Fallberichte in der Misteltherapie - Paul G. Werthmann 12. September 2019, Zürich
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Fallberichte in der
Misteltherapie
Paul G. Werthmann
12. September 2019, Zürich
Institut für Infektionsprävention und Krankenhaushygiene Institut für angewandte Erkenntnistheorie
Uni-Zentrum für Naturheilkunde und medizinische Methodologie
Universitätsklinikum Freiburg • Universität Freiburg An-Institut der Universität Witten/Herdecke
Paul G. Werthmann 1/30
Übersicht über das Projekt
Fallberichte in der Misteltherapie
111 aufgenommene Fälle
6 Fälle in Bearbeitung
93 Fälle nicht weiter
ausgearbeitet
2 Fälle fortgeschritten
Ø Relevanz zu gering
Ø Dokumentation nicht
10 publizierte Fälle ausreichend
Ø Diagnoseänderung bei
Überprüfung
Ø Wunsch des Patienten/ der
Angehörigen
Paul G. Werthmann 2/30
Suchstrategie nach besondere Fällen
Kontakte der Studie
„Qualitative Mistelstudie: Individuelle
onkologische Misteltherapie durch speziell
befähigte Ärzte“
Darstellungen auf Fortbildungen der GAÄD
z.B. Onkologie-Tagung
Kontakte auf Tagungen etc.
Mail-Forum der GAÄD (forum-AM)
Paul G. Werthmann 3/30
Rückmeldungen Paul G. Werthmann 4/30
Wie erfolgt die Ausarbeitung?
Gesichtete Patientenfälle
Einverständnis zur
Einsicht/Publikation
Relevanzprüfung
Validitätsprüfung
Patientenfall für Fallbericht
Paul G. Werthmann 5/30
Validitäts- und Relevanzprüfung
Was ist das Besondere Wie
an diesem Fall? besonders/relevant
ist dieser Fall im
Hinblick auf den
Behandlergespräch aktuellen
Lässt sich der Verlauf Wissensstand
lückenlos nachvollziehen?
Patientenakte Fachliteratur
?
Lenz et al. JGLD. 2011;
20(4):389-396.
Sind alle wichtigen
Patientengespräch CARE-Leitlinie Daten vorhanden?
Ist die Schilderung
Wie wurde der Fall vom vollständig und
Patienten erlebt? sinnvoll gegliedert?
Stimmen die Befunde mit der Behandler/
Schilderung des Patienten Diagnostiker
überein?
Lassen sich die Befunde der
Patientenakte belegen?
Kommen neue Erkenntnisse seit
der Erstbeurteilung hinzu?
Wie werden die Originalbefunde nach dem
Paul G. Werthmann heutigen Stand des Wissens beurteilt? 6/30
Validität von Fallberichten
Markiert Mitosen.
Zytoplasmatisch
saures Gliafaser-
Patientin mit Diagnose „Glioblastom“ mit
HE
MAP2
GFAP
MiB-1
protein und fort-
satztragend MAP2 einer Überlebenszeit von 6 Jahren unter
exprimierende
gliale Zellen
mit hoher
integrativer Therapie
Timeline Patient with anaplastic oligodendroglioma
Proliferationsrate. 1p/19q codeleted
Case report
Initial
elaboration
diagnosis
and revision
Tumor free of the
Glioblastoma multiforme
supratentorial, MGMT +
survival: diagnose
clinical course
66 months
oligodendroglioma
1p/19q codeleted
(till publication)
48 years
Anaplastic
CT-Scan PET-Scan
no relapse
year 2010 2011 2012 2013 2014 2015 2016
VAE ISC P S1 AVF 0,02 AVF 0,1 AVF 0,1 AVF 0,2 AVF 0,2
therapy
HT
TMZ
RTx
local hyperthermia of the left frontal head region local hyperthermia of the left frontal head region local hyperthermia of the left frontal head region
MRI of the head region
Paul G. Werthmann and 1 whole body hyperthermia and 2 whole body hyperthermia 7/30
Validität von Fallberichten
Papilläres, Patientin mit Diagnose Adenokarzinom des Ovars,
Überlebenszeit von 12 Jahren unter alleiniger
seröses
Adeno-
karzinom
des rechten
Ovars Misteltherapie nach Operation
51-jährige Patientin, Diagnose Adenokarzinom des Ovars, Adnektomie und Netzresektion. Überraschend guter
Verlauf bei primär schlechter Prognose bei postoperativ noch vorhandenen Tumoranteilen unter Misteltherapie
ohne Chemotherapie mit einer Nachbeobachtungszeit von mehr als 12 Jahren.
Histologische ... Heute würde man vermutlich einen serösen Borderlinetumor des Ovars
Kontrolle mit invasiven und nicht-invasiven peritonealen Implants diagnostizieren.
Differentialdiagnostisch könnte man noch über ein low grade seröses
Adenokarzinom diskutieren.
Ein high grade seröses Adenokarzinom liegt aber nicht vor.
Paul G. Werthmann 8/30
Validität von Fallberichten
Timeline of the patient with Hodgkin‘s lymphoma IIIb
71 years 78 years
Patientin mit Diagnose M.
Initial
diagnose resolution of peripheral edema Hodgkin,
enlarged nodes of all regions
peripheral edema, dyspnea,
Vollständige Remission
Hodgkin’s lymphoma IIIb
complete remission
unrelated to cancer
unter alleiniger
cardiac death,
first symptoms
BSG 88mm/h
no relapse Misteltherapie
VAE treatment
weeks -5 -4 -3 -2 -1 0 1 2 3 4 5 6 7
// years
hospital treatment: 7 weeks follow-up: 7 years
Histologische
Kontrolle
Paul G. Werthmann 9/30
Publikationen
Werthmann PG, Kempenich R, Lang-Avérous G, Kienle, Gunver S. Long-term Survival of a Patient With Advanced Pancreatic Cancer Under
3.365
Adjunct Treatment With Viscum album Extracts – A Case Report. World J Gastroenterol. March 2019. doi:10.3748/wjg.v25.i12.0000
Werthmann PG, Kindermann L, Kienle GS. Chemoimmunotherapy in Advanced Renal Cell Carcinoma: A Case Report of a Long-Term 1.053
(2013 for Forsch
Survivor Adjunctly Treated with Viscum album Extracts. Complementary Medicine Research. March 2019:1-4. doi:10.1159/000496866 KomplMed)
Werthmann PG, Kempenich R, Kienle GS. Long-Term Tumor-Free Survival in a Patient with Stage IV Epithelial Ovarian Cancer Undergoing
-
High-Dose Chemotherapy and Viscum album Extract Treatment: A Case Report. The Permanente Journal. 2019;23. doi:10.7812/TPP/18-025
Werthmann PG, Inter P, Welsch T, et al. Long-term tumor-free survival in a metastatic pancreatic carcinoma patient with FOLFIRINOX/
Mitomycin, high-dose, fever inducing Viscum album extracts and subsequent R0 resection: A case report. Medicine. 2018;97(49):e13243. 1.804
doi:10.1097/MD.0000000000013243
Reynel M, Villegas Y, Kiene H, Werthmann PG, Kienle GS. Intralesional and subcutaneous application of Viscum album L. (European
mistletoe) extract in cervical carcinoma in situ: A CARE compliant case report. Medicine. 2018;97(48):e13420. 1.804
doi:10.1097/MD.0000000000013420
Gutsch J, Werthmann PG, Rosenwald A, Kienle GS. Complete Remission and Long-term Survival of a Patient with a Diffuse Large B-cell
Lymphoma Under Extracts After Resistance to R-CHOP: A Case Report. Anticancer Research. 2018;38(9):5363-5369. 1.937
doi:10.21873/anticanres.12865
Werthmann PG, Huber R, Kienle GS. Durable clinical remission of a skull metastasis under intralesional Viscum album extract therapy:
2.471
Case report. Head & Neck. June 2018. doi:10.1002/hed.25320
Werthmann PG, Kindermann L, Kienle GS. A 21-year course of Merkel cell carcinoma with adjuvant Viscum album extract treatment: A case
2.084
report. Complementary Therapies in Medicine. April 2018. doi:10.1016/j.ctim.2018.04.001
Werthmann PG, Saltzwedel G, Kienle GS. Minor regression and long-time survival (56 months) in a patient with malignant pleural
mesothelioma under Viscum album and Helleborus niger extracts—a case report. Journal of Thoracic Disease. 2017;3(2). 2.365
doi:10.21037/jtd.2017.11.56
Werthmann PG, Hintze A, Kienle GS. Complete remission and long-term survival of a patient with melanoma metastases treated with high-
1.804
dose fever-inducing Viscum album extract: A case report. Medicine. 2017;96(46):e8731. doi:10.1097/MD.0000000000008731
Paul G. Werthmann 10/30Tumorentitäten der Publikationen
Lymphom
Malignes Melanom
Merkelzellkarzinom
Nierenzellkarzinom
Ovarialkarzinom
