Associations of defect mismatch repair genes with prognosis and heredity in sporadic colorectal cancer.

BACKGROUND: Microsatellite instability arises due to defect mismatch repair (MMR) and occurs in 10-20% of sporadic colorectal cancer. The purpose was to investigate correlations between defect MMR, prognosis and heredity for colorectal cancer in first-degree relatives. MATERIAL AND METHODS: Tumour tissues from 318 patients consecutively operated for colorectal cancer were analysed for immunohistochemical expression of MLH1, MSH2 and MSH6 on tissue microarrays. Information on KRAS and BRAF mutation status was available for selected cases. RESULTS: Forty-seven (15%) tumours displayed MSI. No correlation was seen between patients exhibiting MSI in the tumour and heredity (p = 0.789). Patients with proximal colon cancer and MSI had an improved cancer-specific survival (p = 0.006) and prolonged time to recurrence (p = 0.037). In a multivariate analysis including MSI status, gender, CEA, vascular and neural invasion, patients with MSS and proximal colon cancer had an impaired cancer-specific survival compared with patients with MSI (HR, 4.32; CI, 1.46-12.78). The same prognostic information was also seen in distal colon cancer; no recurrences seen in the eight patients with stages II and III distal colon cancer and MSI, but the difference was not statistically significant. CONCLUSION: No correlation between MSI and heredity for colorectal cancer in first-degree relatives was seen. Patients with MSI tumours had improved survival.

Risk of second primary cancer in patients treated with radiotherapy for rectal cancer.

BACKGROUND: Many patients with rectal cancer receive radiotherapy (RT) to reduce the risk of local recurrence. Radiation may give rise to adverse effects, including second primary cancers. In view of the divergent results of previous studies, the present study evaluated the risk of second primary cancer following RT in all randomized RT rectal cancer trials conducted in Sweden and in the Swedish ColoRectal Cancer Registry (SCRCR). METHODS: Patients included in five randomized trials and the SCRCR were linked to the Swedish Cancer Registry. Cox regression models estimated the hazard ratio (HR) of second primary cancer among patients who received RT compared with those who did not. RESULTS: A total of 13 457 patients were included in this study; 7024 (52·2 per cent) received RT and 6433 (47·8 per cent) had surgery alone. Overall, no increased risk of second primary cancer was observed with RT (HR 1·03; 95 per cent c.i. 0·92 to 1·15), independently of follow-up time and location within or outside of the irradiated volume. In the randomized trials, with longer follow-up (maximum 31 years), a slight increase was observed outside of (HR 1·33, 1·01 to 1·74) but not within (HR 1·11, 0·73 to 1·67) the irradiated volume. Irradiated men had a lower risk of prostate cancer than those treated with surgery alone (HR 0·68, 0·51 to 0·91). CONCLUSION: Overall, there was no increased risk of second primary cancer following RT for rectal cancer within or outside of the irradiated volume up to 20 years of follow-up. Men with rectal cancer who received RT had a reduced risk of prostate cancer.

Time trends, improvements and national auditing of rectal cancer management over an 18-year period.

AIM: The main aims were to explore time trends in the management and outcome of patients with rectal cancer in a national cohort and to evaluate the possible impact of national auditing on overall outcomes. A secondary aim was to provide population-based data for appraisal of external validity in selected patient series. METHOD: Data from the Swedish ColoRectal Cancer Registry with virtually complete national coverage were utilized in this cohort study on 29 925 patients with rectal cancer diagnosed between 1995 and 2012. Of eligible patients, nine were excluded. RESULTS: During the study period, overall, relative and disease-free survival increased. Postoperative mortality after 30 and 90 days decreased to 1.7% and 2.9%. The 5-year local recurrence rate dropped to 5.0%. Resection margins improved, as did peri-operative blood loss despite more multivisceral resections being performed. Fewer patients underwent palliative resection and the proportion of non-operated patients increased. The proportions of temporary and permanent stoma formation increased. Preoperative radiotherapy and chemoradiotherapy became more common as did multidisciplinary team conferences. Variability in rectal cancer management between healthcare regions diminished over time when new aspects of patient care were audited. CONCLUSION: There have been substantial changes over time in the management of patients with rectal cancer, reflected in improved outcome. Much indirect evidence indicates that auditing matters, but without a control group it is not possible to draw firm conclusions regarding the possible impact of a quality control registry on faster shifts in time trends, decreased variability and improvements. Registry data were made available for reference.

