Intensified surveillance after surgery for colorectal cancer significantly improves survival

<p>Abstract</p> <p>Background</p> <p>Postoperative surveillance after curative resection for colorectal cancer has been demostrated to improve survival. It remains unknown however, whether intensified surveillance provides a significant benefit regarding outcome and survival. This study was aimed at comparing different surveillance strategies regarding their effect on long-term outcome.</p> <p>Methods</p> <p>Between 1990 and 2006, all curative resections for colorectal cancer were selected from our prospective colorectal cancer database. All patients were offered to follow our institution's surveillance programm according to the ASCO guidelines. We defined surveillance as "intensive" in cases where > 70% appointments were attended and the program was completed. As "minimal" we defined surveillance with < 70% of the appointments attended and an incomplete program. As "none" we defined the group which did not take part in any surveillance.</p> <p>Results</p> <p>Out of 1469 patients 858 patients underwent "intensive", 297 "minimal" and 314 "none" surveillance. The three groups were well balanced regarding biographical data and tumor characteristics. The 5-year survival rates were 79% (intensive), 76% (minimal) and 54% (none) (OR 1.480, (95% CI 1.135-1.929); <it>p </it>< 0.0001), respectively. The 10-year survival rates were 65% (intensive), 50% (minimal) and 31% (none) (<it>p </it>< 0.0001), respectively. With a median follow-up of 70 months the median time of survival was 191 months (intensive), 116 months (minimal) and 66 months (none) (<it>p </it>< 0.0001). After recurrence, the 5-year survival rates were 32% (intensive, <it>p </it>= 0.034), 13% (minimal, <it>p </it>= 0.001) and 19% (none, <it>p </it>= 0.614). The median time of survival after recurrence was 31 months (intensive, <it>p </it>< 0.0001), 21 months (minimal, <it>p </it>< 0.0001) and 16 month (none, <it>p </it>< 0.0001) respectively.</p> <p>Conclusion</p> <p>Intensive surveillance after curative resection of colorectal cancer improves survival. In cases of recurrent disease, intensive surveillance has a positive impact on patients' prognosis. Large randomized, multicenter trials are needed to substantiate these results.</p

The revised Bethesda guidelines: extent of utilization in a university hospital medical center with a cancer genetics program

<p>Abstract</p> <p>Background</p> <p>In 1996, the National Cancer Institute hosted an international workshop to develop criteria to identify patients with colorectal cancer who should be offered microsatellite instability (MSI) testing due to an increased risk for Hereditary Nonpolyposis Colorectal Cancer (HNPCC). These criteria were further modified in 2004 and became known as the revised Bethesda Guidelines. Our study aimed to retrospectively evaluate the percentage of patients diagnosed with HNPCC tumors in 2004 who met revised Bethesda criteria for MSI testing, who were referred for genetic counseling within our institution.</p> <p>Methods</p> <p>All HNPCC tumors diagnosed in 2004 were identified by accessing CoPath, an internal database. Both the Tumor Registry and patients' electronic medical records were accessed to collect all relevant family history information. The list of patients who met at least one of the revised Bethesda criteria, who were candidates for MSI testing, was then cross-referenced with the database of patients referred for genetic counseling within our institution.</p> <p>Results</p> <p>A total of 380 HNPCC-associated tumors were diagnosed at our institution during 2004 of which 41 (10.7%) met at least one of the revised Bethesda criteria. Eight (19.5%) of these patients were referred for cancer genetic counseling of which 2 (25%) were seen by a genetics professional. Ultimately, only 4.9% of patients eligible for MSI testing in 2004 were seen for genetic counseling.</p> <p>Conclusion</p> <p>This retrospective study identified a number of barriers, both internal and external, which hindered the identification of individuals with HNPCC, thus limiting the ability to appropriately manage these high risk families.</p

Retrospective cohort study: Risk of gastrointestinal cancer in a symptomatic cohort after a complete colonoscopy: Role of faecal immunochemical test

