Peer-to-peer validation of Ki-67 scoring in a pathology quality circle as a tool to assess interobserver variability: are we better than we thought?

Ki-67, a nuclear protein expressed in all stages of cellular proliferation, is a valuable tool to assess tumor proliferation and has been linked to more aggressive tumor behavior. However, interlaboratory staining heterogeneity and inter-observer variability challenge its reproducibility. Round Robin tests are a suitable tool to standardize and harmonize immunohistochemical and molecular analyses in histopathology. The study investigates the interrater and interlaboratory reproducibility of Ki-67-scoring using both manual and automated approaches. Unstained TMA slides comprising diverse tumor types (breast cancer, neuroendocrine tumors, lymphomas, and head and neck squamous cell carcinoma) were distributed to six pathology laboratories, each employing their routine staining protocols. Manual and automated scoring methods were applied, and interrater and interlaboratory agreement assessed using intraclass correlation coefficients (ICC). The results highlight good-to-excellent reliability overall, with automated scoring demonstrating higher consistency (ICC 0.955) than manual scoring (ICC 0.871). Results were more variable when looking at the individual entities. Reliability remained good for lymphomas (ICC 0.878) and breast cancer (ICC 0.784) and was poor in well-differentiated neuroendocrine tumors (ICC 0.354). This study clearly advocates standardized practices and training to ensure consistency in Ki-67-assessment, and it demonstrates that this can be achieved in a peer-to-peer approach in local quality-circles.

Transarterial chemoembolization of colorectal cancer liver metastasis: improved tumor response by DSM-TACE versus conventional TACE, a prospective, randomized, single-center trial.

OBJECTIVES: To prospectively evaluate the therapy response of third-line TACE with DSM or lipiodol in the treatment of CRLM using MRI. METHODS: In this prospective, randomized, single-center trial, patients were randomly assigned to receive TACE therapy with either lipiodol or DSM as the embolization agent. Therapy response was evaluated using MRI. Local tumor response was determined according to RECIST 1.1, and survival data was analyzed using the Kaplan-Meier estimator. RESULTS: Fifty patients (35 male, 15 female) were randomized and included in the survival analysis, whereas 31 patients completed therapy and were considered for evaluation of tumor responses (cTACE: n = 13, DSM-TACE: n = 18). In the cTACE group, PR was observed in 23%, SD in 15%, and PD in 62%. In the DSM-TACE-group, PR was observed in 22% of patients, SD in 56%, and PD in 22% (p = 0.047). In addition, the DSM-TACE group showed statistically significant tumor volume reduction (p = 0.006). Median apparent diffusion coefficient values were not significantly different between both groups at baseline (p = 0.26) and study endpoint (p = 0.83). Median survival in the cTACE group was 13 months (95% confidence interval, range 5-40 months) compared to 16 months (95% confidence interval, range 1-48 months) in the DSM-TACE group, exhibiting no statistically significant difference (p = 0.75). CONCLUSION: DSM-TACE showed a significant difference reducing tumor volume and in tumor response according to RECIST 1.1 compared to cTACE. Thus, patients with CRLM might not only benefit from short embolization effect of DSM-TACE but also from better tumor responses. Apparent diffusion coefficients were not significantly different between both groups and cannot be used as a biomarker for monitoring for therapeutic effect of TACE. KEY POINTS: • To our knowledge, this is the first prospective study that directly compared cTACE and DSM-TACE in patients with CRLM. • DSM-TACE showed a significant difference reducing tumor volume (p = 0.006) and in tumor response according to RECIST 1.1 (p = 0.047) compared to cTACE. • Survival analysis showed a median survival of 13 months in the cTACE group compared to 16 months in the DSM-TACE group (p = 0.75).

Early Detection of a Colorectal Carcinoma in an Asymptomatic Patient Using a Combined DNA Stool Test.

BACKGROUND: Modern, simple stool tests could close the gap regarding the recognition rate (sensitivity) between the current test methods and colonoscopy. METHODS: Here we report a case of a 68-year-old asymptomatic patient, who applied an innovative combined DNA stool test. RESULTS: Due to a positive KRAS mutation, a colonoscopy was performed and an invasive adenocarcinoma was diagnosed. After colonoscopical resection in two steps pathological findings could not be identified anymore. All further parameters, including KRAS, stayed continuously negative. CONCLUSIONS: In this case report, it was demonstrated that a combined DNA stool test can also be successfully applied as alternative diagnostic tool.

Glomus tumor of the trachea - Synopsis of histology & methodology of treatment.

Glomus tumors are neoplasms arising from modified smooth muscle cells surrounding arteriovenous anastomosis in the dermis and subcutaneous tissues, which are contributing to blood flow regulation and temperature control on the skin surface. Glomus cells are sparse or absent in visceral organs, making extracutaneous presentation of glomus tumors an extremely rare finding. We briefly report histological considerations on glomus tumors of the trachea and sum the multidisciplinary aspects of their staged endoscopic and surgical management using the example of a rare case presentation.

Current strategies in interventional oncology of colorectal liver metastases.

The adequate treatment of non-resectable liver metastases from colorectal cancer which are resistant to systemic chemotherapy currently provides a great challenge. The aim is to identify and review key strategies in the treatment of colorectal liver metastases. A search for current literature on the topic of interventional strategies for colorectal metastases was performed in Medline in order to achieve this goal. Studies before 2005 and with <20 patients treated for colorectal metastases were excluded. Transarterial chemoembolization (TACE), transarterial embolization and selective internal radiation therapy (SIRT) were identified as examples of regional strategies for colorectal liver metastases, utilizing the unique blood supply of the liver. Radiofrequency ablation (RFA), microwave ablation (MWA) and cryoablation were selected as examples for currently available ablative techniques. Median survival in the key studies reviewed ranged from 7.7 to 28.6 for TACE, 8.3-12.6 for SIRT, 8.2-53.2 for RFA and 29-43 months for MWA. After review of the literature, it can be concluded that interventional oncologic therapies are a safe and effective method for treating colorectal liver metastases. The use of new chemotherapeutic agents for local therapy and new ablation technologies and techniques may increase patient survival and allows a neoadjuvant therapy setting. In addition, a combination of local therapies may be used to increase effectiveness in the future, which is subject to further research.