Till Örebro universitet

BACKGROUND: The occurrence of metachronous metastases (MM) of colorectal (CRC), colon (CC), and rectal (RC) cancer of population-based studies has not been compiled in a systematic review previously.

METHODS: MEDLINE, Embase, and Cochrane Library were searched for primary studies of any design from inception until January 2021 and updated in August 2023 (CRD42021261648). The PRISMA guidelines were adopted, and the Newcastle-Ottawa Quality Assessment Scale used for risk of bias assessment. Outcomes on overall and organ-specific MM were extracted. A narrative analysis followed.

RESULTS: Out of 2143 unique hits, 162 publications were read in full-text and 37 population-based cohort studies published in 1981-2022 were included. Ten studies adopted time-dependent analyses; eight were registry-based and seven had a low risk of bias. Three studies reported 5-year recurrence rate of MM overall of stages I-III; for CRC, it was 20.5%, for CC, it was 18% and 25.6%, and for RC, it was 23%. Four studies reported 5-year recurrence rate of organ-specific MM of stages I-III-for CRC, it was 2.2% and 5.5% for peritoneal metastases and 5.8% for lung metastases and for CC 4.5% for peritoneal metastases. Twenty-seven studies reported proportions of patients diagnosed with MM, but data on the length of follow-up was incomplete and varied widely. Proportions of patients with CRC stages I-III that developed MM overall was 14.4%-26.1% in 10 studies. In relation to the enrollment period, a downward trend may be discernible.

CONCLUSION: Studies adopting a more appropriate analysis were highly heterogeneous, whereas uncertain data of partly inadequate studies may indicate that MM are overall declining.

BACKGROUND: Surveillance of colorectal neoplasia place great strain on colonoscopy resources, and faecal immunochemical tests (FIT) are under-investigated for this purpose. The aim of this study was to report the outcome of FIT among patients scheduled for post-polypectomy and post-resection colorectal cancer (CRC) surveillance.

METHODS: Patients scheduled for colonoscopy surveillance at five endoscopy units in mid-Sweden in 2016-2020 were eligible. They provided a faecal sample from 2 separate days, which were analysed by iFOBT QuikRead go® (Aidian Oy). Both the colonoscopies, and the FIT analyses were conducted by staff blinded to the other.

RESULTS: Out of 216 included patients, 157 (73%) underwent both a complete colonoscopy and had at least one FIT analysed prior to the examination. The indication for surveillance was previous adenoma in 69 (44%) and post-resection CRC in 88 (56%) patients. Two (1%) in the CRC surveillance group were diagnosed with a metachronous CRC, whereas 49 (56%) patients in the CRC surveillance, and 17 (25%) in the adenoma group had no pathology identified at colonscopy (P < 0.001). The proportion of patients diagnosed with adenomas requiring surveillance according to European Society of Gastrointestinal Society (ESGE) guidelines 2020 was 6 (7%) in the post-CRC resection versus 7 (10%) in the adenoma surveillance group (P = 0.4). Based on one FIT and at cut-off 10 µg Hb/g, sensitivity for CRC was 100%, specificity 83% (95% confidence interval [CI]: 77-89), Positive Predictive Value (PPV) 7% (-2 to 16) and Negative Predictive Value (NPV) 100%. All patients with an adenoma requiring surveillance had a FIT below this cut-off. Adding a second FIT decreased the specificity.

CONCLUSION: Larger studies to evaluate the accuracy and consequences of using FIT for surveillance of colorectal neoplasia are needed. FIT may be more interesting for post-resection CRC surveillance than follow-up of adenoma.

BACKGROUND: Systematic reviews (SRs) are pivotal to evidence-based medicine, yet there is limited research on conflicts of interest in SRs. Our aim was to investigate financial conflicts of interest and risk of bias (RoB) in SRs of a well-defined clinical topic.

METHODS: A librarian searched Medline, Cochrane Library, Embase, and PsycINFO for SRs investigating the effect of methylphenidate on ADHD in December 2020. The selection process adhered to the PRISMA guidelines. Two blinded reviewers independently searched open websites, including other publications, for information on financial conflicts of interest of all authors of the included SRs. A time limit of 3 years before or after the index SR was adopted. Declarations on conflict of interest were extracted from the included SRs for comparison. ROBIS was used for RoB assessment.

RESULTS: Out of 44 SRs included, 15 (34%) declared conflict of interest, 27 (61%) did not, and a declaration of conflict of interest was missing for 2 (5%). On open websites, conflict of interest was found for at least one author of 23 (52%) SRs: disclosed in 15 (34%) and not disclosed in 8 (18%) SRs. Seven (16%) SRs had low, 36 (82%) had high, and 1 (2%) had unclear RoB. Among SRs with financial conflict of interest found in open sources, 6/22 (27%) had low RoB compared to 1/21 (5%) if no such conflict of interest was identified. Among SRs with financial conflict of interest identified, 1/6 (17%) at low RoB did not disclose their conflict of interest, whereas the corresponding proportion among SRs at high RoB was 7/16 (44%). Eight (18%) SRs presented conflict of interest disclosed in the included primary studies. Four of them (50%) had low RoB, compared to 3/36 (8%) for SRs not reporting on this aspect.

