Robert G. Riedl

Accurate Prediction of Pathological Rectal Tumor Response after Two Weeks of Preoperative Radiochemotherapy Using 18F-Fluorodeoxyglucose-Positron Emission Tomography-Computed Tomography Imaging

PURPOSE To determine the optimal time point for repeated (18)F-fluorodeoxyglucose-positron emission tomography (PET)-CT imaging during preoperative radiochemotherapy (RCT) and the best predictive factor for the prediction of pathological treatment response in patients with locally advanced rectal cancer. METHODS AND MATERIALS A total of 30 patients referred for preoperative RCT treatment were included in this prospective study. All patients underwent sequential PET-CT imaging at four time points: prior to therapy, at day 8 and 15 during RCT, and shortly before surgery. Tumor metabolic treatment responses were correlated with the pathological responses by evaluation of the tumor regression grade (TRG) and the pathological TN (ypT) stage of the resected specimen. RESULTS Based on their TRG evaluations, 13 patients were classified as pathological responders, whereas 17 patients were classified as pathological nonresponders. The response index (RI) for the maximum standardized uptake value (SUV(max)) on day 15 of RCT was found to be the best predictive factor for the pathological response (area under the curve [AUC] = 0.87) compared to the RI on day 8 (AUC = 0.78) or the RI of presurgical PET imaging (AUC = 0.66). A cutoff value of 43% for the reduction of SUV(max) resulted in a sensitivity of 77% and a specificity of 93%. CONCLUSIONS The SUV(max)-based RI calculated after the first 2 weeks of RCT provided the best predictor of pathological treatment response, reaching AUCs of 0.87 and 0.84 for the TRG and the ypT stage, respectively. However, a few patients presented with peritumoral inflammatory reactions, which led to mispredictions. Exclusion of these patients further enhanced the predictive accuracy of PET imaging to AUCs of 0.97 and 0.89 for TRG and ypT, respectively.

Endoscopic appearance of proximal colorectal neoplasms and potential implications for colonoscopy in cancer prevention

BACKGROUND In everyday practice, the use of colonoscopy for the prevention of colorectal cancer (CRC) is less effective in the proximal than the distal colon. A potential explanation for this is that proximal neoplasms have a more subtle endoscopic appearance, making them more likely to be overlooked. OBJECTIVE To investigate the differences in endoscopic appearance, ie, diminutive size and nonpolypoid shape, of proximal compared with distal colorectal neoplasms. DESIGN Cross-sectional, single-center study. SETTING Endoscopists at the Maastricht University Medical Center in the Netherlands who were previously trained in the detection and classification of nonpolypoid colorectal lesions. PATIENTS Consecutive patients undergoing elective colonoscopy. MAIN OUTCOME MEASUREMENTS Endoscopic appearance, ie, diminutive size (<6 mm) or nonpolypoid shape (height less than half of the diameter) of colorectal adenomas and serrated polyps (SPs), with a focus on adenomas with advanced histology, ie, high-grade dysplasia or early CRC and SPs with dysplasia or large size. RESULTS We included 3720 consecutive patients with 2106 adenomas and 941 SPs. We found that in both men and women, proximal adenomas with high-grade dysplasia/early CRC (n = 181) were more likely to be diminutive or nonpolypoid than distal ones (76.3% vs 26.2%; odds ratio [OR] 9.24; 95% CI, 4.45-19.2; P < .001). Of the proximal adenomas, 84.4% were diminutive or nonpolypoid compared with 68.0% of the distal ones (OR 2.66; 95% CI, 2.14-3.29; P < .001). Likewise, large/dysplastic SPs in the proximal colon were more often nonpolypoid than distal ones (66.2% vs 27.8%; OR 5.51; 95% CI, 2.79-10.9; P < .001). LIMITATIONS Inclusion of both symptomatic and asymptomatic patients. CONCLUSIONS Proximal colorectal neoplasms with advanced histology frequently are small or have a nonpolypoid appearance. These findings support careful inspection of the proximal colon, if quality of cancer prevention with the use of colonoscopy is to be optimized.

Promoter CpG island methylation markers in colorectal cancer: the road ahead.

