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Transplant Proc. 2016 Nov;48(9):3134-3136. doi: 10.1016/j.transproceed.2016.05.002.

Lymphangioma-like Kaposi Sarcoma in Transplant-Associated

Iatrogenic Immunosuppression: A Case Report.
Garden BC1, Kramer ON2, Aronson IK1, Braniecki M3.

Author information
1
Department of Dermatology, University of Illinois, Chicago, Illinois, USA.
2
University of Illinois, Chicago, Illinois, USA.
3
Department of Pathology, University of Illinois, Chicago, Illinois, USA. Electronic address:
branieck@uic.edu.

Abstract

Lymphangioma-like Kaposi sarcoma (LLKS) is a rare histologic presentation of Kaposi sarcoma

(KS), with only 28 cases reported in the literature. LLKS has been described in acquired
immunodeficiency syndrome and in endemic African-type as well as classic indolent KS. We
present the 1st reported case of LLKS in a transplant-associated iatrogenic immunosuppressed
patient.

Copyright 2016 Elsevier Inc. All rights reserved.

Kaposi Sarcoma in the Genital Area in a Kidney Transplant Patient:
A Case Report and Literature Review.
Imko-Walczuk B1, Kielbowicz M2, Malyszko J3, Malyszko J4, Barczyk M3, Debska-Slizien A5, Mysliwiec M3,
Rutkowski B5.

Author information
1
Copernicus-Independent Public Healthcare Centre, Dermatology & Venereology Clinic, Gdansk,
Poland; College of Health, Beauty and Education in Poznan, Poland. Electronic address:
bimko@wp.pl.
2
College of Health, Beauty and Education in Poznan, Poland.
3
1st Department of Nephrology and Transplantology with Dialysis Unit, Medical University,
Bialystok, Poland.
4
2nd Department of Nephrology Medical University, Bialystok, Poland.
5
Chair & Clinic of Nephrology, Transplantology and Internal Medicine, Gdansk University of
Medical Sciences, Gdansk, Poland.

Abstract

BACKGROUND:

Kaposi sarcoma (KS) is a cancer with an incidence in patients after transplantation (Tx) that
is 500 times greater than that in the healthy population. The risk of KS increases
significantly during therapy, especially when immunosuppressive therapy with cyclosporine
A (CsA) is used. Most cases of KS develop during the first 2 years after transplantation.
After a KS diagnosis, it is recommended to reduce the doses of immunosuppressive
medications. Conversion of immunosuppressive treatment into mammalian target of
rapamycin (m-TOR) inhibitors is strongly suggested.

PATIENTS AND METHODS:

We present the case of a 65-year-old man with end-stage renal disease (ESRD) of unknown
etiology, who had kidney transplantation in 2008. Immunosuppressive protocol was based
on CsA, mycophenolate mofetil (MMF) and prednisolone (PRE). In 2011, during the
dermatological consultation, on the penis glans a purple stain of uneven surface was noted.
Histology study revealed the presence of KS. The treatment was modified. The patient was
converted from CsA to everolimus. Before converting, the creatinine concentration was
1.79 mg/dl and proteinuria less than 0.3 g/day.

RESULTS:

The change in the scheme of immunosuppresion from CsA to everolimus was performed to
treat the Kaposi sarcoma. Gradually, within a year, the KS was cured. However, the graft
function deteriorated, and the graft was lost in one-years' time.

CONCLUSION:
 We present the first documented case of KS in the genital area of a kidney patient. The
reduction in the strength of immunosuppression, and the introduction of an m-TOR inhibitor,
may have contributed to the deterioration of kidney function, however it was substantial in
the treatment of KS.

Copyright 2016 Elsevier Inc. All rights reserved.

PMID:
27496505
DOI:
10.1016/j.transproceed.2016.01.070
[Indexed for MEDLINE]

Kaposi's sarcoma and other rare skin cancers in organ transplant

patients.
Zattra E Coati I1, Alaibac M, Piaserico S.

Author information
1
Unit of Dermatology, Department of Medicine University of Padua, Padua, Italy -
Stefano.piaserico@unipd.it.

