Andrew McKay

Feasibility of Identifying Pancreatic Cancer based on Serum Metabolomics

Background: We postulated that the abundance of various metabolites in blood would facilitate the diagnosis of pancreatic and biliary lesions, which could potentially prevent unnecessary surgery. Methods: Serum samples from patients with benign hepatobiliary disease (n = 43) and from patients with pancreatic cancer (n = 56) were examined by 1H NMR spectroscopy to quantify 58 unique metabolites. Data were analyzed by “targeted profiling” followed by supervised pattern recognition and orthogonal partial least-squares discriminant analysis (O-PLS-DA) of the most significant metabolites, which enables comparison of the whole sample spectrum between groups. Results: The metabolomic profile of patients with pancreatic cancer was significantly different from that of patients with benign disease (AUROC, area under the ROC curve, = 0.8372). Overt diabetes mellitus (DM) was identified as a possible confounding factor in the pancreatic cancer group. Thus, diabetics were excluded from further analysis. In this more homogeneous pancreatic cancer group, compared with benign cases, serum concentrations of glutamate and glucose were most elevated on multivariate analysis. In benign cases, creatine and glutamine were most abundant. To examine the usefulness of this test, a comparison was made to age- and gender-matched controls with benign lesions that mimic cancer, controlling also for presence of jaundice and diabetes (n = 14 per group). The metabolic profile in patients with pancreatic cancer remained distinguishable from patients with benign pancreatic lesions (AUROC = 0.8308). Conclusions: The serum metabolomic profile may be useful for distinguishing benign from malignant pancreatic lesions. Impact: Further studies will be required to study the effects of jaundice and diabetes. A more comprehensive metabolomic profile will be evaluated using mass spectrometry. Cancer Epidemiol Biomarkers Prev; 20(1); 140–7. ©2010 AACR.

Umbilical hernia repair in the presence of cirrhosis and ascites: results of a survey and review of the literature

PurposeUmbilical hernias are common in cirrhotics, yet, their management poses several challenges. The objective of this paper was to evaluate the indications, selection criteria, and technical aspects of umbilical hernia repair in patients with cirrhosis and ascites.MethodsAn extensive review of the literature since 1980 was performed. A survey was also conducted to obtain expert consensus to supplement any available conclusions from the literature.ResultsNineteen surgeons (45%) responded to the survey. For asymptomatic hernias, all would consider hernia repair in Child’s A cirrhosis, but not in more advanced disease, whereas the vast majority would consider the repair of complicated hernias. This seems to reflect the respondents’ higher estimates of morbidity and mortality with more advanced liver disease. However, because the recent literature demonstrates much lower morbidity and mortality than in the past, many authors now advocate early elective repair. In addition, uncontrolled ascites appear to be strongly predictive of hernia recurrence (relative risk [RR] 8.5; 95% confidence interval [CI] 2.7–26.9).ConclusionsWhile acknowledging the limitations of this study, it appears that the early repair of umbilical hernias in patients with cirrhosis and ascites is safer than it was in the past and can be considered for selected patients. This may avoid increased morbidity and mortality associated with urgent repair later on. The control of ascites is critical to a successful outcome. Urgent repair of umbilical hernia in cirrhotic patients is indicated when complications develop.

Long-Term Outcomes Following Hepatic Resection and Radiofrequency Ablation of Colorectal Liver Metastases

Recently some have called for randomized controlled trials comparing RFA to hepatic resection, particularly for patients with only a few small metastases. The objectives were to compare local recurrence and survival following RFA and hepatic resection for colorectal liver metastases. This was a retrospective review of open RFA and hepatic resection for colorectal liver metastases between January 1998 and May 2007. All patients who had RFA were considered to have unresectable disease. 58 patients had hepatic resection and 43 had RFA. A 5-year survival after resection was 43% compared to 23% after RFA. For patients with solitary lesions, a 5-year survival was 48% after resection and 15% after RFA. Sixty percent of patients suffered local recurrences after RFA compared to 7% after hepatic resection. RFA is inferior to resection. The results observed in this study support the consensus that RFA cannot be considered an equivalent procedure to hepatic resection.