Despite increasing knowledge on the biology, detection and treatment of colorectal cancer (CRC), the disease is still a major health problem. Hypermethylation of promoter regions of genes has been studied extensively as a contributor in CRC carcinogenesis. In addition, it is the topic of many studies focusing on biomarkers for the early detection, prediction of prognosis and treatment outcome. Methylation markers may be preferred over current screening and test methods as they are stable and easy to detect. However, almost no methylation marker is currently being used in clinical practice, often due to a lack of sensitivity, specificity, or validation of the results. This review summarizes the current knowledge of hypermethylation biomarkers for CRC detection, progression and treatment outcome.

Endoscopic red flags for the detection of high-risk serrated polyps: an observational study

BACKGROUND AND STUDY AIMS In routine practice, colonoscopy may fail to prevent colorectal cancer (CRC), especially in the proximal colon. A better endoscopic recognition of serrated polyps is important, as this pathway may explain some of the post-colonoscopy cancers. In this study, the endoscopic characteristics of serrated polyps were examined. PATIENT AND METHODS This was a cross-sectional, single-center study of all consecutive patients referred for elective colonoscopy during 1 year. The endoscopists were familiarized with the detection and treatment of nonpolypoid colorectal lesions. Serrated polyps were classified into high risk serrated polyps, defined as dysplastic or large (≥ 6 mm) proximal nondysplastic serrated polyps, and low risk serrated polyps including the remaining nondysplastic serrated polyps. Advanced colorectal neoplasms were defined as multiple (at least three),≥ 10 mm in size, high grade dysplastic adenomas or CRC. RESULTS A total of 2309 patients were included (46.1 % men, mean age 58.4 years), of whom 2.5 % (57) had at least one high risk serrated polyp and 13.9 % (322) had at least one advanced neoplasm. Overall, serrated polyps were more often nonpolypoid than adenomas (16.2 % vs. 11.1 %; P = 0.002). In total, 65 high risk serrated polyps were found, of which 43.1 % (28) displayed a nonpolypoid endoscopic appearance. Patients with advanced neoplasms were more likely to have synchronous high risk serrated polyps than patients without advanced neoplasms: OR 3.66 (95 % CI 2.03 - 6.61, P < 0.001). CONCLUSIONS High risk serrated polyps are frequently nonpolypoid and are associated with synchronous advanced colorectal neoplasms. Advanced colorectal neoplasms may therefore be considered red flags for the presence of high risk serrated polyps. Detection, diagnosis, and treatment of high risk serrated lesions may be important targets to improve the quality of colonoscopic cancer prevention.

Endoscopic characterization of sessile serrated adenomas/polyps with and without dysplasia.

BACKGROUND AND STUDY AIMS Sessile serrated adenomas/polyps (SSA/Ps) are precursors of colorectal cancer (CRC), but their endoscopic detection can be difficult. We therefore examined the endoscopic characteristics of SSA/Ps with and without dysplasia in a cross-sectional study. PATIENTS AND METHODS We reviewed clinical, endoscopic, and histopathologic data from patients undergoing colonoscopy between February 2008 and February 2012. We categorized colorectal polyps according to anatomic site, size, and shape, and classified serrated polyps using the World Health Organization (WHO) classification. Multiple logistic regression analyses examined potential differences regarding site, size, and shape between SSA/Ps and colorectal adenomas (overall and advanced only). RESULTS We examined 7433 patients (mean age 59 years, 45.9 % men) with 5968 colorectal polyps. In total, we found 170 SSA/Ps (170/5968, 2.9 %), including 63 SSA/Ps with dysplasia (1.1 %) and 107 SSA/Ps without dysplasia (1.8 %). Compared with SSA/Ps with dysplasia, SSA/Ps without dysplasia were more often proximally located (odds ratio [OR] 3.3, 95 % confidence interval [95 %CI] 1.7 - 6.4), but less often < 6 mm in size (OR 0.6, 95 %CI 0.3 - 1.1). No significant differences were found regarding location between SSA/Ps with dysplasia and advanced adenomas (proximal colon, 47.6 % vs. 40.1 %). However, SSA/Ps with dysplasia were more often < 6 mm in size than advanced adenomas (OR 0.3, 95 %CI 0.2 - 0.5). Of the 63 dysplastic SSA/Ps, 6 (9.5 %) contained high grade dysplasia, but none invasive carcinoma. CONCLUSIONS SSA/Ps with dysplasia are frequently < 6 mm in size, located throughout the colon and 9.5 % of them contain high grade dysplasia. These findings underscore the importance of high quality colonoscopic examination to maximize protection against CRC.