Abstract

Kaposi's sarcoma and Merkel cell carcinoma represent potentially lethal cutaneous complications in
organ transplanted patients. These neoplasms can severely complicate the clinical outcome of
transplanted patient. Moreover, as the diagnosis is mainly clinical, a knowledge of these clinical entities
may be fundamental in the daily management of this group of patients. In this review we will discuss
these neoplasms in relation to the role of immunosuppression in their onset and progression.

Kaposi's sarcoma in the early post-transplant period in a kidney

transplant recipient.
Ercan Z, Demir ME, Merhametsiz O, Yayar O, Ulas T, Ayli MD.

Comment in

Comment on "Kaposi's sarcoma in the early post-transplant period in a kidney transplant

recipient". [Nefrologia. 2014]

PMID:
24241380
DOI:
10.3265/Nefrologia.pre2013.Jul.12178
Sirolimus for the treatment of Kaposi sarcoma after renal
transplantation: a series of 10 cases.
Yaich S1, Charfeddine K, Zaghdane S, El Aoud N, Jarraya F, Kharrat M, Hachicha J.

Author information
1
Department of Nephrology, Hedi Chaker Hospital, Sfax, Tunisia.

Abstract

The incidence of Kaposi sarcoma (KS) has substantially increased among immunocompromised
patients, suggesting a role for immunosuppressive drugs. The aim of this study was to evaluate the
incidence, features, and outcome of KS among 307 kidney transplantation patients at our center
between January 1994 and June 2010. During the study period, the 10 patients who developed KS
(3.25%) showed a mean age at transplantation of 35.8 8.7 years (range, 22 to 49 years). The mean
interval between transplantation and occurrence of KS was 24.7 21.36 months (range, 6 to 64
months). The mean time of antithymocyte globulin induction was 9.5 days (range, 6 to 13 days). KS
was restricted to the skin in 7 cases, among which, one presented with associated Hodgkin lymphoma.
Visceral involvement (one lung and one colon) was observed in two cases. One patient presented with
a gastric KS without skin lesions. Immunosuppressive treatment was reduced, then withdrawn in three
cases, resulting in regression of KS a few weeks later, but with graft loss requiring hemodialysis at 1, 3
and 4 months. Among the remaining 7 cases, we stopped mycophenalate mofetil (MMF) and switched
from calcineurin inhibitors to sirolimus. Allograft function remained stable after the switch. Only one
patient who already had allograft dysfunction due to biopsy-proven chronic allograft nephropathy.
Deteriorated progressively, undergoing hemodialysis at 2 years after KS diagnosis. In conclusion, we
observed a relatively high incidence of KS among our cases. The introduction of sirolimus resulted in
complete regression of KS lesions with preserved graft function.

Copyright 2012 Elsevier Inc. All rights reserved.

Adv Dent Res. 2011 Apr;23(1):76-8. doi: 10.1177/0022034511399913.

Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 and

Kaposi sarcoma.
Martin JN1.

Author information
1
Department of Epidemiology and Biostatistics, University of California, San Francisco, USA.
martin@psg.ucsf.edu

Abstract

Kaposi sarcoma-associated herpesvirus (KSHV) was discovered in 1994 and is now known to be a
necessary but not sufficient causative agent of Kaposi sarcoma. While KSHV is likely also the
causative agent of primary effusion lymphoma and multicentric Castleman's disease, its causal role
has been refuted in the case of multiple myeloma, sarcoidosis, prostate cancer, and amyotrophic
lateral sclerosis. The epidemiology of KSHV is both intriguing and challenging. Two epidemiologic
findings are clear, but their explanation is unknown. The first is that KSHV is distributed disparately
 throughout the world, with the virus being common in the general population throughout Africa and the
Middle East, but uncommon virtually everywhere else. The second is that even though the virus is
uncommon in the general population in industrialized settings, it is disproportionately concentrated
among homosexual men in these areas. KSHV has special importance to the dental profession
because saliva is the body fluid that harbors it most commonly, although exactly in which ways saliva
spreads the virus are not known.

