A Method for Catchment Scale Mapping of Groundwater-Dependent Ecosystems to Support Natural Resource Management (Queensland, Australia).

Immediate and foreseeable threats to groundwater-dependent ecosystems (GDEs) are widely acknowledged, many linked to altered groundwater regimes including changes in groundwater flow, flux, pressure, level and/or quality (Eamus et al. in Aust J Bot 54:97-114, 2006a). Natural resource managers and other decision-makers often lack sufficient information at an appropriate scale to understand the groundwater dependency of ecosystems and ensure that GDEs are adequately considered in decision-making processes. This paper describes a new catchment scale mapping method for GDEs based on the integration of local expert knowledge with detailed spatial datasets to delineate GDEs at a scale compatible with management and planning activities. This overcomes one of the key criticisms often levelled at broader scale mapping methods-that information from local and regional experts, with significant understanding of landscape processes and ecosystems, is not incorporated into the datasets used by decision-makers. Expert knowledge is conveyed in the form of pictorial conceptual models representing the components, processes and interrelationships of groundwater within a catchment and the ecosystems dependent on it. Each mapped GDE is linked to a pictorial conceptual model and a mapping rule-set to provide decision-makers with valuable information about where, how and why GDEs exist in a landscape.

Canadian Expert Group consensus recommendations: KRAS testing in colorectal cancer.

Monoclonal antibodies against the epidermal growth factor receptor (anti-egfr) when used in the treatment of metastatic colorectal cancer are associated with improved survival. Patients whose tumours harbor a KRAS mutation in codon 12 or 13 have been shown not to benefit from anti-egfr antibodies. The importance of KRAS mutation status in the management of patients with metastatic colorectal cancer has led to the elaboration of Canadian consensus recommendations on KRAS testing, with the aim of standardizing practice across Canada and reconciling testing access with the clinical demand for testing. The present guidelines were developed at a Canadian consensus meeting held in Montreal in April 2010. The best available evidence and expertise were used to develop recommendations for various aspects of KRAS testing, including indications and timing for testing, sample requirements, recommendations for reporting requirements, and acceptable turnaround times.

Promoter methylation of Wnt5a is associated with microsatellite instability and BRAF V600E mutation in two large populations of colorectal cancer patients.

BACKGROUND: In colorectal cancer (CRC), tumour microsatellite instability (MSI) status and CpG island methylator phenotype (CIMP) status are indicators of patient outcome, but the molecular events that give rise to these outcomes remain largely unknown. Wnt5a is a critical regulator of non-canonical Wnt activity and promoter hypermethylation of this gene has emerging prognostic roles in CRC; however the frequency and prognostic significance of this epigenetic event have not been explored in the context of colorectal tumour subtype. Consequently, we investigated the frequency and prognostic significance of Wnt5a methylation in a large cohort of MSI-stratified CRCs. METHODS: Methylation was quantified in a large cohort of 1232 colorectal carcinomas from two clinically distinct populations from Canada. Associations were examined between methylation status and clinicopathlogical features, including tumour MSI status, BRAF V600E mutation, and patient survival. RESULTS: In Ontario, Wnt5a methylation was strongly associated with MSI tumours after adjustment for age, sex, and tumour location (odds ratio (OR)=4.2, 95% confidence interval (CI)=2.4-7.4, P<10(-6)) and with BRAF V600E mutation, a marker of CIMP (OR=12.3, 95% CI=6.9-21.7, P<10(-17)), but was not associated with patient survival. Concordant results were obtained in Newfoundland. CONCLUSION: Methylation of Wnt5a is associated with distinct tumour subtypes, strengthening the evidence of an epigenetic-mediated Wnt bias in CRC.

The genetic basis of colorectal cancer in a population-based incident cohort with a high rate of familial disease.