Optical diagnosis of colorectal polyps using high-definition i-scan: An educational experience

AIM To examine performances regarding prediction of polyp histology using high-definition (HD) i-scan in a group of endoscopists with varying levels of experience. METHODS We used a digital library of HD i-scan still images, comprising twin pictures (surface enhancement and tone enhancement), collected at our university hospital. We defined endoscopic features of adenomatous and non-adenomatous polyps, according to the following parameters: color, surface pattern and vascular pattern. We familiarized the participating endoscopists on optical diagnosis of colorectal polyps using a 20-min didactic training session. All endoscopists were asked to evaluate an image set of 50 colorectal polyps with regard to polyp histology. We classified the diagnoses into high confidence (i.e., cases in which the endoscopist could assign a diagnosis with certainty) and low confidence diagnoses (i.e., cases in which the endoscopist preferred to send the polyp for formal histology). Mean sensitivity, specificity and accuracy per endoscopist/image were computed and differences between groups tested using independent-samples t tests. High vs low confidence diagnoses were compared using the paired-samples t test. RESULTS Eleven endoscopists without previous experience on optical diagnosis evaluated a total of 550 images (396 adenomatous, 154 non-adenomatous). Mean sensitivity, specificity and accuracy for diagnosing adenomas were 79.3%, 85.7% and 81.1%, respectively. No significant differences were found between gastroenterologists and trainees regarding performances of optical diagnosis (mean accuracy 78.0% vs 82.9%, P = 0.098). Diminutive lesions were predicted with a lower mean accuracy as compared to non-diminutive lesions (74.2% vs 93.1%, P = 0.008). A total of 446 (81.1%) diagnoses were made with high confidence. High confidence diagnoses corresponded to a significantly higher mean accuracy than low confidence diagnoses (84.0% vs 64.3%, P = 0.008). A total of 319 (58.0%) images were evaluated as having excellent quality. Considering excellent quality images in conjunction with high confidence diagnosis, overall accuracy increased to 92.8%. CONCLUSION After a single training session, endoscopists with varying levels of experience can already provide optical diagnosis with an accuracy of 84.0%.

Simple clinical risk score identifies patients with serrated polyps in routine practice.

Large, proximal, or dysplastic (LPD) serrated polyps (SP) need accurate endoscopic recognition and removal as these might progress to colorectal cancer. Herewith, we examined the risk factors for having ≥1 LPD SP. We developed and validated a simple SP risk score as a potential tool for improving their detection. We reviewed clinical, endoscopic, and histologic features of serrated polyps in a study of patients undergoing elective colonoscopy (derivation cohort). A self-administered questionnaire was obtained. We conducted logistic regression analyses to identify independent risk factors for having ≥1 LPD SP and incorporated significant variables into a clinical score. We subsequently tested the performance of the SP score in a validation cohort. We examined 2,244 patients in the derivation and 2,402 patients in the validation cohort; 6.3% and 8.2% had ≥1 LPD SP, respectively. Independent risk factors for LPD SPs were age of more than 50 years [OR 2.2; 95% confidence interval (CI), 1.3–3.8; P = 0.004], personal history of serrated polyps (OR 2.6; 95% CI, 1.3–4.9; P = 0.005), current smoking (OR 2.2; 95% CI, 1.4–3.6; P = 0.001), and nondaily/no aspirin use (OR 1.8; 95% CI, 1.1–3.0; P = 0.016). In the validation cohort, a SP score ≥5 points was associated with a 3.0-fold increased odds for LPD SPs, compared with patients with a score <5 points. In the present study, age of more than 50 years, a personal history of serrated polyps, current smoking, and nondaily/no aspirin use were independent risk factors for having LPD SPs. The SP score might aid the endoscopist in the detection of such lesions. Cancer Prev Res; 6(8); 855–63. ©2013 AACR.

