(SANITIZED)UNCLASSIFIED PUBLICATION ON THE INSTITUTE OF ONCOLOGY IN POLAND(SANITIZED)
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OPLASMA
SEPARATUM
EDITOR: ACADEMIA SCIENTIARUM SLOVACA
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NtOPLASMA 0, 3, 1032
Review of the Research Work Carried on at the Institute
of oncology in Poland
itubowsin
ingetate ot ancologyi Warszawa; Poland
Scientific work at the Institute f Oncology in Poland started under particularly
difficult post-war conditions, after the total devastation of the building and the equipment
and with a very limited research staff. In January 1947, when the Institute resumed its
activities after the interval caused by the war, the training of the staff and the organi-
zation of the work were its foremost preoccupations.
Research work was undertaken as the next step, fkientific investigations became one
of the chief tasks of the Institute apart from the services or the activities dealing with the
organization and cancer control in this country.
The evaluation of the present status of research work at the Institute of Oncology in
Poland is not an easy matter in view of the varied and multiple lines of research. The
Institute of Oncology is namely a scientific research institutinn embracing various
branches of specialization such as pathomorphology, radiotherapy, surgery, experimental
oncology and applied physics in the field of radiotherapy, with its proper scientific topic.
Moreover, research is in progress along the lines of chemotherapy and radiobiology.
I shall begin this review of the research work of the experimental oncology which is run-
ning at the present in the Institute.
The essential line tsf research of the Department of Tumour Biology is the problem
of the mechanisni of the morphogenetic action of estrogens. This is not only a theoretical
question, but it is closely related with the hormonal therapy of the tumour, because the
elucidation of the hormone-dependence of the neoplastic tissue is of a great clinical impor-
tance. In order to evaluate the response to estrogens, a test consisting of determination
of alkaline phosphatase activity in the cells of the vagina epithelium was applied. Compa-
ring the response of the normal vagina epithelium with that of the transplantable tumours.
the vagina G93 and. G94 in mice it was established that the neoplastic tissue is 10 000
times less responsive to estrogens than the normal epithelium. The papers dealing with
this problem present the first attempt of a qualitative evaluation of the differences in
response of the normal and the neoplastic tissues in the literature.
Investigations on the problem of the response of neoplasms to hormones constitute
the basis for collaboration of the Department of Biology with the clinic. Endocrinological
examinations of patients with breast cancer, treated by surgical methods (oophorectomy,
adrenalectomy) lead to interesting conclusions, It was revealed that certain operations
of endocrine glands proved to be uneffective in regard to the hormonal balance of the
organism. This discovery makes a thorough endocrinological examination of patients
with breast cancer imperative before undertaking surgical treatment. There are reasons
to hope that following this trend of research it will be possible to formulate appropriate
indications for the hormone-therapy in breast cancer after careful endocrinological
investigations.
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210
PitYDOWSKI
Another line which traces the research in the Department of Tumour Biology repre-
setts the problem of changes in the antigenic properties of neoplasms as demonstrated
by immunological methods. A durable change in the antigen structure of Guerites epit-
helioma in rats was obtained by its temporary transplantation to mice:
In another work the presence of an additional antigen in the transformed neoplasms
was detected, A new subject of investigations is open at the present, namely work on the
mechanism of antigenic transformation of tumours, It was demonstrated that the hew
genetic properties in Guerin's rat tumour can be induced by the DNA extracted from
lymphatic tissues in mice. These studies are going on. The preliminary results indicate
the possibility of the genetic transformation of the somatic cells of higher organisms
(analogous to the well known phenomenon of transformation in bacteria).
