Liver Transplantation Worldwide
Seeding risk following percutaneous approach to hepatocellular carcinoma
Tumour biopsy is usually considered mandatory for patient management by oncologists. Currently percutaneous ablation is used therapeutically for cirrhotic patients with small hepatocellular carcinoma (HCC), not suitable for resection or waiting for liver transplantation. However malignant seeding is a recognized complication of both diagnostic and therapeutic procedures in patients with HCC. Although percutaneous therapy whether with or without biopsy of a suspected HCC nodule may minimize the risk of seeding, this has not been confirmed.
To evaluate the risk of seeding, defined as new neoplastic disease occurring outside the liver capsule, either in the subcutaneous tissue or peritoneal cavity following needle biopsy and/or local ablation therapy (LAT).
A literature search resulted in 179 events in 99 articles between January 1983 and February 2007: 66 seedings followed liver biopsy, 26 percutaneous ethanol injection (PEI), 1 microwave, 22 radiofrequency ablation (RFA), and 64 after combined biopsy and percutaneous treatment (5 microwave; 33 PEI; 26 RFA).
In 41 papers specifying the total number of patients biopsied and/or treated, the median risk of seeding was 2.29% (range 0–11%) for biopsy group; 1.4% (1.15–1.85%) for PEI when used with biopsy and 0.61% (0–5.56%) for RFA without biopsy, 0.95% (0–12.5%) for RFA with biopsy and 0.72% (0–10%) for liver nodules (including non-HCC nodules) biopsied and ablated.
Risk of seeding with HCC is substantial and appears greater with using diagnostic biopsy alone compared to therapeutic percutaneous procedures. This risk is particularly relevant for patients being considered for liver transplantation.
Seeding following percutaneous diagnostic and therapeutic approaches for hepatocellular carcinoma. What is the risk and the outcome? Seeding risk for percutaneous approach of HCC. Stigliano R, Marelli L, Yu D, Davies N, Patch D, Burroughs AK. Cancer Treat Rev 2007. doi:10.1016/j.ctrv.2007.04.001. Available at: http://www.sciencedirect.com.
In a prior review titled “To Biopsy or Not To Biopsy,”1 a strong argument not to biopsy was the risk for seeding of hepatocellular carcinoma (HCC) following diagnostic biopsy. Saborido et al.2 reviewed their experience with preoperative fine needle aspiration biopsy, which caused a large incidence of tumor recurrence following transplantation. Physicians perform other procedures on cirrhotic livers with HCC. What is the seeding risk following the percutaneous approach to HCC?
Stigliano et al. report on their literature search for cases of seeding following percutaneous procedures on livers with HCC. These investigators defined needle tract seeding of liver tumor as the development of new neoplastic disease outside the liver capsule, within the subcutaneous soft tissue of the peritoneal cavity, following needle biopsy and/or local ablation therapy. They found 179 seeding episodes from January 1983 until February 2007 resulting from diagnostic biopsy or local ablation therapy using percutaneous ethanol injection; acetic acid or hot saline injection; radiofrequency ablation; microwave therapy, laser therapy, or cryotherapy; and combinations of diagnostic biopsy and therapeutic procedures. The mean risk for seeding following diagnostic biopsy was 3.17% (range: 0%-11%), and the mean time to diagnosis was 13 months. The mean risk for seeding after diagnostic biopsy and percutaneous ethanol injection was 1.4% (mean time to diagnosis: 11 months). Following biopsy and radiofrequency ablation, the mean risk for seeding was 2.5% (mean time to diagnosis: 7 months). The mean risk for seeding after radiofrequency ablation alone was 1.73% (range: 0%-5.56%). From their literature review, the authors concluded that the risk of the percutaneous approach to HCC is clinically substantial, and biopsy of HCC in patients with cirrhosis should not be routine clinical practice.
The debate continues over whether or not to biopsy. Concerns still exist that seeding following percutaneous procedures on a cirrhotic liver containing HCC is underreported in the literature. If so, the aforementioned percentages are low estimates.
- 1Perkins JD. To biopsy or not to biopsy? Liver Transpl 2006;12:885–886.
- 2Saborido BP, Diaz JC, de Los Galanes SJ, Sequrola CL, de Usera MA, Garrido MD, et al. Does preoperative fine needle aspiration-biopsy produce tumor recurrence in patients following liver transplantation for hepatocellular carcinoma? Transplant Proc 2005;37:3874–3877.
Early Development of Nanoprobes for Diagnostic Imaging
Nanoprobes with near-infrared persistent luminescence for in vivo imaging. le Masne de Chermont Q, Chanéac C, Seguin J, Pellé F, Maîtrejean S, Jolivet JP, et al. Proc Natl Acad Sci U S A 2007;104:9266–9271.
