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1.
Am J Transplant ; 15(1): 259-64, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25376342

ABSTRACT

The detection and management of potential donor-derived infections is challenging, in part due to the complexity of communications between diverse labs, organ procurement organizations (OPOs), and recipient transplant centers. We sought to determine if communication delays or errors occur in the reporting and management of donor-derived infections and if these are associated with preventable adverse events in recipients. All reported potential donor-derived transmission events reviewed by the Organ Procurement and Transplantation Network Ad Hoc Disease Transmission Advisory Committee from January 2008 to June 2010 were evaluated for communication gaps between the donor center, OPO and transplant centers. The impact on recipient outcomes was then determined. Fifty-six infection events (IEs; involving 168 recipients) were evaluated. Eighteen IEs (48 recipients) were associated with communication gaps, of which 12 resulted in adverse effects in 69% of recipients (20/29), including six deaths. When IEs and test results were reported without delay, appropriate interventions were taken, subsequently minimizing or averting recipient infection (23 IEs, 72 recipients). Communication gaps in reported IEs are frequent, occur at multiple levels in the communication process, and contribute to adverse outcomes among affected transplant recipients. Conversely, effective communication minimized or averted infection in transplant recipients.


Subject(s)
Communication , Disease Transmission, Infectious , Organ Transplantation/adverse effects , Tissue Donors/supply & distribution , Tissue and Organ Procurement , Humans , Prognosis , Transplant Recipients
2.
Am J Transplant ; 14(2): 356-66, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24456026

ABSTRACT

We studied whether the use of sirolimus with reduced-dose tacrolimus, as compared to standard-dose tacrolimus, after liver transplantation is safe, tolerated and efficacious. In an international multicenter, open-label, active-controlled randomized trial (2000-2003), adult primary liver transplant recipients (n=222) were randomly assigned immediately after transplantation to conventional-dose tacrolimus (trough: 7-15 ng/mL) or sirolimus (loading dose: 15 mg, initial dose: 5 mg titrated to a trough of 4-11 ng/mL) and reduced-dose tacrolimus (trough: 3-7 ng/mL). The study was terminated after 21 months due to imbalance in adverse events. The 24-month cumulative incidence of graft loss (26.4% vs. 12.5%, p=0.009) and patient death (20% vs. 8%, p=0.010) was higher in subjects receiving sirolimus. A numerically higher rate of hepatic artery thrombosis/portal vein thrombosis was observed in the sirolimus arm (8% vs. 3%, p=0.065). The incidence of sepsis was higher in the sirolimus arm (20.4% vs. 7.2%, p=0.006). Rates of acute cellular rejection were similar between the two groups. Early use of sirolimus using a loading dose followed by maintenance doses and reduced-dose tacrolimus in de novo liver transplant recipients is associated with higher rates of graft loss, death and sepsis when compared to the use of conventional-dose tacrolimus alone.


Subject(s)
Graft Rejection/drug therapy , Graft Survival/drug effects , Immunosuppressive Agents/therapeutic use , Liver Diseases/surgery , Liver Transplantation , Sirolimus/therapeutic use , Tacrolimus/therapeutic use , Adult , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Graft Rejection/etiology , Graft Rejection/mortality , Humans , International Agencies , Liver Diseases/complications , Liver Diseases/mortality , Male , Middle Aged , Prognosis , Prospective Studies , Survival Rate , Time Factors , Transplantation Immunology
3.
Am J Transplant ; 11(7): 1417-26, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21711448

ABSTRACT

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.


Subject(s)
Death , Tissue and Organ Procurement/legislation & jurisprudence , Community-Based Participatory Research , Humans , Informed Consent , New York City , Out-of-Hospital Cardiac Arrest , Tissue and Organ Procurement/methods , Warm Ischemia
4.
Am J Transplant ; 11(6): 1140-7, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21645251

ABSTRACT

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.