Magnetization transfer ratio: a potential biomarker for the assessment of postradiation fibrosis in patients with rectal cancer.

ObjectivesMagnetization transfer-magnetic resonance imaging (MT-MRI) uses differences in the magnetization interaction of the free “unbound” water protons and the macromolecular-bound protons. The aim of this study was to evaluate whether the magnetization transfer ratio (MTR) may be used to identify fibrosis in patients with rectal cancer treated with chemoradiotherapy. Materials and MethodsThis study was part of a rectal cancer imaging study, which was approved by the local institutional review board. Twenty-six patients, treated with neoadjuvant chemoradiotherapy, underwent a standard MRI including T2-weighted sequences and a diffusion-weighted sequence. An axially oriented MT sequence was performed at the center of the (former) tumor location. Regions of interest were manually drawn on the MT-MRI (with reference to the T2-weighted and diffusion-weighted images), covering areas of residual tumor, fibrosis, or the normal or edematous rectal wall. The results were compared with that of the histopathological examination. Differences in MTR between the 4 tissue types were analyzed, and a receiver operating characteristic (ROC) curve was generated to assess the diagnostic potential. ResultsThirty-eight regions of interest were analyzed on the MT-MRI. The mean (SD) MTR of the fibrosis was 37.7% (2.7%), which was significantly higher than that of the residual tumor (29.6% [4.2%]; P < 0.001), the normal rectal wall (30.3% [4.7%]; P = 0.003), and the edematous rectal wall (18.2% [4.0%]; P < 0.001). The use of MTR resulted in an area under the ROC-curve of 0.96, a sensitivity of 88%, and a specificity of 90% for the diagnosis of fibrosis. ConclusionsMagnetization transfer ratio can be used to discriminate postradiation fibrosis from residual tumor and the normal rectal wall after chemoradiotherapy. Magnetization transfer imaging can thus be a promising tool for the unsolved dilemma of interpreting postradiation fibrosis in rectal cancer.

Blood glucose level normalization and accurate timing improves the accuracy of PET-based treatment response predictions in rectal cancer

PURPOSE To quantify the influence of fluctuating blood glucose level (BGLs) and the timing of PET acquisition on PET-based predictions of the pathological treatment response in rectal cancer. MATERIAL AND METHODS Thirty patients, diagnosed with locally advanced-rectal-cancer (LARC), were included in this prospective study. Sequential FDG-PET-CT investigations were performed at four time points during and after pre-operative radiochemotherapy (RCT). All PET-data were normalized for the BGL measured shortly before FDG injection. The metabolic treatment response of the tumor was correlated with the pathological treatment response. RESULTS During RCT, strong intra-patient BGL-fluctuations were observed, ranging from -38.7 to 95.6%. BGL-normalization of the SUVs revealed differences ranging from -54.7 to 34.7% (p < 0.001). Also, a SUV(max) time-dependency of 1.30 +/- 0.66 every 10 min (range: 0.39-2.58) was found during the first 60 min of acquisition. When correlating the percent reduction of SUV(max) after 2 weeks of RCT with the pathological treatment response, a significant increase (p = 0.027) in the area under the curve of ROC-curve analysis was found when normalizing the PET-data for the measured BGLs, indicating an increase of the predictive strength. CONCLUSIONS This study strongly underlines the necessity of BGL-normalization of PET-data and a precise time-management between FDG injection and the start of PET acquisition when using sequential FDG-PET-CT imaging for the prediction of pathological treatment response.

Posttraumatic skull hemangioma: Case report

Intraosseous cavernous hemangiomas of the skull are rare lesions for which the origin is unclear. The authors present a case in which there was a radiologically documented history of trauma preceding the development of a hemangioma in the frontal bone. In a review of the literature the authors found 83 cases of skull hemangiomas, and 43% of the lesions were located in the frontal bone. In 25% of these lesions, previous trauma was reported anamnestically. The present case and radiological findings related to it suggest a causal relationship between trauma and the development of intraosseous hemangioma.