Pankreaskarzinom (2 Fallberichte)
Pleuramesotheliom
Schädelmetastase
Paul G. Werthmann 11/30Ergebnisse der Publikationen
Tumor- Langzeit- Lebensqualitäts-
regression überleben verbesserung
Lymphom
Malignes Melanom
Merkelzellkarzinom
Nierenzellkarzinom
Ovarialkarzinom
Pankreaskarzinom (A)
Pankreaskarzinom (B)
Pleuramesotheliom
Schädelmetastase
Paul G. Werthmann 12/30Besonderheiten der Publikationen
Lymphom Vollständige Remission nach Chemotherapie-Resistenz (R-CHOP)
Malignes Melanom Vollständige Remission von Melanom-Metastasen
Merkelzellkarzinom Langzeitüberleben von 21 Jahren unter chirurgischer Therapie und Misteltherapie
Nierenzellkarzinom Vollständige Remission unter Immunochemotherapie und Misteltherapie
Ovarialkarzinom Langzeitüberleben von 20 Jahren unter chirurgischer Therapie und Misteltherapie
Pankreaskarzinom (A) Teilremission und Langzeitüberleben unter lokaler fieberinduzierender Misteltherapie
Langzeitüberleben von 5 Jahren (63 Monaten) unter Bestrahlung, Chemotherapie,
Pankreaskarzinom (B)
Radiofrequenzablatioin und Misteltherapie
Teilremission und Langzeitüberleben (56 Monate) unter Helleborus niger- und
Pleuramesotheliom
Misteltherapie
Schädelmetastase Teilremission und Langzeitüberleben unter intratumoraler Misteltherapie
Paul G. Werthmann 13/30Zur Therapie
Hersteller Wirtsbäume subcutan intravenös intraläsional
Lymphom Helixor Pini x x
Mali, Mali spez, Quercus,
Malignes Melanom Iscador x x x
Quercus F, Pini
Merkelzellkarzinom Helixor Abietis x
Nierenzellkarzinom Helixor Abietis x x
Ovarialkarzinom Iscador Mali, Pini x
Pankreaskarzinom (A) Abnoba, Iscucin Fraxini, Salicis x x
Pankreaskarzinom (B) Iscador Quercus x
Pleuramesotheliom Abnoba, Helixor, Iscador Pini, Fraxini x x
Schädelmetastase Abnoba Fraxini x x
Paul G. Werthmann 14/30Fallberichte über Misteltherapie
in der heutigen Medizin
Laccourreye O, Werner A, Laccourreye L, Bonfils P. Benefits, pitfalls and risks of phytotherapy in clinical practice
Paul G. Werthmann in otorhinolaryngology. European Annals of Otorhinolaryngology, Head and Neck Diseases. November 2016 15/30ue to cancer in the head and neck induce apoptosis in oral cancer cells in vitro.62 Scutellariae
diammine dichloride is an anticancer radix is one of the most widely used anticancer herbal
cancer therapy but has serious side- medicines in several Asian countries induces apoptosis in
mia. To reduce the adverse effect of chemo-resistant human tongue cancer cells.63 The dried root
y gland function, some additional of Saussurea lappa Dance which has been traditionally used for
o Chinese medical herbal extracts abdominal pain in Asia inhibits oral cancer cell proliferation
ncus effusus and Paeonia suffruticosa
nar cells Herbal medicine … Irani S
from apoptosis. Hence, they
Fallberichte über Misteltherapie
via apoptosis pathway. 64 A previous study on adenoid
cystic carcinoma indicated that intratumoral
Journal of International high-dose
Oral Health 2016; 8(10):989-994
tive drugs to prevent
Received: 13th MayCis-platinum
in der heutigen Medizin
2016 Accepted: 10th injections
August 2016of ABNOBAviscum Quercus and ABNOBAviscum
Conflicts of Interest: None
FraxiniViscum album extracts which are endotoxin-free plant
Source of Support: This research was supported only by Hamadan University of Medical Sciences
Review Article
extracts from European Viscum album extract could decrease Doi: 10.2047/jioh-08-10-09
current parotitis (JRP) is the second the size of tumor without any side effects such as fever, local
Herbal
us salivary glandMedicine
disease and Oral Health:
during swelling, and pain.65 Although low-dose adjunct
A Review
inflammation,
ule is a Soussan
preparation
Irani1,2of an extract of VAE treatment has shown any side effect on head and neck
traditional medicine, and completely cancer patients, cytotoxic effects of VAE have been observed
th a significant reduction of average in head and neck SCC cell lines.66 Table 1 summarizes the
Contributors: effect of herbal medicinetherapyin oraltohealth.
treat different types of cancer such as metastatic
1
Associate Professor, Department of Oral Pathology, Dental bladder cancer in both lungs without chemotherapy or
Research Center, Dental Faculty, Dental Research Center, radiotherapy.7 The metastatic and angiogenic potential of
Table 1: The effect of herbal medicine
Hamadan University of Medical Sciences, Hamadan, Iran; in oral health.
Anisi stellate fructus extract were examined in in vitro and
2 Dental
Lecturer, caries Gingivitis
Department of Pathology,and periodontitis
School Oral diseasein vivo studies.Oral
of Medicine, Griffith Thecancer
results showed that it remarkably reduced
obiomeUniversity, Gold Coast, Australia. the number of pulmonary metastatic colonies in mice and
eolata Correspondence:
Rhus coriaria L. Pomegranate extract (P. granatum) Jinlianqingre Effervescent Pterostilbene
also suppressed in vivo tumor-induced angiogenesis through
Dr. Irani
EmodinS. Dental Faculty, Shahid
Chamomile Fahmideh Street, Hamadan
extract Reduning Vitis vinifera
65178-38741, Iran. Tel.: +98813-8354250, Fax: +98813-8354220.
a reduction of pro-angiogenic factors in tumors.8 One of the
and gall nut Rokumigan Baikal skullcap Insect tea
Email: sousanirani@gmail.com traditional herbal medicines is Guibitang, which induces
ts
apoptotic death in colon cancer cells by regulating the
unculifoliaHow to cite the article: Canavanine Oxitard Iranian orthodox black tea
Irani S. Herbal medicine and oral health: A review. J Int Oral GingerHealth activities of mitogen-activated protein kinases. Furthermore,
Scutellariae radix
2016;8(10):989-994. Guibitang
Chamomilla tincture
stimulates MAPKs and p53 signaling pathways that
Saussurea lappa dance
Abstract: Quercetin
are required for cell growth and tumorigenesis.9 Interestingly,
European Viscum album extract
Medicinal plants have been used since ancient times for the
Zeng Ye decoction
stem cells from human exfoliated deciduous teeth differentiate
treatment of different diseases. Natural sources are one of the
Malva sylvestrisinto
L. functional hepatocyte-like cells by herbal medicine such
important fields of research for preventing immunological as liquorice 10
Alcea digitata (Boiss) Alef or angelica extracts.
complications. Using herbal medicine has decreased as the result
Huangqi granule
of the development of chemical drugs. This review aimed to study Oral health has a great impact on the general quality of life,
herbal medicine regarding the oral cavity. English literature was and poor oral health has a great impact on chronic conditions
searched with the terms “herbal medicine and oral cavity” in two and systemic diseases. In the oral cavity, herbal medicine has
Paul G. Werthmann
data bases of PubMed, and Google scholar Iraniamong
S. Herbal Medicine and
published Oral Health: A Review. Journal of International Oral Health. 2016;8(10):989. 11
studies 16/30www.pancreatica.org Paul G. Werthmann 17/30
Fallberichte zur Misteltherapie
von anderen Autoren
Clinical Case Report Medicine ®
Unexpected outcome (positive or negative) including adverse drug reactions
CASE REPORT
BMJ Case Rep: first published as 10.1136/bcr-2018-227652 on 31 March 2019. Downloaded from http://casereports.bmj.com/ on 2 April 2019 by guest. Protected by copyright.
