Novel prognostic factors for advanced melanoma and localized renal cell carcinoma

This study aimed to evaluate prognostic and predictive factors in melanoma and renal cell carcinoma to tailor optimal treatment and follow-up for cancer patients. Chemotherapy was the standard treatment for advanced melanoma before immune checkpoint inhibitors and targeted therapies. The median overall survival was 8.9 months (95% CI 7.5–10.4) and the five-year survival rate 13% in 146 patients who had received BOLD-IFN chemoimmunotherapy at Turku University Hospital in 1991─2010. Long-term survivors were found especially in patients without visceral metastases (five-year survival rate 28%). The Finnish Melanoma Group conducted a prospective, multicenter trial enrolling 38 patients who received TOL-IFN (temozolomide, lomustine, vincristine, and interferone-alpha) ± vemurafenib for the first-line treatment of advanced cutaneous melanoma. Elevated LDH was associated with shorter overall survival unlike asymptomatic brain metastases. Undetectable circulating tumor DNA in baseline plasma samples correlated with longer progression-free survival and baseline ctDNA levels were inversely associated with overall survival. Patients with persistent detectable ctDNA during treatment had the shortest overall survival. One-third of patients will develop disease recurrence after surgery for localized renal cell carcinoma. Tumor size, tumor grade (Fuhrman), and microvascular invasion were sufficient for the accurate prediction of metastasis-free survival in 196 patients operated for localized clear cell RCC. The three-feature prediction model was validated in an external cohort of 714 patients. It retained similar prediction accuracy as the Leibovich model (C-index 0.836 vs. 0.848, p=0.106) and had better prognostic value for long-term prediction in both cohorts In conclusion, undetectable ctDNA is a novel biomarker indicating favourable prognosis in advanced melanoma. This study suggests that patients with persistent detectable ctDNA may require more frequent monitoring of treatment response and perhaps more intensive therapy. We also introduced a three-feature prediction model for metastasis-free survival as a tool for optimizing postoperative follow-up of localized RCC patients.Edenneen melanooman ja paikallisen munuaissyövän uudet ennustetekijät Tämän väitöskirjatutkimuksen tavoitteena oli löytää uusia ennustetekijöitä, jotka voivat auttaa suunnittelemaan melanooma- ja munuaissyöpäpotilaiden yksilöllistä hoitoa ja seurantaa. Ensimmäisessä osatyössä tutkittiin solunsalpaajahoidon ja alfainterferonin (DOBC-IFN) hyötyä ennustavia tekijöitä. 146 potilasta oli saanut DOBC-IFN-hoitoa TYKS:ssä edenneen ihomelanooman vuoksi vuosina 1991–2010. Potilaiden eliniän mediaani oli 8,9 kuukautta (95 prosentin luottamusväli 7,5–10,4 kk) ja viiden vuoden kohdalla elossa olevien potilaiden osuus oli 13 prosenttia. Jopa 28 prosenttia potilaista, joilla ei ollut todettu sisäelinetäpesäkkeitä, pysyi elossa viisi vuotta. Toisessa ja kolmannessa osatyössä raportoitiin tulokset Suomen Melanoomaryhmän toteuttamasta prospektiivisesta kansallisesta monikeskustutkimuksesta, jossa annettiin 38:lle edennyttä ihomelanoomaa sairastavalle potilaalle solunsalpaajien, alfainterferonin (TOL-IFN) ja vemurafenibin yhdistelmähoitoa. Korkea plasman laktaattidehydrogenaasipitoisuus ennusti lyhyempää elinaikaa, kun taas oireettomat aivometastaasit eivät olleet yhteydessä lyhyempään elinaikaan. Veressä kiertävä kasvain-DNA ennusti nopeampaa taudin etenemistä ja kasvain- DNA:n määrä oli kääntäen verrannollinen elinajan pituuteen. Lyhyin elinaika todettiin potilailla, joilla kasvain-DNA ei hävinnyt hoidon aikana toistetusti otetuista plasmanäytteistä. Neljännessä osatyössä osoitettiin, että syöpäkasvaimen koko, syöpäsolujen erilaistumisaste ja leviäminen hiusverisuoniin ennustavat luotettavasti etäpesäkkeiden ilmaantumista paikallisen kirkassoluisen munuaissyövän leikkauksen jälkeen. Johtopäätöksenä voidaan todeta, että veressä kiertävä kasvain-DNA ennustaa melanoomapotilaiden elinaikaa. Mikäli kiertävä kasvain-DNA ei häviä hoidon aikana, voidaan harkita hoidon tehostamista. Neljännessä osatyössä esitellyn uuden nomogrammin avulla voidaan arvioida potilaan riskiä sairastua levinneeseen munuaissyöpään ja tätä luokittelua voidaan käyttää, kun suunnitellaan potilaan seurantaa paikallisen kirkassoluisen munuaissyövän leikkauksen jälkeen