Complete resolution of oral Kaposi's sarcoma achieved by changing

immunosuppression: a case report.
Johari Y1, Nicholson ML.

Author information
1
Division of Transplantation, University Hospitals of Leicester NHS Trust, Leicester, UK.

Abstract

A 38-year-old Afro-Caribbean woman, who was pre-dialysis with polycystic kidney disease, received a
live-donor kidney transplant from her 55-year-old mother. This study documents her imunosuppression
therapy including resolution of an oral Kaposi's sarcoma and explores the many underlying problems
with converting to an mTOR inhibitor.

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Iran J Kidney Dis. 2009 Jul;3(3):121-6.

Human herpesvirus-8 and Kaposi sarcoma after kidney

transplantation: mechanisms of tumor genesis.
Ahmadpoor P1.

Author information
1
Department of Medicine, Shahid Labbafinejad Medical Center, Shahid Beheshti University of
Medical Sciences, Tehran, Iran. Pedram.ahmadpoor@gmail.com

Abstract

Human herpesviruses (HHVs) are able to escape from complete clearance by the immune system.
Their ability to become latent is due to their delicate interferences with the immune system. This
characteristic makes some of them known as important tumor viruses. Based on the prevalence of the
seropositivity for the HHV-8, the world can be divided into 4 regions, one of which is the Middle East
with a seroprevalence of 5% to 20%. The incidence of iatrogenic Kaposi sarcoma, a cancer linked with
HHV-8 following organ transplantation, is 500 times higher than that in general population. In the
Middle East, Kaposi sarcoma is the most common malignancy reported in kidney transplant recipients.
In an immunocompromised host, the primary infection with HHV-8 presents with fever,
hepatosplenomegaly, lymphoid hyperplasia, pancytopenia, and liver dysfunction. Occasionally, rapid-
onset Kaposi sarcoma develops in association with apparent primary HHV-8 infection. In this article,
the tumor genesis mechanism of HHV-8 in kidney transplant recipients was reviewed

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Rev Med Interne. 2009 May;30(5):446-9. doi: 10.1016/j.revmed.2008.07.016. Epub 2008 Oct 15.

[Association of disseminated nocardiosis and Kaposi's sarcoma after

kidney transplantation].
[Article in French]
Abderrahim E1, Jbali H, Ounissi M, Hedri H, Bakir S, Ben Abdallah T, Ben Maz H, Kheder A.

Author information
1
Service de mdecine interne A, laboratoire de pathologie rnale (sant 02), hpital Charles-
Nicolle, 1006 Tunis, Tunisie. abderrahim.ezzeddine@rns.tn

Abstract

We report a 40-year-old kidney recipient who developed disseminated nocardiosis associated with
cutaneous Kaposi's sarcoma. The withdrawal of immunosuppressive therapy and prolonged antibiotic
therapy, including imipenem and trimethoprim-sulfamethoxazole, resulted in a favourable outcome of
both disorders. Three years later, graft function remains stable with a complete regression of skin and
pulmonary abnormalities. This case report illustrates the predisposing role of immunosuppressive
treatment in the occurrence of infectious and neoplastic complications observed after solid-organ
transplantation

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N Engl J Med. 2005 Mar 31;352(13):1317-23.

Sirolimus for Kaposi's sarcoma in renal-transplant recipients.

Stallone G1, Schena A, Infante B, Di Paolo S, Loverre A, Maggio G, Ranieri E, Gesualdo L, Schena FP,
Grandaliano G.

Author information
1
Division of Nephrology, Department of Emergency and Transplantation, University of Bari, Bari,
Italy.

Abstract

BACKGROUND:

Recipients of organ transplants are susceptible to Kaposi's sarcoma as a result of treatment with
immunosuppressive drugs. Sirolimus (rapamycin), an immunosuppressive drug, may also have
antitumor effects.

