Why is colon cancer survival improving by time? A nationwide survival analysis spanning 35 years.

There is limited information present to explain temporal improvements in colon cancer survival. This nationwide study investigates the temporal changes in survival over a 35-year period (1970-2004) in Iceland and uses incidence, mortality, surgery rate, stage distribution, lymph node yield, tumor location and histological type to find explanations for these changes. Patients diagnosed with colon cancer in Iceland 1970-2004 were identified (n = 1962). All histopathology was reassessed. Proportions, age-standardized incidence and mortality, relative, cancer-specific and overall survival and conditional survival were calculated. When comparing first and last diagnostic periods (1970-1978 and 1997-2004), 5-year relative survival improved by 12% for men and 9% for women. At the same time surgery rate increased by 12% and the proportion of stage I increased by 9%. Stage-stratified, improved 5-year relative survival was mainly observed in stages II and III and coincided with higher lymph node yields, proportional reduction of stage II cancers and proportional increase of stage III cancers, indicating stage migration between these stages. Improvement in 1-year survival was mainly observed in stages III and IV. Five-year survival improvement for patients living beyond 1 year was minimum to none. There were no changes in histology that coincided with neither increased incidence nor possibly influencing improved survival. Concluding, as a novel finding, 1-year mortality, which previously has been identified as an important variable in explaining international survival differences, is in this study identified as also being important in explaining temporal improvements in colon cancer survival in Iceland.

Indications and surgical outcome following pulmonary metastasectomy: a nationwide study.

AIM: The aim of this retrospective nationwide study was to investigate indications and surgical outcome after pulmonary metastasectomy (PM) in a well-defined cohort of patients and to calculate the proportion of cancer patients who were operated on. METHODS: Between 1984 and 2008, 81 patients (age 54.8 years, 50.6% men) underwent 100 PMs with curative intent in Iceland. For all patients, information on demographics, number of metastases, type of surgery, and complications were collected. Overall survival was estimated with median follow-up of 45 months. For the three most common malignancies, the proportion of patients who underwent PM was calculated using information from the Icelandic Cancer Registry on all cases diagnosed. RESULTS: Of 100 PMs, there were 62 wedge resections, 34 lobectomies, and 4 pneumonectomies. The most common complication was persistent air leakage (>96 hour; 11.1%), and operative mortality was 1.2%. Of the 12 kinds of primary malignancies operated, three were most common: colorectal carcinoma (CRC, n = 27), sarcoma (n = 21), and renal cell carcinoma (RCC, n = 14). The proportion of patients who underwent PM was 1.0% for CRC, 6.5% for sarcoma, and 1.4% for RCC, and their 5-year overall survival was 45.2, 18.6, and 38.5%, respectively (p = 0.11). Survival for all patients was 30.8%. CONCLUSION: The surgical outcome and survival of patients who underwent PM in Iceland are comparable to those in the other studies. Although there was no control group and selection bias cannot be eliminated, the survival of PM patients was better than for the nonoperated patients. However, a relatively small proportion of patients with CRC, RCC, and sarcoma underwent metastasectomy.

Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2.

Lynch syndrome, caused by germline mutations in the mismatch repair genes, is associated with increased cancer risk. Here using a large whole-genome sequencing data bank, cancer registry and colorectal tumour bank we determine the prevalence of Lynch syndrome, associated cancer risks and pathogenicity of several variants in the Icelandic population. We use colorectal cancer samples from 1,182 patients diagnosed between 2000-2009. One-hundred and thirty-two (11.2%) tumours are mismatch repair deficient per immunohistochemistry. Twenty-one (1.8%) have Lynch syndrome while 106 (9.0%) have somatic hypermethylation or mutations in the mismatch repair genes. The population prevalence of Lynch syndrome is 0.442%. We discover a translocation disrupting MLH1 and three mutations in MSH6 and PMS2 that increase endometrial, colorectal, brain and ovarian cancer risk. We find thirteen mismatch repair variants of uncertain significance that are not associated with cancer risk. We find that founder mutations in MSH6 and PMS2 prevail in Iceland unlike most other populations.

Loss of heterozygosity at the FHIT gene in different solid human tumours and its association with survival in colorectal cancer patients.

