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Older adults are underrepresented in metastatic colorectal cancer (mCRC) studies and thus may not receive optimal treatment, especially not metastasectomies. The prospective Finnish real-life RAXO-study included 1086 any organ mCRC patients. We assessed repeated centralized resectability, overall survival (OS), and quality of life (QoL) using 15D and EORTC QLQ-C30/CR29. Older adults (>75 years; n = 181, 17%) had worse ECOG performance status than adults (

Thromboprophylaxis protocols in liver surgery vary greatly worldwide. Due to limited research, there is no consensus whether the administration of thromboprophylaxis should be initiated pre- or postoperatively.Patients undergoing liver resection in Helsinki University Hospital between 2014 and 2017 were reviewed retrospectively. Initiation of thromboprophylaxis was changed in the institution in the beginning of 2016 from postoperative to preoperative. Patients were classified into two groups for analyses: thromboprophylaxis initiated preoperatively (Preop-group) or postoperatively (Postop-group). The incidences of VTE and haemorrhage within 30 days of surgery were compared between these groups. Patients with permanent anticoagulation were excluded.A total of 512 patients were included to the study (Preop, n = 253, Postop, n = 259). The incidence of VTE was significantly lower in the Preop-group compared to the Postop-group (3 (1.2%) vs. 25 (9.7%), P =.0001), mainly due to a lower incidence of pulmonary embolisms in the Preop-group (3 (1.2%) vs. 24 (9.3%), P .0001). The rates of posthepatectomy haemorrhage within 30 days of surgery were similar (Preop 38 (15.0%) vs. Postop 36 (13.9%), p = .719).Initiating thromboprophylaxis preoperatively may reduce the incidence of postoperative VTE without affecting the incidence of posthepatectomy haemorrhage in patients undergoing liver resection.

Background Metastasectomy is probably underused in metastatic colorectal cancer. The aim of this study was to investigate the effect of centralized repeated assessment on resectability rate of liver metastases. Methods The prospective RAXO study was a nationwide study in Finland. Patients with treatable metastatic colorectal cancer at any site were eligible. This planned substudy included patients with baseline liver metastases between 2012 and 2018. Resectability was reassessed by the multidisciplinary team at Helsinki tertiary referral centre upfront and twice during first-line systemic therapy. Outcomes were resectability rates, management changes, and survival. Results Of 812 patients included, 301 (37.1 per cent) had liver-only metastases. Of these, tumours were categorized as upfront resectable in 161 (53.5 per cent), and became amenable to surgery during systemic treatment in 63 (20.9 per cent). Some 207 patients (68.7 per cent) eventually underwent liver resection or ablation. At baseline, a discrepancy in resectability between central and local judgement was noted for 102 patients (33.9 per cent). Median disease-free survival (DFS) after first resection was 20 months and overall survival (OS) 79 months. Median OS after diagnosis of metastatic colorectal cancer was 80, 32, and 21 months in R0–1 resection, R2/ablation, and non-resected groups, and 5-year OS rates were 68, 37, and 9 per cent, respectively. Liver and extrahepatic metastases were present in 511 patients. Of these, tumours in 72 patients (14.1 per cent) were categorized as upfront resectable, and 53 patients (10.4 per cent) became eligible for surgery. Eventually 110 patients (21.5 per cent) underwent liver resection or ablation. At baseline, a discrepancy between local and central resectability was noted for 116 patients (22.7 per cent). Median DFS from first resection was 7 months and median OS 55 months. Median OS after diagnosis of metastatic colorectal cancer was 79, 42, and 17 months in R0–1 resection, R2/ablation, and non-resected groups, with 5-year OS rates of 65, 39, and 2 per cent, respectively. Conclusion Repeated centralized resectability assessment in patients with colorectal liver metastases improved resection and survival rates.

