The UMBRELLA SIOP-RTSG 2016 Wilms tumour pathology and molecular biology protocol

On the basis of the results of previous national and international trials and studies, the Renal Tumour Study Group of the International Society of Paediatric Oncology (SIOP–RTSG) has developed a new study protocol for paediatric renal tumours: the UMBRELLA SIOP–RTSG 2016 protocol (the UMBRELLA protocol). Currently, the overall outcomes of patients with Wilms tumour are excellent, but subgroups with poor prognosis and increased relapse rates still exist. The identification of these subgroups is of utmost importance to improve treatment stratification, which might lead to reduction of the direct and late effects of chemotherapy. The UMBRELLA protocol aims to validate new prognostic factors, such as blastemal tumour volume and molecular markers, to further improve outcome. To achieve this aim, large, international, high-quality databases are needed, which dictate optimization and international harmonization of specimen handling and comprehensive sampling of biological material, refine definitions and improve logistics for expert review. To promote broad implementation of the UMBRELLA protocol, the updated SIOP–RTSG pathology and molecular biology protocol for Wilms tumours has been outlined, which is a consensus from the SIOP–RTSG pathology panel

Sex Differences in Neoplastic Progression in Barrett's Esophagus:A Multicenter Prospective Cohort Study

Recommendations in Barrett’s esophagus (BE) guidelines are mainly based on male patients. We aimed to evaluate sex differences in BE patients in (1) probability of and (2) time to neoplastic progression, and (3) differences in the stage distribution of neoplasia. We conducted a multicenter prospective cohort study including 868 BE patients. Cox regression modeling and accelerated failure time modeling were used to estimate the sex differences. Neoplastic progression was defined as highgrade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC). Among the 639 (74%) males and 229 females that were included (median follow-up 7.1 years), 61 (7.0%) developed HGD/EAC. Neoplastic progression risk was estimated to be twice as high among males (HR 2.26, 95% CI 1.11–4.62) than females. The risk of HGD was found to be higher in males (HR 3.76, 95% CI 1.33–10.6). Time to HGD/EAC (AR 0.52, 95% CI 0.29–0.95) and HGD (AR 0.40, 95% CI 0.19–0.86) was shorter in males. Females had proportionally more EAC than HGD and tended to have higher stages of neoplasia at diagnosis. In conclusion, both the risk of and time to neoplastic progression were higher in males. However, females were proportionally more often diagnosed with (advanced) EAC. We should strive for improved neoplastic risk stratification per individual BE patient, incorporating sex disparities into new prediction models

Computer-Aided Assessment of Melanocytic Lesions by Means of a Mitosis Algorithm

An increasing number of pathology laboratories are now fully digitised, using whole slide imaging (WSI) for routine diagnostics. WSI paves the road to use artificial intelligence (AI) that will play an increasing role in computer-aided diagnosis (CAD). In melanocytic skin lesions, the presence of a dermal mitosis may be an important clue for an intermediate or a malignant lesion and may indicate worse prognosis. In this study a mitosis algorithm primarily developed for breast carcinoma is applied to melanocytic skin lesions. This study aimed to assess whether the algorithm could be used in diagnosing melanocytic lesions, and to study the added value in diagnosing melanocytic lesions in a practical setting. WSIs of a set of hematoxylin and eosin (H&amp;E) stained slides of 99 melanocytic lesions (35 nevi, 4 intermediate melanocytic lesions, and 60 malignant melanomas, including 10 nevoid melanomas), for which a consensus diagnosis was reached by three academic pathologists, were subjected to a mitosis algorithm based on AI. Two academic and six general pathologists specialized in dermatopathology examined the WSI cases two times, first without mitosis annotations and after a washout period of at least 2 months with mitosis annotations based on the algorithm. The algorithm indicated true mitosis in lesional cells, i.e., melanocytes, and non-lesional cells, i.e., mainly keratinocytes and inflammatory cells. A high number of false positive mitosis was indicated as well, comprising melanin pigment, sebaceous glands nuclei, and spindle cell nuclei such as stromal cells and neuroid differentiated melanocytes. All but one pathologist reported more often a dermal mitosis with the mitosis algorithm, which on a regular basis, was incorrectly attributed to mitoses from mainly inflammatory cells. The overall concordance of the pathologists with the consensus diagnosis for all cases excluding nevoid melanoma (n = 89) appeared to be comparable with and without the use of AI (89% vs. 90%). However, the concordance increased by using AI in nevoid melanoma cases (n = 10) (75% vs. 68%). This study showed that in general cases, pathologists perform similarly with the aid of a mitosis algorithm developed primarily for breast cancer. In nevoid melanoma cases, pathologists perform better with the algorithm. From this study, it can be learned that pathologists need to be aware of potential pitfalls using CAD on H&amp;E slides, e.g., misinterpreting dermal mitoses in non-melanotic cells.Funding Agencies|Innovative Medicines Initiative 2 Joint Undertaking [945358]; European UnionEuropean Commission; EFPIA</p

