Human epidermal growth factor receptor-2 gene expression positivity determined by silver in situ hybridization/immunohistochemistry methods and associated factors in a cohort of Sri Lankan patients with gastric adenocarcinoma : a prospective study

Objective: Positive human epidermal growth factor 2 (HER2) expression and its predictive clinicopathological features remain unclear in Sri Lankan gastric cancer (GC) patients. Here, we aimed to determine GC HER2 status predictors by analyzing associations between clinicopathological features and HER2 expression using immunohistochemistry (IHC) and silver in situ hybridization (SISH). Methods: During this 4-year prospective study, clinicopathological data were collected from participants in the National Hospital of Sri Lanka. HER2 IHC and SISH were performed using commercial reagents. Using chi-square tests, associations of HER2-IHC/SISH with clinicopathological features were analyzed. Results: Overall, 145 GC patients were included, 69 had gastrectomies and 76 had biopsies. Positive HER2 expression by IHC was associated with age 5/high-power field, with additional perineural invasion and lymphovascular invasion in resections. These features, excluding lymphovascular invasion but including male sex, were associated with HER2 expression by SISH. Conclusions: Age <60 years, high nuclear grade, tumor necrosis, and perineural invasion are associated factors of HER2 status. These could be used to triage GC patients for HER2 status testing in limited resource settings where IHC/SISH analysis is costly

A New Hierarchy of Research Evidence for Tumor Pathology: A Delphi Study to Define Levels of Evidence in Tumor Pathology

Copyright \ua9 2023 The Authors. Published by Elsevier Inc. All rights reserved. The hierarchy of evidence is a fundamental concept in evidence-based medicine, but existing models can be challenging to apply in laboratory-based health care disciplines, such as pathology, where the types of evidence and contexts are significantly different from interventional medicine. This project aimed to define a comprehensive and complementary framework of new levels of evidence for evaluating research in tumor pathology-introducing a novel Hierarchy of Research Evidence for Tumor Pathology collaboratively designed by pathologists with help from epidemiologists, public health professionals, oncologists, and scientists, specifically tailored for use by pathologists-and to aid in the production of the World Health Organization Classification of Tumors (WCT) evidence gap maps. To achieve this, we adopted a modified Delphi approach, encompassing iterative online surveys, expert oversight, and external peer review, to establish the criteria for evidence in tumor pathology, determine the optimal structure for the new hierarchy, and ascertain the levels of confidence for each type of evidence. Over a span of 4 months and 3 survey rounds, we collected 1104 survey responses, culminating in a 3-day hybrid meeting in 2023, where a new hierarchy was unanimously agreed upon. The hierarchy is organized into 5 research theme groupings closely aligned with the subheadings of the WCT, and it consists of 5 levels of evidence-level P1 representing evidence types that merit the greatest level of confidence and level P5 reflecting the greatest risk of bias. For the first time, an international collaboration of pathology experts, supported by the International Agency for Research on Cancer, has successfully united to establish a standardized approach for evaluating evidence in tumor pathology. We intend to implement this novel Hierarchy of Research Evidence for Tumor Pathology to map the available evidence, thereby enriching and informing the WCT effectively

Delay in diagnosis to treatment and impact on survival of gastric adenocarcinoma in a low income setting without screening facility

Abstract The treatment modality of gastric adenocarcinoma (GCA) depends on the stage of the disease at the clinical presentation. Long delays are probably an unfavorable factor for the patient's prognosis. A prospective longitudinal, study involving 145 consecutive GCA was conducted at the National Hospital of Sri Lanka (NHSL). The overall delay (in weeks) was recorded for each patient and divided into four periods-patient, endoscopy, pathology and treatment. The median and Interquartile Range (IQR) duration of delays were calculated and differences were explored with chi square test and Mann Whitney U test Survival analysis was done with Kaplan Meier technique and Cox regression. The median duration of delays for patient, endoscopy, histology reporting delay, other histology delay (specimen transfer delay and report receipt delay) and treatment were 18 (IQR 14–27), 2 (IQR 2–3), 3 (IQR 2–3), 2 (IQR 1–2) and 6 (IQR 4–8) weeks respectively. Delayed patient presentation to hospital was associated with significant adverse median survival 16 (IQR 11.5–22.5) weeks versus 20 (IQR 16–27.5) weeks, p = 0.004. Delay in initiating treatment was associated with significantly lower median survival 04 (IQR 4–6) weeks versus 06 (IQR 4–8) weeks, p = 0.003. Over 60% of both proximal and distal GCA presented at an advanced radiological stage (stage III/IV). The Kaplan Meier analysis showed that the higher hazard function was associated with a higher tumour stage and undergoing chemotherapy. Age of the patient and the treatment modality were significant predictors of the survival. Patient delay and delay in initiation of definitive treatment are the most important factors that adversely affect the outcomes of GCA. Public health interventions aiming to shorten the patient delay time with proper referral for specialist care would play an important role. Also, it is important to minimize these preventable delays and there should be time limits in producing the histopathology report and to establish online portals of hospital and laboratory information systems for easy access of histology reports in future

