Petra Schrotz-King

Potential of fecal microbiota for early-stage detection of colorectal cancer

Several bacterial species have been implicated in the development of colorectal carcinoma (CRC), but CRC‐associated changes of fecal microbiota and their potential for cancer screening remain to be explored. Here, we used metagenomic sequencing of fecal samples to identify taxonomic markers that distinguished CRC patients from tumor‐free controls in a study population of 156 participants. Accuracy of metagenomic CRC detection was similar to the standard fecal occult blood test (FOBT) and when both approaches were combined, sensitivity improved > 45% relative to the FOBT, while maintaining its specificity. Accuracy of metagenomic CRC detection did not differ significantly between early‐ and late‐stage cancer and could be validated in independent patient and control populations (N = 335) from different countries. CRC‐associated changes in the fecal microbiome at least partially reflected microbial community composition at the tumor itself, indicating that observed gene pool differences may reveal tumor‐related host–microbe interactions. Indeed, we deduced a metabolic shift from fiber degradation in controls to utilization of host carbohydrates and amino acids in CRC patients, accompanied by an increase of lipopolysaccharide metabolism.

Declining Bowel Cancer Incidence and Mortality in Germany: An Analysis of Time Trends in the First Ten Years After the Introduction of Screening Colonoscopy

BACKGROUND In October 2002, screening colonoscopy from age 55 onward was introduced as part of the German national statutory cancer screening program. Screening colonoscopy is intended to lower both the mortality and the incidence of bowel cancer by enabling the detection and removal of precursor lesions. METHODS The authors studied trends in bowel cancer incidence and mortality in Germany from 2003 to 2012 on the basis of data from the epidemiological cancer registries and from cause-of-death statistics. RESULTS Over the period of investigation, the age-standardized incidence of bowel cancer (with the European population as a standard) fell from 66.1 to 57.0 cases per 100 000 persons per year (-13.8%) in men and from 42.6 to 36.5 per 100 000 persons per year (-14.3%) in women. In parallel with these changes, the age-standardized mortality from bowel cancer fell by 20.8% in men and by 26.5% in women. In the age groups 55-64, 65-74, and 75-84 years, the cumulative risk of receiving a diagnosis of bowel cancer fell by 17-26%; in persons under age 55, this risk fell by only 3% in men, but increased by 14% in women. Long-term data from the cancer registry in the German federal state of Saarland revealed that the incidence of bowel cancer, but not its mortality, had risen over the decades preceding the study; it was only during the period of investigation that the trend reversed itself. CONCLUSION Within 10 years of the introduction of screening colonoscopy in Germany, the incidence of bowel cancer in persons over age 55 fell by 17-26%, after having risen steadily over the preceding decades.

Declining Bowel Cancer Incidence and Mortality in Germany.

BACKGROUND In October 2002, screening colonoscopy from age 55 onward was introduced as part of the German national statutory cancer screening program. Screening colonoscopy is intended to lower both the mortality and the incidence of bowel cancer by enabling the detection and removal of precursor lesions. METHODS The authors studied trends in bowel cancer incidence and mortality in Germany from 2003 to 2012 on the basis of data from the epidemiological cancer registries and from cause-of-death statistics. RESULTS Over the period of investigation, the age-standardized incidence of bowel cancer (with the European population as a standard) fell from 66.1 to 57.0 cases per 100 000 persons per year (-13.8%) in men and from 42.6 to 36.5 per 100 000 persons per year (-14.3%) in women. In parallel with these changes, the age-standardized mortality from bowel cancer fell by 20.8% in men and by 26.5% in women. In the age groups 55-64, 65-74, and 75-84 years, the cumulative risk of receiving a diagnosis of bowel cancer fell by 17-26%; in persons under age 55, this risk fell by only 3% in men, but increased by 14% in women. Long-term data from the cancer registry in the German federal state of Saarland revealed that the incidence of bowel cancer, but not its mortality, had risen over the decades preceding the study; it was only during the period of investigation that the trend reversed itself. CONCLUSION Within 10 years of the introduction of screening colonoscopy in Germany, the incidence of bowel cancer in persons over age 55 fell by 17-26%, after having risen steadily over the preceding decades.