Subject(s)
Neoplasms/etiology , Organ Transplantation/adverse effects , Humans , Risk Assessment
5.
Am J Transplant ; 9(8): 1929-35, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19538493

ABSTRACT

Donor-derived disease transmission is increasingly recognized as a source of morbidity and mortality among transplant recipients. Policy 4.7 of the Organ Procurement and Transplantation Network (OPTN) currently requires reporting of donor-derived events. All potential donor-derived transmission events (PDDTE) reported to OPTN/UNOS were reviewed by the Disease Transmission Advisory Committee (DTAC). Summary data from January 1, 2005-December 31, 2007, were prepared for presentation. Reports of PDDTE have increased from 7 in 2005, the first full year data were collected, to 60 in 2006 and to 97 in 2007. More detailed information is available for 2007; a classification system for determining likelihood of donor-derived transmission was utilized. In 2007, there were four proven and one possible donor-derived malignancy transmissions and four proven, two probable and six possible donor-derived infectious diseases transmissions. There were nine reported recipient deaths attributable to proven donor transmissions events arising from eight donors during 2007. Although recognized transmission events resulted in significant morbidity and mortality, transmission was reported in only 0.96% of deceased donor donations overall. Improved reporting, through enhanced recognition and communication, will be critical to better estimate the transmission risk of infection and malignancy through organ transplantation.


Subject(s)
Advisory Committees , Communicable Diseases/epidemiology , Communicable Diseases/transmission , Neoplasms/epidemiology , Organ Transplantation/adverse effects , Tissue Donors , Humans , Retrospective Studies , Risk Factors , United States/epidemiology
6.
Am J Transplant ; 8(1): 238-44, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18021286

ABSTRACT

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.


Subject(s)
Death , Lymphoma, Large-Cell, Anaplastic/diagnosis , Lymphoma, Large-Cell, Anaplastic/etiology , Organ Transplantation/adverse effects , Tissue Donors , Adolescent , Adult , Female , Humans , Kidney Transplantation/adverse effects , Liver Transplantation/adverse effects , Lymphoma, Large-Cell, Anaplastic/microbiology , Male , Meningitis, Bacterial/transmission , Middle Aged , Pancreas Transplantation/adverse effects
7.
AJR Am J Roentgenol ; 177(5): 1101-7, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11641180

ABSTRACT

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.


Subject(s)
Cholangiography , Cholestasis, Extrahepatic/diagnosis , Common Bile Duct Diseases/diagnosis , Image Processing, Computer-Assisted , Imaging, Three-Dimensional , Liver Transplantation , Liver/blood supply , Magnetic Resonance Imaging , Postoperative Complications/diagnosis , Vascular Diseases/diagnosis , Adult , Aged , Anastomosis, Surgical , Angiography, Digital Subtraction , Female , Humans , Magnetic Resonance Angiography , Male , Middle Aged , Sensitivity and Specificity
8.
AJR Am J Roentgenol ; 176(6): 1475-82, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11373217

ABSTRACT

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.


Subject(s)
Hepatectomy , Liver Transplantation , Living Donors , Magnetic Resonance Imaging , Adult , Angiography , Bile Ducts/anatomy & histology , Contrast Media , Feasibility Studies , Female , Hepatic Artery/anatomy & histology , Hepatic Veins/anatomy & histology , Humans , Liver/blood supply , Magnetic Resonance Angiography , Male , Portal Vein/anatomy & histology , Prospective Studies
9.
Radiology ; 219(2): 445-54, 2001 May.
Article in English | MEDLINE | ID: mdl-11323471

ABSTRACT

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:


Subject(s)
Carcinoma, Hepatocellular/diagnosis , Liver Cirrhosis/complications , Liver Neoplasms/diagnosis , Liver/pathology , Magnetic Resonance Imaging , Adult , Aged , Carcinoma, Hepatocellular/complications , False Positive Reactions , Female , Humans , Liver Neoplasms/complications , Male , Middle Aged , Sensitivity and Specificity
11.
Radiology ; 218(1): 47-53, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11152778

ABSTRACT

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.


