Donor-transmitted malignancies in organ transplantation: assessment of clinical risk.

The continuing organ shortage requires evaluation of all potential donors, including those with malignant disease. In the United States, no organized approach to assessment of risk of donor tumor transmission exists, and organs from such donors are often discarded. The ad hoc Disease Transmission Advisory Committee (DTAC) of the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) formed an ad hoc Malignancy Subcommittee to advise on this subject. The Subcommittee reviewed the largely anecdotal literature and held discussions to generate a framework to approach risk evaluation in this circumstance. Six levels of risk developed by consensus. Suggested approach to donor utilization is given for each category, recognizing the primacy of individual clinical judgment and often emergent clinical circumstances. Categories are populated with specific tumors based on available data, including active or historical cancer. Benign tumors are considered in relation to risk of malignant transformation. Specific attention is paid to potential use of kidneys harboring small solitary renal cell carcinomas, and to patients with central nervous system tumors. This resource document is tailored to clinical practice in the United States and should aid clinical decision making in the difficult circumstance of an organ donor with potential or proven neoplasia.

Derivation of the uncontrolled donation after circulatory determination of death protocol for New York city.

Evidence from Europe suggests establishing out-of-hospital, uncontrolled donation after circulatory determination of death (UDCDD) protocols has potential to substantially increase organ availability. The study objective was to derive an out-of-hospital UDCDD protocol that would be acceptable to New York City (NYC) residents. Participatory action research and the SEED-SCALE process for social change guided protocol development in NYC from July 2007 to September 2010. A coalition of government officials, subject experts and communities necessary to achieve support was formed. Authorized NY State and NYC government officials and their legal representatives collaboratively investigated how the program could be implemented under current law and regulations. Community stakeholders (secular and religious organizations) were engaged in town hall style meetings. Ethnographic data (meeting minutes, field notes, quantitative surveys) were collected and posted in a collaborative internet environment. Data were analyzed using an iterative coding scheme to discern themes, theoretical constructs and a summary narrative to guide protocol development. A clinically appropriate, ethically sound UDCDD protocol for out-of-hospital settings has been derived. This program is likely to be accepted by NYC residents since the protocol was derived through partnership with government officials, subject experts and community participants.

Transmission of anaplastic large cell lymphoma via organ donation after cardiac death.

Recently, donation after cardiac death (DCD) has been encouraged in order to expand the donor pool. We present a case of anaplastic T-cell lymphoma transmitted to four recipients of solid organ transplants from a DCD donor suspected of having bacterial meningitis. On brain biopsy, the donor was found to have anaplastic central nervous system T-cell lymphoma, and the recipient of the donor's pancreas, liver and kidneys were found to have involvement of T-cell lymphoma. The transplanted kidneys and pancreas were excised from the respective recipients, and the kidney and pancreas recipients responded well to chemotherapy. The liver recipient underwent three cycles of chemotherapy, but later died due to complications of severe tumor burden. We recommend transplanting organs from donors with suspected bacterial meningitis only after identification of the infectious organism. In cases of lymphoma transmission, excision of the graft may be the only chance at long-term survival.

Vascular and extravascular complications of liver transplantation: comprehensive evaluation with three-dimensional contrast-enhanced volumetric MR imaging and MR cholangiopancreatography.