METHODS:

We stopped cyclosporine therapy in 15 kidney-transplant recipients who had biopsy-proven Kaposi's

sarcoma and began sirolimus therapy. All patients underwent an excisional biopsy of the lesion and
one biopsy of normal skin at the time of diagnosis. A second biopsy was performed at the site of a
previous Kaposi's sarcoma lesion six months after sirolimus therapy was begun. We examined biopsy
specimens for vascular endothelial growth factor (VEGF), Flk-1/KDR protein, and phosphorylated Akt
and p70S6 kinase, two enzymes in the signaling pathway targeted by sirolimus.

RESULTS:

Three months after sirolimus therapy was begun, all cutaneous Kaposi's sarcoma lesions had
disappeared in all patients. Remission was confirmed histologically in all patients six months after
sirolimus therapy was begun. There were no acute episodes of rejection or changes in kidney-graft
function. Levels of Flk-1/KDR and phosphorylated Akt and p70S6 kinase were increased in Kaposi's
sarcoma cells. The expression of VEGF was increased in Kaposi's sarcoma cells and even more so in
normal skin cells around the Kaposi's sarcoma lesions.

CONCLUSIONS:

Sirolimus inhibits the progression of dermal Kaposi's sarcoma in kidney-transplant recipients while
providing effective immunosuppression.

Copyright 2005 Massachusetts Medical Society.

Comment in

Immunosuppressive drugs and the risk of cancer after organ transplantation. [N Engl J Med.
2005]
 Kaposi's sarcoma after renal transplantation. [N Engl J Med. 2005]

No effect of sirolimus for kaposi sarcoma in a renal transplant recipient. [Transplantation. 2006]

Kaposi's sarcoma after renal transplantation. [N Engl J Med. 2005]

Kaposi's sarcoma after renal transplantation. [N Engl J Med. 2005]

PMID:
15800227
DOI:
10.1056/NEJMoa042831

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Br J Radiol. 2000 Nov;73(875):1221-3.

Kaposi's sarcoma involving a transplanted kidney, ureter and urinary

bladder: ultrasound and CT findings.
Rha SE1, Byun JY, Kim HH, Baek JH, Hwang TK, Kang SJ.

Author information
1
Department of Radiology, Kangnam St Mary's Hospital, College of Medicine, Catholic University
of Korea, 505, Banpo-Dong, Seocho-Ku, Seoul, 137-040, South Korea.
Abstract

We report the imaging findings in a case of Kaposi's sarcoma involving a transplanted kidney, ureter
and urinary bladder. Ultrasound and CT demonstrated multiple nodular masses in the pelvis of the
transplanted kidney, ureter and bladder. The masses enhanced well on CT following i.v. contrast
medium

Transplant tumor registry: donor related malignancies.

AU
Myron Kauffman H, McBride MA, Cherikh WS, Spain PC, Marks WH, Roza AM
SO
Transplantation. 2002;74(3):358.
BACKGROUNDTransmission of donor malignancies has been intermittently reported since the
early days of clinical transplantation. The incidence of United States donor related malignancies
has not previously been documented.
METHODSAll donor related malignancies reported to the Organ Procurement and
Transplantation Network/United Network for Organ Sharing from 4/1/94-7/1/01 in a cohort of
34,933 cadaveric donors and 108,062 recipients were investigated by contacting the transplant
centers to verify that the reported tumors were of donor origin. Time and mode of discovery, as
well as graft and patient outcome, were determined. The status of other recipients from the donor
was investigated.
RESULTSA total of 21 donor related malignancies from 14 cadaveric and 3 living donors were
reported. Fifteen tumors were donor transmitted and 6 were donor derived. Transmitted tumors
are malignancies that existed in the donor at the time of transplantation. Derived tumors are de
novo tumors that develop in transplanted donor hematogenous or lymphoid cells after
transplantation. The cadaveric donor related tumor rate is 0.04% (14 of 34,993). The donor
related tumor rate among transplanted cadaveric organs is 0.017% (18 of 108,062). Among
patients developing donor related malignancies, the overall mortality rate was 38%, with that of
transmitted tumors being 46% and derived tumors being 33%. The cadaveric donor related tumor
mortality rate is 0.007% (8 of 108,062).
CONCLUSIONSThe United States incidence of donor related tumors is extremely small. The
donor related tumor death rate is also extremely small, particularly when compared with waiting-
list mortality.
AD
Research Department, United Network for Organ Sharing, Richmond, VA 23225, USA.
kauffmhm@unos.org.
PMID
12177614

