What factors influence cellular pathologists' confidence in case reporting?

Histopathology is a challenging interpretive discipline, and the level of confidence a pathologist has in their diagnosis is known to vary, which is conveyed descriptively in pathology reports. There has been little study to accurately quantify pathologists' diagnostic confidence or the factors that influence it. In this study involving sixteen pathologists from six NHS trusts, we assessed diagnostic confidence across multiple variables and four specialties. Each case was reported by four pathologists, with each pathologist reporting each case twice (on light microscopy (LM) and digital pathology (DP)). For each diagnosis, pathologists recorded their confidence on a 7-point Likert scale. This provided 16,187 diagnoses and associated confidence scores for analysis. All variables investigated were found to be significantly predictive of diagnostic confidence, except level of pathologist experience. Confidence was lower for difficult to report cases, cases where there was inter- and intra-pathologist variation in the diagnosis, and cases where the pathologist made an incorrect diagnosis. Confidence was higher, although nominally, for LM diagnoses than DP (rate ratio 1.09 (95% CI 1.01-1.18), p = 0.035), although results indicate pathologists are confident to report on DP. Lowest confidence scores were seen in areas of known diagnostic complexity and cases with quality issues. High confidence in incorrect diagnoses were almost invariably attributed to interpretive diagnostic differences which occurred across both rare and common lesions. The results highlight the value of external quality control schemes and the benefits of selective peer review when reporting.

Digital pathology for reporting histopathology samples, including cancer screening samples - definitive evidence from a multisite study.

AIMS: To conduct a definitive multicentre comparison of digital pathology (DP) with light microscopy (LM) for reporting histopathology slides including breast and bowel cancer screening samples. METHODS: A total of 2024 cases (608 breast, 607 GI, 609 skin, 200 renal) were studied, including 207 breast and 250 bowel cancer screening samples. Cases were examined by four pathologists (16 study pathologists across the four speciality groups), using both LM and DP, with the order randomly assigned and 6 weeks between viewings. Reports were compared for clinical management concordance (CMC), meaning identical diagnoses plus differences which do not affect patient management. Percentage CMCs were computed using logistic regression models with crossed random-effects terms for case and pathologist. The obtained percentage CMCs were referenced to 98.3% calculated from previous studies. RESULTS: For all cases LM versus DP comparisons showed the CMC rates were 99.95% [95% confidence interval (CI) = 99.90-99.97] and 98.96 (95% CI = 98.42-99.32) for cancer screening samples. In speciality groups CMC for LM versus DP showed: breast 99.40% (99.06-99.62) overall and 96.27% (94.63-97.43) for cancer screening samples; [gastrointestinal (GI) = 99.96% (99.89-99.99)] overall and 99.93% (99.68-99.98) for bowel cancer screening samples; skin 99.99% (99.92-100.0); renal 99.99% (99.57-100.0). Analysis of clinically significant differences revealed discrepancies in areas where interobserver variability is known to be high, in reads performed with both modalities and without apparent trends to either. CONCLUSIONS: Comparing LM and DP CMC, overall rates exceed the reference 98.3%, providing compelling evidence that pathologists provide equivalent results for both routine and cancer screening samples irrespective of the modality used.

Discarded livers tested by normothermic machine perfusion in the VITTAL trial: Secondary end points and 5-year outcomes.

Normothermic machine perfusion (NMP) enables pretransplant assessment of high-risk donor livers. The VITTAL trial demonstrated that 71% of the currently discarded organs could be transplanted with 100% 90-day patient and graft survivals. Here, we report secondary end points and 5-year outcomes of this prospective, open-label, phase 2 adaptive single-arm study. The patient and graft survivals at 60 months were 82% and 72%, respectively. Four patients lost their graft due to nonanastomotic biliary strictures, one caused by hepatic artery thrombosis in a liver donated following brain death, and 3 in elderly livers donated after circulatory death (DCD), which all clinically manifested within 6 months after transplantation. There were no late graft losses for other reasons. All the 4 patients who died during the study follow-up had functioning grafts. Nonanastomotic biliary strictures developed in donated after circulatory death livers that failed to produce bile with pH >7.65 and bicarbonate levels >25 mmol/L. Histological assessment in these livers revealed high bile duct injury scores characterized by arterial medial necrosis. The quality of life at 6 months significantly improved in all but 4 patients suffering from nonanastomotic biliary strictures. This first report of long-term outcomes of high-risk livers assessed by normothermic machine perfusion demonstrated excellent 5-year survival without adverse effects in all organs functioning beyond 1 year (ClinicalTrials.gov number NCT02740608).

Seventh Day Syndrome Revisited: Early Recognition of the Clinical Syndrome and an Evolving Understanding of Its Etiology.

Background: Unexplained acute failure of an initially functioning liver graft early post-transplant has been described as Seventh-Day Syndrome (7DS). The aims of this study were to describe the clinical syndrome in detail based on an institutional case series and literature review. Methods: A retrospective review of adult patients that underwent deceased donor liver transplantation at our institution between January 2010 and 2020 was performed to identify patients that developed 7DS. Relevant clinical variables were obtained from medical records. Existing cases in the literature were identified by a systematic literature search according to PRISMA guidelines. Pooled analysis was used to describe the incidence, retransplantation, and mortality rate. Histological findings from institutional and published literature cases were collected and appraised. Results: Six of 1,907 liver transplantations at our institution (0.3%) developed 7DS. Seven case series, describing 42 patients with 7DS, and two single case reports were identified from literature review. Pooled incidence of 7DS was low (2.1%, 95%CI: 0.7-3.9%) and associated with high mortality (74.8%, 95%CI: 49.2-94.6%). Retransplantation was performed in 23/42 (55%) patients and 4/23 (17%) survived. Review of histology showed frequent intrahepatic thrombi and arteritis. Rejection, with features of potential antibody mediated rejection, often preceded or accompanied progressive zonal coagulative necrosis and hemorrhage. Conclusions: 7DS is a rare clinical syndrome after liver transplantation and associated with high mortality. Antibody-mediated rejection, as suggested in early reports, is likely to be involved in the pathogenesis. Early recognition would allow rapid clinical diagnostics and expedited decisions, such as treatment of AMR if diagnosed or early retransplantation.