BACKGROUND AND AIMS: Colorectal cancer (CRC) is the second most frequent cancer in developed countries. Newfoundland has the highest incidence of CRC in Canada and the highest rate of familial CRC yet reported in the world. To determine the impact of mutations in known CRC susceptibility genes and the contribution of the known pathways to the development of hereditary CRC, an incident cohort of 750 patients with CRC (708 different families) from the Newfoundland population was studied. METHODS: Microsatellite instability (MSI) testing was performed on tumours, together with immunohistochemistry analysis for mismatch repair (MMR) genes. Where indicated, DNA sequencing and multiplex ligation-dependent probe amplifications of MMR genes and APC was undertaken. DNA from all patients was screened for MUTYH mutations. The presence of the BRAF variant, p.V600E, and of MLH1 promoter methylation was also tested in tumours. RESULTS: 4.6% of patients fulfilled the Amsterdam criteria (AC), and an additional 44.6% fulfilled the revised Bethesda criteria. MSI-high (MSI-H) was observed in 10.7% (n=78) of 732 tumours. In 3.6% (n=27) of patients, CRC was attributed to 12 different inherited mutations in six known CRC-related genes associated with chromosomal instability or MSI pathways. Seven patients (0.9%) carried a mutation in APC or biallelic mutations in MUTYH. Of 20 patients (2.7%) with mutations in MMR genes, 14 (70%) had one of two MSH2 founder mutations. 17 of 28 (61%) AC families did not have a genetic cause identified, of which 15 kindreds fulfilled the criteria for familial CRC type X (FCCTX). CONCLUSIONS: Founder mutations accounted for only 2.1% of cases and this was insufficient to explain the high rate of familial CRC. Many of the families classified as FCCTX may have highly penetrant mutations segregating in a Mendelian-like manner. These families will be important for identifying additional CRC susceptibility loci.

Rhabdomyosarcoma in patients with constitutional mismatch-repair-deficiency syndrome.

BACKGROUND: Biallelic germline mutations in the mismatch repair genes MLH1, MSH2, MSH6 or PMS2 cause a recessive childhood cancer syndrome characterised by early-onset malignancies and signs reminiscent of neurofibromatosis type 1 (NF1). Alluding to the underlying genetic defect, we refer to this syndrome as constitutional mismatch repair-deficiency (CMMR-D) syndrome. The tumour spectrum of CMMR-D syndrome includes haematological neoplasias, brain tumours and Lynch syndrome-associated tumours. Other tumours, such as neuroblastoma, Wilm tumour, ovarian neuroectodermal tumour or infantile myofibromatosis, have so far been found only in individual cases. RESULTS: We analysed two consanguineous families that had members with suspected CMMR-D syndrome who developed rhabdomyosarcoma among other neoplasias. In the first family, we identified a pathogenic PMS2 mutation for which the affected patient was homozygous. In family 2, immunohistochemistry analysis showed isolated loss of PMS2 expression in all tumours in the affected patients, including rhabdomyosarcoma itself and the surrounding normal tissue. Together with the family history and microsatellite instability observed in one tumour this strongly suggests an underlying PMS2 alteration in family 2 also. CONCLUSION: Together, these two new cases show that rhabdomyosarcoma and possibly other embryonic tumours, such as neuroblastoma and Wilm tumour, belong to the tumour spectrum of CMMR-D syndrome. Given the clinical overlap of CMMR-D syndrome with NF1, we suggest careful examination of the family history in patients with embryonic tumours and signs of NF1 as well as analysis of the tumours for loss of one of the mismatch repair genes and microsatellite instability. Subsequent mutation analysis will lead to a definitive diagnosis of the underlying disorder.

Pathological features of colorectal carcinomas in MYH-associated polyposis.