CONCLUSION: Financial conflict of interest was underreported in 18% of the SRs using our reference standard, and overall it was present for every second SR. This group embraced both SRs at low RoB disclosing conflict of interest and SRs at high RoB not disclosing their conflict of interest. Further studies to explore this heterogeneity are warranted.

Evidensbaserad vård förutsätter opartiska underlag.

Intressekonflikter är ständigt närvarande i medicinsk forskning, och mycket har gjorts för att de ska redovisas på ett transparent sätt.

Enbart transparens löser dock inte problemet.

Studier tyder på att finansiella intressekonflikter i kliniska prövningar påverkar både forskningsfråga, metod, resultat och tolkning.

Icke-finansiella intressekonflikter kan också finnas, men är mindre studerade.

Det behövs mer forskning om intressekonflikter, deras konsekvenser och hur de ska hanteras.

Considerable efforts have been undertaken to optimize the disclosures of authors but transparency alone will not solve the problem. Financial conflicts of interest in clinical trials are known to affect the research question, study design, and results as well as the conclusions. Non-financial conflicts of interest are less well studied. As a non-negligible proportion of studies are associated with conflicts of interest, more research in this field is warranted, in particular on the management and consequences of such conflicts.

BACKGROUND: There is increasing evidence supporting the use of faecal immunochemical tests (FIT) in patients reporting symptoms associated with colorectal cancer (CRC), but most studies until now have focused on selected subjects already referred for investigation. We therefore set out to determine the accuracy and predictive values of FIT in a primary care population.

METHOD: A prospective, multicentre, single-gated comparative diagnostic study on quantitative FIT in patients aged 40 years and above presenting in primary care with symptoms associated with CRC will be conducted. Patients representing the whole spectrum of severity of such symptoms met with in primary care will be eligible and identified by GPs. Participants will answer a short form on symptoms during the last month. They will provide two faecal samples from two separate days. Analyses will be performed within 5 days (QuikRead go®, Aidian Oy). The analytical working range is 10-200 μg Hb/g faeces. Reference test will be linked to the Swedish Colorectal Cancer Registry up to 2 years after inclusion. Accuracy, area under ROC curves, and predictive values will be calculated for one FIT compared to the highest value of two FIT and at cutoff < 10, 10-14.9, 15-19.9 and ≥ 20 μg Hb/g faeces. Subgroup analyses will be conducted for patients with anaemia and those reporting rectal bleeding. A model-based cost-effectiveness analysis based on the clinical accuracy study will be performed. Based on previous literature, we hypothesized that the sensitivity of the highest value of two FIT at cutoff 10 μg Hb/g faeces will be 95% (95% CI + / - 15%). The prevalence of CRC in the study population was estimated to be 2%, and the rate of non-responders to be 1/6. In all, 3000 patients will be invited at 30 primary care centres.

DISCUSSION: This study will generate important clinical real-life structured data on accuracy and predictive values of FIT in the most critical population for work-up of CRC, i.e. patients presenting with at times ambiguous symptoms in primary care. It will help establish the role of FIT in this large group.

TRIAL REGISTRATION: NCT05156307 . Registered on 14 December 2021-retrospectively registered.

BACKGROUND: Some 40% of colorectal cancer (CRC) patients present with anemia. Temporal trends of gradually decreasing Hb are suggested as a supplementary diagnostic tool for CRC. We set out to explore this concept in a strictly defined population.

METHODS: A laboratory database identified patients ≥40 years that had ≥1 Hb test reported from primary care, Örebro county in 2000-17. Linkage to the Swedish Colorectal Cancer Registry identified patients diagnosed with CRC. Other primary care patients served as controls (1:10), matched by age and sex. Prediagnostic Hb in cases and controls were compared and temporal trajectories of Hb modelled using a nonlinear three-parameter logistic function.

RESULTS: primary care was surprisingly low, and was ≥50% annually only in octogenarians.

CONCLUSION: The findings indicate a potential for Hb trends to inform the diagnostic process of CRC but whether it will translate into any clinical advantage is yet uncertain.

Immune checkpoint inhibitors (ICIs) have received much attention not least for melanoma since the award of the Nobel prize in 2018. Here, we review the current state of knowledge about the use of these monoclonal antibodies (mAbs) in non-small cell lung cancer (NSCLC). These drugs have generally been conditionally approved on limited early data and there are few long-term follow-up data from randomized clinical trials. The effect observed for NSCLC thus far is, on average, moderately better than that obtained with chemotherapy. Severe side-effects are more common than might have been expected. The drugs themselves are expensive and are associated with time-consuming histopathologic testing even though the predictive value of these tests can be discussed. In addition, monitoring for side-effects involves increased workload and budgetary expense for clinical chemistry laboratories. Here, we review and summarize the current knowledge, controversies and ambiguities of ICIs for the treatment of NSCLC.