Fluorescence is increasingly used for in vivo imaging and has provided remarkable results. Yet this technique presents several limitations, especially due to tissue autofluorescence under external illumination and weak tissue penetration of low wavelength excitation light. We have developed an alternative optical imaging technique by using persistent luminescent nanoparticles suitable for small animal imaging. These nanoparticles can be excited before injection, and their in vivo distribution can be followed in real-time for more than 1 h without the need for any external illumination source. Chemical modification of the nanoparticles' surface led to lung or liver targeting or to long-lasting blood circulation. Tumor mass could also be identified on a mouse model.
Exciting research on nanotechnology is taking place in the field of radiology.1 Soon to be added to the current diagnostic optical imaging armamentarium of magnetic resonance imaging, positron emission tomography, and optical coherence tomography2 is imaging with luminescent nanoparticles. In this review, le Masne de Chermont et al. highlight their work in lung and liver imaging and tumor visualization in a mouse model.
The authors state that several problems have existed with optical imaging using present-day fluorescent probes. These difficulties include autofluorescence from the tissue organic components due to the constant probe illumination during the testing for signal acquisition and due to deep-tissue signal attenuation.3,4 These problems are overcome with inorganic luminescent nanoparticles, which emit in the red to near-infrared range and can be optically excited before injection. These special nanoparticles eliminate problems with in situ excitation and the resulting autofluorescence. Additionally, the authors point out that the long-lasting afterglow, called persistent luminescence, can last for several hours, allowing for real-time tissue distribution monitoring.
By manipulating the surface charge (positive, neutral, and negative) of the nanoparticles, the authors could change the particles' in vivo biodistribution. Positively charged particles were important for lung retention. Negatively changed particles were rapidly cleared from the blood flow by liver uptake. This uptake was presumed to be by endothelial and Kupffer cells. Manipulation to make neutral particles resulted in a longer time that the particles stayed in the blood circulation.
Even though problems still exist with these new nanoparticles,1 look for them in a radiology suite near you.
- 1Sharma P, Brown S, Walter G, Santra S, Moudgil B. Nanoparticles for bioimaging. Adv Colloid Interface Sci 2006;123–126:471–485.
- 2Perkins JD. Optical coherence tomography: expanding use in the bile duct. Liver Transpl 2007;13:765.
- 3Frangioni JV. In vivo near-infrared fluorescence imaging. Curr Opin Chem Biol 2003;7:626–634.
- 4Cheong WF, Prahl SA, Welch AJ. A review of the optical properties of biological tissues. IEEE J Quantum Electron 1990;26:2166–2185.
Quality of Life After Liver Transplantation for Acute Hepatic Failure
A qualitative study exploring patients perceived quality of life following an emergency liver transplant for acute liver failure. Sargent S, Wainwright SP. Intensive Crit Care Nurs 2007. doi://10.1016/j.iccn.2007.03.005. Available at: http://www.sciencedirect.com.
Liver transplantation is now an accepted and successful therapy for both acute and chronic liver diseases. Whilst the study of health related quality of life (HRQoL) post-transplantation for chronic liver disease (CLD) has been well documented, there is little data measuring HRQoL following liver transplantation for acute liver failure (ALF), despite super urgent transplantation constituting 16.6% of all United Kingdom liver transplantation. Therefore, the aim of the present study was to document the HRQoL in patients who have received an emergency liver transplant for ALF. Data collection employed between method triangulation, using the Short Form 36 quality of life health questionnaire for both ALF (n = 47) and CLD (n = 49), and six semi-structured interviews. Only the qualitative element of the study is reported here. Phenomenological analysis of the semi-structured interviews identified four themes relating to the physical changes encountered (inactivity), physical recovery (health transition); changes made to the transplant recipients life styles (modification); and outlook. The majority of transplanted ALF transplant recipients' stated that they have a good quality of life, which was often comparable to their pretransplantation lifestyle. However, the initial recovery process was often difficult and was related to the physical changes instigated from their multi-organ failure and intensive care stay, which can present numerous physical and emotional challenges.