OPEN
Hwang et al. Medicine (2019) 98:8 Medicine
Prolonged stabilization of platinum-refractory Supportive mistletoe therapy in a patient with
ovarian cancer in a single patient undergoing
long-term Mistletoe extract treatment metastasised neuroblastoma
Case report
Woo Yeon Hwang, MD, Mi Hyun Kang, MD, Seul Ki Lee, MD, Ji Su Yeom, MD, Min Hyung Jung, MD, PhD
∗ Jens Kaestner,1 Dietrich Schlodder,2 Christfried Preussler,3 Bernd Gruhn1
Abstract
Rationale: Advanced ovarian malignancies are associated with poor overall survival; thus, patients often turn to alternative
1
treatments, despite the controversy surrounding their use. Mistletoe extract has been commonly used as complementary medicine Klinik für Kinder- und SUMMARY autologous stem cell transplantation. This form of
Downloaded from https://journals.lww.com/md-journal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3q7dCwSUxuLiwIDB5u4dHFNMAAqil+T/+3Ga1du6qZdFnk0QseUzDAA== on 02/28/2019
to treat patients with cancer for several decades, and has proven benefits in integrative oncology. Jugendmedizin, Friedrich- Therapies of complementary and alternative medicine therapy should always be administered in a paedi-
Patient concerns: A 47-year-old woman with stage IVB ovarian cancer who underwent optimal surgical cytoreduction, but Schiller-Universität Jena, Jena,
whose disease persisted after adjuvant platinum-based combination chemotherapy and 2nd-line chemotherapy. (CAM) are used increasingly in paediatric oncology. atric oncology setting in controlled therapy-optimi-
Germany sation trials.
Hwang et al. Medicine (2019) 98:8
Diagnosis and interventions: The patient discontinued chemotherapy due to her septic condition and acute kidney injury
Medicine
2 We present and discuss the influence of supportive
Research and Development,
accompanied by acute pyelonephritis, and opted for adjuvant treatment with mistletoe extract. mistletoe therapy on factors, such as quality of life, Alongside such vital standard therapies, comple-
Helixor Heilmittel GmbH,
Outcomes: The patient has achieved good health without progression of cancer or ascites over the 42 months since the 1st
Rosenfeld, Germany physical ability
Unexpected and performance,
outcome (positive orandnegative)
course of disease mentarydrug
including adverse oncological
reactionsprocedures are also adminis-
diagnosis and 24 months since the last relapse. 3 based on the case of a female patient diagnosed at age tered in the treatment of childhood cancer. Among
Medical Science, Helixor
Lessions: Our case suggests that mistletoe extract can produce favorable outcomes in patients with platinum-refractory ovarian parents surveyed in a large population-based study,
18 with metastasised neuroblastoma, which responded
BMJ Case Rep: first published as 10.1136/bcr-2018-227652 on 31 March 2019. Downloaded from http://casereports.bmj.com/ on 2 April 2019 by guest. Protected by copy
cancer.
Heilmittel GmbH, Rosenfeld,
Germany insufficiently to chemotherapy. which was conducted in cooperation with the
Abbreviations: CAM = complementary and alternative medicine, CT = computed tomography, QOL = quality of life.
German Childhood Cancer Registry and included
Keywords: complementary and alternative medicine, helixor, mistletoe extract, ovarian cancer, platinum-refractory
Correspondence to 1595 children with malignant tumours, 35% of
Dr Christfried Preussler, respondents stated that their child’s course of treat-
cpreussler@helixor.de BACKGROUND
ment included complementary and alternative ther-
1. Introduction commonly used mistletoe product that we administered to our Neuroblastoma (NB) is a malignant disease that
apies (CAM). Anthroposophic medicine, including
patient. It is an aqueous cold extract made from white-berry Accepted 28 February 2019 develops in certain types of nerve tissue, such as the
Ovarian cancer is widely known as the mostFigure lethal1.disease
Plot ofamong
CA 125 from initial diagnosis (March 2015) through recent date. Paclitaxel/Carboplatin chemotherapy from April 2015 through August 2015 and mistletoe therapy, was an option used by 26.7% of
2019
2019
mistletoe (Viscum album), which grows on various trees. The
gynecological malignancies. Although many Pegylated
treatment liposomal doxorubicin/Bevacizumab chemotherapy from October 2015 through August 2016.
methods, sympathetic nerve trunk, adrenal medulla or other
immunoprotective and tumor-inhibiting properties of mistletoe CAM users. In terms of effect on the disease, 63%
including surgery, chemotherapy, radiotherapy, and hormonal
extract are attributable primarily to the glycoprotein lectin.[4] tissue in the sympathetic nervous system. With of the parents had a positive opinion of CAM.3
and targeted therapy, are well established, these therapies are less
effective for advanced-stage disease, and recurrence remains an
Mistletoe extracts have been shown anticancer effect reducing about 1.1 cases per 100 000 children, it is the most Medicinal products made from white-berry
cancer cell viability in various in-vitro studies.[4] Mistletoe
issue in patients with ovarian cancer due to the side effects and the
treatments are used primarily to improve quality of life (QOL)
frequent extracranial solid tumour of childhood. mistletoe (Viscum album L.) have been clinically
risk of toxicity to normal cells.[1] Thus, adjuvant options for Because NB is an embryonal tumour, the median administered in cancer patients since 1917. The
during conventional therapy, to increase tolerability to chemo-
ovarian cancer treatment must be identified. Complementary and
alternative medicine (CAM) has been developed in the recent
therapy, and to exert beneficial effects on tumor control and age of patients at diagnosis is approximately 2 years. products are registered in several European coun-
survival.[5,6] Repeated intraperitoneal administration of mistletoe
years and is gaining interest.[2]
extract can reduce fluid accumulation in patients with malignant
Less than 5 per cent of newly diagnosed children tries and number among the most frequently admin-
Among CAM therapies, mistletoe extracts are the herbal
ascites.[7] Here, we report the case of a patient with ovarian are over the age of 10.1 istered forms of CAM in oncological treatment.4
extracts applied most commonly to treat cancer.[3] Helixor is a
cancer who developed progressive disease after conventional The initial symptoms of NB depend on the Both their biologically active substances (mistletoe
2nd-line chemotherapy, but achieved stable disease status after
Editor: N/A. Figure 1. Plot of CA 125 from initial diagnosis (March 2015) 24
through recentofdate.
months Paclitaxel/Carboplatin
treatment chemotherapy
with a mistletoe product from
as April 2015 through August 2015 and
an alternative
tumour location and are often vague. They can lectin, viscotoxins, oligosaccharides and polysac-
Pegylated liposomal doxorubicin/Bevacizumab chemotherapy from October 2015 through August 2016.
The authors have no conflicts of interest to disclose. therapy. include visible or palpable swelling on the neck or charides, and polyphenols and flavonoids) and their
Department of Obstetrics and Gynecology, Kyung Hee University Medical Center, abdomen, bone pain, weight loss and changes in pharmacological effects, such as apoptosis induc-
Seoul, South Korea.