PubMed
TI
Risk for tumor and other disease transmission by transplantation: a population-based study of
unrecognized malignancies and other diseases in organ donors.
 AU
Birkeland SA, Storm HH
SO
Transplantation. 2002;74(10):1409.
BACKGROUNDOrgan donation may involve the risk of transmittal of unwanted host factors such
as infections and malignancy. These may be concealed in the emergent donation process. It may
be unavoidable if first observed in a donor postmortem. A number of reports on transferred
cancers have been published, but quantification of the risk has never been reliably performed.
We report here the first population-based analysis of unrecognized malignancies and other
diseases in cadaveric or living-related donors and the possible consequences for the recipients.
METHODSWe compiled a cohort of all organ donors through 27 years (1969-1996) in one single
kidney transplant center covering a population on one million people. This cohort was linked to
the Danish Cancer Registry, the Danish National Hospital Register, and the Danish Register of
Causes of Death by means of the unique personal identification number, and all cancers,
diagnosis from hospital admissions, and causes of death were identified. Follow-up was to the
end of 1996.
RESULTSA total of 626 donors (491 cadaveric and 135 living-relateddonors) was included in the
study. Ten carcinoma in situ or dysplasia cervix uteri (by definition nonmalignant), and 13
malignant tumors (5 of these were detected in living-related donors after donation) were detected
by linkage to the cancer registry. All together, 17 recipients received organs from donors with
carcinoma in situ or dysplasia cervix uteri and 20 from donors with malignancies. Two recipients
from organ donors with carcinoma in situ or dysplasia of the cervix uteri and two recipients from
donors with malignancies had a cancer detected; however, these were likely unrelated. One died
1 year after transplantation from a melanoma transmitted from the donor. Two cadaveric donors
had previous admissions for glomerulonephritis, five for pyelonephritis, five for nephrolithiasis or
ureterolithiasis, four for cystitis, and one for hydronephrosis.
CONCLUSIONDespite all efforts to secure a safe organ for transplantation, transmission of donor
malignancy and other diseases nevertheless can happen, as is recorded many times in the
literature. We have quantified the risk using the population-based cancer registry and found a risk
of 8 in 626 (1.3%) for having a donor with undetected malignancy and a risk of 1 in 626 (0.2%)
for transmitting a cancer. The risk for getting some transmitted glomerulonephritis is 2 in 626
(0.3%). None of the donors with cerebral malignancies transmitted any tumors to the recipients.
Compared with the benefits of organ transplantation, these risks are small; however, if time
allows, a search for additional medical information from registries could further minimize the risk
of transmission of malignancies or other diseases. However, this requires updated, accurate, and
accessible registries and legislation that allows access to personal data and transmission of such
data across administrative borders.
AD
Department of Nephrology, Odense University Hospital, Odense, Denmark.
S.A.Birkeland@Birkeland.dk.
P
MI
D
12451241
 PubMed
TI
Epidemiologic study on the origin of cancer after kidney transplantation.
AU
Pedotti P, Poli F, Longhi E, Frison S, Caldara R, Chiaramonte S, Gotti E, Marchini F, Maresca C,
Sandrini S, Scalamogna M, Taioli E
SO
Transplantation. 2004;77(3):426.
BACKGROUNDSubjects who underwent solid organ transplantation are at higher risk for a wide
variety of cancers.
METHODSThe authors investigated the origin of cancer in a cohort of 2,526 patients followed up
for 60.7 +/- 35.6 months after kidney transplantation between 1990 and 2000 in seven transplant
centers.
RESULTSOne hundred four of them developed cancer. All subjects who developed solid cancer
within 6 months after transplantation (n=10) and a group of subjects who developed solid cancer
after 6 months posttransplant (n=10) were selected. Short tandem repeat analysis was
performed on paraffin-embedded biopsy specimens of tumors and on both donor and recipient
pretransplant peripheral blood. Biologic material was obtained in 17 of the 20 selected patients
(85.0%). The analysis showed that 16 of 17 tumors were genetically identical to the recipient.
CONCLUSIONSThe authors' results suggest that donor transmission of solid canceris an unlikely
event in their population.
AD
Molecular and Genetic Epidemiology Unit, IRCCS, Ospedale Maggiore Policlinico, Milan, Italy.
P
MI
D
14966419