Growth differentiation factor 15: a prognostic marker for recurrence in colorectal cancer.

BACKGROUND: Growth differentiation factor 15 (GDF15) belongs to the transforming growth factor beta superfamily and has been associated with activation of the p53 pathway in human cancer. The aim of this study was to assess the prognostic value of GDF15 in patients with colorectal cancer (CRC). METHODS: Immunohistochemistry and tissue microarrays were used to analyse GDF15 protein expression in 320 patients with CRC. In a subgroup of 60 patients, the level of GDF15 protein in plasma was also measured using a solid-phase proximity ligation assay. RESULTS: Patients with CRC with moderate to high intensity of GDF15 immunostaining had a higher recurrence rate compared with patients with no or low intensity in all stages (stages I-III) (HR, 3.9; 95% CI, 1.16-13.15) and in stage III (HR, 10.32; 95% CI, 1.15-92.51). Patients with high plasma levels of GDF15 had statistically shorter time to recurrence (P=0.041) and reduced overall survival (P=0.002). CONCLUSION: Growth differentiation factor 15 serves as a negative prognostic marker in CRC. High expression of GDF15 in tumour tissue and high plasma levels correlate with an increased risk of recurrence and reduced overall survival.

High expression of tumour-associated trypsin inhibitor correlates with liver metastasis and poor prognosis in colorectal cancer.

Increased expression of tumour-associated trypsin inhibitor (TATI) in tumour tissue and/or serum has been associated with poor survival in various cancer forms. Moreover, a proinvasive function of TATI has been shown in colon cancer cell lines. In this study, we have examined the prognostic significance of tumour-specific TATI expression in colorectal cancer, assessed by immunohistochemistry (IHC) on tissue microarrays (TMAs) with tumour specimens from two independent patient cohorts. Kaplan-Meier analysis and Cox proportional hazards modelling were used to estimate time to recurrence, disease-free survival and overall survival. In both cohorts, a high (>50% of tumour cells) TATI expression was an independent predictor of a significantly shorter overall survival. In cohort II, in multivariate analysis including age, gender, disease stage, differentiation grade, vascular invasion and carcinoembryonal antigen (CEA), high TATI expression was associated with a significantly decreased overall survival (HR=1.82; 95% CI=1.19-2.79) and disease-free survival (HR=1.56; 95% CI=1.05-2.32) in curatively treated patients. Moreover, there was an increased risk for liver metastasis in both cohorts that remained significant in multivariate analysis in cohort II (HR=2.85; 95% CI=1.43-5.66). In conclusion, high TATI expression is associated with liver metastasis and is an independent predictor of poor prognosis in patients with colorectal cancer.

Late gastrointestinal disorders after rectal cancer surgery with and without preoperative radiation therapy.

BACKGROUND: The aim of the study was to analyse late gastrointestinal disorders necessitating hospital admission following rectal cancer surgery and to determine their relationship to preoperative radiation therapy. METHODS: Curatively treated patients participating in the Swedish Rectal Cancer Trial during 1987-1990, randomized to preoperative irradiation (454 patients) or surgery alone (454), were matched against the Swedish Hospital Discharge Registry. Hospital records for patients admitted with gastrointestinal diagnoses were reviewed. RESULTS: Irradiated patients had an increased relative risk (RR) of late small bowel obstruction (RR 2.49 (95 per cent confidence interval (c.i.) 1.48 to 4.19)) and abdominal pain (RR 2.09 (95 per cent c.i. 1.03 to 4.24)) compared with patients treated by surgery alone. The risk of late small bowel obstruction requiring surgery was greatly increased (RR 7.42 (95 per cent c.i. 2.23 to 24.66)). Irradiated patients with postoperative anastomotic leakage were at increased risk for late small bowel obstruction (RR 2.99 (95 per cent c.i. 1.07 to 8.31)). The risk of small bowel obstruction was also related to the radiation technique and energy used. CONCLUSION: Small bowel obstruction is more common in patients with rectal cancer treated with preoperative radiation therapy.