BACKGROUND: Faecal immunochemical test (FIT) has been recommended to assess symptomatic patients for colorectal cancer (CRC) detection. Nevertheless, some conditions could theoretically favour blood originating in proximal areas of the gastrointestinal tract passing through the colon unmetabolized. A positive FIT result could be related to other gastrointestinal cancers (GIC). AIM: To assess the risk of GIC detection and related death in FIT-positive symptomatic patients (threshold 10 µg Hb/g faeces) without CRC. METHODS: Post hoc cohort analysis performed within two prospective diagnostic test studies evaluating the diagnostic accuracy of different FIT analytical systems for CRC and significant colonic lesion detection. Ambulatory patients with gastrointestinal symptoms referred consecutively for colonoscopy from primary and secondary healthcare, underwent a quantitative FIT before undergoing a complete colonoscopy. Patients without CRC were divided into two groups (positive and negative FIT) using the threshold of 10 µg Hb/g of faeces and data from follow-up were retrieved from electronic medical records of the public hospitals involved in the research. We determined the cumulative risk of GIC, CRC and upper GIC. Hazard rate (HR) was calculated adjusted by age, sex and presence of significant colonic lesion. RESULTS: We included 2709 patients without CRC and a complete baseline colonoscopy, 730 (26.9%) with FIT = 10 µgr Hb/gr. During a mean time of 45.5 ± 20.0 mo, a GIC was detected in 57 (2.1%) patients: An upper GIC in 35 (1.3%) and a CRC in 14 (0.5%). Thirty-six patients (1.3%) died due to GIC: 22 (0.8%) due to an upper GIC and 9 (0.3%) due to CRC. FIT-positive subjects showed a higher CRC risk (HR 3.8, 95%CI: 1.2-11.9) with no differences in GIC (HR 1.5, 95%CI: 0.8-2.7) or upper GIC risk (HR 1.0, 95%CI: 0.5-2.2). Patients with a positive FIT had only an increased risk of CRC-related death (HR 10.8, 95%CI: 2.1-57.1) and GIC-related death (HR 2.2, 95%CI: 1.1-4.3), with no differences in upper GIC-related death (HR 1.4, 95%CI: 0.6-3.3). An upper GIC was detected in 22 (0.8%) patients during the first year. Two variables were independently associated: anaemia (OR 5.6, 95%CI: 2.2-13.9) and age = 70 years (OR 2.7, 95%CI: 1.1-7.0). CONCLUSION: Symptomatic patients without CRC have a moderate risk increase in upper GIC, regardless of the FIT result. Patients with a positive FIT have an increased risk of post-colonoscopy CRC

Anticipating implementation of colorectal cancer screening in The Netherlands: a nation wide survey on endoscopic supply and demand

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) screening requires sufficient endoscopic resources. The present study aims to determine the Dutch endoscopic production and manpower for 2009, evaluate trends since 2004, determine additional workload which would be caused by implementation of a CRC screening program, and inventory colonoscopy rates performed in other European countries.</p> <p>Methods</p> <p>All Dutch endoscopy units (N = 101) were surveyed for manpower and the numbers of endoscopy procedures performed in 2009. Based on calculations in the report issued by the Dutch Health Council, future additional workload caused by faecal immunochemical test (FIT) screening was estimated. The number of colonoscopies performed in Europe was evaluated by a literature search and an email-inquiry.</p> <p>Results</p> <p>Compared to 2004, there was a 24% increase in total endoscopies (N = 505,226 in 2009), and a 64% increase in colonoscopies (N = 191,339 in 2009) in The Netherlands. The number of endoscopists had increased by 4.6% (N = 583 in 2009). Five years after stepwise implementation of FIT-based CRC screening, endoscopic capacity needs to be increased an additional 15%. A lack of published data on the number of endoscopies performed in Europe was found. Based on our email-inquiry, the number of colonoscopies per 100,000 inhabitants ranged from 126 to 3,031 in 15 European countries.</p> <p>Conclusions</p> <p>Over the last years, endoscopic procedures increased markedly in The Netherlands without a corresponding increase in manpower. A FIT-based CRC screening program requires an estimated additional 15% increase in endoscopic procedures. It is very likely that current colonoscopy density varies widely across European countries.</p

Modeling screening, prevention, and delaying of Alzheimer's disease: an early-stage decision analytic model

<p>Abstract</p> <p>Background</p> <p>Alzheimer's Disease (AD) affects a growing proportion of the population each year. Novel therapies on the horizon may slow the progress of AD symptoms and avoid cases altogether. Initiating treatment for the underlying pathology of AD would ideally be based on biomarker screening tools identifying pre-symptomatic individuals. Early-stage modeling provides estimates of potential outcomes and informs policy development.</p> <p>Methods</p> <p>A time-to-event (TTE) simulation provided estimates of screening asymptomatic patients in the general population age ≥55 and treatment impact on the number of patients reaching AD. Patients were followed from AD screen until all-cause death. Baseline sensitivity and specificity were 0.87 and 0.78, with treatment on positive screen. Treatment slowed progression by 50%. Events were scheduled using literature-based age-dependent incidences of AD and death.</p> <p>Results</p> <p>The base case results indicated increased AD free years (AD-FYs) through delays in onset and a reduction of 20 AD cases per 1000 screened individuals. Patients completely avoiding AD accounted for 61% of the incremental AD-FYs gained. Total years of treatment per 1000 screened patients was 2,611. The number-needed-to-screen was 51 and the number-needed-to-treat was 12 to avoid one case of AD. One-way sensitivity analysis indicated that duration of screening sensitivity and rescreen interval impact AD-FYs the most. A two-way sensitivity analysis found that for a test with an extended duration of sensitivity (15 years) the number of AD cases avoided was 6,000-7,000 cases for a test with higher sensitivity and specificity (0.90,0.90).</p> <p>Conclusions</p> <p>This study yielded valuable parameter range estimates at an early stage in the study of screening for AD. Analysis identified duration of screening sensitivity as a key variable that may be unavailable from clinical trials.</p