∗
Correspondence: Min Hyung Jung, Department of Obstetrics and Gynecology,
2. Case report the skin or around the eyes. Many diagnoses occur tion via the mitochondrial pathway, and immuno-
Kyung Hee University Medical Center, Seoul 90034, South Korea A 47-year-old female patient who presented with painless unexpectedly during routine paediatric check-ups modulation and DNA protection in lymphocytes,
(e-mail: webhospital@naver.com). abdominal distension over 2 months was referred to our or exams involving other concerns. are well documented (see5 for an overview).
Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc. institution for evaluation and treatment. She had no specific
This is an open access article distributed under the terms of the Creative medical history except for abdominal distension and dyspnea. The course of disease can vary widely among In a review of numerous clinical studies, 21
Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-
ND), where it is permissible to download and share the work provided it is
The abdomen was distended with bulging flanks, dullness to individuals and depends largely on risk factors as prospective randomised trials that involved the
properly cited. The work cannot be changed in any way or used commercially percussion, and a positive shifting dullness. Her serum CA 125 well as the level of tumour infiltration, patient age, administration of oncological mistletoe therapy
without permission from the journal. level was 768 IU/mL (Fig. 1) and her C-reactive protein level was
Medicine (2019) 98:8(e14536) elevated. Computed tomography (CT) of the abdomen and pelvis and molecular genetic alterations (N-Myc amplifi- satisfied the strict criteria established by Cochrane.4
Received: 19 October 2018 / Received in final form: 17 January 2019 / revealed cancer peritonitis with peritoneal seeding around both cation) and chromosome 1 mutations (1 p deletion, In 14 out of 16 studies that examined quality of life,
ovaries and the uterus, liver, and spleen, with omental cake
Accepted: 23 January 2019
1 p imbalance or loss of heterozygosity of the 1 p mistletoe therapy was linked to a positive influence
http://dx.doi.org/10.1097/MD.0000000000014536 formation and ascites (Fig. 2A). Although CT did not reveal the
chromosomal arm) in tumour cells. At the time of on quality of life and a better tolerance of chemo-
1 diagnosis, about one-half of all the patients present therapy. Moreover, a recent study also demon-
with some form of metastasis, typically occurring in strated a significant impact of mistletoe therapy on
the bone or bone marrow, lymph nodes, liver, skin survival of cancer patients.6 This result is supported
and, less frequently, in the CNS or lung.2 by previous series of studies, though their method-
Figure 2. Computed tomography (CT) images. (A) Initial computed tomography images showing cancer peritonitis with massive ascites and peritoneal seeding of
unknown primary origin. (B) CT after conventional chemotherapy showing progression of peritoneal carcinomatosis associated with large amount of ascites with
Standard treatment includes surgical removal ological quality is notably weaker.7
increased peritoneal nodularites. CT = computed tomography. © BMJ Publishing Group of the tumour elements, chemotherapy, and radi- All of the above trials involved the treatment of
Limited 2019. Re-use ation and administration of metaiodobenzylguani- adult cancer patients. In paediatric settings, we can
permitted under CC BY-NC. No
2 Figure 1 Treatment and course of dine (MIBG)
the disease. HR, highwith a radioactive
risk; MIBG, tracer for
metaiodobenzylguanidine; NB, internal
neuroblastoma; draw on decades
PNET, primitive of experience in administering
neuroectodermal
commercial re-use. See rights
tumour. targeted radiation therapy of the NB tumour. V. album L. to children in specialised anthropos-
Hwang WY, Kang MH, Lee SK, Yeom JS, Jung MH. Prolonged and permissions. Published Kaestner J, Schlodder D, Preussler C, Gruhn B. Supportive
MIBG is an organic compound that is structurally ophic hospitals during or after standard therapy.8
by BMJ.
stabilization of platinum-refractory ovarian cancer in a single mistletoe therapy in a When
related to norepinephrine. patient withtometastasised
attached radio- There are also some individual case reports
Figure 2. Computed tomography (CT) images. (A) Initial computed tomography images showing cancer peritonitis with massive ascites and peritoneal seeding of Topractice, up to 12.5
cite: Kaestner J, mg (0.25 mLactive
Helixor A 50 mg). During this the scintiscan and the MRI showed new tumour growth in the
patient
unknown primary origin. (B) CT after conventional undergoing
chemotherapy showing progressionlong-term Mistletoe
of peritoneal carcinomatosis associated withextract
large amount oftreatment:
ascites with Case time, theD,patient
Schlodder
neuroblastoma.
experienced
Preussler C,
iodine,
a significant it can
increase BMJ
be usedCase
in physical to
lefttreat Reports.
neuroendocrine
proximal humerus, the2019;12(3):e227652.
seconddetailing
right rib, onimpressive developments in the course of
the angulus infe-
increased peritoneal nodularites. CT = computed tomography.
report. Medicine. 2019;98(8):e14536. and subjective well-being. She tumours herasstamina
well
doi:10.1136/bcr-2018-227652
regained as
to for nuclear
accom- riormedicine and
scapulae, and in molec- wing. Yet,9–11
the right iliacdisease. the Yet, there
patient is still a lack of formal clinical
did not
et al. BMJ Case Rep
plish everyday activities, and even sports,
ular imaging. such as cycling, were report any pain or restrictions. Diagnostic imaging in March and
2019;12:e227652. trials on mistletoe therapy in paediatric cancer.
doi:10.1097/MD.0000000000014536 2 once again possible. The patient felt well and her symptoms had May 2013 showed an enlargement of the lesion in the left prox-
doi:10.1136/bcr-2018- High-risk patients
disappeared. She was able to complete her schooling in summer may additionally require Given the above
imal humerus while the other tumour foci remained unchanged. situation, a prospective, multi-
227652 myeloablative high-doseinchemotherapy followed
showed byelevatedcentre
levels ofrandomised phase IV trial was conducted
Paul G. Werthmann 2012 and start a university degree
October 2012.
programme in psychology Urine samples also
HVA and VMA. On the basis of the patient’s good general
the tumour markers
18/30®
Year
Clinical Case Report Medicine
0
OPEN
cM0,
Initial
excision
61 years
pT1a, N0,
> Surgical
Diagnosis
Complete remission and long-term survival of a
left auricle,
MCM of the
patient with melanoma metastases treated with
high-dose fever-inducing Viscum album extract
Paul G. Werthmann
A case report
∗
1
Paul G. Werthmann, MDa, , Alexander Hintze, MDb, Gunver S. Kienle, MDa,c
left
lesion
Abstract
auricle
excision
65 years
> Surgical
Introduction: Metastatic malignant cutaneous melanoma (MCM)—a highly immunogenic cancer—typically has a poor prognosis.
Recurrent
Timeline
Viscum album extracts (VAEs) have strong immune-stimulating, apoptogenic, and cytotoxic effects.
Case presentation: A 66-year-old MCM patient with newly diagnosed lymph node metastases opted for sole VAE treatment.
VAEs were initially applied subcutaneously, and then later in exceptionally high, fever-inducing doses, both intravenously and
intralesionally. The metastases shrunk over the following months, and after 2 years, all lesions had completely remitted (regional
and hilar lymph nodes). The patient has been tumor free for 3.5 years at the time of publication (and for 5 years since initiation of
2
intensified VAE treatment). Besides fever and flu-like symptoms, no side effects occurred.
Discussion: We presume that VAE triggered an increased release of tumor-associated antigens, enhanced immunologic
recognition, and increased immune response against the tumor tissue and induced tumor remission.
Abbreviations: AJCC = American Joint Committee on Cancer, BRAF = rapidly growing fibrosarcoma type B gene, FDG =
Fludeoxyglucose (18F), MCM = malignant cutaneous melanoma, ML = mistletoe lectin, PET-CT = positron emission tomography–
computed tomography, UICC = Union internationale contre le cancer, VAE = Viscum album extracts, VT = viscotoxin.
Keywords: complete remission, fever, malignant cutaneous melanoma, Mistletoe, Viscum album extract
5
3
hilar left
gland and
metastases
Editor: Satyabrata Pany.