Simple Summary Metastatic colorectal cancer is the second most common cause of cancer death. Long-term survival and cure can be achieved after intensive treatments, including metastasectomy, i.e., the removal of all metastases. We wanted to clarify whether a patient health-related quality of life (HRQoL) was reduced by treatments that aimed to maximise metastasectomy rates, and whether HRQoL of treated patients is comparable to the general population. In a cross-sectional study of 444 patients (1751 questionnaires) in the RAXO-study population, we show that HRQoL of intensively treated patients, sometimes with multiple and multisite metastasectomies-usually combined with systemic therapy-remains at a high level during and after curative treatment and when compared with the general population. Good HRQoL was also seen during non-curative treatment from first- to later-lines, with an impaired HRQoL only at end-of-life. Thus, we should aim at maximising metastasectomies since they give long-term survival and sometimes cure with a high HRQoL. Metastasectomy and/or local ablative therapy in metastatic colorectal cancer (mCRC) patients often provide long-term survival. Health-related quality of life (HRQoL) data in curatively treated mCRC are limited. In the RAXO-study that evaluated repeated resectability, a multi-cross-sectional HRQoL substudy with 15D, EQ-5D-3L, QLQ-C30, and QLQ-CR29 questionnaires was conducted. Mean values of patients in different treatment groups were compared with age- and gender-standardized general Finnish populations. The questionnaire completion rate was 444/477 patients (93%, 1751 questionnaires). Mean HRQoL was 0.89-0.91 with the 15D, 0.85-0.87 with the EQ-5D, 68-80 with the EQ-5D-VAS, and 68-79 for global health status during curative treatment phases, with improvements in the remission phase (disease-free >18 months). In the remission phase, mean EQ-5D and 15D scores were similar to the general population. HRQoL remained stable during first- to later-line treatments, when the aim was no longer cure, and declined notably when tumour-controlling therapy was no longer meaningful. The symptom burden affecting mCRC survivors' well-being included insomnia, impotence, urinary frequency, and fatigue. Symptom burden was lower after treatment and slightly higher, though stable, through all phases of systemic therapy. HRQoL was high in curative treatment phases, further emphasizing the strategy of metastasectomy in mCRC when clinically meaningful.

Background Outcomes after metastasectomy for metastatic colorectal cancer (mCRC) vary with RAS and BRAF mutational status, but their effects on resectability and conversion rates have not been extensively studied. Methods This substudy of the prospective RAXO trial included 906 patients recruited between 2011 and 2018. We evaluated repeated centralised resectability assessment, conversion/resection rates and overall survival (OS), according to RAS and BRAF status. Results Patients included 289 with RAS and BRAF wild-type (RAS and BRAFwt), 529 with RAS mutated (RASmt) and 88 with BRAF mutated (BRAFmt) mCRC. Metastatic prevalence varied between the RAS and BRAFwt/RASmt/BRAFmt groups, for liver (78%/74%/61%), lung (24%/35%/28%) and peritoneal (15%/15%/32%) metastases, respectively. Upfront resectability (32%/29%/15%), conversion (16%/13%/7%) and resection/local ablative therapy (LAT) rates (45%/37%/17%) varied for RASa and BRAFwt/RASmt/BRAFmt, respectively. Median OS for patients treated with resection/LAT (n = 342) was 83/69/30 months, with 5-year OS-rates of 67%/60%/24%, while systemic therapy-only patients (n = 564) had OS of 29/21/15 months with 5-year OS-rates of 11%/6%/2% in RAS and BRAFwt/RASmt/BRAFmt, respectively. Resection/LAT was associated with improved OS in all subgroups. Conclusions There were significant differences in resectability, conversion and resection/LAT rates according to RAS and BRAF status. OS was also significantly longer for RAS and BRAFwt versus either mutant. Patients only receiving systemic therapy had poorer long-term survival, with variation according to molecular status. Clinical trial registration NCT01531621/EudraCT2011-003158-24