OBJECTIVE: Our purpose was to evaluate a comprehensive MR imaging strategy for recipients of liver transplants that relies on dynamic interpolated three-dimensional (3D) MR imaging for simultaneous vascular, parenchymal, and extrahepatic imaging. MATERIALS AND METHODS: Twenty-three consecutive adult patients underwent 30 MR imaging examinations between 2 days and 99 months (mean, 15 months) after transplantation using a breath-hold 3D gradient-echo sequence (TR range/TE range, 3.7-4.7/1.8-1.9; flip angle, 12-30 degrees ) with an intermittent fat-saturation pulse and interpolation in the section-select direction to enable pixel size 3 mm or less in all dimensions. Unenhanced and triphasic contrast-enhanced 3D imaging (average dose, 0.13 mmol/kg of gadopentetate dimeglumine) was performed. A subset of patients (n = 13) also underwent MR cholangiopancreatography using half-Fourier single-shot turbo spin-echo imaging. MR imaging examinations were correlated with digital subtraction angiography (n = 8), contrast-enhanced cholangiography (n = 9), sonography (n = 13), and histopathology (n = 14). RESULTS: MR imaging revealed abnormal findings in 27 (90%) of 30 examinations, including vascular disease in nine, biliary complications in four, and evidence of intra- or extra-hepatic hepatocellular carcinoma recurrence in six. Digital subtraction angiography confirmed seven MR angiography examinations but suggested disease overestimation in one. Contrast-enhanced cholangiography confirmed findings of MR cholangiopancreatography in seven cases but suggested disease underestimation in two. CONCLUSION: Dynamic interpolated 3D MR imaging combined with dedicated MR cholangiopancreatography can provide a comprehensive assessment of vascular, biliary, parenchymal, and extrahepatic complications in most recipients of liver transplants.

MR imaging as the sole preoperative imaging modality for right hepatectomy: a prospective study of living adult-to-adult liver donor candidates.

OBJECTIVE: Our aim was to investigate the feasibility of MR imaging as a comprehensive preoperative imaging test for examination of liver donor candidates for adult-to-adult right lobe transplantation. SUBJECTS AND METHODS: Twenty-five consecutive donor candidates were examined at 1.5 T using a torso phased array coil with breath-hold T1- and T2-weighted imaging of the abdomen, MR cholangiography using T2-weighted turbo spin-echo imaging, and MR angiography and venography of the liver using two interpolated three-dimensional spoiled gradient-echo sequences (average dose of gadolinium contrast material, 0.17 mmol/kg). Images were interpreted for liver parenchymal and extrahepatic abnormalities; measurements of right and left lobe liver volumes; definition of hepatic arterial, portal venous, and hepatic venous anatomy; and definition of the biliary branching pattern. Findings were compared with those of conventional angiography in 13 patients, 11 of whom also had surgical findings for comparison. RESULTS: Nine patients were excluded as candidates for donation on the basis of MR imaging findings that included parenchymal or extrahepatic abnormalities in five patients, vascular anomalies in two, and biliary anomalies in three. Two patients who did not undergo surgery underwent conventional angiography that confirmed MR angiographic findings except for a small (<2 mm) accessory left hepatic artery missed on MR imaging. Of the nine patients who underwent successful right hepatectomy, all MR imaging findings were corroborated intraoperatively. In two patients, right hepatectomy was aborted at laparotomy because of intraoperative cholangiography findings; in one of them, the biliary finding was unsuspected on MR imaging. CONCLUSION: A comprehensive MR imaging examination has the potential to serve as the sole preoperative imaging modality for living adult-to-adult liver donor candidates provided improvements in definition of intrahepatic biliary anatomy can be achieved.

Hepatocellular carcinoma and dysplastic nodules in patients with cirrhosis: prospective diagnosis with MR imaging and explantation correlation.