75
PubMed
TI
Donor transmitted disease: cancer.
AU
Penn I
SO
Transplant Proc. 1991;23(5):2629.
AD
University of Cincinnati Medical Center, Department of Surgery, Ohio 45220.
PMID
1926512
 PubMed
TI
Transmission of human herpesvirus 8 infection from renal-transplant donors to recipients.
AU
Regamey N, Tamm M, Wernli M, Witschi A, Thiel G, Cathomas G, Erb P
SO
N Engl J Med. 1998;339(19):1358.
BACKGROUNDHuman herpesvirus 8 (HHV-8) has been detected in all forms of Kaposi's
sarcoma, including transplantation-associated Kaposi's sarcoma. To investigate the possibility of
transmission of HHV-8 through allografts, we measured the seroprevalence of HHV-8 before and
after renal transplantation.
METHODSUsing an enzyme-linked immunosorbent assay with the recombinant HHV-8 protein
orf 65.2, we analyzed serum samples from 220 renal-transplant recipients for the presence of
antibodies to HHV-8 on the day of transplantation and one year later. Positive results were
confirmed by an indirect immunofluorescence assay that detects antibodies to latent antigen and
by Western blotting. Follow-up lasted at least four years.
RESULTSThe seroprevalence of HHV-8 in graft recipients increased from 6.4 percent on the day
of transplantation to 17.7 percent one year after transplantation. Seroconversion occurred within
the first year after transplantation in 25 patients, and Kaposi's sarcoma developed in 2 of them
within 26 months after transplantation. Sequential serum samples were obtained from 10 of the
patients with seroconversion, and in 8 of these patients, IgM antibodies to HHV-8 appeared
within three months after transplantation. In the case of six patients who seroconverted, serum
samples from the donors were available, and five (83 percent) tested positive for HHV-8. In a
control group of eight patients who were seronegative at the time of transplantation and who
received allografts from HHV-8-negative donors, none seroconverted within the year after
transplantation.
CONCLUSIONSHHV-8 is transmitted through renal allografts and is a risk factor for
transplantation-associated Kaposi's sarcoma.
AD
Institute for Medical Microbiology, University of Basel, Switzerland.
P
MI
D
9801396
68
PubMed
TI
Post-transplant Kaposi sarcoma originates from the seeding of donor-derived progenitors.
AU
Barozzi P, Luppi M, Facchetti F, Mecucci C, AlM, Sarid R, Rasini V, Ravazzini L, Rossi E, Festa
S, Crescenzi B, Wolf DG, Schulz TF, Torelli G
SO
Nat Med. 2003;9(5):554.
Kaposi sarcoma (KS) is a vascular tumor that can develop in recipients of solid tissue transplants
as a result of either primary infection or reactivation of a gammaherpesvirus, the KS- associated
herpesvirus, also known as human herpesvirus-8 (HHV-8). We studied whether HHV-8 and the
elusive KS progenitor cells could be transmitted from the donor through the grafts. We used a
variety of molecular, cytogenetic, immunohistochemical and immunofluorescence methods to
show that the HHV-8-infected neoplastic cells in post-transplant KS from five of eight renal
transplant patients harbored either genetic or antigenic markers of their matched donors. These
data suggest the use of donor-derived HHV-8-specific T cells for the control of post-transplant
KS.
AD
Department of Oncology and Hematology, University of Modena and Reggio Emilia, Modena,
Italy.