Pall Helgi Möller

Colon cancer in Iceland—A nationwide comparative study on various pathology parameters with respect to right and left tumor location and patients age

Increasing evidence suggests genetic, biological and demographical difference between right and left colon cancer. Studies have also indicated age differences in the pathology of colon cancer. There is a scarcity of large‐scale studies that closely examine the pathological differences regarding age and tumor location. The aim of our study was to do an extensive comparison of right‐ and left‐ sided colon cancers as well as comparing patients <50 years with older patients. A retrospective, population‐based study was carried out on all patients with colon cancer in Iceland between 1955 and 2004. A total of 2293 cases were analyzed (1148 men, 1145 women). All histopathology material was re‐evaluated. Differences in tumor characteristics between right and left location and younger (<50) and older (≥50) patients was evaluated in particular. Higher TNM‐stage, larger tumors, vessel invasion, mucinous type, high grade and expanding tumor border occurred more frequently in right‐ versus left‐sided lesions while annular and polypoid tumors were more common in left‐sided tumors (p < 0.05). Young patients had more frequent lymph node metastases, vessel invasion, nonpolypoid lesions and infiltrating tumor border (p < 0.05). Right‐sided lesions show more aggressive features, reflected in morphology and stage. Younger patients present more frequently with adverse features than do older patients. Frequency of right‐ and left‐sided colon cancer differs by age with pronounced age‐location differences in females. This supports the assumption of differences in etiology and carcinogenesis of right‐ and left‐sided colon cancer, and between young and old patients.

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.

Association of symptoms of colon cancer patients with tumor location and TNM tumor stage

Abstract Objective. Colon cancer is the second most common cause of cancer death in Iceland and accounts for 8% of malignancies. We related information on symptoms of colon cancer patients with information on tumor location and pTNM-stage. Material and methods. The study is retrospective and population-based. Information on all patients diagnosed with colon cancer in Iceland in 1995–2004 was obtained. Information on symptoms of patients and blood hemoglobin was collected from patients files. The pathological parameters were derived from a previously performed study. Results. A total of 768 patients (422 males, 346 females) participated in this study. Median age was 73 years. Nearly 60% had anemia at the time of diagnosis, 53% had visible blood in stools, and 65% had changes in bowel habits. Around 84% had visible blood in stools and/or anemia. Of those with right-sided tumors, 75% had anemia and were more likely to be diagnosed incidentally (40%) than those with left-sided tumors (20%). Left-sided tumors were associated with blood in stools (68% compared to 41%, p < 0.05) and changes in bowel habits (74% compared to 57%, p < 0.05). Multivariate analysis indicated that blood in stools was strongly associated with a lower TNM-stage (OR = 0.75, p < 0.05). Anemia was strongly associated with a higher TNM-stage (OR = 1.84, p < 0.05). Conclusion. Right-sided tumors were associated with anemia and incidental diagnosis; left-sided tumors were associated with visible blood in stools and changes in bowel habits. Visible blood in stools was significantly associated with lower TNM-stage, whereas abdominal pain, general and acute symptoms were associated with higher TNM-stage.

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.

Colon cancer: association of histopathological parameters and patients' survival with clinical presentation

Available data correlating symptoms of colon cancer patients with the severity of the disease are very limited. In a population‐based setting, we correlated information on symptoms of colon cancer patients with several pathological tumor parameters and survival. Information on all patients diagnosed with colon cancer in Iceland in 1995–2004 for this retrospective, population‐based study was obtained from the Icelandic Cancer Registry. Information on symptoms of patients and blood hemoglobin was collected from patients files. Pathological parameters were obtained from a previously performed standardized tumor review. A total of 768 patients entered this study; the median age was 73 years. Tumors in patients presenting at diagnosis with visible blood in stools were significantly more likely to be of lower grade, having pushing border, conspicuous peritumoral lymphocytic infiltration, and lower frequency of vessel invasion. Patients with abdominal pain and anemia were significantly more likely to have vessel invasion. Logistic regression showed that visible blood in stools was significantly associated with protecting pathological factors (OR range 0.38–0.83, p < 0.05). Tumors in patients presenting with abdominal pain were strongly associated with infiltrative margin and scarce peritumoral lymphocytic infiltration (OR = 1.95; 2.18 respectively, p < 0.05). Changes in bowel habits were strongly associated with vessel invasion (OR = 2.03, p < 0.05). Cox regression showed that blood in stools predicted survival (HR = 0.54). In conclusion, visible blood in stools correlates significantly with all the beneficial pathological parameters analyzed and with better survival of patients. Anemia, general symptoms, changes in bowel habits, acute symptoms, and abdominal pain correlate with more aggressive tumor characteristics and adverse outcome for patients.

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

AIMnThe 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.nnnMETHODSnBetween 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.nnnRESULTSnOf 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%.nnnCONCLUSIONnThe 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.

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 (nu2009=u20091962). 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.