Lääkärin ammatillinen kutsumus ja sen kehittyminen koulutuksen ja työkokemuksen myötä

TIIVISTELMÄ Ammatillinen kutsumus liitetään lääkäri-profession tunnuspiirteisiin. Se kuvaa lääkäriammatin laatua yhtäältä yksilöiden palvelijana ja toisaalta yhteiskunnallisten, valtiollisten ja juridisten velvoitteiden täyttäjänä. Perinteiseen käsitykseen kutsumusammatista liittyy vaativia arvolatauksia ja hyveellisiä, emotionaalisia ja spiritualistisia jännitteitä, jotka saattavat välittää lääkärikutsumuksesta ahtaan ja rajoittavan mallin. Tämän tutkimuksen tavoitteena on kartoittaa lääkärikutsumuksen olemusta ja ilmenemistä lääketieteen opiskelijoiden ja eri toimenkuvissa työskentelevien lääkärien keskuudessa. Kyseessä on laadullinen ja määrällinen tutkimus, joka toteutettiin asiantuntijahaastatteluin ja opiskelijakyselyin Turun yliopiston lääketieteellisessä tiedekunnassa vuosina 2013˗2019. Seurantatutkimukseni perusteella lääketieteen opiskelijoiden kutsumuksellinen asenne vaihtelee opintojen eri vaiheissa. Koulutuksen alkaessa opiskelijoiden kutsumus suuntautuu oppimiseen. Aineistossani vain 16 % opintonsa aloittavista lääketieteen opiskelijoista uskoi kutsumuksellisuuden liittyvän lääkärin ammattiin. Lääketieteen peruskoulutus ei vaikuta lisäävän opiskelijoiden kutsumusta lääkärin työtä kohtaan. Sen sijaan yli 90 % tutkintoonsa valmistuvista opiskelijoista ilmaisi voimakasta sitoutumista lääkäriammattiin. Lisensiaatti-tutkintoon valmistumisen ja yhdeksän kuukauden työkokemuksen jälkeen kolme neljästä nuoresta lääkäristä koki toimivansa kutsumusammatissaan. Kutsumus-käsitteen vaikeaselkoisuus ja yksilölliset erot sen tulkinnassa vaikeuttavat johtopäätöksiä lääkärikutsumuksen ilmenemisestä. Tutkimushavainnoissani ammatillinen kutsumus ilmenee monimuotoisena yhdistelmänä yksilöllisiä mielenkiinnon kohteita, persoonallisia ominaisuuksia, ammattitaitoa ja työkokemusta. Näiden pohjalta lääkärikutsumus syntyy sisäisestä palkitsevuuden tunteesta ja mahdollisuudesta yksilöllisen eettisen arvomaailman seuraamiseen. Haastattelemieni lääkärien mielipiteissä lääkärikutsumus näyttäytyy altruistisena pyrkimyksenä parantamiseen, terveyden edistämiseen ja auttamiseen sekä kokemuksena ammatillisesta vastuusta ja velvollisuudesta. Lääkärin työn yhteiskunnallisella merkityksellä, yhteisöllisyydellä ja kollegiaalisuudella on tärkeä merkitys ammatillisen kutsumuksen kokemuksessa. Haastattelututkimukseni osoittaa, että lääkäriammattia voi harjoittaa kutsumuksellisista lähtökohdista monenlaisissa toimenkuvissa ja työtehtävissä, yhtä hyvin potilastyössä kuin perinteisestä lääkärityöstä poikkeavilla aloilla. Tulokseni osoittavat myös, että lääkärin kokema kutsumus voi muuttua ja ilmetä eri tavoin työuran eri vaiheissa. Kutsumuksen ideaali on säilynyt lääkäriammatin määritteenä siitä huolimatta, että työelämän muutos on heijastunut myös lääkärin työnkuvaan. Kutsumuksellisella asenteella saattaa olla edullisia vaikutuksia potilastyölle, terveydenhuolto-organisaation toiminnalle ja lääkärille itselleen. Ammatillisen kutsumuksen kokemusta edistävät työssä onnistuminen, työn tulosten näkeminen, kokemukset oman työn hallinnasta, esikuvalliset lääkärimallit ja työstä saatu positiivinen palaute. Nuorten lääkärien kokeman ammatillisen kutsumuksen kannalta keskeistä ovat työtehtävien sujuvuus, joustava esimiestoiminta, koulutusmahdollisuudet ja työyhteisön hyvä ilmapiiri. Voimakkaimmin ammatillista kutsumusta tukee lääkärin mahdollisuus perustehtävänsä toteuttamiseen, potilaan hoitamiseen. ASIASANAT: kutsumus, ammatillinen kutsumus, lääkärikoulutus, professionaalisuusABSTRACT Vocational calling is one of the characteristics of the medical profession. It is made up of the role of a physician, on one hand, in serving individual patients and, on the other hand, in fulfilling societal, national and juridical duties and responsibilities. The traditional in-terpretation of a vocational profession involves value judgments and virtuous, emotional and spiritual tensions, which may convey a narrow and restrictive model of a medical doctor’s calling. The aim of this study is to survey the nature and manifestations of professional calling among medical students and physicians practicing in various health care professions. This qualitative and quantitative study involves expert interviews and questionnaires adminis-tered to medical students in the Faculty of medicine, University of Turku, during 2013-2019. This survey reveals that the vocational attitude of medical students varies at different levels of their education. At the beginning of the medical program, the students direct their vocational intentions towards learning. In the present material, only 16 % of first-year medical students associated vocational attitude with the medical profession. Medical undergraduate education does not appear to increase the students’ calling towards the pro-fession. Instead, over 90 % of graduating medical students expressed strong commitment to the profession. After graduation and a nine-month period of clinical experience three quarters of the young physicians described their occupation as a calling. The findings may be hampered by the complexity and individual variations in interpreting the concept of vocational calling. According to the interviewed physicians, professional calling manifests itself in a complex combination of individual interests, personal characteristics, expertise and work experience. As a consequence, medical calling appears to arise from a sense of internal reward and the possibility to follow individual priorities and ethical values. In the inter-views, medical calling presented as an altruistic attempt toward helping, healing and pro-moting health as well as a sense of professional duty and responsibility. Societal purpose, sense of community and collegiality also played important roles in the experience of med-ical calling. The results indicate that medical calling can be exhibited in various job descriptions, in clinical work as well as in complementary medical occupations. In addition, medical calling may develop and be manifested in various ways during different phases of a medical career. Despite the general developments of working life having also been reflected in the health professions, the ideal of vocational calling has endured in the medical profession. Vocational attitude may have positive effects on different aspects of medicine, includ-ing clinical work, and health care organization as well as the medical doctor’s professional life. The medical calling may be fostered by experiences of success and effectiveness in clinical work, as a result of managing workflow, by exemplary role models and by receiv-ing positive feedback. Fluent job procedures, flexibility of leadership, educational oppor-tunities and a positive work atmosphere are especially important for the vocational devel-opment of young physicians. The strongest support for sustaining the medical calling are the physician’s opportunities to fulfil their basic duty of treating patients. KEY WORDS: calling, vocation, medical education, professionalis

