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American Journal of Transplantation Images in Transplantation—Continuing Medical Education (CME)

Each month, the American Journal of Transplantation will feature Images in Transplantation, a journal-based CME activity, chosen to educate participants on current developments in the science and imaging of transplantation. Participants can earn 1 AMA PRA Category 1 Credit™ per article at their own pace.

This month's feature article is titled: “Jaundice Six Months Following Liver Transplantation.”

Accreditation and Designation Statement

This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of Blackwell Futura Media Services, the American Society of Transplant Surgeons and the American Society of Transplantation. Blackwell Futura Media Services is accredited by the ACCME to provide continuing medical education for physicians.

Blackwell Futura Media Services designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Statement of Need

Given the expanding population of posttransplant patients, the prevention and early diagnosis of posttransplantation lymphoproliferative disorder (PTLD), as well as the successful treatment, are essential for maintenance of posttransplant patient survival. This activity will present a case that illustrates several learning points related to PTLD.

Purpose of Activity

This activity is intended to improve the practitioner's ability to establish the diagnosis, understand the pathology, and institute the effective treatment in the management of PTLD.

Identification of Practice Gap

The prevention, as well as the accurate and timely diagnosis and management of PTLD, rely on a broad clinical understanding of the potential etiologies in the posttransplant patient population. Delay in institution of therapy, or application of inappropriate therapy, can prevent the successful remission of PTLD.

Learning Objectives

Upon completion of this educational activity, participants will be able to:

  • Understand the significant risk factors for development of PTLD
  • Recognize the incidence of PTLD in the liver transplant recipient population, as well as the differences in incidence between adult and pediatric populations
  • Define the pathological categories for PTLD and the association with donor and recipient seropositivity/seronegativity
  • Determine the various treatment options for PTLD

Target Audience

This activity has been designed to meet the educational needs of physicians and surgeons in the field of transplantation.

Disclosures

No commercial support has been accepted related to the development or publication of this activity. Blackwell Futura Media Services has reviewed all disclosures and resolved or managed all identified conflicts of interest, as applicable. The following authors, editors, and staff reported no relevant financial relationships with respect to this activity.

Editor-in-Chief

Allan D. Kirk, MD, PhD, FACS

Editors

Sandy Feng, MD, PhD

Douglas W. Hanto, MD, PhD

Authors

Parsia A. Vagefi, MD, Peter B. Kelsey, MD, Ephraim P. Hochberg, MD, and Camille N. Kotton, MD

ASTS Staff

Mina Behari, Director of Education

This manuscript underwent peer review in line with the standards of editorial integrity and publication ethics maintained by the American Journal of Transplantation. The peer reviewers have no relevant financial relationships to disclose. The peer review process for the American Journal of Transplantation is blinded. As such, the identities of the reviewers are not disclosed in line with the standard accepted practices of medical journal peer review.

Instructions on Receiving CME Credit

This activity is designed to be completed within an hour. Physicians should claim only those credits that reflect the time actually spent in the activity. This activity will be available for CME credit for 12 months following its publication date. At that time, it will be reviewed and potentially updated and extended for an additional 12 months.

Follow these steps to participate, answer the questions and claim your CME credit:

  • Log on to https://www.wileyhealthlearning.com/ajt
  • Read the learning objectives, target audience, and activity disclosures.
  • Read the article in print or online format.
  • Reflect on the article.
  • Access the CME Exam, and choose the best answer to each question.
  • Complete the required evaluation and print your CME certificate.

A 71-year-old male with a history of Laennec's cirrhosis and hepatorenal syndrome necessitating prolonged renal replacement therapy underwent combined liver and kidney transplant from a 56-year-old heart-beating donor. His postoperative course was remarkable only for delayed graft function of the renal transplant, requiring four sessions of hemodialysis. The patient was sent to a rehabilitation facility on postoperative day 17, and 3 weeks later was discharged. Postoperatively he was maintained on prednisone, tacrolimus, and mycophenolate mofetil. Six months following transplant, the patient presented with 2 weeks of light-colored stools and tea-colored urine, as well as 4 days of jaundice. In addition, he reported fatigue and decreased appetite. Serum creatinine was 1.5 mg/dL (near baseline), but there was a marked elevation in liver function tests (total bilirubin 9.9 mg/dL, direct bilirubin 7.8 mg/dL, SGOT 109 U/L, SGPT 185 U/L, alkaline phosphatase 1066 U/L). Liver ultrasound was significant for moderate intrahepatic biliary dilatation and the patient underwent endoscopic retrograde cholangiopancreatography with biliary sphincterotomy and placement of a stent (Figure 1, curved line marking long segment biliary stricture prior to stent placement). Computed tomography (CT) scan of the abdomen demonstrated an ill-defined soft tissue density in the porta hepatis (Figure 2, arrow) and surrounding the hilum of the transplanted kidney. CT-guided biopsy of the porta hepatis mass was performed; cytology demonstrated a diffuse infiltrate of large lymphoid cells with vesicular nuclei and prominent nucleoli (Figure 3), which were positive for EBV-encoded RNA (EBER) by in situ hybridization (Figure 3). These findings were consistent with posttransplantation lymphoproliferative disorder, EBV positive monomorphic type. The EBV viral load was 64,600 (previously undetectable). Liver function tests normalized following stent placement, tacrolimus and mycophenolate mofetil were discontinued, and the patient began a rituximab-based regimen for treatment of his diffuse large B cell lymphoma.

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Figure 1. ERCP image demonstrating long segment biliary stricture (curved line) prior to stent placement.

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Figure 2. CT scan image of the abdomen demonstrating an ill-defined soft tissue density in the porta hepatis (arrow).

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Figure 3. Hilar biopsy demonstrating a diffuse infiltrate of large lymphoid cells with vesicular nuclei and prominent nucleoli (3A, hematoxylin and eosin stain), which were positive for EBV-encoded RNA by in situ hybridization (3B).

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Questions

  1. Significant risk factors for the development of PTLD are:
    1. donor age and cold ischemic time
    2. recipient age and warm ischemic time
    3. donor age and donor EBV serostatus
    4. degree of immunosuppression and recipient EBV serostatus
    5. degree of immunosuppression and warm ischemic time
  2. PTLD is more commonly seen in recipients of:
    1. bone marrow transplants
    2. small bowel and multiorgan transplants
    3. cardiothoracic transplants
    4. kidney and liver transplants
    5. pancreas and islet transplants
  3. Early PTLD is most commonly:
    1. EBV+
    2. EBV neg
    3. CMV+
    4. CMV neg
    5. EBV+ and CMV+
  4. Initial treatment of monoclonal PTLD is directed at:
    1. reduction of immunosuppression and complete surgical excision
    2. radiation therapy and complete surgical excision
    3. reduction of immunosuppression and chemotherapy
    4. chemotherapy and retransplantation
    5. reduction of immunosuppression and antiviral therapy
  5. The use of rituximab in the management of PTLD is based upon:
    1. its ability to bind and deplete CD 19 positive B cells
    2. its ability to bind and deplete CD 20 positive B cells
    3. its ability to bind and deplete CD 52 positive B cells
    4. its ability to bind and deplete CD 4 positive T cells
    5. its ability to bind and deplete CD 8 positive T cells

To complete this activity and earn credit, please go to https://www.wileyhealthlearning.com/ajt