AIMS: MYH is a DNA glycosylase in the base excision repair pathway. Germ-line biallelic mutations in the MYH gene are associated with the development of multiple colorectal adenomas and colorectal carcinoma (CRC). A slightly increased risk of CRC is suggested in monoallelic MYH mutation carriers. The aim was to characterize the histopathological features of carcinomas from biallelics and monoallelics. METHODS AND RESULTS: Clinicopathological features of 57 colorectal carcinomas from 50 patients identified in familial CRC registries were recorded. These included 16 cancers from 14 MYH biallelics; 25 cancers from 22 MYH monoallelics; and 16 cancers from 14 controls. Carcinomas in biallelics demonstrated tubular, papillary or cribriform patterns as the predominant histological subtype, and main histological groups differed according to mutation status (P = 0.0053). All biallelic cancers were low grade, with high-grade tumours more common in monoallelics and controls (P = 0.002). Synchronous polyps were observed in 75% of biallelics, 33% of monoallelics and 43% of controls (P = 0.035). Serrated carcinoma was the predominant type in 12% (3/25) of the monoallelics but in none of the biallelics or controls. MYH immunohistochemistry failed to distinguish between groups. CONCLUSIONS: Neither pathological features nor immunohistochemistry could predict the MYH mutation status of CRCs in this study.

Sclerosing pancreatitis presenting as a periampullary tumour.

BACKGROUND: Sclerosing lesions of the pancreatic duct are rare and may be secondary to primary sclerosing cholangitis (PSC) or the result of a primary sclerosing process (the recently described lymphoplasmacystic sclerosing pancreatitis, LSP). Occasionally this process may present as a mass lesion. CASE OUTLINE: A 21 -year-old man presented with abdominal pain and jaundice, giving a high index of suspicion for a periampullary malignancy. There were minimal symptoms suggestive of PSC. The resected head of the pancreas demonstrated changes of chronic pancreatitis with a fibro-inflammatory process of the pancreatic duct suggesting an underlying ductal sclerosing process. DISCUSSION: Clinical presentation and imaging characteristics of PSC involving the pancreas are often misleading and may suggest a neoplasm as the underlying disorder. Conclusive diagnosis is usually not determined until after surgical intervention. Although racial differences in pancreatic duct involvement have been suggested, the underlying histopathology is the same as in PSC involving the biliary ducts.

Palliative care by family physicians in the 1990s. Resilience amid reform.

OBJECTIVE: To explore issues family physicians face in providing community-based palliative care to their patients in the context of a changing health care system. DESIGN: Focus groups. SETTING: Small (< 10,000 population), medium-sized (10,000 to 50,000), and large (> 50,000) communities in Nova Scotia. PARTICIPANTS: Twenty-five men and women physicians with varying years of practice experience in both solo and group practices. METHOD: A semistructured approach was used, asking physicians to reflect on recent palliative care experiences in order to explore issues of care. MAIN FINDINGS: Five themes emerged from the discussions: resources needed, availability of family support, time and money supporting physicians' activities, symptom control for patients, and physicians' emotional reactions to caring for dying patients. CONCLUSION: With downsizing of hospitals and greater emphasis on community-based care, the issues identified in this study will need attention, particularly in designing an integrated service delivery model for palliative care.

Correlation of p53 mutations in ThinPrep-processed fine needle breast aspirates with surgically resected breast cancers.

Mutations of the p53 gene are one of the most common genetic changes found in cancer; their presence may be prognostic and even influence treatment for breast cancer. In this study, we investigated whether DNA could be extracted from the residual cells left in ThinPrep-processed breast fine-needle aspirates and whether p53 gene changes could be detected in the DNA. The results were then correlated with DNA extracted from the matched formalin-fixed, paraffin-embedded, surgically resected breast cancer when available. DNA was successfully extracted from 54 of 62 aspirates and all 31 surgical specimens. p53 gene mutations were detected in 10 of the 54 cytology specimens (18.5%) and consisted of base pair substitutions or deletions. Silent or intronic p53 changes were found in five additional aspirates. One of the aspirates had two gene alterations, resulting in a total of six gene changes. Five of these changes were located in introns 6 or 9 and the sixth was a silent (no amino acid change) change in exon 6. p53 Polymorphisms were detected in nine aspirates (16.3%) and were located in codon 47 (one aspirate), codon 72 (six aspirates), and codon 213 (two aspirates). All cases with surgical material available showed identical p53 mutations, alterations, and polymorphisms in the resected tumors compared with those detected in the corresponding aspirates. The results of this study show that DNA suitable for analysis of p53 gene sequence changes can be successfully extracted from ThinPrep-processed breast fine-needle aspirates, and that identical alterations are detected in both the cytology and surgical specimens.