Improved survival in cancer of the colon and rectum in Sweden.

AIMS: To analyse time-trends in survival of patients with colon and rectal cancer in Sweden. PATIENTS AND METHODS: Data including all patients diagnosed with adenocarcinoma of the colon and rectum between 1960 and 1999, from the Swedish Cancer Registry, were analysed. The observed and relative survival rates were calculated according to the Hakulinen cohort method. RESULTS: Five-year relative survival rate for cancer of the colon improved significantly from 39.6% in 1960--1964 to 57.2% in 1995--1999 and for rectal cancer from 36.1 to 57.6%, respectively. Corresponding observed survival improved from 31.2 to 44.3% for colon cancer and from 28.4 to 45.4% for rectal cancer. The largest improvement of survival were seen during the later part of the period observed. CONCLUSION: The survival of patients with colon and rectal cancer in Sweden continues to improve, especially in rectal cancer, which now has a 5-year observed and relative survival rate comparable to that for colon cancer. The survival improvement in rectal cancer is probably a result of the implementation of total mesorectal excision and pre-operative radiotherapy.

Acute pancreatitis: a prospective study of its incidence, aetiology, severity, and mortality in Iceland.

OBJECTIVE: To evaluate the incidence, aetiology, severity and mortality of patients with acute pancreatitis. DESIGN: Prospective study. SETTING: University hospital, Iceland. PATIENTS AND METHODS: All 50 patients diagnosed with acute pancreatitis during the one-year period October 1998-September 1999 inclusive. MAIN OUTCOME MEASURES: APACHE II, and Ranson and Imrie scores, and C-reactive protein (CRP) concentrations. The Balthazar-Ranson criteria were used for scoring of computed tomograms (CT). RESULTS: 27 of the 50 patients were male. The median age of the whole series was 60 years (range 19-85). The estimated incidence was 32/100000 for the first attack of acute pancreatitis. The causes were; gallstones 21 (42%), alcohol 16 (32%), miscellaneous 12 (24%), and idiopathic 1 (2%). 15 (33%) of the patients had APACHE II scores > or = 9, 17 (38%) had Ranson scores of > or = 3, 23 (50%) had Imrie scores of > or = 3, and 16 (34%) had CRP concentrations over 210 mg/L during the first 4 days or > 120 mg/L during the first week. Seven patients had severe pancreatitis. 2 patients in the whole group died, and both had clinically severe pancreatitis. CONCLUSIONS: This study indicates that the incidence of less severe acute pancreatitis is rising. Prospective assessment makes it possible to evaluate the aetiological factors more accurately. Measurement of the CRP concentration is an attractive and simple alternative to the severity scoring systems currently in use.

[Kingella kingae ostemyelitis and septic arthritis in paediatric patients. Six cases from the Department of Pediatrics, National University Hospital of Iceland.].

Kingella kingae (K. kingae) is a gram negative rod most often associated with septic arthritis and osteomyelitis in children. Infections caused by K. kingae had not been reported in Iceland when six cases were diagnosed at the Pediatric Department at the National University Hospital of Iceland. In this report we describe those cases and review the literature.

[The effect of pregnancy on the survival of women diagnosed with breast cancer.].