Development of Quality Indicators of Care for Patients Undergoing Hepatic Resection for Metastatic Colorectal Cancer Using a Delphi Process

BACKGROUND Very few quality indicators of care exist for surgical procedures. These may be used to both score the quality of care received, and as a method of improving the quality of care delivered (quality improvement initiatives). MATERIALS AND METHODS The goal of this study was to develop a set of evidence-based quality indicators by expert consensus for patients undergoing hepatic resection of colorectal metastases to the liver. A Delphi approach was used to develop a set of evidence-based quality indicators for patients undergoing hepatic resection of colorectal metastases to liver. A panel of experts was formed through nomination by members of the Canadian Hepatopancreaticobiliary Society (CHPBS). The Delphi process consisted of three iterations of questionnaires. During each round, the panel members were asked to score the potential indicators and suggest any new indicators. RESULTS A list of 70 potential indicators was generated from the literature, of which 27 achieved consensus for inclusion in the final list of quality indicators. After consolidating similar or redundant indicators, the final list had 18 quality indicators. All of the indicators in the final list were from our original literature search. CONCLUSIONS This Delphi process has used the best available evidence, along with a consensus methodology employing the opinion of experts in the field, to identify 18 quality indicators for patients undergoing hepatic resection for metastatic colorectal cancer. These indicators will provide a means for benchmarking quality of care among surgeons, institutions, and health regions.

Determinants of Tuberculin Reactivity among Health Care Workers: Interpretation of Positivity following BCG Vaccination

OBJECTIVE To determine the extent to which a history of Bacille Calmette-Guerin (BCG) vaccination influences the likelihood of positive tuberculin skin test (TST) results. DESIGN Cross-sectional survey using a hospital-based tuberculosis surveillance program. SETTING Health Sciences Centre, a tertiary care hospital in Winnipeg, Manitoba. METHODS The 476 health care workers (HCWs) who had TST as part of the surveillance program between 1993 and 1997 constituted the study population. The two-step test was done in 91% of the participants who did not have a positive initial test, defined as 10 mm or greater of induration. Data were gathered through chart review supplemented by a short questionnaire administered to the HCWs. MAIN RESULTS One hundred and thirty-eight HCWs (29%) had a positive TST. In a stepwise, multiple logistic model controlling for age, sex, job title, work area, age of receiving BCG, time since BCG and duration of employment, only a history of BCG vaccination (odds ratio [OR] 22; 95% CI 12 to 41) and birth outside of Canada (OR 2.6; 95% CI 1.4 to 5.8) were significantly associated with a positive TST. When the definition of a positive TST was modified by increments of 1 mm, from 10 mm up to 20 mm of induration in BCG recipients, BCG was associated with positive reactions with indurations up to 19 mm but not 20 mm or greater. The OR declined with each increment. Of the 84 HCWs who were documented to have at least 20 years between BCG vaccination and testing, 41 (49%) had positive reactions. CONCLUSIONS BCG vaccination can produce lasting tuberculin reactivity, and indurations of 19 mm or less may be due to the effects of the vaccine.

How should we inform women at higher risk of breast cancer about tamoxifen? An approach with a decision guide

SummaryBackground. Tamoxifen has been shown to reduce the incidence of invasive breast cancer in women at higher risk. Translating these research results to clinical practice is challenging. Our objective was to develop and evaluate a decision-making guide and process that can be used in clinical practice to inform eligible women of chemoprevention with tamoxifen.Methods. A decision guide explaining the benefits and risks of tamoxifen was developed with input from health care professionals and two focus groups of women both with and without cancer. Following consent, 51 eligible women presenting to a multi-disciplinary diagnostic facility for breast problems were given the decision guide/questionnaire to read, fill out and return by mail. Women with further questions or wanting to take tamoxifen were encouraged to re-contact their physicians.Results. Atypia was seen in 60% of subjects. Median 5-year Gail risk was 3.7 (range 1.7–9.4). Only 6 (11.8% 95% CI = 2.9, 20.6%) women reported they would like to take tamoxifen while 6 (11.8% 95% CI = 2.9, 20.6%) remained uncertain.Conclusion. We have developed a decision-making guide and process that is acceptable to providers and women to identify and inform women at higher risk of breast cancer with regard to chemoprevention with tamoxifen. Few women in this select group, when provided with a balanced decision guide, wished to pursue chemoprevention with tamoxifesn