PURPOSE: To determine the sensitivity and specificity of magnetic resonance (MR) imaging for detection of hepatocellular carcinoma (HCC) and dysplastic nodules (DNs) by using explantation correlation in patients with cirrhosis and no known HCC. MATERIALS AND METHODS: Seventy-one patients without a known history of HCC who underwent MR imaging and subsequent transplantation within 90 days were examined. Breath-hold turbo short inversion time inversion-recovery and/or T2-weighted turbo spin-echo MR images were obtained. Dynamic two- or three-dimensional gadolinium-enhanced gradient-echo MR images were obtained in the hepatic arterial, portal venous, and equilibrium phases. Prospective MR image interpretations were compared directly with explanted liver pathologic results. RESULTS: Eleven (15%) of 71 patients had hepatic malignancies; MR imaging enabled diagnosis of tumor in six (54%) of 11 patients. On a lesion-by-lesion basis, MR imaging depicted 11 of 20 hepatic neoplasms, for an overall sensitivity of 55%. MR imaging depicted four (80%) of five lesions larger than 2 cm, six (50%) of 12 lesions 1-2 cm, and one (33%) of three lesions smaller than 1 cm. MR imaging depicted only nine (15%) of 59 DNS: The specificities of MR imaging for detection of HCC and DNs on a per patient basis were 60 (86%) of 70 patients and 53 (85%) of 62 patients, respectively. CONCLUSION: MR imaging is insensitive for the diagnosis of small (<2-cm) HCCs and DNS:

Siderotic nodules in the cirrhotic liver at MR imaging with explant correlation: no increased frequency of dysplastic nodules and hepatocellular carcinoma.

PURPOSE: To determine the sensitivity of magnetic resonance (MR) imaging for detection of siderotic nodules in patients with cirrhosis and whether the frequency of hepatocellular carcinoma (HCC) and dysplastic nodules is greater if siderotic nodules are present. MATERIALS AND METHODS: MR imaging (1.5 T) was performed within 0-117 days (mean, 30 days) before liver transplantation in 77 patients. Two readers retrospectively evaluated gradient-echo (GRE) (echo time [TE], > or = 9 and 4-5 msec) and turbo short inversion time inversion-recovery or T2-weighted images for low-signal-intensity nodules. Whole-explant pathologic correlation was available in every case. RESULTS: At explantation, 28 (36%) of 77 patients had HCC, 25 (32%) had dysplastic nodules, and nine (12%) had both; 35 (45%) patients had siderotic nodules. The sensitivity of GRE imaging with 9-msec or longer TE for the detection of siderotic nodules was 80% (28 of 35) but decreased to 31% (11 of 35) with 4-5-msec TE. Frequency of HCC was not significantly higher (P =.27) in patients with (43% [15 of 35]) than in patients without (31% [13 of 42]) siderotic nodules. Frequency of dysplastic nodules also was not significantly higher (P =.42) in patients with (37% [13 of 35]) than in patients without (29% [12 of 42]) siderotic nodules. CONCLUSION: Sensitivity of MR imaging for the detection of siderotic nodules was improved with use of GRE pulse sequences with longer TEs of 9 msec or greater (80%) versus 4-5 msec (31%); however, there was no significant increased frequency of HCC or dysplastic nodules in patients with pathologically proved siderotic nodules.

Siderotic nodules at MR imaging: regenerative or dysplastic?

OBJECTIVE: To determine if iron containing "siderotic" nodules detected at magnetic resonance (MR) imaging are regenerative (RN) or dysplastic (DN) and to attempt to identify features that may distinguish them. MATERIAL AND METHODS: MR imaging (1.5 T) was performed on 77 cirrhotic patients who underwent orthotopic liver transplantation within 0-117 days (mean 30 days) of MR imaging. Two readers retrospectively evaluated breath-hold gradient-echo pulse sequences (echo time > or =9.0 ms, flip angle < or =45 degrees) for the presence of hypointense nodules, which were classified as micronodular (< or =3 mm), macronodular (>3 mm), or mixed. Nodule distribution was classified as focal (<5), scattered (5-20), or diffuse (>20) per slice. Thin section pathologic correlation was available in all cases, and Prussian blue iron stains were performed. RESULTS: Of 35 patients with pathologically proven siderotic nodules, 10 (29%) had at least 2 siderotic DN. MR detected siderotic nodules in 10 of 10 (100%) patients with siderotic DN and RN, and in 18 of 25 patients (72%) with siderotic RN only. CONCLUSION: Siderotic RN cannot be reliably distinguished from siderotic DN with MR imaging, and therefore the widely used term "siderotic regenerative nodule" should be avoided and replaced by "siderotic nodule."

