infect me with Psoriasis?

MAYBE try
http://en.wikipedia.org/wiki/Interferon_alfa-2b
because of this article:
http://www2.cochrane.org/reviews/en/ab001425.html

Or infect me with Psoriasis?
http://informahealthcare.com/doi/pdf/10.1080/02841860902882451


Spontaneous Remission of Cancer –
Enigma and Paradigm
Herbert W. Kappauf
Internistische Schwerpunktpraxis, Onkologie – Hämatologie – Psychoonkologie, Starnberg, Germany

Spontaneous remission of cancer (SR) is defined as a com-
plete or partial, temporary or permanent disappearance of all
or at least some relevant parameters of a soundly diagnosed
malignant disease in the absence of medical treatment or with
a therapy that does not adequately explain the resulting re-
gression. It is a rare but valid phenomenon which has been
observed throughout history of medicine. It represents an in-
structive in-vivo model of biological tumour control and, re-
maining enigmatical in most cases, it nevertheless has con-
tributed to paradigmatic shifts in oncology.
Exactly one hundred years ago at the first International Con-
ference on Cancer Research, held in Germany at Heidelberg
and Frankfurt, one of the pioneers of modern oncology and
founding father of the German Cancer Society Vincenz Cz-
erny gave a still very remarkable key note lecture ‘On unex-
pected recoveries from cancer’[1].
‘...I would like to share some observations which show that
even in malignant tumours unexpected recoveries do exist and
they caution us to ascribe clinical improvement or recovery in
such a case exclusively to the used remedy. In animal studies it
may be held for ascertained that some, namely smaller tu-
mours are capable of spontaneous regression. […] In humans
off and on cases have been observed in which an apparent
worst prognosis proved to be wrong in the further course of
disease. Usually a wrong diagnosis was assumed and as one
doesn’t decide with pleasure to this confession, those observa-
tions have been either withheld or told bashfully with a ques-
tion mark.’ And cancer surgeon Czerny finished his lecture:
‘In recapitulating we see that without any doubt malignant tu-
mours are capable of regression. Very rarely this happens
without a surgical intervention. Sometimes a surgical inter-
vention may accelerate tumour growth due to incomplete de-
struction of the tumour tissue and thus harm the patient. In
other cases with incomplete cancer resection the human or-
ganism is enabled to neutralize or even to destroy the residual
tumour. We do not know the particulars which make this dif-
ference in outcome, but there is no doubt that the pathohisto-
logical constitution of the tumours plays a decisive role… But
I don’t want to be misunderstood that – because of occasional
observations of cancer remissions in spite of incomplete re-
section – I would discredit surgery as early and radical as pos-
sible, which hitherto alone made us advance’ (translation by
H. K.) .
In 2006 Czerny’s words are still valid and SR remains a scien-
tifically exciting phenomenon. But surprisingly up to now only
two major conferences have dealt with SR as a main topic: In
1974 a conference held at the Johns Hopkins University at
Baltimore/USA [2] and in 1997 an international symposium
held at the German Centre for Cancer Research (DKFZ) at
Heidelberg/Germany [3].
Many scientists are still reluctant to focus their attention on
SR. They may fear to jeopardize their academic reputation
when dealing with a topic which is often found in catching sto-
ries of the yellow press and pamphlets propagating unconven-
tional cancer therapies. In fact, cases of SR are considered to
be ‘a vital factor in perpetuating many quackery treatmens,
whether by ”faith healing”, machines, holistic nutrition or
placebo drugs’ [4].
But science learns from reflection on anomalies which help to
change paradigms. Historical observations of spontaneous re-
missions of breast cancer after the onset of menopause lead
to approaches of hormonal treatment which nowadays are a
mainstay of adjuvant and palliative therapy in breast cancer.
Moreover, modern oncological immunotherapy was stimulat-
ed by a case of spontaneous remission in a patient with
metastatic gastric cancer who survived bacterial peritonitis
after resection of the primary and just biopsy of hepatic
metastasis [5].
The perception of cancer as a monoclonal uncontrolled prolif-
eration of cells implicitly adhered to a model of a snowball
triggering an avalanche. And avalanches never have been ob-
served to reverse. That is why until this day doubts on the va-
lidity of SR have been prevailing even among academic opin-
ion leaders in spite of impeccable case reports. Nowadays we
know that accelerated proliferation is not sufficient for can-
cerogenesis. Proliferating cells have to dodge apoptosis to
manifest a malignant tumour [6]. Apoptosis represents a fun-
damental biological pathway both for ontogenesis and for the
maintenance of tissue function and genome stability in every
multicellular organism. According to its physiological impor-
tance apoptosis is controlled in a very complex way and linked
not only with checkpoints of cell proliferation and differentia-
tion but also with angiogenesis/anti-angiogenesis, endocrine
modulation, and immunoreactive pathways. In patients with
spontaneously regressing tumours malignant cells apparently
loose their malignant immortality and become subject to
apoptosis again [7]. And case reports of SR in different tu-
mour entities demonstrate that apoptosis in fact may be trig-
gered by endocrine factors, immunoreactive mechanisms asso-
ciated with viral or bacterial infections, cytotoxic chemothera-
py, or transfusion of blood products. Surgical interventions
with incomplete tumour resection are part of the medical his-
tory of most cases of SR. But only on rare occasions this in-
complete resection entails spontaneous regression of the
residual tumour. This may be due to a higher antiangiogenic
potential in the residual tumour tissue leading to apoptosis [8].
Systematic research on SR has to cope with several method-
ological difficulties: for instance, patient accrual is somewhat
unpredictable when dealing with a rare phenomenon. But the
prevalence of SR is quite different in different tumour entities.
Anecdotal reports on SR exist for about every type of malig-
nancy but most cases of SR refer to but a few nosological enti-
ties: malignant melanoma, renal cell carcinoma, malignant
lymphoma, basal cell carcinoma and childhood neuroblas-
toma. This epidemiological incongruence of cancer prevalence
and SR underlines Cerny’s statement that the histopathologi-
cal properties of tumours play an important role in SR.
In frequent malignancies such as lung, colorectal, gastric or
cervical cancer SR occurs in less than 1 in 1,000,000 patients.
On the other hand metastases of malignant melanoma regress
in about 1 in 400 patients and the prevalence of SR in patients
with renal carcinoma with only lung metastases may be more
than 10%. [10]. With effective innovative treatment options
‘wait and see’ approaches become more and more exceptional
in the management of metastatic disease. Thus the assessment
of the prevalence of SR in absence of specific oncological
treatment has to be based on incomplete historical data.
Therefore scrupulously documented case reports of SR like the
one by Gaussmann et al. [11] in this issue of ONKOLOGIE are
very valuable. The case report underlines the importance of
continuity of clinical care in order to recognize cases of SR.
Probably many cases elude clinical attention in segmented pa-
tient care. Research on SR requires a close cooperation of clin-
icians who observe this phenomenon and basic scientists who
may decode the biological pathways of spontaneous tumour
regression and may thus reveal new therapeutic strategies.