There are three main lines in the research studies at the Department of Biology of
Tumours at Gliwice: biochemical, histochemical and cytochemical Biochemical studies
have been carried on on the incorporation of the labelled DNA by means of biosynthesis
in the cells of Ehrlich ascites carcinoma. The other problem dealing with the transaminaze
activity has been investigated in homogenates of some tumours and particularly of the
hepatoma in comparison to the normal liver tissue. A drop in the transaminaze enzymes
activity in the liver of hosts has been demonstrated in the majority of cases after inducing
neoplastic growth in an animal.
irlistochemical studies included the investigation dealing with the activity of various
enzymes (leucyaminopeptydaze, dehydrogenaze, phosphorylaze) i the organs and in
the neoplastic tissues. Cytochemical methods have been employed to determine the
distribution of enzymes (among others of ATP-aze) in the particular fractions of cells.
The lack of studies concerning the virological trend in the Polish experimental oncology
reqttires attention. There is no laboratory in this country working systematically on
tumour viruses, while in other countries this problem is considered as of paramount
importance in the experimental oncology.
Pathomorphology is another field of the research work at the Institute of Oncology.
It is generally accepted that histopathology is the most valuable and reliable diagnostic
method regarding oncology. This does not mean, however, that it involves no gaps and
obscurities. There exists namely in the field of oncology a number of pathological entities
requiring further study and investigation and the establishment of a close relation between
the microscopic structure, the clinical symptoms and the biological behaviour of tumours.
One of the most important lines which pathology should trace in research work is the
study of the histoclinical features of the neoplastic process. This consists in the confron
tation of the microscopic picture with the biological course and the clinical symptoms
of tumour growth: this work at the oncological clinic is intrinsically linked with the
pathology.
Pathology involves another trend of investigation 1. e. nosology, the purpose of whit
is to establish and to describe pathological entities so far unknown and to give Ow ?
exact morphological, biological and clinical characteristics. It is worth metioning thibt
in the last few years, 10 so far unreported pathological entities have been established -.uch
as: tumours of the ovary (interstitioma ovarii), of the testicle (folliculoma lipibcum
testis), of the thyroid gland (carcinoma byalinicum glandulae thyreoideae) and others
This year a piper on sarcoma aponeuroticum with specific microscopic and clinics'
features has been published. In Collaboration with the laboratory of X-ray diagnom-
edetailed evaluation of calcifications in tumours of the soft somatic tissues has
made, supplying thus a basis for tissue diagnostics both in non-neoplastic process.--
well as in tumours originating in the soft somatic tissues.
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Finally work is being tarried on along diagnostic lines. This trend in ontological
pathomorphology is extending the register of mioroscopic diagnostics to ontological
entities unknown in Poland or so far erroneously identified. This refers particularly to
the newly noteworthy skeletal tumours.
The Department of Pathology at the Krak6w branch of the Institute of (Oncology;
has finished studies on pathomorphology of gastrie mucosa in the peptic ulcer and cancer
of the stomach. These studies, based upon 377 operative specimens, have revealed, that
in the gastric mucosa which shows no macroscopic abnormalities, typical changes either
of inflammatory or of metaplaatic character take place in the microscopic picture. Very
advanced regenerative changes constitute morphologic evidence of the patient being
exposed to the danger of a malignant metaplasia. Pathomorphology of the ulcer ? cancer
lesions has also been studied on the material of 351 cases! in 835 per cent of the cases the
typical pattern of cancer was ascertained in the ulcer wall and in 8 per cent of the cases
there was found that the advanced gastrin carcinoma had developed front the preexisting
peptic ulcer. Significant, from the pathoolinical point of view, features of carcinomas,
ulcer cancers and gastric ulcers have been also established. Scientific work at the
Department of Pathology of the Institute of oncology, Gliwice Branch, has also been
carried on along the histoclinical and diagnostic lines.
A large scale research work on the cytology of cancer has been developed at the Insti-
tute of Oncology in Gliwice with special reference to the cancer of the uterine cervix
and to the bronchial cancer. In the cancer of the uterine cervix under study there were
not only problems as for the diagnosis. but also as for the evaluation of advantages and
disadvantages of the treatment based on observations of postirradiation changes in
tancer cells and in the normal epithelium of the cervix. The study of the extensive group
of patients with cancer of the lung and other pulmonary lesions (broneltiectasis) enables
to establish precise criterions for the cytologic differential diagnosis.