Family Medicine residents' knowledge and attitudes about end-of-life care.

The medical management of end-of-life symptoms, and the psychosocial care of the dying and their families have not been a specific part of the curriculum for undergraduate medical students or residency training programs. The purpose of our research was to assess family medicine residents' knowledge of and attitudes toward care of the dying. All entering (PGY1) and exiting (PGY2) residents of the Dalhousie University Family Medicine Residency Program were given a 50-item survey on end-of-life care. They survey contains two 25-item subscales concerning attitudes/opinions toward end-of-life care, and knowledge about care. Thirty-one of the 33 entering PGY1s 94%) and 26 of the 30 exiting PGY2s (86%) completed the surveys. Overall attitude scores were felt to be high among both groups, with little difference between them. Areas of concern regarding the adequacy of knowledge were found in relation to managing opioid drugs and the symptom of dyspnea. Interventions are now in development to address these issues in the residency program. In an era of subspecialties, the challenge of integrating these areas into the curriculum without creating rotations in specialist palliative care is an issue faced by most family medicine residency programs.

Breast fine-needle aspiration. A comparison of ThinPrep and conventional smears.

Fine-needle aspiration (FNA) of the breast has been used in our institution since 1969. In August 1993, ThinPrep (Cytyc Corp, Boxbotough, MA) processing of breast FNA biopsy specimens was introduced. Comparing conventionally prepared breast FNA specimens (21,193 cases) with ThinPrep processed material (7,903 cases) shows a decrease in the unsatisfactory rate with the ThinPrep processing (29.5% to 27.7%) with no significant change in sensitivity (84.4% vs 86.3%) or positive predictive value (96.5 vs 95.0%). However, there is a slight decrease in specificity (98.6% vs 96.5%) and negative predictive value (91.1% vs 88.0%) with the ThinPrep specimens. The results span 28 years, during which time the breast cancer population has changed, with a higher prevalence of malignancy in the last decade of our study. When the 4 most recent years of conventional cytology are compared with the 4 years of ThinPrep processing, there is no significant difference in diagnostic accuracy. The results of the present study show that the ThinPrep processing technique provides an effective method for preparing breast FNA. specimens.

High-grade papillary cystadenocarcinoma of the tongue.

AIMS: Salivary gland tumours of the tongue are rare. The most common type is low-grade mucoepidermoid carcinoma followed by adenoid cystic carcinoma. Papillary cystadenocarcinoma of salivary glands are uncommon lesions with low-grade mucoepidermoid carcinoma followed by adenoid cystic carcinoma. Papillary cystadenocarcinoma of salivary glands are uncommon lesions with low-grade histological and clinical features. We report a high-grade papillary cystadenocarcinoma in an 80-year-old man who presented with a tongue mass and metastatic disease in the neck. METHODS AND RESULTS: He was treated with partial glossectomy and bilateral neck dissection but developed local and regional recurrences 6 months later. The tumour had a prominent cystic appearance and had areas of necrosis. The cyst lumen was occupied by numerous papillae lined by pseudostratified columnar cells with a high nuclear-cytoplasmic ratio. The cytoplasm was eosinophilic, the nuclei were pleomorphic and exhibited irregular nuclear membranes, vesicular chromatin and prominent eosinophilic nucleoli. The mitotic activity was high and there were occasional abnormal mitotic figures. Metastatic carcinoma was present in four lymph nodes. The differential diagnosis of this unusual lesion includes cystadenoma, salivary duct carcinoma and metastases. CONCLUSIONS: This case and a review of the literature indicates that papillary cystadenocarcinomas of salivary gland origin exhibit a wider morphologic spectrum than described in the latest World Health Organization (WHO) classification which defines these lesions as low-grade neoplasms.