Transplantation in the hepatitis B patient and current therapies to prevent recurrence.

Hepatitis B is the sixth most common indication for liver transplantation in the United States, accounting for about 7% of all transplants among adults. Transplantation for hepatitis B is especially problematic because the virus is not eradicated and there is great potential for reinfection that can lead to graft failure or death. This risk is higher still in patients with active viral replication and chronic liver disease. Treatment with short-term hepatitis B immune globulin (HBIG) delays reinfection of the allograft, but only long-term treatment with HBIG has led to a decline in the reinfection rate. Combination therapy using HBIG with nucleoside analogues will likely become the standard of care to maintain stable serum titers of protective anti-HBs antibody and to prevent posttransplantation reinfection.

Case studies of the hepatitis B patient: a panel discussion.

In recent years, there have been significant advances in the treatment of patients with hepatitis B who are candidates for liver transplantation. This includes the prevention and management of hepatitis B posttransplantation. However, there is no established protocol for treating these patients. Ultimately, the goal would be to have patients HBV-DNA negative pretransplantation and then to prevent HBV recurrence posttransplantation to help ensure their quality of life. Several clinical case scenarios are presented and possible treatment solutions have been suggested. The timing of a transplant is critical due to the risk of viral mutation while the patient is on a nucleoside analogue antiviral agent and waiting for an organ. One successful option might be to start therapy pretransplant and continue it posttransplant. Combination therapy appears to provide the most effective course of treatment. This should include a nucleoside analogue and patients should be covered with hepatitis B immune globulin throughout the course of therapy. Several other variations of combination therapy are discussed, but many clinical issues remain to be resolved. Guidelines for future studies designed to answer these questions are proposed.

MR-guided needle aspiration biopsies of hepatic masses using a closed bore magnet.

PURPOSE: Our purpose was to assess the efficacy of MR-guided biopsies with a conventional superconducting MR scanner and describe the techniques used to achieve successful results. METHOD: Fourteen biopsies were completed under MR guidance in 11 patients. Seven patients with previously detected lesions were referred for biopsy under MR guidance when hepatic lesions were identified by MRI but not with prebiopsy noncontrast CT or ultrasound (US). Additionally referred for MR-guided biopsy were four patients in whom previous CT- or US-guided biopsies of focal lesions were nondiagnostic. A 22 gauge MR-compatible needle was used in each case. Lesions ranged in size from 8 to 32 mm. Eleven lesions (eight patients) were suspected of being hepatomas, and three lesions (three patients) were suspected of being metastases. RESULTS: Thirteen of 14 MR-guided biopsies (93%) were diagnostic. Hepatocellular carcinoma was confirmed in 6 of 11 lesions suspected of representing hepatoma. One lesion, in a patient treated with chemoembolization, demonstrated necrotic material. One lesion yielded nondiagnostic material despite repeated visualization of the needle tip in the target lesion. Three lesions demonstrated metastatic carcinoma. Benign hepatocytes were detected in three biopsy specimens. Seven of the lesions that were successfully biopsied measured < 2.5 cm in diameter. CONCLUSION: With use of a closed bore 1.5 T system, diagnostic MR-guided needle aspiration biopsies of hepatic masses and subcomponents, including small lesions (< 2.5 cm), can be successfully obtained.

Immunohistochemical detection of hepatitis C antigen by monoclonal antibody TORDJI-22 compared with PCR viral detection.