As for clinical oncology, research is conducted chiefly in the sphere of tumour surgery,
radiotherapy, hormone- and chemotherapy. The main task of the ontological surgery is
the development of new methods of operative treatment of neoplasms, based on their
pathology, dynamics and clinical behaviour as well as improvement of methods of combined
treatment with radiotherapy, hormonal therapy and chemotherapy. New surgical meth-
ods of treatment are induced on the basis of well verified clinical data. In this way the
usefulness of the following surgical methods of treatment has been proved: radical and
paliative surgery of cardio-oesophagal carcinoma, combination of preoperative irradiation
with high X-ray doses and radical surgery in breast cancer or so-called extended mastec-
tomy including the parasternal lymph-nodes dissection in cancer located in the median
quadrants or the central area of the breast. Further experiences are being collected in the
hormonal treatment of advanced cases of breast cancer and in the surgical-chemothera-
peutical procedure in particularly malignant growths in prognostically unfavourable
cases. This concerns primary malignant-tumours of the bone, cancer of the stomach and
malignant melanomas.
Experimental work on regional perfusion was performed. For the purpose of perfusion
a de Wall exygenator was constructed. In 12 experimental perfusions of the extremities
on dogs various cytotoxic drugs were applied, as: Endoxan, Trenimon. Thio-tepa in
increasing concentrations. The optimal doses were finally established and methods were
developed for reducing the toxicity of the cytostatic substances.
Large scale team-work carried on at the Krak6w Branch on the problem of the cancer
of the stomach deserves particular attention. In this center many materials which provide
a basis for evaluation of the end-results of treatment have been collected, ietabolic
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312 notaiwala
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studies in the eases of gastric carcinoma have also been carried out by investigation of
the behaviour of the metabolism of sodium, potassium, gliao- and lipoproteins and by
investigation of the liver function in patients with cancer of the Stomach. Biocheinical
analysis of eases of gastric carcinoma revealed that fatt-tissues and also the tissues
metabolically active (muscular and nervous system and parenchymatous organs) account
for the weight loss ht the patients.
The Department of Surgery, Gliwice Branch, has workad on the evaluation of the
efficacy of operative technibis in the treatment of gastric cancer, cancer of the rectum and
of malignant melanomas. Moreover, diagnostics of neoplasms located in the chest, parti-
cularly of cancer of the bronchus have been improved,
Chemotherapy is the youngest branch Of tumour therapy in the Institute of Oncology.
The lack of a laboratory serving as base and the lack of adequately trained personal
makes it impossible to undertake experimental work within the scope of the ?preelinical
program" (term used by the Cancer Chemotherapy National Service Center Program).
As for the clinical experiment, i. e. the clinical evaluation of the efficacy of a drug after
establishing its properities, the mode of application, the dosage, the toxicity etc the
work is, however, progressing. Particular attention is devoted to the application of che.,
micah therapeutics in the treatment of primary lung cancer. In 70 histopathologically
verified cases benzoquinone derivatives. phosphorainities, nitrogen mustard and actino-
mycin K were tested.
The relation between the microscopic structure of the neoplasm and the improvement
of the condition of the patient is the subject of detailed analysis. In ovarian tumours
mainly benzoquinone derivatiVes (E-39, Trenimon) were applied intravenously or intra-
peritoneally. The best results were obtained after intraperitoneal administration of
benzoquinone in eases of' ovarian tumours with ascites.
In the treatment of tumours of the lymphatic system mostly alkylating agents (Dopan,
Sarcolysin, Degranol, Mitomen) and in some cases adrenal hormones were used,.
The study of the extensive material of patients receiving various chemical drugs in
combined chemotherapeutic treatment in the course of the last few years will enable
to establish more accurate medical indications and to evaluate the method.