HSD17B1 expression induces inflammation-aided rupture of mammary gland myoepithelium

Hydroxysteroid (17-beta) dehydrogenase type 1 (HSD17B1) converts low-active estrogen estrone to highly active estradiol. Estradiol is necessary for normal postpubertal mammary gland development; however, elevated estradiol levels increase mammary tumorigenesis. To investigate the significance of the human HSD17B1 enzyme in the mammary gland, transgenic mice universally overexpressing human HSD17B1 were used (HSD17B1TG mice). Mammary glands obtained from HSD17B1TG females at different ages were investigated for morphology and histology, and HSD17B1 activity and estrogen receptor activation in mammary gland tissue were assessed. To study the significance of HSD17B1 enzyme expression locally in mammary gland tissue, HSD17B1-expressing mammary epithelium was transplanted into cleared mammary fat pads of wild-type females, and the effects on mammary gland estradiol production, epithelial cells and the myoepithelium were investigated. HSD17B1TG females showed increased estrone to estradiol conversion and estrogen-response element-driven estrogen receptor signaling in mammary gland tissue, and they showed extensive lobuloalveolar development that was further enhanced by age along with an increase in serum prolactin concentrations. At old age, HSD17B1TG females developed mammary cancers. Mammary-restricted HSD17B1 expression induced lesions at the sites of ducts and alveoli, accompanied by peri- and intraductal inflammation and disruption of the myoepithelial cell layer. The lesions were shown to be estrogen dependent, as treatment with an antiestrogen, ICI 182,780, starting when lesions were already established reversed the phenotype. These data elucidate the ability of human HSD17B1 to enhance estrogen action in the mammary gland in vivo and indicate that HSD17B1 is a factor inducing phenotypic alterations associated with mammary tumorigenesis.</p

Varying outcomes of triple-negative breast cancer in different age groups-prognostic value of clinical features and proliferation