Background Resection of colorectal cancer (CRC) metastases provides good survival but is probably underused in real-world practice. Methods A prospective Finnish nationwide study enrolled treatable metastatic CRC patients. The intervention was the assessment of resectability upfront and twice during first-line therapy by the multidisciplinary team (MDT) at Helsinki tertiary referral centre. The primary outcome was resection rates and survival. Findings In 2012–2018, 1086 patients were included. Median follow-up was 58 months. Multiple metastatic sites were present in 500 (46%) patients at baseline and in 820 (76%) during disease trajectory. In MDT assessments, 447 (41%) were classified as resectable, 310 (29%) upfront and 137 (18%) after conversion therapy. Six-hundred and ninety curative intent resections or local ablative therapies (LAT) were performed in 399 patients (89% of 447 resectable). Multiple metastasectomies for multisite or later developing metastases were performed in 148 (37%) patients. Overall, 414 liver, 112 lung, 57 peritoneal, and 107 other metastasectomies were performed. Median OS was 80•4 months in R0/1-resected (HR 0•15; CI95% 0•12–0•19), 39•1 months in R2-resected/LAT (0•39; 0•29–0•53) patients, and 20•8 months in patients treated with “systemic therapy alone” (reference), with 5-year OS rates of 66%, 40%, and 6%, respectively. Interpretation Repeated centralized MDT assessment in real-world metastatic CRC patients generates high resectability (41%) and resection rates (37%) with impressive survival, even when multisite metastases are present or develop later. Funding The funders had no role in the study design, analysis, and interpretation of the data or writing of this report. Tiivistelmä Tausta Kolorektaalisyövän etäpesäkkeiden leikkaushoitoa käytetään todennäköisesti liian vähän tosielämän hoidoissa. Menetelmät RAXO on maanlaajuinen suomalainen tosielämän prospektiivinen interventiotutkimus, joka rekrytoi lääkehoitokuntoisia, levinnyttä suolistosyöpää sairastavia potilaita. Tutkimuksessa arvioitiin keskitetysti etäpesäkkeiden leikattavuutta levinneen syövän toteamisvaiheessa ja kahdesti ensilinjan hoidon aikana Helsingin yliopistollisen sairaalan moniammatillisessa hoitokokouksessa. Tulokset Vuosina 2012-2018 tutkimukseen otettiin 1086 potilasta. Mediaaniseuranta-aika oli 58 kuukautta. Usean elimen etäpesäkkeet todettiin 500:lla (46 %) levinneen syövän toteamisvaiheessa ja 820:lla (76 %) seurannan aikana. Moniammatillisessa arvioinnissa 447 luokiteltiin leikattavaksi 310 (29%) toteamisvaiheessa ja 137 (18%) konversiohoidon jälkeen. Kuusisataayhdeksänkymmentä etäpesäkekirurgista ja/tai paikallishoitotoimenpidettä tehtiin 399 potilaalle (89 % 447:sta), joista parantavalla tavoitteella R0/1-resektio 326 potilaalle ja R2-resektio ja/tai paikallistoimenpide 73:lle. Useita toimenpiteitä tehtiin 148 (37%) potilaalle useamman elimen etäpesäkkeiden tai uusien etäpesäkekohtien ilmentymisen takia. Kaiken kaikkiaan tehtiin 414 maksa-, 112 keuhko-, 57 peritoneaalikarsinoosi- ja 107 muuta toimenpidettä. Mediaanielinaika oli 80,4 kuukautta R0/1-resekoiduilla potilailla (HR 0,15; 95 % luottamusväli 0,12–0,19), 39,1 kuukautta R2-resekoiduilla/paikallishoidetuilla (0,39; 0,29–0,53), ja 20,8 kuukautta vain lääkehoitoa saaneilla (referenssi), ja vastaavat viiden vuoden elossaololuvut olivat 66%, 40% ja 6%. Merkitys Keskitetyllä, toistetulla moniammatillisella toiminnalla saavutetaan korkea arvio etäpesäkkeiden leikattavuudesta (41%). Etäpesäkkeiden leikkaus- ja/tai paikallishoito toteutuu 37 prosentilla erinomaisin tuloksin silloinkin, kun syöpä on levinnyt useaan elimeen sairauden toteamisvaiheessa tai sen aikana Tuki Tutkimuksen tukijat eivät osallistuneet tutkimussuunnitelman kirjoittamiseen, datan analysointiin tai tulkintaan, eivätkä tämän raportin kirjoittamiseen. Abstrakt Bakgrund Resektion av kolorektalcancermetastaser ger god överlevnad, men används troligen suboptimalt i normal praktik. Metod RAXO-studien är en prospektiv finsk studie som inkluderade behandlingsbara patienter med spridd kolorektalcancer. Studiens intervention utvärderade möjligheten till metastasoperation vid centraliserad multidisciplinär konferens (MDK) på Helsingfors universitetssjukhus vid behandlingsinitiering och två gånger under första linjens behandling. Det primära syftet var att undersöka resekabilitet och resektioner, samt överlevnad. Fynd 1086 patienter inkluderades 2012-2018. Medianuppföljningstiden var 58 månader. Multipel metastasering sågs hos 500 (46%) av patienterna vid metastasdiagnostidpunkten och hos 820 (76%) under uppföljningen. I MDK-utvärderingen klassificerades 447 (41%) som operabla, varav 310 (29%) vid metastastasdiagnos och 137 (18%) efter konversionsbehandling. Sexhundranittio åtgärder gjordes hos 399 patienter (89% av de 447 operabla), med R0/1-resektion hos 326 och R2-resektion eller lokalbehandling hos 73. Flera åtgärder gjordes hos 148 (37%) patienter med multipla metastasorgan eller nya metastaslokaler under uppföljningen; totalt 414 lever-, 112 lung-, 57 peritoneal-, och 107 andra åtgärder. Medianöverlevnaden var 80,4 månader hos R0/1-opererade (HR 0,15; 95% konfidensintervall 0,12–0,19), 39,1 månader hos R2-opererade/lokalbehandlade (0,39; 0,29–0,53) och 20,8 månader hos ”enbart systembehandlade” (referens), och femårsöverlevnaden var 66%, 40% och 6% i respektive grupp. Betydelse Upprepad centraliserad MDK-utvärdering vid spridd kolorektalcancer visar att 41% av metastaserna någon gång bedöms som resekabla och att operation och/eller lokalbehandling är möjlig i 37% av fallen. Imponerande överlevnad ses även i fall med multipla metastaslokaler vid diagnostillfället eller under uppföljningen. Finansiering Finansiärerna hade ingen roll i utformningen av denna studie, i dataanalys, tolkning av data eller i skrivandet av denna forskningsrapport. publishedVersion