Early detection of recurrence by 18FDG-PET in the follow-up of patients with colorectal cancer

We assessed the potential benefits of including systematic 18fluorodeoxyglucose positron emission tomography (FDG-PET) for detecting tumour recurrence in a prospective randomised trial. Patients (N=130) who had undergone curative therapy were randomised to undergo either conventional (Con) or FDG-PET procedures during follow-up. The two groups were matched at baseline. Recurrence was confirmed histologically. ‘Intention-to-treat' analysis revealed a recurrence in 46 patients (25 in the FDG-PET group, and 21 in the Con group; P=0.50), whereas per protocol analysis revealed a recurrence in 44 out of 125 patients (23 and 21, respectively; P=0.60). In another three cases, PET revealed unexpected tumours (one gastric GIST, two primary pulmonary cancers). Three false-positive cases of FDG-PET led to no beneficial procedures (two laparoscopies and one liver MRI that were normal). We failed to identify peritoneal carcinomatosis in two of the patients undergoing FDG-PET. The overall time in detecting a recurrence from the baseline was not significantly different in the two groups. However, recurrences were detected after a shorter time (12.1 vs 15.4 months; P=0.01) in the PET group, in which recurrences were also more frequently (10 vs two patients) cured by surgery (R0). Regular FDG-PET monitoring in the follow up of colorectal cancer patients may permit the earlier detection of recurrence, and influence therapy strategies

The Biodiversity of the Mediterranean Sea: Estimates, Patterns, and Threats

The Mediterranean Sea is a marine biodiversity hot spot. Here we combined an extensive literature analysis with expert opinions to update publicly available estimates of major taxa in this marine ecosystem and to revise and update several species lists. We also assessed overall spatial and temporal patterns of species diversity and identified major changes and threats. Our results listed approximately 17,000 marine species occurring in the Mediterranean Sea. However, our estimates of marine diversity are still incomplete as yet—undescribed species will be added in the future. Diversity for microbes is substantially underestimated, and the deep-sea areas and portions of the southern and eastern region are still poorly known. In addition, the invasion of alien species is a crucial factor that will continue to change the biodiversity of the Mediterranean, mainly in its eastern basin that can spread rapidly northwards and westwards due to the warming of the Mediterranean Sea. Spatial patterns showed a general decrease in biodiversity from northwestern to southeastern regions following a gradient of production, with some exceptions and caution due to gaps in our knowledge of the biota along the southern and eastern rims. Biodiversity was also generally higher in coastal areas and continental shelves, and decreases with depth. Temporal trends indicated that overexploitation and habitat loss have been the main human drivers of historical changes in biodiversity. At present, habitat loss and degradation, followed by fishing impacts, pollution, climate change, eutrophication, and the establishment of alien species are the most important threats and affect the greatest number of taxonomic groups. All these impacts are expected to grow in importance in the future, especially climate change and habitat degradation. The spatial identification of hot spots highlighted the ecological importance of most of the western Mediterranean shelves (and in particular, the Strait of Gibraltar and the adjacent Alboran Sea), western African coast, the Adriatic, and the Aegean Sea, which show high concentrations of endangered, threatened, or vulnerable species. The Levantine Basin, severely impacted by the invasion of species, is endangered as well

Keep off the grass?:Cannabis, cognition and addiction

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.In an increasing number of states and countries, cannabis now stands poised to join alcohol and tobacco as a legal drug. Quantifying the relative adverse and beneficial effects of cannabis and its constituent cannabinoids should therefore be prioritized. Whereas newspaper headlines have focused on links between cannabis and psychosis, less attention has been paid to the much more common problem of cannabis addiction. Certain cognitive changes have also been attributed to cannabis use, although their causality and longevity are fiercely debated. Identifying why some individuals are more vulnerable than others to the adverse effects of cannabis is now of paramount importance to public health. Here, we review the current state of knowledge about such vulnerability factors, the variations in types of cannabis, and the relationship between these and cognition and addiction.This work was supported by grants from the US National Institutes of Health to L.H.P. (AA020404, AA006420, AA022249 and AA017447) and by grants from the UK Medical Research Council to H.V.C. and C.J.A.M. (G0800268; MR/K015524/1)