ABSTRACT
BACKGROUND AND AIMS: Germline mutations in mismatch repair (MMR) genes cause a greatly increased risk of cancer of the gastrointestinal and female reproductive tracts (hereditary non-polyposis colorectal cancer (HNPCC)). Loss of MMR expression is common in colorectal cancer (CRC) overall. Such loss is assumed to be acquired predominantly, although a population of CRC cases will include individuals with unrecognised MMR mutations. This study examines the association between MMR gene expression and family history of cancer among the CRC population. METHODS: Individuals with CRC were identified from two well characterised populations: (1) consecutive hospital patients (n = 644) and (2) a population based cases series (n = 249). CRC was examined for expression of hMLH1 and hMSH2 using immunohistochemistry, and expression was related to family history using logistic regression. RESULTS: hMLH1 and hMSH2 expression was assessed in 732 CRCs with 8% showing loss of expression. No association was seen overall for hMLH1 or hMSH2 expression and family history of CRC. Loss of hMSH2 was predicted by family history of extracolonic cancer (odds ratio (OR) 5.78 (95% confidence interval (CI) 0.95-35.18)) and family history suggestive of HNPCC (OR 27.84 (95% CI 4.37-177.56)). Loss of hMLH1 was not predicted by family history of extracolonic cancer or a family history suggestive of HNPCC but was for a family history of at least two affected relatives (OR 4.88 (95% CI 1.25-19.03)). CONCLUSIONS: Individuals with hMSH2 deficient CRC in the general population exhibit a family history and other characteristics suggestive of HNPCC, and may carry germline MMR mutations. Loss of hMLH1 is only associated with a strong family history of extracolonic cancer at older ages, suggesting a novel mechanism of susceptibility.
Subject(s)
Base Pair Mismatch/genetics , Colorectal Neoplasms/genetics , DNA Repair , Adaptor Proteins, Signal Transducing , Adult , Age Factors , Aged , Aged, 80 and over , Carrier Proteins , Case-Control Studies , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , DNA, Neoplasm/genetics , DNA-Binding Proteins/metabolism , Family , Female , Germ-Line Mutation , Humans , Logistic Models , Male , Microsatellite Repeats/genetics , Middle Aged , MutL Protein Homolog 1 , MutS Homolog 2 Protein , Neoplasm Proteins/metabolism , Nuclear Proteins/metabolism , Proto-Oncogene Proteins/metabolismABSTRACT
BACKGROUND: Many hospitals lack the facilities for high dependency care, and patients requiring this level of care are nursed on the surgical ward. The aim of this study was to assess the extent of this problem in a district general hospital, looking at the impact of providing high dependency unit (HDU) care at ward level. METHODS: A 28 bed surgical ward was studied for 39 consecutive days. Patients were assessed as being either appropriately placed (routine) or inappropriately placed (HDU). Nursing interventions and observations over each 24 hour period were recorded for the most dependent patient in each group. RESULTS: Data were collected for a total of 1092 bed days. Median bed occupancy was 22 patients/day (78%). Inappropriately placed HDU patients accounted for 55 bed days (5%, mean 1.4 patients/day). These patients required more nursing intervention than routine patients. HDU patients received more observations during a 24 hour period than routine patients (mean 11.3 and 4.2 respectively, p<0.005). The number of observations recorded for a routine patient in a 24 hour period fell when a HDU patient was nursed concurrently on the ward (mean 5.1/24 hours, falling to 3.8 /24 hours in the presence of an HDU patient, p<0.02). CONCLUSIONS: HDU patients require more intensive nursing care than routine surgical patients, and the nursing of HDU patients on the ward adversely affects the quantity of care available for less dependent patients. High dependency care should therefore be provided in dedicated units. HDU is an essential facility for all surgical patients, including those who require intensive nursing, and the routine surgical patient whose nursing is compromised by the failure to provide comprehensive postoperative care.