Mechanized Energy Wood Harvesting from Early Thinnings

The felling and bunching of small diameter trees in Finland is still largely carried out manually using a chain saw and clearing saw. The felling of small diameter trees has been developed and mechanized. In addition to the high felling costs of small trees, the move towards mechanized harvesting is also caused by a shortage of professional lumberjacks, the possibility of all-year-round mechanized energy wood harvesting, and an increasing demand for energy wood. The research investigated the productivity, costs and silvicultural result of the guillotine blade equipped, multi-tree-processing Naarva-Grip 1600-40, for small diameter energy wood harvesting. Work-studies were carried out in six young stands at the first thinning stage. In mechanized energy wood harvesting with the Naarva-Grip 1600-40, an average of 73% of the trees felled were multi-tree-processed. The multi-tree-processed proportion increased to 96% in dense Scots pine (Pinus sylvestris L.) sites with small trees. One bunch consisted of approximately 3.2 trees. The average density and volume of removal had the greatest effect on the productivity of the felling-bunching work. Felling-bunching was carried out on the sites at a rate of 106-422 trees per effective hour (E0, excluding delay times). Productivity on the different sites varied from 3.0 to 7.2 m3/E0, giving an average of 4.7 m3/E0 (weighted by felling volume) with an average tree size on the site of 32 dm3. When the size of the felled trees was under 20 dm3, the felling-bunching costs were over 20 US$/m3. When the average tree size on the site increased to 50-70 dm3, the felling-bunching costs approached the 10 US$/m3 level. During the research, the Naarva-Grip 1600-40 proved to be competitive compared to the other multi-tree-processing, energy wood felling heads on the market. In order to keep the felling-bunching costs at a reasonable level, mechanized harvesting should be targeted at sites where the average size of the trees removed is over 30 dm3, and the energy wood volume at felling over 30 m3/ha

Syöpälääkkeiden aiheuttamat iho-ongelmat

Syöpälääkkeet aiheuttavat yleensä tyypillisiä lääkeryhmittäisiä ihohaittoja, kuten hiustenlähtöä, ­käsi-jalkaoireyhtymää, kynsivallin tulehduksia ja ihottumia.Niiden diagnosointi ja hoito kuuluvat erikoissairaanhoitoon.Erotusdiagnostiikassa tulee huomioida syövän leviäminen iholle, ihon infektiot, ­paraneoplastiset iho-oireet ja aiemmat ihosairaudet.On tärkeää ehkäistä ja hoitaa iho-ongelmat, jotta syöpälääke voidaan annostella tehokkaasti ja ­säilyttää potilaan elämänlaatu siedettävänä.</p

Immuuniaktivaation vapauttajien, kaksoisspesifisten vasta-aineiden ja CAR-T-soluhoitojen sydänhaitat