Suitability of Circulating miRNAs as Potential Prognostic Markers in Colorectal Cancer

miRNAs are crucial in cellular processes and have been shown to be abnormally expressed in cancer tissue and the circulation. Circulating miRNAs may serve as a novel class of minimally invasive biomarkers for prognosis. Within a first methodologic study, we evaluated the miRNA profile kinetics in the plasma of patients with colorectal cancer after surgical tumor removal to identify potential suitability as prognostic biomarkers. This pilot study is based on the ColoCare Study, a cohort study of newly diagnosed patients with stage I–IV colorectal cancer. Colorectal cancer pre- and postsurgical blood (2–7 days after surgery) and 6 months follow-up blood from 35 patients were examined and candidate miRNAs were investigated in the plasma. miRNA levels were measured by two-step qRT-PCR. Statistical analysis was performed using log-transformed normalized CT values using SAS 9.3. Comparing pre- and postsurgical miRNA levels revealed a statistically significant decrease of nine circulating miRNAs after surgery (miR92a, miR18a, miR320a, miR106a, miR16-2, miR20a, miR223, miR17, and miR143). Analyses of plasma levels over all three time points demonstrated a statistically significant decrease from presurgery to postsurgery and re-increase from postsurgery to the six months follow-up time point of four circulating miRNAs (miR92a, miR320a, miR106a, and miR18a). We were able to show for the first time that in plasma miRNA profiles change within days after colorectal cancer surgery. Our results underscore the role of the investigated miRNAs in colorectal cancer and their potential utility as prognostic biomarkers. See all the articles in this CEBP Focus section, “Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology.” Cancer Epidemiol Biomarkers Prev; 23(12); 2632–7. ©2014 AACR.

Resection of pancreatic cancer in Europe and USA: an international large-scale study highlighting large variations

Objective Resection can potentially cure resectable pancreatic cancer (PaC) and significantly prolong survival in some patients. This large-scale international study aimed to investigate variations in resection for PaC in Europe and USA and determinants for its utilisation. Design Data from six European population-based cancer registries and the US Surveillance, Epidemiology, and End Results Program database during 2003–2016 were analysed. Age-standardised resection rates for overall and stage I–II PaCs were computed. Associations between resection and demographic and clinical parameters were assessed using multivariable logistic regression models. Results A total of 153 698 records were analysed. In population-based registries in 2012–2014, resection rates ranged from 13.2% (Estonia) to 21.2% (Slovenia) overall and from 34.8% (Norway) to 68.7% (Denmark) for stage I–II tumours, with great international variations. During 2003–2014, resection rates only increased in USA, the Netherlands and Denmark. Resection was significantly less frequently performed with more advanced tumour stage (ORs for stage III and IV versus stage I–II tumours: 0.05–0.18 and 0.01–0.06 across countries) and increasing age (ORs for patients 70–79 and ≥80 versus those <60 years: 0.37–0.63 and 0.03–0.16 across countries). Patients with advanced-stage tumours (stage III–IV: 63.8%–81.2%) and at older ages (≥70 years: 52.6%–59.5%) receiving less frequently resection comprised the majority of diagnosed cases. Patient performance status, tumour location and size were also associated with resection application. Conclusion Rates of PaC resection remain low in Europe and USA with great international variations. Further studies are warranted to explore reasons for these variations.