1. Introduction
Authorship: PGW, AH, and GSK contributed to the case report design. AH was Malignant cutaneous melanoma (MCM) is the sixth most
the physician in charge and provided the patient’s information. PGW and AH common of all cancers and the deadliest of all skin cancers, with
collected and provided the data. PGW was the principle author of the paper, had
increasing incidence worldwide (incidence and mortality are 9.3–
full access to all data, and is the guarantor. GSK supervised the case report and
publication processes. 10.2 and 1.2–2.0 per 100,000 people, respectively). MCM has a
4
fair prognosis in local disease (20-year survival of 75%) but a
biopsy
Funding/support: This case report was prepared following the CARE Guidelines.
66 years
and hilar
dismal prognosis in metastatic disease (5-year survival of 5–
Informed consent was received from the patient for the publication of the report
metastases
Lymph node Lymph node
19%). Risk factors are male gender, light skin (non-Hispanic
confirmed by
left parotid parotid gland
and accompanying images. The patient read the submission version of the report
and confirmed its content. whites), increased ultraviolet (UV) index (intense, intermittent
The authors declared the following potential conflicts of interest with respect to sun exposure; tanning beds), and immunosuppression. Complete
the research, authorship, and/or publication of this article: IFAEMM has received
Stays in IAM hospital
surgical excision is the standard of care for early melanoma
restricted research grants, honoraria, and travel expenses from Weleda, Abnoba, treatment and can cure minimally invasive and in situ lesions.
and Helixor. None of them had any influence on the design, conduction, analysis,
Excision of lymph nodes and systemic adjuvant immunotherapy
and publication of the study. AH declared no conflict of interest.
a
is recommended for locally advanced disease. Metastatic disease
Institute for Applied Epistemology and Medical Methodology (IFAEMM) at the
5
University of Witten/Herdecke, Freiburg i. Brsg., Germany, b Klinik Arlesheim,
is treated with surgical metastasectomy, immunotherapy,
Arlesheim, Switzerland, c Center for Complementary Medicine, Institute for targeted therapies, and radiation therapy. Chemotherapy is
Environmental Health Sciences and Hospital Infection Control, Medical Center – restricted to patients whose disease cannot be controlled with
University of Freiburg, Freiburg, Germany. immunotherapy or targeted agents.[1]
∗
Metastasis
decreasing
left parotid
Correspondence: Paul G. Werthmann, Institute for Applied Epistemology and MCM shows a high immunogenicity and has played a key role
gland stable,
Medical Methodology at the University of Witten/Herdecke, Zechenweg 6, D- in the development of tumor immunology. Of particular interest
79111 Freiburg i. Brsg., Germany (e-mail: paul.werthmann@ifaemm.de).
is the unusually high rate of spontaneous regression of primary
Copyright © 2017 the Author(s). Published by Wolters Kluwer Health, Inc.
lesions (3.7–15% but without impacting survival); a fair rate of
This is an open access article distributed under the Creative Commons
Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build spontaneous remission of metastatic disease (about 0.23% with a
upon the work, even for commercial purposes, as long as the author is credited positive impact on survival); regression of MCM after infections
6
6
and the new creations are licensed under the identical terms. or immunologic active treatments; and lymphocyte infiltration in
Medicine (2017) 96:46(e8731) regressed lesions and depigmentation of the site of regression.[2]
Enlarged timeline on therapy and diagnostic intervention
hilar metastasis No brain
Received: 1 June 2017 / Received in final form: 12 October 2017 / Accepted: 13 Furthermore, an increased number of infections and episodes of
metastases
October 2017 high fever, as well as previous history of certain vaccinations,
http://dx.doi.org/10.1097/MD.0000000000008731 are correlated with a reduced risk of developing MCM.[3,4]
1
Subcutaneous VAE therapy
Intravenous VAE therapy
Intralesional VAE therapy
7
remission,
Metastasis
decreasing
hilar metastasis
parotid gland in
8
treated with high-dose fever-inducing Viscum album extract: A case report. Medicine. November 2017;96(46):e8731.
Werthmann PG, Hintze A, Kienle GS. Complete remission and long-term survival of a patient with melanoma metastases
Remission unter alleiniger Misteltherapie
PET-Scan
9
Metastasis left
no suspect FDG
parotid gland and
hilar metastasis in
uptake at follow-up
complete remission,
VAE: Viscum album extract
FDG: 18F-Fluorodeoxyglucose
Patientin mit Melanom-Metastasen und vollständiger
10
Magnetic Resonance Imaging
MCM: Malignant cutaneous melanoma
IAM: Integrative Anthroposophic Medicine
19/30
72
yearsexcision
Patientin mit Melanom-Metastasen
Year
0 1 2 3 4 5 6 7 8 9 10
Timeline
Enlarged timeline on therapy and fever response
39.5
response (°C)
39.4
39.0
Fever
38.8
38.5
38.0
37.5 37.6
200
200
Viscum album
Qu F (mg)
Intralesional
150
150
100
80
50
40
0
Iscador M
200
200
200
200
Intravenous VAE
Iscador Qu
200
200
100
200
Iscador M Spez
100
200
(mg)
200
Viscum album Qu F
200 200
200
200
200
120
160
280
Iscador P
200
200
120
300
100
200
200
200
200
200
®
150
Medicine
120
82.5
600
500
500
400
120
300
135
165
800
150
120
15
45
600
39
105
60
200
75
90
1000
1300
1600
2000
2000
2000
2000
1400
1400
1200
1400
240
200
600
Subcutan.
Iscador P 60 mg s.c. 3x per week
VAE
6 7
Fever response: the highest body temperature during every treatment and follow-up period is indicated. Intravenous-VAE: VAE was
administered in a 500 mL normal saline solution and infused slowly over a period of 3 hours (infusion speed 2.7mL/Min).
Werthmann PG, Hintze A, Kienle GS. Complete remission and long-term survival of a patient with melanoma metastases
Paul G. Werthmann treated with high-dose fever-inducing Viscum album extract: A case report. Medicine. November 2017;96(46):e8731. 20/30Patientin mit Melanom-Metastasen
39,5
39
mean
lowest temperature
38,5
Temperature (°C)
38
highest temperature
37,5
37
®
Medicine
36,5
intravenous infusion of VAE
36
0 30 60 90 120 150 180 210 240 270 300 330 360
Time (minutes)
Werthmann PG, Hintze A, Kienle GS. Complete remission and long-term survival of a patient with melanoma metastases
Paul G. Werthmann treated with high-dose fever-inducing Viscum album extract: A case report. Medicine. November 2017;96(46):e8731. 21/30®
e (10.5
ase, no
natural
e, is in
of this
herapy
(range
eport Medicine
OPEN
used.
withThe
e remission and long-term survival of a
Paul G. Werthmann
a rectal/vaginal
ith melanoma metastases treated with
patient also
e fever-inducing Viscum album extract
temperature
ort
suffered
∗
n, MDa, , Alexander Hintze, MDb, Gunver S. Kienle, MDa,c
3 suffered a cranial base fracture.
probe.
astatic malignant cutaneous melanoma (MCM)—a highly immunogenic cancer—typically has a poor prognosis.
cts (VAEs) have strong immune-stimulating, apoptogenic, and cytotoxic effects.
magnesium, the patient took fish oil capsules.
n: A 66-year-old MCM patient with newly diagnosed lymph node metastases opted for sole VAE treatment.
pplied subcutaneously, and then later in exceptionally high, fever-inducing doses, both intravenously and
3. Antecedent and concomitant therapies
etastases shrunk over the following months, and after 2 years, all lesions had completely remitted (regional
es). The patient has been tumor free for 3.5 years at the time of publication (and for 5 years since initiation of
ment). Besides fever and flu-like symptoms, no side effects occurred.
he 3 years after recurrence of the tumor and the 2 years of intensified VAE therapy.
presume that VAE triggered an increased release of tumor-associated antigens, enhanced immunologic
life events from her early childhood.[29] In addition to nutritional
provided by her health insurance, where she worked on negative
supplements containing sodium, calcium, potassium, and
The patient participated in seminars on mental healing,
conization. Forty-three years before diagnosis with MCM, she
initial diagnosis of MCM, the patient had been diagnosed with
from advanced osteochondrosis
medicine.[28] No other cancer-specific medical treatments were
individualized therapy concept of integrative anthroposophic
intervertebralis, goiter, and migraine. Fourteen years before the
In this case, high-dose VAE therapy was used within an
carcinoma in situ of the cervix, which was treated with laser
reased immune response against the tumor tissue and induced tumor remission.