Subject(s)
Carcinoma, Hepatocellular/pathology , Liver Cirrhosis/pathology , Liver Neoplasms/pathology , Magnetic Resonance Imaging , Adult , Aged , Carcinoma, Hepatocellular/epidemiology , Female , Humans , Liver Neoplasms/epidemiology , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity , Siderosis/pathology
12.
J Comput Assist Tomogr ; 24(5): 773-6, 2000.
Article in English | MEDLINE | ID: mdl-11045701

ABSTRACT

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."


Subject(s)
Liver Cirrhosis/pathology , Liver Regeneration , Liver/pathology , Magnetic Resonance Imaging , Siderosis/pathology , Female , Humans , Liver/physiology , Liver Cirrhosis/physiopathology , Liver Cirrhosis/surgery , Liver Transplantation , Male , Middle Aged , Retrospective Studies
13.
Clin Transplant ; 14 Suppl 2: 44-50, 2000.
Article in English | MEDLINE | ID: mdl-10965964

ABSTRACT

Five cases that were referred to the Division of Transplantation at NYU School of Medicine for consideration for liver transplantation were discussed among a panel of hepatitis B and liver transplant experts. Opinions were obtained on the management at every stage of treatment of patients with the following initial information: Case one: young Asian woman in stage IV hepatic coma; intubated; prothrombin time (PT): 30 s; serum glutamic oxaloacetic transaminase (SGOT): 8,000 IU; total bilirubin: 25 mg/dL; hepatitis B surface antigen (HBsAg) positive. Case two: 70-yr-old woman, native of Greece; decompensated cirrhosis with encephalopathy; Child-Pugh Class C; HBsAg positive; hepatitis B surface antibody (HBsAb) negative; hepatitis B e antigen (HBeAg) positive; hepatitis B e antibody (HBeAb) negative; hepatitis B virus (HBV) DNA titer: 10,000. Case three: Muscular detective working full-time; cirrhosis; Child Pugh Class B; ascites controlled with spironolactone and furosemide; PT: 19s; HBsAg positive; HBsAb negative; HBV DNA titer: 50,000; low platelet count. Case four: 45-yr-old baker; cirrhosis and resectable 4-cm hepatoma; Child-Pugh Class B; PT: 16 s; Blood type O; United Network for Organ Sharing (UNOS) 2B; HBV DNA titer: 3,000. Case five: 40-yr-old Indian man; 300 pounds with massive ascites; Child Pugh Class C; PT: 17 s; HBsAg positive; HBV DNA titer: 22,000; transplanted with intra-operative hypotension; tacrolimus; graft functioning; HBIg 10,000 IU intra-operative and around the clock during the first post-operative week; required huge doses of hepatitis B immune globulin (HBIg) to maintain adequate HBsAb level; daily loss of 5 6 L of ascites fluid; post-operative day 8: anuric, blood urea nitrogen (BUN) 127, creatinine 3, mental status changes.


Subject(s)
Hepatitis B/surgery , Liver Transplantation , Adult , Aged , Antiviral Agents/therapeutic use , Ascites/therapy , Carcinoma, Hepatocellular/surgery , Female , Hepatic Encephalopathy/surgery , Hepatitis B/prevention & control , Humans , Immunization, Passive , Immunoglobulins/administration & dosage , Immunosuppressive Agents/adverse effects , Liver Cirrhosis/surgery , Liver Neoplasms/surgery , Middle Aged , Tacrolimus/adverse effects
15.
Semin Liver Dis ; 20 Suppl 1: 7-12, 2000.
Article in English | MEDLINE | ID: mdl-10895438

ABSTRACT

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.