Radiotherapy played from the very beginning an important role in the development
of research in the Institute.
At the present in all Institutes of Oncology special attention is drawn to the clinical
problems related to the radiation treatment of cancer of the uterus, ovaries, urinary
bladder, larynx, breast, thyroid gland and cancer of the oesophagus. In addition to the
classical forms of curie- and static convetional X-ray therapy, new methods of radiothe-
rapy were applied: the rotation technique in the treatment of cancer of the oesophagus
and the cobalt-60-teletherapy in cases of cancer of the urinary bladder, larynx and in
tumours of other localizations. Our own experience is collected in the clinical application
of izotopes: 1-131, metalic and colloidal Au-198 and P-32.
In the last years a great deal has been done on working out the basis for applied physics
in the radiotherapy and to introduce the precise physical principles of treatment.
A team-work with the Department of Surgery is in progress. The main subject of investi-
gation is the combined radiotberapeutic and surgical treatment, particularly in cancer of
the breast, uterus and ovaries.
The problem of the hormonal therapy of the breast cancer has been investigated in
all Institutes. At the clinical departments of the Institute, studies on etiology and improve-
ment of the diagnostic methods of tumours have been carried on continuously. These
studies have dealt in particular with the relation between tababco smoking and carci-
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CANCER RESEARCA n4 POLANb
Noma of the bronchus, larynx, lower lip, mouth ahd oesophagus (Gliwice). The present
results obtained in large scale investigations on the possible relation between tobacco
smoking and cancer of the bronchus and oesophagus deserve particular attention also
in foreign cancer centers.
Concluding my report I should like to add some words on the research work in the
radiobiology. The main problems investigated at the Isotope Department of the Institute
of Oncology in Warsaw are the calcium metabolism in man and the comperative biological
efficiency of radiations and cytostatics. These investigations are carried on at the Clinical
Ward and at the Radiobiological Laboratory of the Department.
The radioactive isotope ? calcium-47 is used as a tracer of the calcium metabolism
in normal people and in patients with primary and secondary bone tumours. The analysis
of data collected during a period of 2 years enables to construct the model of calcium-47
turn-over in men; an original mathematical method of data-analysis has been applied
and on this base several hypothetical compartments have been quantitatively characte-
rized. The problem of the late exchange of the isotope between the ?inaccessible" bone
calcium and the body fluids was also investigated. At the same time the metabolism
of scandium, a daughter element of cakium-47 has been studied in men and in
animals.
The Radiobiological team is interested since several years in the comparison of the
effects exerted by radiations and cytostatics on the biological systems in vitro. Shortterm
culture of the bone-marrow cells in rats and mouse Ehrlich carcinoma cells has been
used; the biosynthesis of nucleic acids has been investigated, using labeled NA precursors
(thymidine-C-14 and orotic acid-C-14). The obtained dose response curves show that
the mechanism of action of the agents tinder investigation (radiation and radiomimetic
drugs) is different.
The respective clinical and research units at the Institute of Oncology in Gliwice are
specially interested in the use of radioactive iodine in the treatment of the cancer of the
thyoid gland, in the use of strontium-85 as a diagnostic tool in bone tumours and in the
role of the oxydative process in the radiation effects. The clinical material of the thyroid
cancers amounts to more than 100 cases treated and followed-up during the last five
years. The use of strontium-85 is a new development and our own experience is rather
scarce. The influence of the oxygen on the radiation response of the cells and the consunii; -
lion of oxygen by the irradiated cells and tissues is a main part of the racliobiological
programme of the Gliwice Institute.
The scientific programme of the five Cancer-Congresses, which took place in the post-war
period, consisted chiefly of the studies performed by means of the common effort of various
Departments of the Institute of Oncology. At the Congresses many topics were discussed
in (letail; there were the following problems among them: cancer of the breast and uterus,
precaneerous conditions, the methods of work in the field of oncology, tumours of the
soft somatic tissues, hormone therapy of cancer, application of isotopes in the oncology.