JCC = American Joint Committee on Cancer, BRAF = rapidly growing fibrosarcoma type B gene, FDG =
F), MCM = malignant cutaneous melanoma, ML = mistletoe lectin, PET-CT = positron emission tomography–
hy, UICC = Union internationale contre le cancer, VAE = Viscum album extracts, VT = viscotoxin.
ete remission, fever, malignant cutaneous melanoma, Mistletoe, Viscum album extract
4. Patient’s view
1. Introduction
GSK contributed to the case report design. AH was Malignant cutaneous melanoma (MCM) is the sixth most
provided the patient’s information. PGW and AH common of all cancers and the deadliest of all skin cancers, with
data. PGW was the principle author of the paper, had
increasing incidence worldwide (incidence and mortality are 9.3–
s the guarantor. GSK supervised the case report and
10.2 and 1.2–2.0 per 100,000 people, respectively). MCM has a
Patientenperspektive
report was prepared following the CARE Guidelines.
fair prognosis in local disease (20-year survival of 75%) but a
dismal prognosis in metastatic disease (5-year survival of 5–
ived from the patient for the publication of the report
The patient read the submission version of the report 19%). Risk factors are male gender, light skin (non-Hispanic
whites), increased ultraviolet (UV) index (intense, intermittent
llowing potential conflicts of interest with respect to sun exposure; tanning beds), and immunosuppression. Complete
d/or publication of this article: IFAEMM has received surgical excision is the standard of care for early melanoma
onoraria, and travel expenses from Weleda, Abnoba, treatment and can cure minimally invasive and in situ lesions.
ad any influence on the design, conduction, analysis,
Figure 2. Course of body temperature during 10 sample treatments with intravenous infusions of VAE in the day clinic. Temperature was continuously recorded
before further therapy was continued. During this time, I
University Hospital that it would most likely be a month
found out about intensive Mistletoe Therapy and the hospital
confidence in myself and that I could contribute to my own
Following the diagnosis of the metastases, I was told at the
offering Anthroposophic Medicine. I learnt that I could have
Excision of lymph nodes and systemic adjuvant immunotherapy
. AH declared no conflict of interest.
is recommended for locally advanced disease. Metastatic disease
mology and Medical Methodology (IFAEMM) at the
e, Freiburg i. Brsg., Germany, b Klinik Arlesheim,
is treated with surgical metastasectomy, immunotherapy,
nter for Complementary Medicine, Institute for targeted therapies, and radiation therapy. Chemotherapy is
es and Hospital Infection Control, Medical Center – restricted to patients whose disease cannot be controlled with
urg, Germany.
Patientin mit Melanom-Metastasen
immunotherapy or targeted agents.[1]
Werthmann, Institute for Applied Epistemology and MCM shows a high immunogenicity and has played a key role
University of Witten/Herdecke, Zechenweg 6, D- in the development of tumor immunology. Of particular interest
rmany (e-mail: paul.werthmann@ifaemm.de).
is the unusually high rate of spontaneous regression of primary
r(s). Published by Wolters Kluwer Health, Inc.
lesions (3.7–15% but without impacting survival); a fair rate of
le distributed under the Creative Commons
Werthmann P, Hintze A, Kienle GS. Vollständige Metastasenremission und Langzeitüberleben bei einer Melanompatientin unter
se 4.0, which allows others to remix, tweak, and build spontaneous remission of metastatic disease (about 0.23% with a
mercial purposes, as long as the author is credited positive impact on survival); regression of MCM after infections
hochdosierter, fieberinduzierender Viscum-album-Extrakt-Therapie. Der Merkurstab. 2019;72(1):36-42. doi:10.14271/DMS-21048-DE
tragen, weil ich mich in der Behandlung sicher fühlte.“
icensed under the identical terms. or immunologic active treatments; and lymphocyte infiltration in
ich die intensivierte Misteltherapie und das Spital mit
die teils schmerzhaften Injektionen konnte ich gut ver-
den und gehen – auch wenn es Ärzte gab, die mich über-
die weitere Therapie geplant würde. In dieser Zeit lernte
Unispital gesagt, dass ich einen Monat Zeit hätte, bevor
„Nach der Diagnose der Metastasen wurde mir im
te dankbar zu sein für alles, was in mir gesund war. Das
beitragen konnte. Ich bemerkte, dass es mein eigenes
Selbstvertrauen haben und zu meinem Heilungsprozess
Anthroposophischer Medizin kennen. Ich lernte, dass ich
Engagement brauchte um gesund zu werden, und lern-
therapie mit hohem Fieber und Nebenwirkungen sowie
zeugen wollten, diesen Weg nicht zu gehen. Die Mistel-
konnte ich auch einen eigenen Weg in der Therapie fin-
das zu entlarven, was an innerer Sabotage in mir lebt. So
Bewusstsein für meine Biografie zu entwickeln und all
Engagement für meine Gesundheit beinhaltete auch, ein
1) regressed lesions and depigmentation of the site of regression.[2]
ceived in final form: 12 October 2017 / Accepted: 13 Furthermore, an increased number of infections and episodes of
22/30
high fever, as well as previous history of certain vaccinations,
[3,4]RFA
USG
World Journal of
Year
scan
Gastroenterology
imaging
WJ G
ultrasound
Submit a Manuscript: https://www.f6publishing.com World J Gastroenterol 2019 March 28; 25(12): 1524-1530
DOI: 10.3748/wjg.v25.i12.1524 ISSN 1007-9327 (print) ISSN 2219-2840 (online)
cystic lesion of
Epigastric pain,
the pancreas in
Ultrasonography
CASE REPORT
Magnetic resonance
-1
Computed tomography
Radiofrequency ablation
Long-term survival of a patient with advanced pancreatic cancer
under adjunct treatment with Viscum album extracts: A case report
Paul G Werthmann, Robert Kempenich, Gerlinde Lang-Avérous, Gunver S Kienle
Paul G. Werthmann
of the tail of
Cystic lesion
the pancreas
ORCID number: Paul G Werthmann Paul G Werthmann, Gunver S Kienle, Department of Methodology, Institute for Applied
(0000-0002-1808-7787); Robert Epistemology and Medical Methodology (IFAEMM), Freiburg 79111, Germany
Kempenich (0000-0002-4499-0267);
Gerlinde Lang-Avérous Paul G Werthmann, Gunver S Kienle, Center for Complementary Medicine, Institute for
(0000-0002-4151-5567); Gunver S Environmental Health Sciences and Hospital Infection Control, Medical Center - University of
Kienle (0000-0001-9498-5944). Freiburg, Freiburg 79106, Germany
lesions
Author contributions: Werthmann Robert Kempenich, Private Praxis, General Practitioner with Specialization in Oncology,
Multiple
PG, Kempenich R, Lang-Av rous Strasbourg F-67000, France
pancreatic
G and Kienle GS contributed to the
case report design. Kempenich R Gerlinde Lang-Avérous, Department of Pathology, Hôpital de Hautepierre, University Hospital
procedures
was the physician in charge who of Strasbourg, Strasbourg F-67000, France
Therapeutic
provided the patient’s information.