BACKGROUND: Genomic alterations and abnormal expression of the FHIT gene have been reported for a number of cancers. FHIT encompasses FRA3B, the most common fragile site in the human genome, and is suggested to be a candidate tumour suppressor gene. MATERIALS AND METHODS: We analysed and compared the loss of heterozygosity (LOH) pattern in 397 solid human tumours from 9 different locations, using four polymorphic microsatellite markers within the gene (D3S1234, D3S1300, D3S2757 and D3S4260), and two markers (D3S1313 and D3S1600) flanking the gene. In addition, we tested whether there was an association between FHIT LOH and overall patient survival in colorectal cancer. RESULTS: LOH at the FHIT gene affecting at least one of the investigated markers was detected in 166 out of 332 informative tumours, or 50%. The highest detected LOH was in lung tumours (66%) while the lowest was in thyroid and endometrium tumours, (30% and 31%, respectively). Breakpoints were found inside the gene in all tumour types in 12-80% of the tumours with FHIT LOH depending on tumour type, and up to 41% could additionally be located adjacent to the 3' or 5' end of the FHIT gene. Thus we were able to locate breakpoints within or in the vicinity of the FHIT gene in 25-100% of different tumours with LOH. Although not statistically significant, we observed a trend towards a poorer survival of patients with FHIT LOH versus those with retention of heterozygosity. CONCLUSION: Based on our results, LOH of the FHIT gene is a common event in all tumour types analysed with a possible association with poorer survival in colorectal cancer patients. LOH at all markers analysed was, in most of the tumour types, a more common pattern of alterations than breakpoints.

Acute pancreatitis: a prospective study on incidence, etiology, and outcome.

BACKGROUND AND AIMS: Prospective and population-based studies on the incidence of acute pancreatitis (AP) are lacking. Alcohol consumption has increased considerably in Iceland during the last decade. We aimed to determine the incidence, etiology, severity, and complications of AP and compare the results with a previous study on AP in Iceland. METHODS: A prospective population-based study of patients diagnosed with AP at the National University Hospital of Iceland during 1 year (2010-2011). Information on symptoms, etiology, and complications was registered. RESULTS: During the study period, 134 patients were diagnosed with AP, 78 men (58%), median age 57 years (interquartile range 42-71). Overall, 89/104 (86%) patients had their first attack of pancreatitis, yielding a crude incidence of 40/100 000 inhabitants/year. The major etiological groups were as follows: gallstones, 52 cases (42%); alcohol 29, (23%); postendoscopic retrograde cholangio-pancreatography in 12 (9.5%); medications in eight (6.3%); and idiopathic in 15 (12%). Alcohol was more often the cause in men (25 vs. 4, P<0.05) but the incidence of gallstone-induced pancreatitis was similar in men and women (26 vs. 27). Seven patients had severe complications, three had pancreatic necrosis, two had pseudocysts, and one developed renal failure. Another patient developed acute respiratory distress syndrome and was admitted to the ICU. No patient died of AP during the study period. CONCLUSION: The incidence of AP has not increased significantly in Iceland in the last decade. Alcohol-induced pancreatitis has not increased proportionally despite increased alcohol consumption in Iceland. In a population-based setting, the vast majority of AP is of mild severity.

Familial risk of colon and rectal cancer in Iceland: evidence for different etiologic factors?

The aim of this study was to characterize the familial risk of colon and rectal cancer using 2 population-based registries in Iceland, the Icelandic Cancer Registry and a genealogy database. The standardized incidence ratio (SIR) was used to estimate the risk among relatives of colorectal cancer index cases diagnosed in Iceland over a 46-year period (1955-2000). The 2,770 colorectal cancer patients had 23,272 first-degree relatives. Among first-degree relatives, there was an increased risk of both colon (SIR 1.47, 95% confidence interval (CI) 1.34-1.62) and rectal cancer (SIR 1.24, 95% CI 1.04-1.47). An increased risk of colon cancer was observed among siblings of colon cancer patients (SIR 2.03, 95% CI 1.76-2.33), whereas no such increase was observed for parents or offspring. Furthermore, the risk of rectal cancer was only increased among brothers (SIR 2.46 95% CI 1.46-3.89) of rectal cancer patients and not among their sisters (SIR 1.0 95% CI 0.40-2.06). The added risk of colon cancer among first-degree relatives was independent of site of colon cancer in the proband. Our results confirm that family history of colorectal cancer is a risk factor for the disease. However, family history has a different association with colon cancer than with rectal cancer, suggesting that the 2 cancer types may have different etiologic factors. Our results have implications for colon and rectal cancer screening programs.