Background Colorectal cancer liver metastases respond to chemotherapy and targeted agents not only by shrinking, but also by morphologic and metabolic changes. The aim of this study was to evaluate the value of advanced magnetic resonance imaging (MRI) methods in predicting treatment response and survival. Patients and methods We investigated contrast-enhanced MRI, apparent diffusion coefficient (ADC) in diffusion-weighted imaging and 1H-magnetic resonance spectroscopy (1H-MRS) in detecting early morphologic and metabolic changes in borderline or resectable liver metastases, as a response to first-line neoadjuvant or conversion therapy in a prospective substudy of the RAXO trial (NCT01531621, EudraCT2011-003158-24). MRI findings were compared with histology of resected liver metastases and Kaplan–Meier estimates of overall survival (OS). Results In 2012-2018, 52 patients at four Finnish university hospitals were recruited. Forty-seven patients received neoadjuvant or conversion chemotherapy and 40 liver resections were carried out. Low ADC values (below median) of the representative liver metastases, at baseline and after systemic therapy, were associated with partial response according to RECIST criteria, but not with morphologic MRI changes or histology. Decreasing ADC values following systemic therapy were associated with improved OS compared to unchanged or increasing ADC, both in the liver resected subgroup (5-year OS rate 100% and 34%, respectively, P = 0.022) and systemic therapy subgroup (5-year OS rate 62% and 23%, P = 0.049). 1H-MRS revealed steatohepatosis induced by systemic therapy. Conclusions Low ADC values at baseline or during systemic therapy were associated with treatment response by RECIST but not with histology, morphologic or detectable metabolic changes. A decreasing ADC during systemic therapy is associated with improved OS both in all patients receiving systemic therapy and in the resected subgroup., Highlights • Colorectal liver metastases respond to systemic therapy by shrinking but also by morphological and metabolic changes. • Advanced MRI technologies (DWI and 1H-MRS) might provide more detailed insight into cancer treatment-induced changes. • We compare changes seen in MRI with histology. • Reduction of ADC during chemotherapy was associated with improved survival after liver resection.

IntroductionRemote ischaemic preconditioning (RIPC) using a non-invasive pneumatic tourniquet is a potential method for reducing ischaemia-reperfusion injury. RIPC has been extensively studied in animal models and cardiac surgery, but scarcely in solid organ transplantation. RIPC could be an inexpensive and simple method to improve function of transplanted organs. Accordingly, we aim to study whether RIPC performed in brain-dead organ donors improves function and longevity of transplanted organs.Methods and analysesRIPTRANS is a multicentre, sham-controlled, parallel group, randomised superiority trial comparing RIPC intervention versus sham-intervention in brain-dead organ donors scheduled to donate at least one kidney. Recipients of the organs (kidney, liver, pancreas, heart, lungs) from a randomised donor will be included provided that they give written informed consent. The RIPC intervention is performed by inflating a thigh tourniquet to 300 mm Hg 4 times for 5 min. The intervention is done two times: first right after the declaration of brain death and second immediately before transferring the donor to the operating theatre. The sham group receives the tourniquet, but it is not inflated. The primary endpoint is delayed graft function (DGF) in kidney allografts. Secondary endpoints include short-term functional outcomes of transplanted organs, rejections and graft survival in various time points up to 20 years. We aim to show that RIPC reduces the incidence of DGF from 25% to 15%. According to this, the sample size is set to 500 kidney transplant recipients.Ethics and disseminationThis study has been approved by Helsinki University Hospital Ethics Committee and Helsinki University Hospital’s Institutional Review Board. The study protocol was be presented at the European Society of Organ Transplantation congress in Copenhagen 14−15 September 2019. The study results will be submitted to an international peer-reviewed scientific journal for publication.Trial registration numberNCT03855722.