Immuuniaktivaation vapauttajia, kaksoisspesifisiä vasta-aineita ja CAR-T-soluhoitoja käytetään syöpäpotilaiden hoidossa yhä enemmän. Immuuniaktivaation vapauttajien aiheuttamat sydänhaitat, kuten myokardiitti, perikardiitti, sydäninfarkti, rytmihäiriöt ja sydämen vajaatoiminta ovat harvinaisia. Diabetes, tupakointi, aiemmat sydäntoksiset syöpähoidot sekä sydän- ja verisuonitaudit saattavat lisätä immuuniaktivaation vapauttajilla hoidettavien potilaiden sydänhaittariskiä. Kaksoisspesifiset vasta-aineet ja CAR-T-soluhoidot aiheuttavat antamisen jälkeen yleisesti elimistöön sytokiinimyrskyn. Se voi aiheuttaa verenpaineen laskua, rytmihäiriöitä, sydämen vajaatoimintaa ja sydänperäisiä äkkikuolemia. Kaksoisspesifisiä vasta-aineita ja CAR-T-soluhoitoja saaneita potilaita seurataan tiiviisti sairaalassa hoidon jälkeen. Haittavaikutusten varhainen tunnistaminen voi pelastaa potilaan hengen.publishedVersionPeer reviewe

Inflammatory bowel disease-related economic costs due to presenteeism and absenteeism

Background: Inflammatory bowel disease (IBD), consisting of Crohn's disease and ulcerative colitis, can be a lifelong burden generating high costs to an economic system. Data regarding the cost of workplace presenteeism and absenteeism in workers with IBD are limited. Our objective was to assess these costs in employed adults.Methods: A structured questionnaire, hospital records and national registers were combined to assess the economic costs involved with workplace presenteeism and absenteeism in employed patients. Our final sample comprised 320 IBD patients. The costs were calculated as productivity-loss costs by using a Human Capital Approach.Results: Due to IBD, the mean annual economic costs of workplace presenteeism were euro643.90/patient, and mean annual absenteeism costs were euro740.90/patient. Women had higher costs (euro955/patient/year) from absenteeism compared to men (euro531/patient/year) especially when working blue-collar jobs. These findings were also evident in presenteeism. CD and UC patients had similar total costs due to presenteeism and absenteeism. The use of biologics did not have a major impact on these costs.Conclusion: IBD patients had moderate economic costs from workplace presenteeism and absenteeism. Interestingly, women, working blue-collar jobs, had higher costs than men.</div

Immuuniaktivaation vapauttajien, kaksoisspesifisten vasta-aineiden ja CAR-T-soluhoitojen sydänhaitat

Immuuniaktivaation vapauttajia, kaksoisspesifisiä vasta-aineita ja CAR-T-soluhoitoja käytetään syöpäpotilaiden hoidossa yhä enemmän. Immuuniaktivaation vapauttajien aiheuttamat sydänhaitat, kuten myokardiitti, perikardiitti, sydäninfarkti, rytmihäiriöt ja sydämen vajaatoiminta ovat harvinaisia. Diabetes, tupakointi, aiemmat sydäntoksiset syöpähoidot sekä sydän- ja verisuonitaudit saattavat lisätä immuuniaktivaation vapauttajilla hoidettavien potilaiden sydänhaittariskiä. Kaksoisspesifiset vasta-aineet ja CAR-T-soluhoidot aiheuttavat antamisen jälkeen yleisesti elimistöön sytokiinimyrskyn. Se voi aiheuttaa verenpaineen laskua, rytmihäiriöitä, sydämen vajaatoimintaa ja sydänperäisiä äkkikuolemia. Kaksoisspesifisiä vasta-aineita ja CAR-T-soluhoitoja saaneita potilaita seurataan tiiviisti sairaalassa hoidon jälkeen. Haittavaikutusten varhainen tunnistaminen voi pelastaa potilaan hengen

Inflammatory bowel disease: perceived impact on leisure-time activities

Objective: Inflammatory bowel disease, consisting of Crohn's disease and ulcerative colitis, is known to negatively impact an individual's quality of life. Leisure-time activities are an important part of life by creating and strengthening social networks. The aim of this study was to thoroughly evaluate the perceived impact of inflammatory bowel disease on leisure-time activities by quantifying limitations in activities caused by the disease.Methods: A structured questionnaire, hospital records and national registers were combined to assess limitations caused by the disease in a patient's leisure-time activities. The final study sample was 561 patients.Results: More than half of the patients (52.8%) reported that IBD had caused limitations in their leisure-time activities. Women perceived that their limitations were greater when compared to the reports by men. One-third of the patients (33.3%) reported reducing and 17.6% abandoning at least one leisure-time activity due to their disease. Most often mentioned activities that were reduced and abandoned were physical activities. The IBDQ32 score had a significant correlation with all of the studied outcomes. Laboratory tests results and the patient's age or the level of income did not correlate with limitations in leisure-time activities.Conclusions: In conclusion, this study showed that patients with inflammatory bowel disease perceived a marked limitation in their leisure-time activities due to their disease.</div

Immuuniaktivaation vapauttajien haittavaikutukset : Miten tunnistan ja hoidan?