References

1 Czerny V: Über unerwartete Krebsheilungen. Z
Krebsforschung 1907;3:27–35.
2 Proceedings of a conference held at the Johns
Hopkins Medical Institutions, Baltimore, MD, May
9–10, 1974. Baltimore, 1976.
3 Heim M, Schwarz R (eds): Spontanremissionen bei
Krebs. Stuttgart, Schattauer, 1998, pp 1–264.
4 Lowy AD Jr, Erickson ER: Spontaneous 19-year
regression of oat cell carcinoma with scalene node
metastasis. Cancer 1986;58:978–980.
5 Rosenberg SA, Fox E, Churchill WH: Spontaneous
regression of hepatic metastases from gastric carci-
noma. Cancer 1972;29:472–474.
6 Gassmann A, Holmgren L, O’Reilly MS, Folkman
J: Dormancy of micrometastasis: Balanced prolife-
ration and apoptosis in the presence of antiangio-
genesis suppression. Nature Med 1995;1:149–153.
7 Kaufmann Y, Many A, Rechavi G, Mor O, Biniami-
nov M, Rosenthal E, Levanon M, Davidsohn J,
Aizman I, Mark Z, et al.: Brief report: lymphoma
with recurrent cycles of spontaneous remission and
relapse – possible role of apoptosis. N Engl J Med
1995;332:507–510.
8 Kappauf H, Gallmeier WM, Wünsch P, Mittelmeier
HO, Birkmann J, Büschel G, Kaiser G, Kraus J:
Spontaneous remission of metastases in a patient
with non-small cell lung cancer. Ann Oncol 1997;8:
1031–1039.
9 Kappauf H: Wunder sind möglich. Spontanheilung
bei Krebs. Freiburg, Herder, 2003, pp 1–192.
10 Gaussmann A, Imhoff D, Lambrecht E, Menzel C,
Mose S: Spontaneous remission of metastases of
cancer of the uterine cervix. Onkologie 2006;29:
159–161.