Time trends in axilla management among early breast cancer patients: Persisting major variation in clinical practice across European centers

Abstract Background We examined time trends in axilla management among patients with early breast cancer in European clinical settings. Material and methods EUROCANPlatform partners, including population-based and cancer center-specific registries, provided routinely available clinical cancer registry data for a comparative study of axillary management trends among patients with first non-metastatic breast cancer who were not selected for neoadjuvant therapy during the last decade. We used an additional short questionnaire to compare clinical care patterns in 2014. Results Patients treated in cancer centers were younger than population-based registry populations. Tumor size and lymph node status distributions varied little between settings or over time. In 2003, sentinel lymph node biopsy (SLNB) use varied between 26% and 81% for pT1 tumors, and between 2% and 68% for pT2 tumors. By 2010, SLNB use increased to 79–96% and 49–92% for pT1 and pT2 tumors, respectively. Axillary lymph node dissection (ALND) use for pT1 tumors decreased from between 75% and 27% in 2003 to 47% and 12% in 2010, and from between 90% and 55% to 79% and 19% for pT2 tumors, respectively. In 2014, important differences in axillary management existed for patients with micrometastases only, and for patients fulfilling the ACOSOG Z0011 criteria for omitting ALND. Conclusion This study demonstrates persisting differences in important aspects of axillary management throughout the recent decade. The results highlight the need for international comparative patterns of care studies in oncology, which may help to identify areas where further studies and consensus building may be necessary.

Minimally invasive colorectal cancer surgery in Europe

AbstractMinimally invasive surgery (MIS) of colorectal cancer (CRC) was first introduced over 20 years ago and recently has gained increasing acceptance and usage beyond clinical trials. However, data on dissemination of the method across countries and on long-term outcomes are still sparse.In the context of a European collaborative study, a total of 112,023 CRC cases from 3 population-based (N = 109,695) and 4 institute-based clinical cancer registries (N = 2328) were studied and compared on the utilization of MIS versus open surgery. Cox regression models were applied to study associations between surgery type and survival of patients from the population-based registries. The study considered adjustment for potential confounders.The percentage of CRC patients undergoing MIS differed substantially between centers and generally increased over time. MIS was significantly less often used in stage II to IV colon cancer compared with stage I in most centers. MIS tended to be less often used in older (70+) than in younger colon cancer patients. MIS tended to be more often used in women than in men with rectal cancer. MIS was associated with significantly reduced mortality among colon cancer patients in the Netherlands (hazard ratio [HR] 0.66, 95% confidence interval [CI] (0.63–0.69), Sweden (HR 0.68, 95% CI 0.60–0.76), and Norway (HR 0.73, 95% CI 0.67–0.79). Likewise, MIS was associated with reduced mortality of rectal cancer patients in the Netherlands (HR 0.74, 95% CI 0.68–0.80) and Sweden (HR 0.77, 95% CI 0.66–0.90).Utilization of MIS in CRC resection is increasing, but large variation between European countries and clinical centers prevails. Our results support association of MIS with substantially enhanced survival among colon cancer patients. Further studies controlling for selection bias and residual confounding are needed to establish role of MIS in survival of patients.

CT-based compartmental quantification of adipose tissue versus body metrics in colorectal cancer patients

AbstractPurposeWhile obesity is considered a prognostic factor in colorectal cancer (CRC), there is increasing evidence that not simply body mass index (BMI) alone but specifically abdominal fat distribution is what matters. As part of the ColoCare study, this study measured the distribution of adipose tissue compartments in CRC patients and aimed to identify the body metric that best correlates with these measurements as a useful proxy for adipose tissue distribution.Materials and methodsIn 120 newly-diagnosed CRC patients who underwent multidetector computed tomography (CT), densitometric quantification of total (TFA), visceral (VFA), intraperitoneal (IFA), retroperitoneal (RFA), and subcutaneous fat area (SFA), as well as the M. erector spinae and psoas was performed to test the association with gender, age, tumor stage, metabolic equivalents, BMI, waist-to-height (WHtR) and waist–to-hip ratio (WHR).ResultsVFA was 28.8 % higher in men (pVFA<0.0001) and 30.5 % higher in patients older than 61 years (pVFA<0.0001). WHtR correlated best with all adipose tissue compartments (rVFA=0.69, rTFA=0.84, p<0.0001) and visceral-to-subcutaneous-fat-ratio (VFR, rVFR=0.22, p=<0.05). Patients with tumor stages III/IV showed significantly lower overall adipose tissue than I/II. Increased M. erector spinae mass was inversely correlated with all compartments.ConclusionDensitometric quantification on CT is a highly reproducible and reliable method to show fat distribution across adipose tissue compartments. This distribution might be best reflected by WHtR, rather than by BMI or WHR.Key Points• Densitometric quantification of adipose tissue on CT is highly reproducible and reliable. • Waist-to-height ratio better correlates with adipose tissue compartments and VFR than BMI or waist-to-hip ratio. • Men have higher a higher visceral fat area than women. • Patients older than 61 years have higher visceral fat area. • Patients with tumor stages III/IV have significantly lower adipose tissue than those in stages I/II.

