse rates were lower than those reported in the literature despite using a strict definition of alcohol relapse. Furthermore, post‐LT CDT measurement proved to be a useful supplementary tool for detecting alcohol relapse.     

Cellular and Molecular Foundation for Fracture Healing in Children

Abstract Dealing with pediatric fracture patients requires a funded knowledge of complications and remodeling capability of the youth skeleton to find the accurate therapy decision and to avoid unnecessary invasive procedures. Due to the different mechanical environment, fractures in children occur at specific fracture-vulnerable areas. One of those is the growth plate, which on one hand gives rise to the unique ability of correcting angular deformities by specifically increasing the growth rate in definite regions, and on the other hand leads to complications like growth arrest or angular deformity. The pediatric diaphysis presents the exclusive greenstick fracture, only seen in the growing skeleton, which occurs because of the different composition of the pediatric bone. To understand these very specific features of the youth skeleton, the molecular and cellular basis should be taken into consideration. Therefore, this review will present the common characteristics of skeletal development and fracture healing. An insight into the mechanotransduction as part of the remodeling and self-correcting ability of pediatric bone is given to span the bridge between clinical treatment options and scientific background.     

Mildly decreased preoperative bilirubin levels are associated with infections after shoulder and knee arthroplasty

Increasing numbers of arthroplasties are also accompanied by postoperative infections. The main purpose was to evaluate preoperative serum bilirubin levels between patients with and without infections after shoulder and knee arthroplasties. For this retrospective case-control single-center study, a total of 108 patients were extracted from a prospectively collected database. Eighteen patients with infections after shoulder (n = 8) and knee (n = 10) arthroplasty were matched by age, gender, and implant type in a 1:5-scenario to 90 patients (40 shoulders and 50 knees) without postoperative infection. Demographic data, preoperative blood parameters, and postoperative infection-related outcomes were evaluated. Total bilirubin was the only preoperative parameter significantly different between the infection (8.21 ± 3.25 μmol/L or 0.48 ± 0.19 mg/dL) and noninfection (10.78 ± 4.62 μmol/L or 0.63 ± 0.27 mg/dL; P = .014) group, while C-reactive protein and other liver parameters were similar between the groups. Significantly more controls (92.1%) had preoperative bilirubin levels above 8.72 μmol/L or 0.51 mg/dL than cases (7.9%; P = .007). The 5-year infection survival-rate was 65.6% for patients with preoperative bilirubin levels < 8.72 μmol/L or < 0.51 mg/dL and 91.2% with ≥ 8.72 μmol/L or ≥ 0.51 mg/dL. Mildly decreased preoperative bilirubin levels with a cutoff at 8.72 μmol/L or 0.51 mg/dL were significantly associated to patients with infections after shoulder and knee arthroplasty. There were no differences in other blood parameters or comorbidities between patients with infections and their matched-controls.     

Bone mineral density measurements performed by cone-beam computed tomography in the bisphosphonate-related osteonecrosis-affected jaw

Objectives

The aims of this study were to determine the bone mineral density (BMD) in bisphosphonate-related osteonecrosis of the jaw (BRONJ) by cone-beam computed tomography (CBCT) measurements and to correlate these measurements with the current stages recommended by the American Association of Oral and Maxillofacial Surgeons (AAOMS).

Methods

Bone mineral density measurements of various areas in 24 bisphosphonate-related osteonecrosis (BRON) jaws were evaluated by CBCT. Another 24 age- and sex-matched patients without any bone pathologies served as the control group. Data acquisition was highly standardized to ensure maximum reliability in the comparisons of BMD measurements by CBCT.

Results

Compared with the control group, the bisphosphonate patients had significantly higher (p????0.01) BMDs in the non-affected jaw areas ipsilateral and contralateral to the BRON within the maxilla and mandible. The highest BMDs within the BRON jaws were observed in the BRON-adjacent areas relative to the non-affected ipsilateral and contralateral areas. Regarding the correlation with the AAOMS stages, the BMDs of the evaluated areas of BRONJ showed no significant differences (p????0.05) between the stages.

Conclusions

Bisphosphonate-related bone pathologies can be detected by CBCT and are associated with increased BMDs, not only in clinically obvious BRONJ areas, but also in clinically unapparent areas, suggesting a subclinical general osteosclerosis of the jaw. The data transferability to other CBCT devices needs to be further elucidated and compared with multislice CT.     

Clearance of topically-applied PVP-iodine as a solution or gel in periodontal pockets in men

Abstract Objectives. The aim of the study was to investigate the clearance of PVP-iodine applied as a gel or solution in periodontal pockets. Methods. Teeth of 12 subjects with at least eight periodontal pockets of ≥5 mm probing depth were isolated with a rubber dam to allow contamination-free access to the pockets. In each subject, three pockets were filled with PVP-iodine gel (10%) and three with PVP-iodine solution (10%). One pocket of each subject without iodine application served as a negative control. The treatment allocation was assigned randomly. Any excess material was removed subsequently. After 1, 5 and 15 min, a paper point was used to collect the sulcus liquid and the concentration of PVP-iodine was chemically determined. In addition, PVP-iodine gel was administered into 12 periodontal pockets immediately after sub-gingival ultrasound debridement and the concentration of PVP-iodine was determined after 1 min. Results. Descending concentrations of PVP-iodine were determined at 1, 5 and 15 min after the application. No PVP-iodine was found in the pockets serving as negative controls. The mean concentrations of the gel and solution were 6.14 μg/ml and 4.44 μg/ml (1 min; p ≥ 0.028), 3.20 μg/ml and 1.44 μg/ml (5 min; p ≥ 0.126), 0.69 μg/ml and 0.23 μg/ml (15 min; p ≤ 0.019), respectively. In the pockets with previous debridement the mean concentration was 1.68 ± 1.97 μg/ml. Conclusion. The application of PVP-iodine gel in periodontal pockets allows a prolonged remnant effect as compared to that of the solution formula.