Editorial
Onkologie 2006;29:129–130
DOI: 10.1159/000092029
Dr. med. Herbert W. Kappauf
Internistische Schwerpunktpraxis
Onkologie – Hämatologie – Psychoonkologie
MediCenter, Oßwaldstr. 1a, 82319 Starnberg, Germany
Tel. +49 8151 559-302, Fax -303
E-Mail onkologie.starnberg=at=t-online.de

=================================

Spontaneous regression of renal cell carcinoma lung metastases
in a patient with psoriasis
Spontaneous regression of metastases is a rare out-
come of neoplastic disease. Although instances of
spontaneous regression have been documented
across the spectrum of malignant disorders, most
cases have been documented in malignant melanoma
or renal cell carcinoma (RCC) [1]. RCC is a tumor
of peculiar biological behavior characterized by great
variations in the clinical course, including, on the
one hand, spontaneous regression of metastases or
indolent course of metastatic disease, and, on the
other hand, rapidly fatal metastases, paraneoplastic
syndromes, or metastases in unusual sites. The
mutation or epigenetic changes in the von Hippel-
Lindau gene, that are present in most cases of
RCC, result in increased production of vascular
endothelial growth factor (VEGF) that could be
responsible for some of the biological peculiarities
Correspondence: Bohuslav Melichar, Department of Oncology, Palacky ´ University Medical School & Teaching Hospital, I.P. Pavlova 6, 775 20 Olomouc,
Czech Republic. Tel: 420 588444288. Fax: 420 588442522. E-mail: bohuslav.melichar@fnol.cz
Spontaneous regression and psoriasis 925
(Received 27 February 2009; accepted 9 March 2009)
ISSN 0284-186X print/ISSN 1651-226X online # 2009 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS)
DOI: 10.1080/02841860902882451
Acta Oncol Downloaded from informahealthcare.com by 202.180.107.68
For personal use only.of RCC [2]. In RCC, many instances of spontaneous
regression have been observed after nephrectomy.
The pathogenesis of spontaneous regression remains
unknown. Different theories have been proposed to
explain this rare phenomenon, and in most hypoth-
eses the pathogenesis of spontaneous regression is
thought to involve the activation of the host immune
system [1]. We present here a patient who had
spontaneous regression of lung metastases of RCC
after nephrectomy associated with a flare of psoriasis.
A 68-year-old female with a history of hyperten-
sion, diabetes mellitus and psoriasis presented in
December 2004 with a cough. Multiple lung metas-
tases were detected on chest x-ray, and confirmed by
CT scan. Subsequent investigations identified a
tumor in the right kidney. The patient underwent
right nephrectomy on February 16, 2005. Histologic
examination of surgical specimen revealed clear cell
carcinoma of the kidney. Therapy with interferon-
alpha was planned, and for response evaluation, a
control CT scan was performed that revealed a
substantial regression of lungmetastases. Subsequent
CT scan demonstrated a complete regression of lung
metastases. Because of complete regression of metas-
tases, originally planned therapy was deferred. About
one month after nephrectomy and simultaneously to
regression of lung metastases, a flare of psoriasis was
observed with psoriatic lesions appearing first in the
nephrectomy scar and subsequently spreading to the
back, extremities and the head. Local therapy includ-
ing dexamethasone was prescribed. Because of per-
sistent psoriasis complicated by psoriatic arthritis the
therapywith oralmethotrexatewas started inOctober
2005 leading to regression of skin lesions.The patient
was well until March 2006. In late March 2006, the
patient presented with left pleural effusion. At that
time, only few psoriatic lesions were present on the
skin of the back. The therapy with oral methotrexate
was interrupted. A bloody exudate was evacuated
during repeated pleurocenteses. Administration of
interferon-alpha (9 MU 3 times per week) was
initiated in May 2006. The therapy was followed by
an almost complete regression of pleural effusion on