Endo-
Body weight
Lang-Av rous G provided the Corresponding author: Paul G Werthmann, MD, Academic Research, Department of
histologic images and confirmed
papillary
Methodology, Institute for Applied Epistemology and Medical Methodology (IFAEMM),
the diagnosis and contributed the
mucinous
neoplasm
details about the histologic
Zechenweg 6, Freiburg 79111, Germany. paul.werthmann@ifaemm.de
Intraductal
diagnosis. Werthmann PG and Telephone: +49-15771984421
sonography:
Kempenich R collected and
USG
provided the data. Werthmann PG
was the principle author of the
paper, had full access to all data, Abstract
0
and is the guarantor. Kienle GS
BACKGROUND
supervised the report and the
90 kg
Advanced pancreatic cancer (aPC) has a poor prognosis with limited survival
2013
publication process. All authors
Surgical
excision
read and confirmed the final benefit from current standard treatment. Viscum album extracts (VAE) are used by
version of this article. many cancer patients, showing immune-stimulating effects, improved quality of
Initial
M0 R1
cancer
life, and a survival benefit in patients with aPC.
pT3 pN1
Supported by Stiftung Integrative
60 years
Diagnosis
Advanced
pancreatic
Medizin Stuttgart, Germany. CASE SUMMAR
A 59-year-old architect developed epigastric pain. A cystic lesion of the pancreas
Informed consent statement:
Informed consent was received of 45-mm diameter was detected. In a follow-up magnetic resonance imaging,
from the patient for the publication about one year later, multiple lesions were seen in the corpus and the tail of the
59.4 Gy
of the report and accompanying pancreas; CA-19-9 was elevated to 58.5 U/mL. A distal pancreatectomy with
images. The patient read the splenectomy was performed, and a tumor of 7 cm 5 cm 3.5 cm was excised.
submission version of the report
Histologic investigation showed an intraductal papillary mucinous neoplasm-
and confirmed its content.
associated invasive adenocarcinoma with invasion of the lymph vessels,
Conflict-of-interest statement: The perineural invasion, and positive nodes (2/27); surgical margins showed tumor
authors have declared no conflicts cells, and the tumor was classified as pT3 N1 M0 R1. The patient was treated with
of interest. radiation of the tumor bed and capecitabine/oxaliplatin followed by gemcitabine
and FOLFIRINO . Seven months after surgery, a liver metastasis was detected
Hepatic
CARE Checklist (2016) statement:
and treatment with FOLFIRINO was started. Four months after detection of the
metastasis
This case report was prepared
Segment VIII
following the CARE Guideline. metastasis, the patient opted for additional treatment with VAE. Another month
later, the metastasis was treated with radiofrequency ablation (RFA). Eight
Open-Access: This article is an months later, the hepatic lesion recurred and was again treated with RFA. The
CAPOX GEMC 8xFOLFIRINOX
WJG https://www.wjgnet.com 1524 March 28, 2019 Volume 25 Issue 12
78 kg
1
RFA
of hepatic
metastasis
No change
1st Radiofrequency
ablation of the hepatic
metastasis Segment VIII
metastasis
the hepatic
No relapse,
scar tissue of
lesion
RFA
hepatic
Relapsed
2nd Radiofrequency
2
ablation of the hepatic
metastasis Segment VIII
90 kg
IscadorⓇ Q 10-20 mg 3x/week IscadorⓇ Q 40 mg 3x/week
3
39 months without relapse
adjunct treatment with Viscum album extracts: A case report. World Journal of Gastroenterology. 2019;25(12):1524-1530.
4
63 months since initial diagnosis
Werthmann PG, Kempenich R, Lang-Avérous G, Kienle GS. Long-term survival of a patient with advanced pancreatic cancer under
IscadorⓇ Q 40 mg + IscadorⓇ P 10-20mg 3x/week
Langzeit-Überleben (5 Jahre) eines Patienten mit
Pankreaskarzinom unter begleitender Misteltherapie
5
his job
65 years
23/30
90 kg
working full-time in
good state of health,Langzeit-Überleben (5 Jahre) eines Patienten mit
Pankreaskarzinom unter begleitender Misteltherapie
Primarius
World J Gastroenterol 2019 March 28; 25(12): 1524-1530
ISSN 1007-9327 (print) ISSN 2219-2840 (online)
Gastroenterology
Rezidiv der Lebermetastase
World Journal of
Submit a Manuscript: https://www.f6publishing.com
Figure 2 Patient’s tumor, haematoxylin and eosin stain.
A: 100; B: 200; C :( 400) invasive mucinous adenocarcinoma;
WJ G
DOI: 10.3748/wjg.v25.i12.1524
D and E: ( 100) perineural invasion.
Werthmann PG, Kempenich R, Lang-Avérous G, Kienle GS. Long-term survival of a patient with advanced pancreatic cancer under
Paul G. Werthmann adjunct treatment with Viscum album extracts: A case report. World Journal of Gastroenterology. 2019;25(12):1524-1530. 24/30dition.[5]
®
Months
Clinical Case Report Medicine
months -7
OPEN
thmann et al. Medicine (2018) 97:49
ower methodological quality.[12]
Cholestasis of unknown cause, DHC-draining
CA 19-9 (U/mL)
Complete remission and long-term survival of a no tumor suspect lesion seen in endosonography
-6
patient with melanoma metastases treated with
-5
high-dose fever-inducing Viscum album extract
h standard treatment and added hyperthermia and VAE
We present a case of a young patient with advanced PC, treated
ameters, and exhibited positive weight gain effects.[10,11]
monstrated better outcomes for several quality of life
ents, a survival benefit of 2.1 months (hazard ratio = 0.49;
ly available, and are used as supportive therapy in patients
es, for intralesional or intravenous application) are commer-
E preparations (typically for subcutaneous use, or in some
., transforming growth factor b and matrix-metalloprotei-
s result is in line with previous investigations, though these are
up, which received best supportive care only, the VAE group
creatic cancer treated with VAE. Compared to the control
.0001) was documented in cases of inoperable advanced
re rarely, pseudo allergic reactions, VAE are safe, even when
tletoe lectins (ML), viscotoxins, oligo- and polysaccharids,
d in higher dosages.[9] In a phase III randomized trial with 220
rythema at the injection site, fever, flu-like symptoms, and
h cancer.[9] Besides a more common range of side effects such
iogenesis.[6–8] Pharmacologically active compounds include
es), reduction of cell migration, and interference with tumor
uction, immune stimulation, downregulation of cancer genes
neoplastic properties including cytotoxic effects, apoptosis
city, it is restricted to younger patients with favorable overall
onoids, and triterpene acids.[8] Different injectable forms of
opean mistletoe (Viscum album L.)—possess a variety of
iscum album extracts (VAE)—aqueous extracts made from
2
Paul G. Werthmann
cular ductal pancreatic adenocarcinoma) before treatment (obj.-magn. 10!).
A case report
-4
∗
Paul G. Werthmann, MDa, , Alexander Hintze, MDb, Gunver S. Kienle, MDa,c
-3
Abstract Stent removed
Introduction: Metastatic malignant cutaneous
62,2 melanoma (MCM)—a highly immunogenic cancer—typically has a poor prognosis.
2. Case presentation
apoptogenic,
Viscum album extracts (VAEs) have strong immune-stimulating,Restenting after
and another effects.
cytotoxic cholangitis
-2
Case presentation: A 66-year-old MCM patient with newly Adenomadiagnosed lymph Papilla
of thenode metastases
Vateri opted for sole VAE treatment.
VAEs were initially applied subcutaneously, and then later in exceptionally high, fever-inducing doses, both intravenously and
intralesionally. The metastases shrunk over the following months, and after 2 years, all lesions had completely remitted (regional
-1
and hilar lymph nodes). The patient has been tumor free for 3.5Diagnostic time of publication (and for 5 years since initiation of
years at thelaparotomy:
intensified VAE treatment). Besides fever and flu-like symptoms, no side effects occurred.