Rückgang der Inzidenz und Mortalität von Darmkrebs in Deutschland

BACKGROUND In October 2002, screening colonoscopy from age 55 onward was introduced as part of the German national statutory cancer screening program. Screening colonoscopy is intended to lower both the mortality and the incidence of bowel cancer by enabling the detection and removal of precursor lesions. METHODS The authors studied trends in bowel cancer incidence and mortality in Germany from 2003 to 2012 on the basis of data from the epidemiological cancer registries and from cause-of-death statistics. RESULTS Over the period of investigation, the age-standardized incidence of bowel cancer (with the European population as a standard) fell from 66.1 to 57.0 cases per 100 000 persons per year (-13.8%) in men and from 42.6 to 36.5 per 100 000 persons per year (-14.3%) in women. In parallel with these changes, the age-standardized mortality from bowel cancer fell by 20.8% in men and by 26.5% in women. In the age groups 55-64, 65-74, and 75-84 years, the cumulative risk of receiving a diagnosis of bowel cancer fell by 17-26%; in persons under age 55, this risk fell by only 3% in men, but increased by 14% in women. Long-term data from the cancer registry in the German federal state of Saarland revealed that the incidence of bowel cancer, but not its mortality, had risen over the decades preceding the study; it was only during the period of investigation that the trend reversed itself. CONCLUSION Within 10 years of the introduction of screening colonoscopy in Germany, the incidence of bowel cancer in persons over age 55 fell by 17-26%, after having risen steadily over the preceding decades.

Quantitative fecal immunochemical tests for colorectal cancer screening: Stool tests for colorectal cancer screening: A review

Fecal immunochemical tests (FITs) for hemoglobin (Hb) are increasingly used for colorectal cancer (CRC) screening. We aimed to review, summarize and compare reported diagnostic performance of various FITs. PubMed and Web of Science were searched from inception to July 24, 2017. Data on diagnostic performance of quantitative FITs, conducted in colonoscopy‐controlled average‐risk screening populations, were extracted. Summary receiver operating characteristic (ROC) curves were plotted and correlations between thresholds, positivity rates (PRs), sensitivities and specificities were assessed. Seven test brands were investigated across 22 studies. Although reported sensitivities for CRC, advanced adenoma (AA) and any advanced neoplasm (AN) varied widely (ranges: 25–100%, 6–44% and 9–60%, respectively), with specificities for AN ranging from 82% to 99%, the estimates were very close to the respective summary ROC curves whose areas under the curve (95% CI) were 0.905 (0.88–0.94), 0.683 (0.67–0.70) and 0.710 (0.70–0.72) for CRC, AA and AN, respectively. The seemingly large heterogeneity essentially reflected variations in test thresholds (range: 2–82 µg Hb/g feces) and showed moderate correlations with sensitivity (r = −0.49) and specificity (r = 0.60) for AN. By contrast, observed PRs (range: 1–21%) almost perfectly correlated with sensitivity (r = 0.84) and specificity (r = −0.94) for AN. The apparent large heterogeneity in diagnostic performance between various FITs can be almost completely overcome by appropriate threshold adjustments. Instead of simply applying the threshold recommended by the manufacturer, screening programs should adjust the threshold to yield a desired PR which is a very good proxy indicator for the specificity and the subsequent colonoscopy workload.