control CT in September 2006. The regression of
metastases was again accompanied by a flare of
psoriasis with lesions appearing on the trunk and
extremities. Because of toxicity associated with ther-
apy, the dose of interferon-alpha was reduced to 6
MU 3 times per week in September 2006 and
subsequently interrupted in December 2006. In
March 2007 the patient complained about dyspnea.
CT scan in April 2007 revealed multiple lung
metastases involving both lungs and a tumor mass
in left pleural space the infiltrated the abdominal
cavity and ribs. No psoriatic lesions were observed.
Because of general status, only symptomatic therapy
was possible. The patient died on June 26, 2007. An
autopsy was not performed.
We present here an observation of an apparent
association between spontaneous regression of meta-
static RCC and activity of psoriasis. The spontaneous
regression of lung metastases was accompanied by
the exacerbation of psoriasis, and remission of
psoriasis was associated with tumor progression.
The response of recurrent metastatic disease to the
therapy with interferon-alpha was again accompanied
with exacerbation of psoriasis, and during final
progression the activity of psoriasis was low. The
rare occurrence of spontaneous regression of
metastasis in RCC precludes a systematic study of
this phenomenon. The pathogenesis of spontaneous
regression is still unknown. Many theories have
been proposed, some of them based on anecdotal
observation like the present case. RCC is resistant
to virtually all cytotoxic agents. Therefore, biologic
agents, including cytokines, and, more recently,
targeted agents, were studied in metastatic RCC.
Interferon-alpha and interleukin-2 have only a mod-
erate effect on the natural course of metastatic RCC.
In randomized clinical trials, administration of inter-
feron-alpha resulted in survival benefit of fewmonths
[3]. The use of interleukin-2 in metastatic RCC is
based on demonstration of a durable complete
response in aminority of patients [4].Targeted agents
(multiple tyrosine kinase inhibitors sunitinib and
sorafenib, anti-VEGF antibody bevacizumab and
mammalian target of rapamycin inhibitor temsiroli-
mus) were first introduced as second line agents in
patients failing cytokine therapy, but have now also
significant role in the first line setting.
Although tyrosine kinase inhibitors and bevacizu-
mab may be superior to cytokines in efficacy in
metastatic RCC, these agents are still not curative.
Immune system may play an important role in
determining the outcome of metastatic RCC.
Durable complete response has been observed in
patients treated with interleukin-2. Durable re-
sponses were also observed in patients treated with
allogeneic non-myeloablative transplantation, and
these responses could be maintained by donor
lymphocyte infusions [5]. VEGF plays an important
role in the pathogenesis of RCC, andmost new agents
used in metastatic RCC target also the VEGF path-
way [2]. VEGF has an inhibitory effect on adaptive
immune response. VEGF has been shown to inhibit
the function of lymphocytes and dendritic cells, and
anti-VEGF therapy has lead to augmentation of
antitumor response in experimental animals [6].
Immune mechanisms also play a crucial role in the
pathogenesis of psoriasis [7]. The exacerbations of
psoriasis are known to be triggered by infections or
medication. To our best knowledge the present case
926 B. Melichar et al.
Acta Oncol Downloaded from informahealthcare.com by 202.180.107.68
For personal use only.could be the first description of a relation between the
activation of psoriasis and spontaneous regression of
metastases. Similar observation has recently been
reported in a patient with rheumatoid arthritis and
marginal zone B cell lymphoma treated with inflix-
imab and methotrexate [8]. In that case spontaneous
remission was noted after the withdrawal of infliximab
andmethotrexate. Allogeneic hematopoietic stemcell
transplantation may be viewed as adoptive immu-