We sought to determine the sensitivity and specificity of immunohistochemistry using the TORDJI-22 MoAb (BioGenex, San Ramon, Calif), which is specific for the C-100 protein of the hepatitis C virus, compared with reverse transcriptase-polymerase chain reaction (RT-PCR) of tissue for viral RNA. RT-PCR had been performed on 52 fixed tissue specimens. Immunohistochemistry was performed using prediluted antibody with the alkaline phosphatase/fast red (BioGenex) technique. Predigestion with Protease XXIV (BioGenex) and other procedures followed the manufacturer's protocols. Positive immunohistochemistry was narrowly defined as tightly clumped, perinuclear red granules in hepatocytes. Of the specimens, 28 were positive by RT-PCR. With RT-PCR as the standard of comparison, immunohistochemistry yielded a sensitivity of 70% and specificity of 84%. Positive cells, when present, were usually very rare. With stringent criteria, immunohistochemistry with the TORDJI-22 monoclonal antibody is a very specific, fairly sensitive diagnostic test for hepatitis C virus in fixed liver tissues.

Dysplastic nodules and hepatocellular carcinoma: thin-section MR imaging of explanted cirrhotic livers with pathologic correlation.

PURPOSE: To evaluate detection and characterization of hepatocellular nodules in fresh whole explanted cirrhotic livers at thin-section magnetic resonance (MR) imaging. MATERIALS AND METHODS: T1-weighted spin-echo and T2-weighted fast spin-echo MR imaging (5-mm-thick sections) were performed in a head coil at 1.5 T in the whole cirrhotic livers of 28 consecutive patients within 4 hours of explantation. MR imaging findings were correlated with findings at pathologic examination, and new international terminology was used to classify the hepatocellular nodules. RESULTS: At pathologic examination, 42 suspect (other than regenerative) nodules were identified in 11 patients. MR imaging depicted 41 of 42 (98%) of these nodules (five of five hepatocellular carcinomas [HCCs {diameter, > or = 2 cm}], 10 of 10 small HCCs [diameter, < 2 cm], two of two dysplastic nodules with subfoci of HCC, three of three high-grade dysplastic nodules, and 21 of 22 low-grade dysplastic nodules. Lesions demonstrated the following combinations of signal intensity characteristics on thin-section T1- and T2-weighted images, respectively: HCC, hyperintense, hypointense (n = 3); hyperintense, hyperintense (n = 1); hypointense, isointense (n = 1). Small HCC, hyperintense, hypointense (n = 7); hypointense, hyperintense (n = 2); hyperintense, hyperintense (n = 1). Both dysplastic nodules with subfoci of HCC, hyperintense, hypointense. All seven nonsiderotic low-grade dysplastic nodules, hyperintense, hypointense. All 14 siderotic low-grade dysplastic nodules, hypointense, hypointense. All three high-grade dysplastic nodules, hyperintense, hypointense. CONCLUSION: The variable signal intensity characteristics of HCCs made reliable diagnosis impossible, but the thinsection unenhanced in vitro MR images were sensitive for detection of HCCs and dysplastic nodules in cirrhotic livers.

Incidence and treatment of recurrent hepatitis C after liver transplantation.

Recurrence of hepatitis C is a significant problem after liver transplantation. This prospective study was done to assess the rate of recurrence and discuss two possible treatment modalities that have been successful in avoiding retransplantation. Twenty-one patients underwent orthotopic liver transplantation for hepatitis C at a metropolitan medical center over a 34-month period. The mean follow-up interval was 13.4 +/- 2.2 months (range 5-28 months). The patients were routinely evaluated with clinic visits and liver function tests, specifically total bilirubin, serum glutamic-oxaloacetic transaminase, and gamma-glutamyl transpeptidase. If values were elevated, the patient was admitted to the hospital for liver biopsy. Ten of the 21 patients demonstrated recurrence on biopsy. Two of 10 patients required no therapy. Interferon A was initiated in the remaining eight. Three of the eight patients had no significant response to interferon and were given intravenous ribavirin under an experimental protocol. Two of these three showed significant improvement in liver function values. The third died of chronic rejection. The incidence of recurrent hepatitis C after liver transplantation is significant. Many centers have had to resort to retransplantation. Our results show that with early detection and aggressive treatment with interferon and ribavirin, hepatitis C can be controlled and retransplantation may be avoided.