Validation of Whole-slide Digitally Imaged Melanocytic Lesions : Does Z-Stack Scanning Improve Diagnostic Accuracy?

Background: Accurate diagnosis of melanocytic lesions is challenging, even for expert pathologists. Nowadays, whole-slide imaging (WSI) is used for routine clinical pathology diagnosis in several laboratories. One of the limitations of WSI, as it is most often used, is the lack of a multiplanar focusing option. In this study, we aim to establish the diagnostic accuracy of WSI for melanocytic lesions and investigate the potential accuracy increase of z-stack scanning. Z-stack enables pathologists to use a software focus adjustment, comparable to the fine-focus knob of a conventional light microscope. Materials and Methods: Melanocytic lesions (n = 102) were selected from our pathology archives: 35 nevi, 5 spitzoid tumors of unknown malignant potential, and 62 malignant melanomas, including 10 nevoid melanomas. All slides were scanned at a magnification comparable to use of a ×40 objective, in z-stack mode. A ground truth diagnosis was established on the glass slides by four academic dermatopathologists with a special interest in the diagnosis of melanoma. Six nonacademic surgical pathologists subspecialized in dermatopathology examined the cases by WSI. Results: An expert consensus diagnosis was achieved in 99 (97%) of cases. Concordance rates between surgical pathologists and the ground truth varied between 75% and 90%, excluding nevoid melanoma cases. Concordance rates of nevoid melanoma varied between 10% and 80%. Pathologists used the software focusing option in 7%-28% of cases, which in 1 case of nevoid melanoma resulted in correcting a misdiagnosis after finding a dermal mitosis. Conclusion: Diagnostic accuracy of melanocytic lesions based on glass slides and WSI is comparable with previous publications. A large variability in diagnostic accuracy of nevoid melanoma does exist. Our results show that z-stack scanning, in general, does not increase the diagnostic accuracy of melanocytic

Prophylactic Medication for the Prevention of Endoscopic Recurrence in Crohn's Disease: a Prospective Study Based on Clinical Risk Stratification

BACKGROUND: To prevent recurrence after ileocolonic resection [ICR] in Crohn's disease [CD], postoperative prophylaxis based on risk stratification is recommended in international guidelines. This study aimed to evaluate postoperative CD recurrence after implementation of a clinical management algorithm and to determine the predictive value of clinical and histological risk factors [RFs]. METHODS: In this multicentre, prospective cohort study, CD patients [≥16 years] scheduled for ICR were included. The algorithm advised no postoperative medication for low-risk patients, and treatment with prophylaxis [immunosuppressant/biological] for high-risk patients [≥1 RF: active smoking, penetrating disease, prior ICR]. Clinical and histological RFs [active inflammation, granulomas, plexitis in resection margins] for endoscopic recurrence [Rutgeerts' score ≥i2b at 6 months] were assessed using logistic regression and ROC curves based on predicted probabilities. RESULTS: In total, 213 CD patients after ICR were included [age 34.5 years; 65% women] (93 [44%] low-risk; 120 [56%] high-risk: 45 [38%] smoking; 51 [43%] penetrating disease; 51 [43%] prior ICR). Adherence to the algorithm was 82% in low-risk [no prophylaxis] and 51% in high-risk patients [prophylaxis]. Endoscopic recurrence was higher in patients treated without prophylaxis than with prophylaxis in both low [45% vs 16%, p = 0.012] and high-risk patients [49% vs 26%, p = 0.019]. Clinical risk stratification including the prescription of prophylaxis corresponded to an area under the curve [AUC] of 0.70 (95% confidence interval [CI] 0.61-0.79). Clinical RFs combined with histological RFs increased the AUC to 0.73 [95% CI 0.64-0.81]. CONCLUSION: Adherence to this management algorithm is 65%. Prophylactic medication after ICR prevents endoscopic recurrence in low- and high-risk patients. Clinical risk stratification has an acceptable predictive value, but further refinement is needed