notherapy, and is frequently accompanied by graft-
versus-host disease.A case of graft-versus-host disease
manifesting as with psoriatic skin lesions has been
described [9]. We can only speculate about the
mechanism(s) of association between the course of
psoriasis andmetastaticRCCin the present patient.T
lymphocytes isolated from psoriatic lesions exhibit
cross reactivity to microbial and self antigens [7]. It is
possible that similar cross reactivity exists between the
putative tumor antigens responsible for tumor rejec-
tion and autoantigens in the skin, but this hypothesis
remains speculative. The risk of cancer may be
increased in patients with psoriasis, possibly as the
result of therapy [10], but increased incidence of RCC
has not been observed and RCC is a rare event in
patients with psoriasis.
In conclusion, this case report presents further
indication that immune response may play a role in
spontaneous regression of RCC metastases after
nephrectomy.
Acknowledgement
Supported by Research Project MZO 00179906.
References
[1] Lokich J. Spontaneous regression of metastatic renal cancer:
Case report and literature review. Am J Clin Oncol 1997;/ 20:/
416 8.
[2] Rini BI, Small EJ. Biology and clinical development of
vascular endothelial growth factor-targeted therapy in renal
cell carcinoma. J Clin Oncol 2005;/ 23:/ 1028 43.
[3] Medical Research Council Renal Cancer Collaborators.
Interferon-alpha and survival in metastatic renal carcinoma:
Early results of a randomised controlled trial. Lancet
1999;353:14 7.
[4] Fisher RI, Rosenberg SA, Sznol M, Parkinson DR, Fyfe G.
High-dose aldesleukin in renal cell carcinoma: Long-term
survival update. Cancer J Sci Am 1997;/ 3:/ S70 2.
[5] Yun T, Lee KW, Song EG, Na II, Shin HC, Yoon SS, et al.
Non-myeloablative allogeneic stem cell transplantation for
metastatic renal cell carcinoma. Clin Transplant 2007;/ 21:/
337 43.
[6] Gabrilovich DI, Chen HL, Girgis KR, Cunningham T,
Meny GM, Nadaf S, et al. Production of vascular endothelial
growth factor by human tumors inhibits the functional
maturation of dendritic cells. Nat Med 1996;/ 2:/ 1096 103.
[7] Sabat R, Philipp S, Hoflich C, Kreutzer S, Wallace E,
Asudullah K, et al. Immunopathogenesis of psoriasis. Exp
Dermatol 2007;/ 16:/ 779 98.
[8] Thonhofer R, Gaugg M, Kriessmayr M, Neumann HJ,
Erlacher L. Spontaneous remission of marginal zone B cell
lymphoma in a patient with seropositive rheumatoid arthritis
after discontinuation of infliximab-methotrexate treatment.
Ann Rheum Dis 2005;/ 64:/ 1098 9.
[9] Matsushita T, Hasegawa M, Shirasaki F, Fujimoto M,
Yamazaki H, Sato S, et al. A case of acute cutaneous graft-
versus-host disease mimicking psoriasis vulgaris. Dermato-
logy 2008;/ 216:/ 34 67.
[10] Hannuksela-Svahn A, Pukkala E, Laara E, Poikolainen K,
Karvonen J. Psoriasis, its treatment, and cancer in a cohort
of Finnish patients. J Invest Dermatol 2000;/ 114:/ 587 90.
The reverse side of the victory: Flare up of symptoms after
discontinuation of sunitinib or sorafenib in renal cell cancer patients.
A report of three cases
INGRID M. E. DESAR1
, SASJA F. MULDER1
, ALEXANDER B. STILLEBROER2
,
DICK-JOHAN VAN SPRONSEN3
, WINETTE T. A. VAN DER GRAAF1
, PETER F.
A. MULDERS2
& CARLA M. L. VAN HERPEN1
1
Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands,
2
Department
of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands and 3
Department of Internal
Medicine, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands
Correspondence: I. M. E. Desar, Department of Medical Oncology 452, Radboud University Nijmegen Medical Centre PO Box 9101, 6500 HB Nijmegen,
The Netherlands. E-mail: i.desar@aig.umcn.nl
Flare up disease after discontinuation of sunitinib or sorafenib in mRCC 927
(Received 27 February 2009; accepted 9 March 2009)
ISSN 0284-186X print/ISSN 1651-226X online # 2009 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS)
DOI: 10.1080/02841860902974167
Acta Oncol Downloaded from informahealthcare.com by 202.180.107.68
For personal use only.