Immuuniaktivaation vapauttajat ovat uusia syöpälääkkeitä, joiden haittavaikutuksena voi ilmaantua tulehduksia. Jos päivystyspotilasta on hoidettu näillä lääkkeillä, hänen oireitaan tulee epäillä lääkkeen haittavaikutuksiksi, kunnes toisin on osoitettu. Samanaikainen infektio on mahdollinen

Teaching limited compression ultrasound to general practitioners reduces referrals of suspected DVT to a hospital: a retrospective cross-sectional study

Background The aim of this study was to retrospectively determine whether teaching limited compression ultrasound (LCUS) to general practitioners (GP) would reduce the number of patients with a suspected lower extremity DVT referred to a hospital for ultrasound (US) examination. According to the current literature, an LCUS protocol is a safe way to diagnose or exclude lower extremity deep venous thrombosis (DVT) and a good option to radiologist-performed whole-leg ultrasound (US), especially in remote health care units where there may be a limited availability of radiological services. MethodsBetween 2015 and 2016, altogether 13 GPs working in the same primary care unit were trained in LCUS for DVT diagnostics. The number of annual referrals due to a suspected DVT from Saarikka primary care unit to the closest hospital was evaluated before and after training. The incidence of DVT was considered to be constant. Thus, the reduction of referrals was attributed to the fact that these patients were diagnosed and treated in primary health care. Incidence rate ratio of hospital referrals was calculated. As a measure of safety, all patients diagnosed with a pulmonary embolism in the nearest hospital were evaluated to determine if they had undergone LCUS by a GP in primary care. Results Before training in 2014, there were 60 annual referrals due to a suspected DVT; in 2017, after training, the number was reduced to 16, i.e., a 73.3% decrease. The incidence of referrals decreased from 3.21 to 0.89 per 1000 person-years. (IRR 3.58, 95% CI 2.04-6.66, p Conclusions Teaching LCUS to GPs can safely reduce the number of patients with a suspected DVT referred to a hospital substantially.</p

Smoking is an Independent Marker of Poor Prognosis in Cutaneous Melanoma

Previous studies have suggested that persistent tobacco smoking impairs survival in cutaneous melanoma, but the effects of smoking and other prognostic factors have not been described in detail. This study examined the association of smoking (persistent, former, or never) with melanoma-specific (MSS) and overall survival (OS) in patients with cutaneous melanoma treated in Southwest Finland during 2005 to 2019. Clinical characteristics were obtained from electronic health records for 1,980 patients. Smoking status was available for 1,359 patients. Patients were restaged according to the 8th edition of the tumour-node-metastasis (TNM) classification. Smoking remained an independent prognostic factor for inferior melanoma-specific survival regardless of age, sex, stage, and comorbidities. The hazard ratio of death from melanoma was 1.81 (1.27-2.58, p = 0.001) in persistent and 1.75 (1.28-2.40, p = 0.001) in former smokers compared with never smokers. In 351 stage IV patients, smoking was associated with increased melanoma-specific and overall mortality: median MSS 10.4 (6.5-14.3), 14.6 (9.1-20.1), and 14.9 (11.4-18.4) months, p = 0.01 and median OS 10.4 (6.5-14.3), 13.9 (8.6-19.2), and 14.9 (11.7-18.1) months, p = 0.01 in persistent, former, and never smokers, respectively. In conclusion, since smoking represents an independent modifiable poor prognostic factor in patients with cutaneous melanoma, smoking habits should be proactively asked about by healthcare professionals, in order to support smoking cessation.</p