Several health-related quality of life reports have appeared since the early days of liver transplantation. Hellgren et al.1 found that liver recipients were more hindered post-transplantation than healthy subjects with respect to bodily pain and physical activities but were equal in social functioning and mental health. Gross et al.2 reported that patients' quality of life after liver transplantation for cholestatic liver disease substantially improved in all aspects, including symptoms; physical, social, and emotional functioning; health perceptions; and overall quality of life. Dudley et al.3 reported that quality of life may be worse following liver transplantation for hepatitis C in comparison with the posttransplant quality of life of patients who underwent transplantation for other liver diseases. Gutteling et al.4 confirmed that among sufferers of chronic liver disease, patients with hepatitis C have the worst health-related quality of life. However, Estraviz et al.5 reported that those with alcoholic or viral cirrhosis have the poorest quality of life prior to transplantation, but after transplantation, there is no difference observed among the various diagnostic groups.
Patients with chronic liver disease who receive a transplant are able to compare life with chronic liver disease to life after transplantation. Additionally, persons with chronic liver disease have the opportunity to undergo patient education prior to transplantation, which helps to prepare them for what to expect with a new liver. This is different from patients with acute liver failure, who usually have no previous chronic disease and have no time to receive transplant patient education. Do acutely ill liver recipients perceive life with a transplant differently than recipients who had prior chronic liver disease?
In this review, Sargent and Wainwright document the health-related quality of life of patients undergoing emergency liver transplantation for acute liver failure. Four themes emerged post-transplantation. Physical inactivity was the most prevalent theme. For most patients, it was difficult to recover from the severe chronic fatigue brought about by such factors as major weight loss, loss of muscle tone, intensive care stay, and long periods of immobility. Health transition was another theme, involving physical recovery and health restoration, regaining autonomy, and learning to manage immunosuppressive medications. The third theme was modification, referring to modification from pretransplant lifestyles in some way, ranging from the necessity of becoming more organized to changing careers. Finally, as the fourth theme, all patients reported changes in their outlook on life. Some experienced loss of confidence, insecurity, social isolation (1 patient made a suicide attempt), and fear of infection. Most patients enjoyed positive changes in their outlook. Many felt that, having been close to death, they now had a second chance in life.
The majority of patients who underwent transplantation for acute liver failure affirmed that their health-related quality of life was comparable to their pretransplant state. Sargent and Wainwright also found that acute patients' posttransplantation quality of life was comparable to that of patients who underwent transplantation for chronic liver disease.6 The most difficult aspect of the recovery process, which took between 6 and 15 months, was recuperating from the physical aspects of their diseases.
Awareness of the posttransplantation challenges unique to patients who had acute liver failure will allow greater understanding of their needs and facilitate their recovery process.
- 1Hellgren A, Berglund B, Gunnarsson U, Hansson K, Norberg U, Bäckman L. Health-related quality of life after liver transplantation. Liver Transpl Surg 1998;4:215–221.
- 2Gross CR, Malinchoc M, Kim WR, Evans RW, Wiesner RH, Petz JL, et al. Quality of life before and after liver transplantation for cholestatic liver disease. Hepatology 1999;29:356–364.
- 3Dudley T, Chaplin D, Clifford C, Mutimer DJ. Quality of life after liver transplantation for hepatitis C infection. Qual Life Res 2007. doi://10.1007/s11136-007-9244-y. Available at: http://www.springerlink.com.
- 4Gutteling JJ, de Man RA, Busschbach JJ, Darlington AS. Overview of research on health-related quality of life in patients with chronic liver disease. Neth J Med 2007;65:227–234.
- 5Estraviz B, Quintana JM, Valdivieso A, Bilbao A, Padierna A, de Urbina JO, et al. Factors influencing change in health-related quality of life after liver transplantation. Clin Transplant 2007;21:481–499.
- 6Sargent S, Wainwright SP. Quality of life following emergency liver transplantation for acute liver failure. Nurs Crit Care 2006;11:168–176.
Evolving Treatment of Biliary Strictures Following Liver Transplantation
Endoscopic treatment of anastomotic biliary strictures after deceased donor liver transplantation: outcomes after maximal stent therapy. Pasha SF, Harrison ME, Das A, Nguyen CC, Vargas HE, Balan V, et al. Gastrointest Endosc 2007;66:44–51.