OBJECTIVE: To answer the question whether the prognosis of women with breast cancer is affected by pregnancy after diagnosis. MATERIAL AND METHODS: We used information from the Icelandic Cancer Registry, the Birth Registry and the Genetic Committee. We identified all women who were diagnosed with breast cancer in the years 1927-1992 and who later became pregnant. Controls were women without a history of childbirth after diagnosis of breast cancer. They were matched on tumour size, axillary lymph node status and years of birth and diagnosis, with four year deviation. RESULTS: In the years 1927-1992, 838 women at ages below 50 were diagnosed with breast cancer in Iceland. Of those, 29 gave birth to a child after the diagnosis. Fourteen cases and 33 matched controls fulfilled the inclusion criteria of the study. Survival was better in the group of women who became pregnant after diagnosis, but the difference was not statistically significant (P=0.06). DISCUSSION: Our results do not indicate that the prognosis of women who become pregnant after the diagnosis of breast cancer is worse than of those who do not become pregnant. The group was too small to make definite conclusions. However, the results are in concordance with results from other studies.

Metanephric adenoma.

A 59-year old woman was diagnosed with a tumour in her right kidney. A nephrectomy was performed, and a 45 mm diameter tan-pink coloured tumour was found. Microscopy revealed small, dark cells in organized arrays of small round acini and tubules with glomeruloid infoldings. A diagnosis of metanephric adenoma was made. The tumour cells proved diploid on flow cytometry and immunohistochemical staining was positive for CAM 5.2 and AE-3. FISH analysis of three chromosomes did not reveal any abnormal karyotype. It is important to differentiate metanephric adenoma from renal cell carcinoma and adult Wilm's tumour, since it has a benign course.

Pyomyositis due to non-haemolytic streptococci.

We present a unique case of a multifocal non-tropical pyomyositis due to non-haemolytic streptococci in a 36-y-old woman. The initial infection was in an area of contused muscle in the left anterior thigh and spread to the contralateral femoral and gluteal musculature. There was a previous history of Staphylococcus aureus pyomyositis and colitis ulcerosa. The patient was treated successfully with surgical drainage and parenteral antibiotics.

[The prevalence of fibromyalgia and chronic widespread musculoskeletal pain in Iceland.].

OBJECTIVE: To determine the prevalence of fibromyalgia and chronic widespread musculoskeletal pain (CWP) in Iceland in two demographic different areas. MATERIAL AND METHODS: Population based prevalence study on 1200 females and 1200 males 18-79 years old in South-West- and South-Iceland. Established musculoskeletal pain questionnaire and telephone screening of nonresponders was used. Tender point examination was done on the subjects with CWP and the diagnosis of fibromyalgia was made in accordance with the American College of Rheumatology (ACR) 1990 criteria. RESULTS: The prevalence of fibromyalgia in females based on 60.4% of the sample is 9.8%. The comparable prevalence in males based on 46.4% of the sample is 1.3%. The prevalence of CWP is 26.9% in females and 12.9% in males. A sharp increase in the prevalence of fibromyalgia and CWP in females is seen in the age group 31-40 compared with the age group 18-30. For female responders a statistical higher prevalence of CWP but not fibromyalgia is seen in South-West-Iceland, compared with South-Iceland. No regional differences were seen for males. CONCLUSION: The prevalence of fibromyalgia and CWP is very high in Iceland. A matter of special concern is the high prevalence in young females. Possible causes are long working hours and stressful living conditions.

Kingella kingae infections in paediatric patients: 5 cases of septic arthritis, osteomyelitis and bacteraemia.

Kingella kingae is a Gram-negative rod most often recognized as 1 of the organisms causing septic arthritis and osteomyelitis in children. Infection caused by K. kingae had not been diagnosed in Iceland until 5 cases were diagnosed at the Paediatric Department at the University Hospital of Iceland over a 1 year period. In this report we describe these 5 children with invasive infection caused by K. kingae (2 with septic arthritis, 1 with osteomyelitis, 1 with septic arthritis and osteomyelitis, and 1 with bacteraemia) and review the literature. All bacterial isolates were identified by the Bactec culture system.