PurposeTriple-negative breast cancer (TNBC) is an aggressive disease lacking specific biomarkers to guide treatment decisions. We evaluated the combined prognostic impact of clinical features and novel biomarkers of cell cycle-progression in age-dependent subgroups of TNBC patients.MethodsOne hundred forty seven TNBC patients with complete clinical data and up to 18 year follow-up were collected from Turku University Hospital, Finland. Eight biomarkers for cell division were immunohistochemically detected to evaluate their clinical applicability in relation to patient and tumor characteristics.ResultsAge at diagnosis was the decisive factor predicting disease-specific mortality in TNBC (p = 0.002). The established prognostic features, nodal status and Ki-67, predicted survival only when combined with age. The outcome and prognostic features differed significantly between age groups, middle-aged patients showing the most favorable outcome. Among young patients, only lack of basal differentiation predicted disease outcome, indicating 4.5-fold mortality risk (p = 0.03). Among patients aged > 57, the established prognostic features predicted disease outcome with up to 3.0-fold mortality risk for tumor size ≥ 2 cm (p = 0.001). Concerning cell proliferation, Ki-67 alone was a significant prognosticator among patients aged > 57 years (p = 0.009). Among the studied cell cycle-specific biomarkers, only geminin predicted disease outcome, indicating up to 6.2-fold increased risk of mortality for tumor size p = 0.03).ConclusionTraditional clinical features do not provide optimal prognostic characterization for all TNBC patients. Young age should be considered as an additional adverse prognostic feature in therapeutic considerations. Increased proliferation, as evaluated using Ki-67 or geminin immunohistochemistry, showed potential in detecting survival differences in subgroups of TNBC.</p

A prognostic model based on cell-cycle control predicts outcome of breast cancer patients

Background A prognostic model combining biomarkers of metaphase-anaphase transition of the cell cycle was developed for invasive breast cancer. The prognostic value and clinical applicability of the model was evaluated in comparison with the routine prognosticators of invasive breast carcinoma. Methods The study comprised 1135 breast cancer patients with complete clinical data and up to 22-year follow-up. Regulators of metaphase-anaphase transition were detected immunohistochemically and the biomarkers with the strongest prognostic impacts were combined into a prognostic model. The prognostic value of the model was tested and evaluated in separate patient materials originating from two Finnish breast cancer centers. Results The designed model comprising immunoexpressions of Securin, Separase and Cdk1 identified 8.4-fold increased risk of breast cancer mortality (p 75%) of patients resulting with favorable as opposed to unfavorable outcome of the model. Along with nodal status, the model showed independent prognostic impact for all breast carcinomas and for subgroups of luminal, N+ and N- disease. Conclusions The impact of the proposed prognostic model in predicting breast cancer survival was comparable to nodal status. However, the model provided additional information in N- breast carcinoma in identifying patients with aggressive course of disease, potentially in need of adjuvant treatments. Concerning N+, in turn, the model could provide evidence for withholding chemotherapy from patients with favorable outcome.</div

Tumor margins that lead to reoperation in breast cancer: A retrospective register study of 4,489 patients

Background and Objectives Optimal margins for ductal carcinoma in situ (DCIS) remain controversial in breast-conserving surgery (BCS) and mastectomy. We examine the association of positive margins, reoperations, DCIS and age. Methods A retrospective study of histopathological reports (4489 patients). Margin positivity was defined as ink on tumor for invasive carcinoma. For DCIS, we applied 2 mm anterior and side margin thresholds, and ink on tumor in the posterior margin. Results The incidence of positive side margins was 20% in BCS and 5% in mastectomies (p p p = 0.013). Of BCS patients with invasive carcinoma in the side margin, 73% were reoperated on. A reoperation was performed in 70% of patients with a close (p = 0.002). The reoperation rates were 55% in invasive carcinoma with close DCIS, 66% in close extensive intraductal component (EIC), and 83% in close pure DCIS (p Conclusions Individual assessment as opposed to rigid adherence to guidelines was used in the decision on reoperation.</p

Proliferation-associated miRNAs-494, -205, -21 and -126 detected by in situ hybridization: expression and prognostic potential in breast carcinoma patients

PurposeTo visualize by in situ hybridization (ISH) the levels of a set of proliferation-associated miRNAs and to evaluate their impact and clinical applicability in prognostication of invasive breast carcinoma.MethodsTissue specimen from breast carcinoma patients were investigated for miRNAs-494, -205, -21 and -126. Prognostic associations for levels of miRNAs were analyzed based on complete clinical data and up to 22.5-year follow-up of the patient material (n = 285). For detection of the miRNAs, an automated sensitive protocol applying in situ hybridization was developed.ResultsMiRNA-494 indicated prognostic value for patients with invasive breast carcinoma. Among node-negative disease reduced level of miRNA-494 predicted 8.5-fold risk of breast cancer death (p = 0.04). Altered levels and expression patterns of the studied miRNAs were observed in breast carcinomas as compared to benign breast tissue.ConclusionsThe present paper reports for the first time on the prognostic value of miRNA-494 in invasive breast cancer. Particularly, detection of miRNA-494 could benefit patients with node-negative breast cancer in identifying subgroups with aggressive disease. Based on our experience, the developed automatic ISH method to visualize altered levels of miRNAs-494, -205, -21 and -126 could be applied to routine pathology diagnostics providing that conditions of tissue treatment, especially fixation delays, are managed.</div