Background: The optimal endoscopic treatment for anastomotic biliary strictures after deceased donor liver transplantation is undefined. Endoscopic therapy with conventional methods of biliary dilation and stent placement has been successful but often requires prolonged therapy. Objective: To determine the outcomes of an aggressive endoscopic approach that uses endoscopic dilation followed by maximal stent placement. Setting: Tertiary-care academic medical center. Patients: Of 176 patients who underwent deceased donor liver transplantation between June 1999 and July 2004, 25 were diagnosed with anastomotic biliary strictures. Interventions: Patients were treated endoscopically with a combined technique of balloon dilation and maximal stent placement. Main Outcome Measurements: Treatment outcomes, including bile-duct patency, a need for surgical intervention, morbidity, and mortality, were evaluated retrospectively. Results: Endoscopic dilation followed by maximal stent placement was performed until resolution of strictures in 22 of 25 patients (88% immediate success on intent-to-treat analysis). Persistent resolution of strictures was achieved in 18 of these 22 patients. Re-treatment was successful in 2 of 4 patients with recurrent strictures. Overall, 20 of 22 patients who completed endoscopic therapy (91%) avoided surgical intervention. Median duration of endoscopic treatment was 4.6 months. Patients with early onset strictures required a significantly shorter duration of endoscopic therapy (3 vs 9 months; P < .01). Multiple stent placement was not technically difficult, and no major complications were encountered. Conclusions: Aggressive endoscopic therapy with combined biliary dilation and maximal stent placement allows resolution of anastomotic biliary strictures after deceased donor liver transplantation in a relatively short period, with sustained success and minimal complications.
There is a long history in the treatment of biliary strictures following liver transplantation.1 In the early days, most strictures were attacked surgically.2 In 1995, Zajko et al.3 reported on their 10-year experience with transhepatic balloon dilation. Of 72 patients with biliary strictures, 56 had anastomotic strictures, and 16 had nonanastomotic strictures. For anastomotic strictures, the success rate was 66% ± 7.3% at 6 years, and for nonanastomotic strictures, the success rate was 85% ± 10% at 5 years. In 1995, Sherman et al.4 reported on the role of endoscopic methods in treating biliary complications after liver transplantation. Their report covered 5 patients with biliary strictures. In 1998, Rizk et al.5 reported on endoscopic therapy with dilation and stenting in 22 patients (10 with anastomotic strictures and 12 with donor hepatic duct strictures). At 22 months' follow-up, 90% of the anastomotic strictures were stent-free, and 73% of the donor hepatic duct strictures were stent-free.
In 2000, to determine the optimal therapy for anastomotic biliary strictures following liver transplantation, Schwartz et al.6 reviewed their use of endoscopic therapy with balloon dilation alone. Dilation was successfully carried out in 11 of their 15 patients with anastomotic strictures, but only 4 (27%) had a good outcome. These investigators concluded that endoscopic balloon dilation alone is not a reliable therapy for anastomotic strictures. In 2003, Morelli et al.7 reported on 25 patients with anastomotic strictures following liver transplantation treated endoscopically by stent placement. Of these 25 patients, 22 (88%) had a technically successful stent placement, and 20 patients (80%) had long-term success. In 2006, Zoepf et al.8 reported in Liver Transplantation their comparison of treatment with balloon dilation alone versus treatment with balloon dilation plus placement of bile duct endoprostheses. Dilation alone was initially successful in 89% of their patients, but strictures recurred in 62%. Dilation plus endoprostheses was initially successful in 87% of study cases, with a recurrence rate of 31%. Alazmi et al.9 reported that 18% of patients previously treated successfully with balloon dilation and stenting have a late stricture recurrence.
In the present review, Pasha et al. report on an aggressive endoscopic approach using repeated dilation followed by maximal stent placement until resolution. Their study reviewed 25 patients who developed anastomotic biliary strictures following deceased donor liver transplantation. Anastomotic biliary stricture was defined as a dominant narrowing at the anastomotic site, without effective passage of contrast material. The aggressive endoscopic approach consisted of dilation by high-pressure pneumatic biliary dilation balloons ranging in size from 4 to 10 mm, followed by insertion of the maximum number of polyethylene straight stents that could be accommodated within the stricture. The number of inserted stents (size range: 7-11.5F) ranged from 1 to 4. Follow-up endoscopy was performed at intervals from 2 to 3 months, at which the stents were extracted and a cholangiogram was obtained. If a stricture persisted, balloon dilation and maximal stent placement were repeated. A successful outcome was defined as improvement in the liver enzymes and patency of the anastomotic site determined by withdrawal of an 8.5- to 9-mm balloon through the site followed by emptying of contrast material. Endoscopic dilation with maximal stent placement was completed in 22 (88%) of the 25 patients. Of the 22 treated endoscopically, 18 (82%) had sustained resolution of their strictures. Four patients had recurrence after initial success, with mean recurrence at 3.3 months (2.2-7 months). Two of the patients with recurrent strictures were successfully retreated with endoscopic therapy, and the other 2 patients underwent surgical treatment after endoscopic therapy was unsuccessful.
Despite aggressive treatment of biliary anastomotic strictures, a small percentage of patients still require surgical therapy. Evolving technology will hopefully make this percentage even smaller.