References
[1] Motzer RJ, Hutson TE, Tomczak P, Michaelson MD,
Bukowski RM, Rixe O, et al. Sunitinib versus interferon
alfa in metastatic renal-cell carcinoma. N Engl J Med
2007;356:115 24.
[2] Figlin RA, Hutson TE, Tomczak P, Michaelson MD,
Bukowski RM, Ne ´grier S, et al. Overall survival with
sunitinib versus interferon (IFN)-alfa as first-line treatment
of metastatic renal cell carcinoma (mRCC). Oral (abstract
5024). Presented at the 44th American Society of Clinical
Oncology Annual meeting, Chicago, USA, May 30 June 3,
2008.
[3] Demetri GD, van Oosterom AT, Garrett CR, Blackstein
ME, Shah MH, Verweij J, et al. Efficacy and safety of
sunitinib in patients with advanced gastrointestinal stromal
tumour after failure of imatinib: A randomized controlled
trial. Lancet 2006;368:1329 38.
[4] Schmidinger M, Zielinski CC, Vogl UM, Bojic A, Bojic M,
Schukro C, et al. Cardiac toxicity of sunitinib and sorafenib
in patients with metastatic renal cell carcinoma. J Clin Oncol
2008;26:5204 12.
[5] Force T, Krause DS, Van Etten RA. Molecular mechanisms
of cardiotoxicity of tyrosine kinase inhibition. Nat Rev
Cancer 2007;7:332 44.
[6] Chu TF, Rupnick MA, Kerkela R, Dallabrida SM,
Zurakowski D, Nguyen L, et al. Cardiotoxicity associated
with tyrosine kinase inhibitor sunitinib. Lancet 2007;370
(9604):2011 19.
[7] Cardinale D, Colombo A, Sandri MT, Lamantia G,
Colombo N, Civelli M, et al. Prevention of high-dose
chemotherapy-induced cardiotoxicity in high-risk patients
by angiotensin-converting enzyme inhibition. Circulation
2006;114:2474 81.
[8] Pfizer Inc. SUTENT, Summary of Product Characteristics.
January 2008. Accessed 23/04/2008. http://emc.medicines.
org.uk/emc/industry/default.asp?page displaydoc.asp&doc
umentid 18531
[9] Porta C, Szczylik C, Bracarda S, Hawkins R, Oudard S,
Lee SH, et al. Short- and long-term safety with sunitinib in
an expanded access trial in metastatic renal cell carcinoma
(mRCC). Oral (abstract 5114). Presented at the 44th
American Society of Clinical Oncology Annual meeting,
Chicago, USA, May 30 June 3, 2008.
[10] Cooney MM, van Heeckeren W, Bhakta S, Ortiz J,
Remiack SC. Drug insight: Vascular disrupting agents and
angiogenesis novel approaches for drug delivery. Nat Clin
Pract Oncol 2006;3:682 92.
[11] Joensuu H. Cardiotoxicity of sunitinib. Lancet 2007;370:
1978 9.


BOHUSLAV MELICHAR 1,6
AROSLAVA VANE ˇC ˇ KOVA ´ 2
ETR MORA ´VEK3
HANA URMINSKA ´ 4 & MIROSLAV PODHOLA5

1
Department of Oncology & Radiotherapy, Charles University Medical School & Teaching Hospital, Hradec Kra ´ love ´, Czech
Republic,
2
Department of Dermatology, Charles University Medical School & Teaching Hospital, Hradec Kra ´ love ´, Czech
Republic,
3
Department of Urology, Charles University Medical School & Teaching Hospital, Hradec Kra ´ love ´, Czech
Republic,
4
Department of Radiology Charles University Medical School & Teaching Hospital, Hradec Kra ´ love ´, Czech
Republic,
5
Department of Pathology, Charles University Medical School & Teaching Hospital, Hradec Kra ´ love ´, Czech
Republic
6
Department of Oncology, Palacky ´ University Medical School & Teaching Hospital, Olomouc, Czech Republic