Adenocarcinoma of the pancreas with
is presented in accordance to the CARE guideline.[13]
0
Initial
Discussion: We presume that VAE triggered an increased release of tumor-associated antigens, enhanced immunologic
28 years
liver metastases cT4, cN1, cM1
diagnose
recognition, and increased immune response against the tumor tissue and induced tumor remission.
re 1. (A) Liver metastasis of an adenocarcinoma with immunophenotype ([B] CK 7 pos.; [C] S100P pos.; [D] CK 20 neg.) of a primary in the upper GI-tract (in
50 mg, a 1-hour infusion of leucovorin 400 mg, a bolus of
medical treatments such as hyperthermia (locoregional deep
of 1000 mg). This was supported with additional integrative
fluorouracil 500 mg, and a subsequent 24-hour continuous infusion
FOLFOX/Mitomycin (administered as an intravenous bolus of
of the palliative treatment plan, the patient was commenced on a
whereas carcinoembryonic antigen was in the normal range. As part
first chemotherapy cycle (2 treatments with an interval of 7 days) of
of cytokeratin-7 and S100-protein, but no cytokeratin-20 staining
pleomorphism, multiple atypical mitoses, and a strong expression
investigation of the liver metastasis biopsy showed a moderately
laparotomy, which surprisingly revealed an adenocarcinoma of the
tumor markers. Six months later, the patient underwent explorative
likely resulting from ampullary adenoma without elevation of
He was initially diagnosed with obstruction of the bile duct, most
leading to response to treatment and long-term survival. The case
differentiated ductal adenocarcinoma, displaying moderate nuclear
with no family history of cancer, presented with painless jaundice.
mitomycin C 5 mg, followed by a 30-minutes infusion of oxaliplatin
(see Fig. 1). Carbohydrate antigen 19-9 was elevated to 895.5 U/mL,
segment VIII) (cT4, cN1, cM1: UICC stage IV). Histologic
segment II/III, 18 ! 12 mm in segment V, and 5 mm diameter in
pancreatic head (56 ! 40 mm), and liver metastases (26 ! 20 mm in
Medicine
A lean, nonsmoking, 28-year old Caucasian marketing manager,
= rapidly growing
Abbreviations: AJCC = American Joint Committee on Cancer, BRAFPancreatic head tumor 56x40mm,
fibrosarcoma B gene,
typeliver FDG
metast. =
Seg.
1
Fludeoxyglucose (18F), MCM = malignant cutaneous melanoma, ML = mistletoe lectin, PET-CT
II/III (26x20 = positron
mm), V (18x12 mm)emission
and VIIItomography–
(5 mm)
computed tomography, UICC = Union internationale contre le cancer, VAE = Viscum album extracts, VT = viscotoxin.
895,5
2
Keywords: complete remission, fever, malignant cutaneous melanoma, Mistletoe, Viscum album extract
Regression of liver metast. (seg. II/III
273,3
3
13 mm, V 12x10mm, VIII 6 mm)
Intratumoral VAE, fever response
of 39.9°C
4
Subcutaneous VAE
42,5 1. Introduction
Editor: Satyabrata Pany.
FOLFOX/Mitomycin
Authorship: PGW, AH, and GSK contributed to the case report design. AH was MalignantLivercutaneous
metastasesmelanoma
not (MCM) is the sixth most
5
the physician in charge and provided the patient’s information.
14,9 PGW and AH of all cancers
commondetectable and the deadliest of all skin cancers, with
collected and provided the data. PGW was the principle author of the paper, had
12,4 anymore
increasing incidence worldwide (incidence and mortality are 9.3–
full access to all data, and is the guarantor. GSK supervised the case report and
10.2 and 1.2–2.0 per 100,000 people, respectively). MCM has a
6
FOLFIRINOX/Mitomycin
publication processes.
Funding/support: This case report was prepared following the CARE Guidelines.
Pancreatico-duodenectomy
fair prognosis in local disease (20-year survival of 75%) but a
dismal
with atypical in metastatic
prognosisliver resectiondisease (5-year survival of 5–
Informed consent was received from the patient for the publication of the report
19%). Risk factors are male gender, light skin (non-Hispanic
7
and accompanying images. The patient read the submission version of the report
and confirmed its content. whites),Hospital
increasedstay
ultraviolet (UV) index (intense, intermittent
The authors declared the following potential conflicts of interest with respect to sun exposure; tanning beds), and immunosuppression. Complete
8
the research, authorship, and/or publication of this article: IFAEMM has received surgical excision is the standard of care for early melanoma
restricted research grants, honoraria, and travel expenses from Weleda, Abnoba, treatment and can cure minimally invasive and in situ lesions.
and Helixor. None of them had any influence on the design, conduction, analysis,
Excision of lymph nodes and systemic adjuvant immunotherapy
and publication of the study. AH declared no conflict of interest.
9
a
is recommended for locally advanced disease. Metastatic disease
Institute for Applied Epistemology and Medical Methodology (IFAEMM) at the
University of Witten/Herdecke, Freiburg i. Brsg., Germany, b Klinik Arlesheim,
is treated with surgical metastasectomy, immunotherapy,
Arlesheim, Switzerland, c Center for Complementary Medicine, Institute for targeted therapies, and radiation therapy. Chemotherapy is
10
Environmental Health Sciences and Hospital Infection Control, Medical Center – restricted to patients whose disease cannot be controlled with
University of Freiburg, Freiburg, Germany. immunotherapy or targeted agents.[1]
∗
Correspondence: Paul G. Werthmann, Institute for Applied Epistemology and MCM shows a high immunogenicity and has played a key role
11
Medical Methodology at the University of Witten/Herdecke, Zechenweg 6, D- in the development of tumor immunology. Of particular interest
79111 Freiburg i. Brsg., Germany (e-mail: paul.werthmann@ifaemm.de).
is the unusually high rate of spontaneous regression of primary
Copyright © 2017 the Author(s). Published by Wolters Kluwer Health, Inc.
lesions (3.7–15% but without impacting survival); a fair rate of
12
This is an open access article distributed under the Creative Commons
Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build spontaneous remission of metastatic disease (about 0.23% with a
upon the work, even for commercial purposes, as long as the author is credited positive impact on survival); regression of MCM after infections
and the new creations are licensed under the identical terms. or immunologic active treatments; and lymphocyte infiltration in
13
Medicine (2017) 96:46(e8731) regressed lesions and depigmentation of the site of regression.[2]
Received: 1 June 2017 / Received in final form: 12 October 2017 / Accepted: 13 Furthermore, an increased number of infections and episodes of
October 2017
14
high fever, as well as previous history of certain vaccinations,
http://dx.doi.org/10.1097/MD.0000000000008731 are correlated with a reduced risk of developing MCM.[3,4]
Mistelherapie
No relapse
1
15
Werthmann PG, Inter P, Welsch T, et al. Long-term tumor-free survival in a metastatic pancreatic carcinomaFigure
16
Tumor free survival: 33 months
high-dose, fever inducing Viscum album extracts and subsequent R0 resection: A case report. Medicine.
patient
Time from initial diagnose: 49 months
metastasis with necrosis,
17
Working full-time
without limitations
18
Werthmann et al. Medicine (2018) 97:49
//
20
24
2018;97(49):e13243.
19,5
Patient mit Pankreaskarzinom mit
28
40,6
66,3
46,5
with FOLFIRINOX/Mitomycin,
32
130,9
Relapse: CA-19-9: 291.4 U/ml, tumor cells in the pancreatic tail
291,4
293,9 FOLFIRINOX/Mitomycin
148,6 356,8
36
221
Resizierbarkeit und Langzeitüberleben nach
86,1
66,6
62
40
83,2 Complete resection of the
60
remaining pancreas
magnification of A (obj. magn. 40!). (C) Micrometastasis to a regional peripancreatic lymph node (Obj.-magn. 10!). (D) Complete
44
48
in good
25/30
32 years,
condition
(14): (A) pancreatic tissue with dense fibrosis and single groups of residual tumor/carcinoma cells (HE, obj.-magn. 20!). (B) Residual tumor cells, high
tumor regression of a liv
fibrosis and no residual cancer cells (HE, obj.-magn, 1!). (E) Resorptive inflammatory reaction with histiocytes, multinucleated histiocyt
Medicin
4. Pylorus-preserving pancreaticoduodenectomy specimen and liver metastasis after neoadjuvant treatment showing major histopathological responsSie können auch lesen