1 great majority of the research papers from the Institute have been published in the
isoiodical ..Nowotwory",, which is the organ of the Polish Cancer Society and the Insti-
1 lit.. of Oncology. This year the printing of the XII-th volume of this periodical has been
started
This review gives no idea of the difficulties and the conditions under which research
work is carried out in the Institute of Oncology. All the work is done by a small group
of research workers, who in addition are burdened with an excess of organisation- and
Rervice duties resting on the Institute and its workers.
In view of the overcome difficulties of the Institute, its research achievements (about
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514 RUDOW8K/
600 papers published since 1948) should be appreciated. They inspire the hope that in
the forthcoming years further scientific results will be achieved in accordance with the
Institute's research programme.
References
(11 Annual reports on the research work of the Institute of Oncology in Poland 1958, 1959, 1960.
[2] Dux, K.: Experimental research work in oncology. Nowotwory 2, 121-128, 1958.
[3] Dux, K. Theoretical grounds of ho'rmonetherapy of cancer. Nowotwory 1-2, 115-127, 1961.
(4) KOLODZIEJSKA, H., MAnziozvx, A.: Some aspects of the methods and organisation work in
oncology. Nowotwory 2, 129-185, 1958.
(51 Itsthixt, W.: Application of isotopes in oncology. Nowotwory ?2, 177-180, 1961,
[61 KOSZAROWSKI, T. The role of surgery in treatment of cancer. Nowotwory 2, 147-154, 1958.
(7) LAskowsxt, J.: The role of pathomorphology in the tumour clink. Nowotwory 2, 111-120,1958.
(8) RuDowskt, W.: Evaluation of the research work and the scientific achievements of the Institute
of Oncology in the post-war period. Nowotwory 3-4, 311-321, 1958.
(9] Itunowskt, W.: Review of the research work carried on at the Warsaw Institute of Oncology
IV Omological Meeting, Sept., Bratislava 1961.
[101 SWIECKI, J.: Radiotherapy of tumours in Poland. Nowotwory 2, 137-146, 1958.
List ol addresses
1. Maria Sklodowska-Curie's Institute of Oncology, Warszawa 22, Wawelska 15.
Director: Prof. W. JASINSKi M. D.
2. Institute of Oncology ? Gliwice Branch, Gliwice, Wybrzeze Armii Czerwonej 15,
Director: 3. SWIECKI M. D.
1 Institute of Oncology ? Krakow Branch, Krakow, Gernearska 11,
Director: Doc. H. KOLODZIEJSKA M. D.
Independent research workers (lull-time stall) ol the Institute of Oncology
Warszawa
1. Prof. K. Dux, M. D., Warszawa, Nowowiejska 8-8.
2. Prof. W. JASINSKI M. D., Warszawa, Tamka 84a-4.
3. Prof. T. KOSZAROWSKI M. D., Warszawa 22, Wawelska 15.
4. Prof. J. LASKOWSKI M. D., Warszawa 22, Wawelska 15.
5. Prof. W. RuDowski M. D., Warszawa. 22, Glogera 8-18.
6. Dot. L. TARLOWSRA M. D., Warszawa, Marszalkowska 18.
Gliwice
1. Doc. M. CRORAZE M. D., Gliwice, Wybrzeze Armii Czerwonej 16.
2. Doe. H. GODLEWSKI M. D., Gliwice, Wybrzeze Armii Czerwonej 16.
8. Doc. A. VORBRODT M. D., Gliwice, Lelika 17.
Krakaw
1. Doc. H. KOLODZIEJSKA. M. D., Krakow, Germanise 11.
2. Prof. J. OSUMI M. D., Krakow, Sarego 8-16.
3. Doc. A. URBAN M. D., Krakow, Garncerska IL
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