Stromal interaction molecule 1 (STIM1) knock down attenuates invasion and proliferation and enhances the expression of thyroid-specific proteins in human follicular thyroid cancer cells

Stromal interaction molecule 1 (STIM1) and the ORAI1 calcium channel mediate store-operated calcium entry (SOCE) and regulate a multitude of cellular functions. The identity and function of these proteins in thyroid cancer remain elusive. We show that STIM1 and ORAI1 expression is elevated in thyroid cancer cell lines, compared to primary thyroid cells. Knock-down of STIM1 or ORAI1 attenuated SOCE, reduced invasion, and the expression of promigratory sphingosine 1-phosphate and vascular endothelial growth factor-2 receptors in thyroid cancer ML-1 cells. Cell proliferation was attenuated in these knock-down cells due to increased G1 phase of the cell cycle and enhanced expression of cyclin-dependent kinase inhibitory proteins p21 and p27. STIM1 protein was upregulated in thyroid cancer tissue, compared to normal tissue. Downregulation of STIM1 restored expression of thyroid stimulating hormone receptor, thyroid specific proteins and increased iodine uptake. STIM1 knockdown ML-1 cells were more susceptible to chemotherapeutic drugs, and significantly reduced tumor growth in Zebrafish. Furthermore, STIM1-siRNA-loaded mesoporous polydopamine nanoparticles attenuated invasion and proliferation of ML-1 cells. Taken together, our data suggest that STIM1 is a potential diagnostic and therapeutic target for treatment of thyroid cancer.Peer reviewe

Formin Proteins FHOD1 and INF2 in Triple-Negative Breast Cancer: Association With Basal Markers and Functional Activities

Basal-like breast cancer is an aggressive form of breast cancer with limited treatment options. The subgroup can be identified immunohistochemically, by lack of hormone receptor expression combined with expression of basal markers such as CK5/6 and/or epidermal growth factor receptor (EGFR). In vitro, several regulators of the actin cytoskeleton are essential for efficient invasion of basal-like breast cancer cell lines. Whether these proteins are expressed in vivo determines the applicability of these findings in clinical settings. The actin-regulating formin protein FHOD1 participates in invasion of the triple-negative breast cancer cell line MDA-MB-231. Here, we measure the expression of FHOD1 protein in clinical triple-negative breast cancers by using immunohistochemistry and further characterize the expression of another formin protein, INF2. We report that basal-like breast cancers frequently overexpress formin proteins FHOD1 and INF2. In cell studies using basal-like breast cancer cell lines, we show that knockdown of FHOD1 or INF2 interferes with very similar processes: maintenance of cell shape, migration, invasion, and proliferation. Inhibition of EGFR, PI3K, or mitogen-activated protein kinase activity does not alter the expression of FHOD1 and INF2 in these cell lines. We conclude that the experimental studies on these formins have implications in the clinical behavior of basal-like breast cancer.</p

Overexpression of Human Estrogen Biosynthetic Enzyme Hydroxysteroid (17beta) Dehydrogenase Type 1 Induces Adenomyosis-like Phenotype in Transgenic Mice

Hydroxysteroid (17beta) dehydrogenase type 1 (HSD17B1) is an enzyme that converts estrone to estradiol, while adenomyosis is an estrogen-dependent disease with poorly understood pathophysiology. In the present study, we show that mice universally over-expressing human estrogen biosynthetic enzyme HSD17B1 (HSD17B1TG mice) present with adenomyosis phenotype, characterized by histological and molecular evaluation. The first adenomyotic changes with endometrial glands partially or fully infiltrated into the myometrium appeared at the age of 5.5 months in HSD17B1TG females and became more prominent with increasing age. Preceding the phenotype, increased myometrial smooth muscle actin positivity and increased amount of glandular myofibroblast cells were observed in HSD17B1TG uteri. This was accompanied by transcriptomic upregulation of inflammatory and estrogen signaling pathways. Further, the genes upregulated in the HSD17B1TG uterus were enriched with genes previously observed to be induced in the human adenomyotic uterus, including several genes of the NFKB pathway. A 6-week-long HSD17B1 inhibitor treatment reduced the occurrence of the adenomyotic changes by 5-fold, whereas no effect was observed in the vehicle-treated HSD17B1TG mice, suggesting that estrogen is the main upstream regulator of adenomyosis-induced uterine signaling pathways. HSD17B1 is considered as a promising drug target to inhibit estrogen-dependent growth of endometrial disorders. The present data indicate that HSD17B1 over-expression in TG mice results in adenomyotic changes reversed by HSD17B1 inhibitor treatment and HSD17B1 is, thus, a potential novel drug target for adenomyosis.</p