Background-10% of sporadic colorectal cancers are characterised by a low level of microsatellite instability (MSI-L). These are not thought to diVer substantially from microsatellite-stable (MSS) cancers, but MSI-L and MSS cancers are distinguished clinicopathologically and in their spectrum of genetic alterations from cancers showing high level microsatellite instability (MSI-H). Aims-To study the distribution of molecular alterations in a series of colorectal cancers stratified by DNA microsatellite instability. Methods-A subset of an unselected series of colorectal cancers was grouped by the finding of DNA MSI at 0 loci (MSS) (n = 51), 1-2 loci (MSI-L) (n = 38) and 3-6 loci (MSI-H) (n = 25). The frequency of K-ras mutation, loss of heterozygosity (LOH) at 5q, 17p and 18q, and patterns of p53 and catenin immunohistochemistry was determined in the three groups. Results-MSI-H cancers had a low frequency of K-ras mutation (7%), LOH on chromosomes 5q (0%), 17p (0%) and 18q (12.5%), and a normal pattern of immunostaining for p53 and catenin. MSI-L cancers diVered from MSS cancers in terms of a higher frequency of K-ras mutation (54% v 27%) (p = 0.01) and lower frequency of 5q LOH (23% v 48%) (p = 0.047). Whereas aberrant catenin expression and 5q LOH were concordant (both present or both absent) in 57% of MSS cancers, concordance was observed in only 20% of MSI-L cancers (p = 0.01). Conclusions-MSI-L colorectal cancers are distinct from both MSI-H and MSS cancers. This subset combines features of the suppressor and mutator pathways, may be more dependent on K-ras than on the APC gene in the early stages of neoplastic evolution, and a proportion may be related histogenetically to the serrated (hyperplastic) polyp. (J Clin Pathol 1999;52:455-460)
Predicting patient outcome for colorectal carcinoma (CRC) with lymph node but not distant metastases remains challenging. Various prognostic markers have been identified including microsatellite instability (MSI) and possibly expression of the MHC Class II protein, HLA-DR. About 15% of sporadic CRC exhibits MSI associated with methylation of the DNA mismatch repair gene hMLH1 promoter. In addition, a significant proportion of unselected CRC demonstrates expression of HLA-DR. We sought to examine the relationship between HLA-DR expression, MSI status and prognosis in sporadic Australian Clinicopathological (ACP) Stage C CRC. Two hundred seventy consecutive patients with sporadic ACP Stage C CRC were treated at Concord Repatriation General Hospital between 1986 and 1992. None of these patients received adjuvant chemotherapy and all were followed for a minimum of 5 years or until death. DNA was extracted from paraffin sections and MSI status determined by PCR. HLA-DR expression was determined immunohistochemically using an antibody against the HLA-DR a chain. MSI status could be assigned in 235 cases: 176 CRCs (74.9%) were microsatellite stable, whereas 23 (9.8%) had high levels of MSI (MSI-H) and 36 (15.3%) had low levels of MSI (MSI-L). HLA-DR expression by CRC cells was seen in 148 (60.1%) cases and correlated with the presence of tumor-infiltrating lymphocytes (p 5 0.0005) and peritumoral lymphocytes (p 5 0.003), but not other clinicopathological features or MSI status. HLA-DR-positive CRCs were strongly associated with better patient outcome (p < 0.0001). ' 2009 UICC
Background
Obstetric anal sphincter injuries (OASIs) are a significant complication of vaginal delivery, and a leading cause of anal incontinence in women.
Aims
The aims were to explore the management of OASIs in Australia and New Zealand (ANZ) by colorectal surgeons and how this compares with current recommendations and international experience, and to identify the deterrents to the provision of best‐practice care among colorectal surgeons.
Materials and Methods
Three hundred colorectal surgeons of the Colorectal Surgical Society of ANZ were mailed questionnaires. Areas of interest included: surgeon demographics; exposure to OASIs; understanding of current recommendations; and opinions regarding the importance of symptoms and assessment tools in OASIs.
Results
There were 94 completed questionnaires (response rate 31.3%). Fifty‐seven surgeons (60.6%) reported low exposure to OASIs during their fellowship training. Greater than 90% believed patients with grade three tears and above should have anal sphincter assessment. Sixty‐six (70.2%) reported that they routinely review women who have had OASIs. However, 56.4% were unaware if their obstetrics department followed a standard protocol for OASIs. Surgeons practising in metropolitan centres reported higher rates of their obstetrics department following a protocol (P = 0.013), and greater access to investigative tools (P < 0.001), when compared to rural‐based surgeons.
Conclusions
Most ANZ colorectal surgeons have had minimal training in OASI management. Colorectal surgeons are more commonly involved with OASI patients in the non‐acute setting. Management protocols involving a multidisciplinary team of both colorectal surgeons and obstetricians should be clearly defined, and the gap between metropolitan and rural centres needs to be reviewed.
Available literature suggest that internal anal sphincter in systemic sclerosis is invariably thinned and hyperechoic. This series suggests that two distinct morphologic changes are possible.
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