Trans rectal ultra sound guided prostate biopsies: a single centre experience in Sri Lanka

Background Trans rectal ultrasound guided prostate biopsy (TRUS) was introduced to Sri Lanka in 2002. Objectives 1. To study clinicopathological features of males subjected to TRUS biopsy 2. To compare estimation of tumour burden by two methods in carcinoma prostate (CaP). Methods 749 symptomatic males subjected to TRUS biopsy over 64 months at a single centre. Information was retrieved from case records. Tumour burden in CaP was calculated as: 1. Calculated tumour burden (CTB) – total percentage tumour in each core/total number of cores 2. Percentage positive biopsy cores (PPBC) – number of positive cores / total number of cores X 100. SPSS 15.0, student&apos;s t test and Spearman’s rank correlation coefficients were used for statistical analysis. Results 35.2 % had CaP, microacinar in type. 34.88 % were poorly differentiated. CaP was frequent among older patients (P&lt;0.00001). The prostate volume in CaP was significantly lower than in the benign group (P&lt;0.05). Prostate specific antigen (PSA) level was significantly higher in CaP (P&lt;0.00001). A 99.6 % sensitivity and 4.7% specificity was observed at PSA of 4ng/ml for detecting CaP. Specificity was 98 % at 25.5ng/ml, with a sensitivity of 44.4%. CTB and PPBC had similar correlations with biochemical/histological parameters of CaP and were strongly correlated (0.786). Interpretation Males with CaP were older, had higher PSA levels and smaller prostates. A cut off level of PSA&gt;4ng/ml could be used for directing symptomatic patients for TRUS biopsy to detect CaP, keeping in mind that specificity is 98 % only at 25.5ng/ml. Both CTB and PPBC could be used to calculate tumour burden in TRUS with CaP

Counting mitoses: SI(ze) matters!

Mitoses are often assessed by pathologists to assist the diagnosis of cancer, and to grade malignancy, informing prognosis. Historically, this has been done by expressing the number of mitoses per n high power fields (HPFs), ignoring the fact that microscope fields may differ substantially, even at the same high power (×400) magnification. Despite a requirement to define HPF size in scientific papers, many authors fail to address this issue adequately. The problem is compounded by the switch to digital pathology systems, where ×400 equivalent fields are rectangular and also vary in the area displayed. The potential for error is considerable, and at times this may affect patient care. This is easily solved by the use of standardized international (SI) units. We, therefore, recommend that features such as mitoses are always counted per mm2, with an indication of the area to be counted and the method used (usually “hotspot” or “average”) to obtain the results

Toll-like receptor 5 and 8 in hepatocellular carcinoma

Abstract Toll-like receptors (TLRs) are components of innate immunity, but also have a role in carcinogenesis. The prognostic value of TLR5 and TLR8 tumor expression was examined in contrast with known risk markers Ki67 and p53. All HCC patients from Oulu University Hospital with available representative tumor sample were included in this study (n = 182). TLR5, TLR8, Ki67, and p53 expression were investigated by immunohistochemistry. The relation between patient survival and TLR, Ki67, and p53 expression was calculated with Cox regression adjusted for confounding factors. TLR5 cytoplasm intensity was associated with 5-year overall (strong 0.0% vs weak 23.4%, p &lt; 0.001) and disease-specific (strong 0.0% vs weak 34.9%, p &lt; 0.001) survival. TLR5 nuclei percentage was associated with poor 5-year disease-specific survival (high 16.3% vs low 31.5%, p = 0.022). In adjusted analysis, strong TLR5 cytoplasm intensity was an independent risk factor for poor 5-year overall (adjusted HR 1.88, 95% CI 1.26–2.81) and disease-specific (adjusted HR 2.00, 95% CI 1.27–3.15) survival. High Ki67 and p53 expression associated with 5-year overall- and disease-specific survival. TLR8 was not associated with patient survival. This study suggests that TLR5 expression is independently prognostic in HCC with similar point estimate as previously known p53