Subject(s)
Hepatitis B/surgery , Liver Transplantation , Adult , Female , Hepatitis B/prevention & control , Hepatitis B Vaccines , Humans , Immunization, Passive , Immunoglobulins/therapeutic use , Lamivudine/therapeutic use , Liver Transplantation/methods , Male , Reverse Transcriptase Inhibitors/therapeutic use , Risk Factors , Secondary Prevention , Survival Analysis
16.
Semin Liver Dis ; 20 Suppl 1: 29-35, 2000.
Article in English | MEDLINE | ID: mdl-10895442

ABSTRACT

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.


Subject(s)
Hepatitis B/surgery , Liver Transplantation , Adult , Antiviral Agents/therapeutic use , Female , Hepatitis Antigens , Hepatitis B/prevention & control , Humans , Immunization, Passive , Liver Transplantation/methods , Male , Middle Aged , Quality of Life , Risk Factors , Secondary Prevention
17.
Hepatology ; 32(1): 11-6, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10869283

ABSTRACT

It has been shown in animal models that hepatocytes and cholangiocytes can derive from bone marrow cells. We have investigated whether such a process occurs in humans. Archival autopsy and biopsy liver specimens were obtained from 2 female recipients of therapeutic bone marrow transplantations with male donors and from 4 male recipients of orthotopic liver transplantations from female donors. Immunohistochemical staining with monoclonal antibody CAM5.2, specific for cytokeratins 8, 18, and 19, gave typical strong staining of hepatocytes, cholangiocytes, and ductular reactions in all tissues, to the exclusion of all nonepithelial cells. Slides were systematically photographed and then restained by fluorescence in situ hybridization (FISH) for X and Y chromosomes. Using morphologic criteria, field-by-field comparison of the fluorescent images with the prior photomicrographs, and persistence of the diaminiobenzidene (DAB) stain through the FISH protease digestion, Y-positive hepatocytes and cholangiocytes could be identified in male control liver tissue and in all study specimens. Cell counts were adjusted based on the number of Y-positive cells in the male control liver to correct for partial sampling of nuclei in the 3-micron thin tissue sections. Adjusted Y-positive hepatocyte and cholangiocyte engraftment ranged from 4% to 43% and from 4% to 38%, respectively, in study specimens, with the peak values being found in a case of fibrosing cholestatic recurrent hepatitis C in one of the liver transplant recipients. We therefore show that in humans, hepatocytes and cholangiocytes can be derived from extrahepatic circulating stem cells, probably of bone marrow origin, and such "transdifferentiation can replenish large numbers of hepatic parenchymal cells.


Subject(s)
Bone Marrow Cells/physiology , Liver/cytology , Stem Cells/physiology , Adult , Bone Marrow Transplantation , Female , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Liver Transplantation , Male , Middle Aged
19.
Am J Clin Pathol ; 110(1): 32-7, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9661920

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal , Antigens, Viral , Hepacivirus/immunology , Hepatitis C Antigens/analysis , Hepatitis C/diagnosis , RNA, Viral/analysis , Viral Nonstructural Proteins/immunology , Bile Ducts/pathology , Bile Ducts/virology , Epithelium/pathology , Epithelium/virology , Hepacivirus/genetics , Hepacivirus/isolation & purification , Hepatitis C Antibodies , Humans , Immunoenzyme Techniques , Liver/pathology , Liver/virology , Polymerase Chain Reaction/methods , Reagent Kits, Diagnostic , Sensitivity and Specificity
20.
J Comput Assist Tomogr ; 22(4): 633-7, 1998.
Article in English | MEDLINE | ID: mdl-9676459

ABSTRACT

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.


Subject(s)
Biopsy, Needle/methods , Liver Neoplasms/pathology , Liver/pathology , Magnetic Resonance Imaging/methods , Magnetics , Adult , Aged , Biopsy, Needle/instrumentation , Evaluation Studies as Topic , Female , Humans , Magnetic Resonance Imaging/instrumentation , Male , Middle Aged , Needles
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