3532 Background: Outcomes of metastasectomy varies with RAS and BRAF-status, but the effect on resectability, conversion and resection rates has not been extensively studied. Methods: The prospective Finnish RAXO study (NCT01531621) included 1086 patients 2011-2018 (Osterlund et al TLRHE 2021, Isoniemi et al BJS 2021) of which 906 were included in this secondary endpoint analysis. Excluded had missing KRAS/ NRAS/ BRAF-V600E test, were untreatable or had an atypical BRAF mutation. We studied repeated centralized resectability assessment, conversion and resectability rates in mCRC, and overall survival (OS) after resection and/or local ablative therapy (LAT) and systemic therapy. Results: Included were 289 RAS& BRAFwt, 529 RASmt (overrepresented) and 88 BRAFmt, with median age 65.8/66.1/66.9 years. Demographics per RAS& BRAFwt, RASmt and BRAFmt showed significant differences in male proportion (68/61/39%), ECOG PS 2-3 groups (16/14/25%), primary tumour location (right colon 16/30/69%, left colon 47/34/17%, rectum 38/36/14%), but not for Charlson comorbidity index, BMI, resection of primary, synchronous presentation or adjuvant therapy (Bonferroni corrected Chi-square). Metastatic profile was different for liver (78/74/61% per RAS& BRAFwt, RASmt and BRAFmt), lung (24/35/28%) and peritoneal (15/15/32%) metastases, but not for lymph nodes or other sites, nor for number of metastatic sites (1 in 53/54/52%). Upfront resectability rates were different with 32/29/15% for RAS& BRAFwt, RASmt and BRAFmt, respectively, as were conversion rates with 16/13/7%, and resection/LAT rates with 45/37/17%, respectively. Kaplan-Meier median OS estimate in R0/1/2-resected and/or LAT group (n = 342) was 83/69/30 months for RAS& BRAFwt, RASmt and BRAFmt groups, respectively and 5-year OS-rates 67/60/24%, with Cox HR ref/1.53 (95% CI 1.04-2.25)/3.11 (1.49-6.49). In the “systemic therapy only” (n = 564) OS was 29/21/15 months and 5-year OS-rates 11/6/2% respectively, with HR ref/1.43 (1.15-1.76)/2.34 (1.73-3.17). Resection/LAT patients had improved OS over “systemic therapy only” patients in all subgroups, HR 5.74 (3.90-8.44)/5.06 (3.92-6.55)/2.89 (1.43-5.86). Conclusions: There were significant differences in resectability, conversion and resection/LAT rates according to RAS& BRAFwt, RASmt and BRAFmt status. OS was also significantly longer for RAS& BRAFwt versus either mutant. Resected/LAT had better OS than “systemic therapy alone” patients in all subgroups. Clinical trial information: NCT01531621.

The aim of this study was to evaluate the effect of myoblast transplantation on left ventricular function, perfusion, and scar formation after compromised coronary flow.A coronary vessel with Ameroid-induced stenosis was ligated and skeletal muscle was biopsied for isolation and cultivation of myoblasts. Two weeks after ligation, animals were randomly selected to receive intramyocardial injections of 2 x 10(6) myoblasts or vehicle. Fifteen animals survived the whole study period (n=9 and n=6, respectively). All animals underwent cardiac magnetic resonance imaging (MRI) and angiography pretreatment and four weeks posttreatment.Peak filling rate of the left ventricle improved in the myoblast group (p=0.0048), but not in the control group. Peak ejection rate and duration of diastole improved only in the myoblast group (p=0.049 and p=0.0039, respectively). Ejection fraction or local thickening did not change. Fibrosis and perfusion were similar in both groups, but more microvessels were present histologically in the myoblast group.In this preclinical study, autologous myoblast transplantation improved ischemic heart function via enhanced diastolic filling of the left ventricle.

The prevalence and characteristics of headache were studied in a national cohort of 177 pediatric patients with kidney, liver, and heart transplants. All patients received triple drug immunosuppression with CsA, Aza, and MP. Data on headaches were collected by sending two questionnaires and reviewing the medical records. Statements on headache were found in the medical records of 46% of the patients. According to a questionnaire, two thirds had experienced headaches sometime after transplantation, and 40% had present headaches. The episodes had significantly affected the quality of life in a third of the patients, and resulted in neurological examination in 15%. Most of the subjects (61%) described typical episode as mild or moderate, and 39% as severe or very severe. The usual episodes lasted4 h in 73% of the patients and4 h in 27%. The headache could be classified as migraine, probable migraine or headache without specific features in 33%, 31%, and 36%, respectively. Most patients (82%) had used pain-killers, mainly acetaminophen and ibuprofen. Headache episodes may significantly impair the quality of life in children and adolescents after organ transplantation.