Kidney transplantation in Icelandic patients, 2000-2019: are outcomes affected by low volume?

Background: In Iceland, a small number of kidney transplants from living donors (LDs) are performed at Landspitali University Hospital (LUH) in Reykjavik, while deceased donor transplants have until recently invariably been carried out abroad. In this study, we evaluated the outcome of kidney transplantation in Icelandic patients. Methods: This was a retrospective study that included all Icelandic residents who underwent kidney transplantation between 1 January 2000 and 31 December 2019. Data were obtained from the Icelandic End-Stage Kidney Disease Registry, medical records at LUH, and the Scandiatransplant database. The Chronic Kidney Disease Epidemiology Collaboration equation was used to calculate estimated glomerular filtration rate from serum creatinine for recipients and donors aged >18 years, and the modified Schwartz equation for those aged ≤18 years. Survival was estimated using the Kaplan-Meier method, and the log-rank test was employed for group comparisons. Results: A total of 229 kidney transplants in 221 patients were performed during the 20-year period, of which 135 (58.9%) were from LDs. Transplants carried out at LUH were 118 (51.5%), of which 116 were from LDs. During a median follow-up of 7.4 years (range 0.1-20), 27 (12.2%) patients died, 20 (74%) of whom had a functioning graft. One-year patient survival was 99.1% [95% confidence interval (CI), 97.9-100], 5-year survival was 95.7% (95% CI, 92.7-98.7), and 10-year survival was 87.7% (95% CI, 82.4-93.4). Death-censored graft survival was 98.3% (95% CI, 96.6-100), 96.8% (95% CI, 94.4-99.2), and 89.2% (95% CI, 84.1-94.7) at 1, 5, and 10 years, respectively. Conclusions: Patient and graft survival are comparable with those of large transplant centers, demonstrating the feasibility of running a quality kidney transplant program in a small nation in collaboration with a larger center abroad.

An epidemiological and clinicopathological study of type 1 vs. type 2 morphological subtypes of papillary renal cell carcinoma- results from a nation-wide study covering 50 years in Iceland.

INTRODUCTION: Papillary renal cell carcinoma (pRCC) is the second most common histology of renal cell carcinoma (RCC), accounting for 10-15% of cases. Traditionally, pRCC is divided into type 1 and type 2, although this division is currently debated as a prognostic factor of survival. Our aim was to investigate the epidemiology and survival of the pRCC subtypes in a whole nation cohort of patients during a 50-year period. MATERIALS AND METHODS: A Population based retrospective study including consecutive cases of RCC in Iceland from 1971-2020. Comparisons were made between histological classifications of RCC, with emphasis on pRCC subtypes (type 1 vs. 2) for outcome estimation. Changes in RCC incidence were analyzed in 5-year intervals after age standardization. The Kaplan-Meier method and Cox regression were used for outcome analysis. RESULTS: A total of 1.725 cases were identified, with 74.4%, 2.1% and 9.2% having clear cell (ccRCC), chromophobe (chRCC), and pRCC, respectively. The age standardized incidence (ASI) of pRCC was 1.97/100.000 for males and 0.5/100.000 for females, and the proportion of pRCC increased from 3.7% to 11.5% between the first and last intervals of the study (p < 0.001). Age standardized cancer specific mortality (ASCSM) of pRCC was 0.6/100.000 and 0.19/100.000 for males and females, respectively. The annual average increase in ASI was 3.6% for type 1 pRCC, but the ASI for type 2 pRCC and ASCSM for both subtypes did not change significantly. Male to female ratio was 4.4 for type 1 pRCC and 2.3 for type 2. The average tumor size for type 1 and 2 was 58.8 and 73.7 mm, respectively. Metastasis at diagnosis was found in 8.7% in the type 1 pRCC, compared to 30.0% of patients with type 2 pRCC (p < 0.001). Estimated 5-year cancer-specific survival (CSS) were 94.4%, 80.7%, and 69.3% for chRCC, pRCC and ccRCC, respectively (p < 0.001). For the pRCC subtypes, type 1 was associated with better 5-year CSS than type 2 (86.3% vs. 66.0%, p < 0.001), although this difference was not significant after adjusting for cancer stage and grading. CONCLUSIONS: pRCC histology was slightly less common in Iceland than in other countries. Males are more than three times more likely to be diagnosed with pRCC, compared to other RCC histologies. The subtype of pRCC was not found to be an independent risk factor for worse survival, and as suggested by the most recent WHO Classification of Urinary Tumors, grade and TNM-stage seem to be the most important factors for estimation of survival for pRCC patients.

Actionable Genotypes and Their Association with Life Span in Iceland.

BACKGROUND: In 2021, the American College of Medical Genetics and Genomics (ACMG) recommended reporting actionable genotypes in 73 genes associated with diseases for which preventive or therapeutic measures are available. Evaluations of the association of actionable genotypes in these genes with life span are currently lacking. METHODS: We assessed the prevalence of coding and splice variants in genes on the ACMG Secondary Findings, version 3.0 (ACMG SF v3.0), list in the genomes of 57,933 Icelanders. We assigned pathogenicity to all reviewed variants using reported evidence in the ClinVar database, the frequency of variants, and their associations with disease to create a manually curated set of actionable genotypes (variants). We assessed the relationship between these genotypes and life span and further examined the specific causes of death among carriers. RESULTS: Through manual curation of 4405 sequence variants in the ACMG SF v3.0 genes, we identified 235 actionable genotypes in 53 genes. Of the 57,933 participants, 2306 (4.0%) carried at least one actionable genotype. We found shorter median survival among persons carrying actionable genotypes than among noncarriers. Specifically, we found that carrying an actionable genotype in a cancer gene was associated with survival that was 3 years shorter than that among noncarriers, with causes of death among carriers attributed primarily to cancer-related conditions. Furthermore, we found evidence of association between carrying an actionable genotype in certain genes in the cardiovascular disease group and a reduced life span. CONCLUSIONS: On the basis of the ACMG SF v3.0 guidelines, we found that approximately 1 in 25 Icelanders carried an actionable genotype and that carrying such a genotype was associated with a reduced life span. (Funded by deCODE Genetics-Amgen.).