Physician attitudes and treatment patterns for pancreatic cancer

BackgroundSurgery appears to be an underutilized treatment option for pancreatic cancer. Nihilistic physician attitudes may be partly responsible. The study objectives were to analyze physician attitudes towards this disease and determine treatment patterns and outcomes including rates of surgical referral.MethodsA survey was administered to 420 physicians in Manitoba to document general knowledge and attitudes. Population based administrative data was accessed for all patients diagnosed with pancreatic cancer between 2004 and 2006 to examine treatment patterns and outcomes.Results181 physicians responded to the survey. Most (73%) believed that surgical resection was worthwhile. Of the 413 Manitobans diagnosed with pancreatic cancer, only 11% underwent an attempt at surgical resection. There were 124 patients with stage I or II disease (i.e. potentially resectable), 85 of these patients received no treatment and 39% were not referred to a surgeon. These patients were older than those referred, but did not have more comorbidities.ConclusionMost physicians were insightfully aware of both the survival benefit and potential risks of surgical resection. However, some did overestimate the surgical mortality and underestimate the associated survival benefit. Although advanced age may justly account for some of the patients not receiving a referral, it is reasonable to assume that nihilistic physician attitudes is contributing to the apparent underutilization of surgery for pancreatic cancer. Efforts should be made to ensure that eligible patients are at least offered surgery as a potential treatment option.

Synoptic operative reports enhance documentation of best practices for rectal cancer.

Implementation of best practices surgical checklists improves patient safety and outcomes. However, documenting performance of these practices can be challenging. The American Society of Colon and Rectal Surgeons developed a Best Practices for Rectal Cancer Checklist (RCC) to standardize and improve the quality of rectal cancer surgery. This study compared the degree to which synoptic (SR) and narrative (NR) operative reports document RCC items.

Geographical disparities of rectal cancer local recurrence and outcomes: a population-based analysis.

BACKGROUND: Challenges exist in providing high-quality cancer treatments to populations spread over large geographical areas. Local recurrence of rectal cancer is a complicated clinical problem associated with high morbidity and mortality. OBJECTIVES: The objectives of this study were to evaluate population-based rates and predictors of local recurrence of rectal cancer in the Province of Manitoba, Canada, with emphasis on the effects of geography. DESIGN: This was a population-based retrospective analysis. Administrative data from the Manitoba Cancer Registry and individual patient charts were reviewed. SETTINGS: Patients with stages I to III rectal cancer who underwent surgery with curative intent in Manitoba between 2004 and 2006 were included. MAIN OUTCOME MEASURES: The primary outcome was the development of local recurrence after surgical resection. RESULTS: Three hundred seventy patients with a mean age of 67 years were identified. The 5-year local recurrence rate was 17.4%. In multivariate analysis, relative to Winnipeg residents, rural residents, regardless of where they underwent surgery, had an increased risk of local recurrence (HR, 3.47; 95% CI, 1.74–6.92 for surgery in Winnipeg; HR, 2.98; 95% CI, 1.59–5.57 for surgery in rural Manitoba). The absence of both neoadjuvant radiotherapy and adjuvant chemotherapy was associated with a higher risk of local recurrence. Higher risk of mortality was noted for rural patients (HR, 1.90; 95% CI, 1.24–2.89) and for those who developed local recurrence (HR, 2.01; 95% CI, 1.27–3.19). CONCLUSION: Local recurrence rates for rectal cancer are high in Manitoba. Geography is an important variable, because rural status is associated with higher local recurrence rates and decreased survival. The use of neoadjuvant radiotherapy was an important predictor of lower local recurrence rates. Further initiatives are imperative to identify why rural patients experience differences in outcomes in Manitoba.

Challenges of Multisite Surgical Teaching Programs: A Review of Surgery Clerkship

OBJECTIVE As the enrollment in medical schools increases, the need for affiliated sites to participate in clerkship teaching will continue. The aim of this literature review was to provide a summary of measures that have been used to compare the training in affiliated community hospital sites with the tertiary teaching hospitals. METHODS An extensive literature search was conducted using PubMed, MEDLINE, and EMBASE. A total of 386 articles were identified, of which 20 were found to be relevant to this topic. The references of those articles were also consulted and were included in the preparation of this manuscript when deemed appropriate. RESULTS A significant difference does not seem to exist in either written examination or clinical performance evaluations among medical students who receive training at either tertiary care teaching hospitals or affiliated community hospital sites. Positive role models are important in influencing the choice of a surgical career, regardless of where clerkship training takes place. CONCLUSIONS Although more research is merited in this area, the current evidence suggests that affiliated sites are comparable in their ability to train medical students during their surgical clerkship.