An Adaptation, Extension and Pre-Testing of an Interactive Decision Aid for Men Diagnosed with Localized Prostate Cancer in Iceland: A Mixed-Method Study.

In this study an interactive decision aid (DA) for men diagnosed with localized prostate cancer was adapted, extended and pre-tested. The DA's prototype was based on a literature review and other empirically tested DAs. Semi-structured interviews with 12 men (age 65-80) diagnosed with localized prostate cancer were conducted to get feedback on content, usability, and the DA's layout. The interviews were analyzed using thematic analysis and themes were identified using deductive and inductive coding. Participants found the accessibility of the information and the explicit values clarification tool helpful. Four themes were identified: (1) usability and design, (2) content and knowledge, (3) deciding factors of decision-making, and (4) social support. Participants valued receiving extensive and realistic information on surgery/radiation therapy side effects and getting unbiased presentations of treatment options. Following the thematic analysis, the DA was revised and tested in a survey among 11 newly diagnosed prostate cancer patients (age 60-74). The participants valued the DA and found it helpful when making a treatment decision, and all reported that they would recommend it to others making a prostate cancer treatment decision. The DA is currently being tested in a randomized clinical trial (RCT). This is the first DA developed for prostate cancer patients in Iceland and if the results of the RCT show that it is more effective than standard care in assisting newly diagnosed patients with their treatment decision, the DA can be easily translated and adapted to cultures similar to Iceland such as the Nordic countries.

Transition from open to robotically assisted approach on radical prostatectomies in Iceland. A nationwide, population-based study.

OBJECTIVES: In January 2015, radical prostatectomies (RPs) in Iceland changed almost entirely from being performed as open (ORP) to robotically assisted (RARP). This study assesses early surgical and short-term oncological outcome after ORP and RARP and evaluates the safety of transition between the two surgical techniques. METHODS: The study population involved 160/163 (98%) of all radical prostatectomies performed in Iceland between January 2013 and April 2016. Data on patients was collected retrospectively from medical records. Early surgical and short-term oncological outcomes were compared between the two surgical techniques. RESULTS: The ORP and RARP cohorts were comparable with respect to all clinical and pathological variables, except for median prostate volume, which was 45 mL in the ORP cohort and 37 mL in the RARP cohort (p = 0.03). Intraoperative blood loss was higher, hospital stay longer, catheterization time longer, and risk of complications within 30 days of surgery higher after ORP than RARP (p < 0.01). The operative time, positive surgical margin rate and recurrence free survival, within two years, was comparable between the two surgical techniques. CONCLUSIONS: The transition from ORP to RARP in Iceland was safe and resulted in improved early surgical outcome. However, no conclusion can be drawn from this study regarding oncological outcome, due to short follow up and a small sample size.

Genome-wide associations for benign prostatic hyperplasia reveal a genetic correlation with serum levels of PSA.

Benign prostatic hyperplasia and associated lower urinary tract symptoms (BPH/LUTS) are common conditions affecting the majority of elderly males. Here we report the results of a genome-wide association study of symptomatic BPH/LUTS in 20,621 patients and 280,541 controls of European ancestry, from Iceland and the UK. We discovered 23 genome-wide significant variants, located at 14 loci. There is little or no overlap between the BPH/LUTS variants and published prostate cancer risk variants. However, 15 of the variants reported here also associate with serum levels of prostate specific antigen (PSA) (at a Bonferroni corrected P < 0.0022). Furthermore, there is a strong genetic correlation, rg = 0.77 (P = 2.6 × 10-11), between PSA and BPH/LUTS, and one standard deviation increase in a polygenic risk score (PRS) for BPH/LUTS increases PSA levels by 12.9% (P = 1.6×10-55). These results shed a light on the genetic background of BPH/LUTS and its substantial influence on PSA levels.

Extended pelvic lymphadenectomy for prostate cancer: will the previously reported benefits be reproduced in hospitals with lower surgical volumes?

OBJECTIVE: In the European Association of Urology guidelines on prostate cancer an extended pelvic lymphadenectomy (ePLND) is now recommended, instead of a dissection limited to the obturator fossae (lPLND). This recommendation relies on studies reporting that metastatic disease is identified twice as often with ePLND as with lPLND, with only moderately increased complications. However, these studies were from high-volume centres. This study investigated whether these results could be repeated in a hospital with lower surgical volume, more typical for the Nordic countries. MATERIAL AND METHODS: From January 2002 to September 2007 172 patients underwent radical prostatectomy and PLND at the University Hospital of Lund, 108 with ePLND and 64 with lPLND. Perioperative complications and the number of lymph-node metastases found were registered. RESULTS: A median of 17 lymph nodes was identified with ePLND compared with seven with lPLND. Metastases were identified in four out of 64 patients in the lPLND group (6%), versus 22 out of 108 in the ePLND group (20%). In the ePLND group 10 of the patients with metastases had such exclusively outside the obturator fossae. Complications were significantly more common after ePLND (p=0.007): lymphoceles (18 vs 9%), pulmonary embolism (4.6 vs 1.6%), deep venous thrombosis (1 vs 1.5%) and other (haematomas and infectious including sepsis (8 vs 0%). CONCLUSIONS: Almost half of the patients with metastases are misclassified by lPLND. Complications are significantly more common after ePLND. This implies that ePLND should be performed, but in selected patients and by high-volume surgeons only.