Assessment of Pathology Domain-Specific Knowledge of ChatGPT and Comparison to Human Performance.

CONTEXT.­: Artificial intelligence algorithms hold the potential to fundamentally change many aspects of society. Application of these tools, including the publicly available ChatGPT, has demonstrated impressive domain-specific knowledge in many areas, including medicine. OBJECTIVES.­: To understand the level of pathology domain-specific knowledge for ChatGPT using different underlying large language models, GPT-3.5 and the updated GPT-4. DESIGN.­: An international group of pathologists (n = 15) was recruited to generate pathology-specific questions at a similar level to those that could be seen on licensing (board) examinations. The questions (n = 15) were answered by GPT-3.5, GPT-4, and a staff pathologist that recently passed their Canadian pathology licensing exams. Participants were instructed to score answers on a 5-point scale and to predict which answer was written by ChatGPT. RESULTS.­: GPT-3.5 performed at a similar level to the staff pathologist, while GPT-4 outperformed both. The overall score for both GPT-3.5 and GPT-4 was within the range of meeting expectations for a trainee writing licensing examinations. In all but one question, the reviewers were able to correctly identify the answers generated by GPT-3.5. CONCLUSIONS.­: By demonstrating the ability of ChatGPT to answer pathology-specific questions at a level similar to (GPT-3.5) or exceeding (GPT-4) a trained pathologist, this study highlights the potential of large language models to be transformative in this space. In the future, more advanced iterations of these algorithms with increased domain-specific knowledge may have the potential to assist pathologists and enhance pathology resident training.

The role of online symptom questionnaires to support the diagnosis of cow's milk allergy in children for healthcare professionals - A Delphi consensus study.

BACKGROUND: Cow's milk allergy (CMA) is one of the most common food allergies world-wide. The emergence of online CMA symptom questionnaires, aimed at parents and/or healthcare professionals (HCP), may raise awareness about the possible diagnosis of CMA, but also increases the risk for overdiagnosis leading to unnecessary dietary restriction impacting on growth and nutrition. This publication sets out to establish the availability of these CMA symptom questionnaires and critically assesses the development and validity. METHODS: Thirteen HCP working in the field of CMA, from different countries, were recruited to participate. A combination of a Pubmed and CINAHL literature and online review using the Google search engine in English language was used. Symptoms in the questionnaires were assessed, using the European Academy for Allergy and Clinical Immunology guidelines for food allergy. Following the assessment of both the questionnaires and literature, the authors followed the modified Delphi approach to generate consensus statements. RESULTS: Six hundred and fifty-one publications were identified, of which 29 were suitable for inclusion, with 26 being associated with the Cow's Milk-Related Symptoms Score. The online search yielded 10 available questionnaires: 7/10 were sponsored by formula milk companies and 7/10 were aimed at parents and three at HCP. Following the assessment of data, 19 statements were generated in two rounds of anonymous voting reaching 100% agreement. CONCLUSIONS: Online CMA questionnaires, available to parents and HCP's, are varied in symptoms, and most were not validated. The overarching consensus generated from authors is that these questionnaires should not be used without the involvement of HCP.

Recommendations for standardizing biopsy acquisition and histological assessment of immune checkpoint inhibitor-associated colitis.

Immune checkpoint inhibitor-associated colitis (ICIC) affects approximately 15% of cancer patients treated with immunotherapy. Although histological evaluation is potentially valuable for both the diagnosis of ICIC and evaluation of disease activity, use in clinical practice is heterogeneous. We aimed to develop expert recommendations to standardize histological assessment of disease activity in patients with ICIC. Using the modified Research and Development/University of California Los Angeles (RAND/UCLA) appropriateness methodology, an international panel of 11 pathologists rated the appropriateness of 99 statements on a 9-point Likert scale during two rounds of anonymous voting. Results were discussed between rounds using moderated videoconferences. There are currently no disease-specific instruments for assessing histological features of ICIC. The panel considered that colonoscopy with at least three biopsies per segment from a total of at least five segments, including both endoscopically normal and inflamed areas, was appropriate for tissue acquisition. They agreed that biopsies should be oriented such that the long axis of the colonic crypts is visualized and should be stained with hematoxylin and eosin. Histological items that the panel voted were appropriate to evaluate in ICIC included the degree of structural/architectural change, chronic inflammatory infiltrate, lamina propria and intraepithelial neutrophils, crypt abscesses and destruction, erosions/ulcerations, apoptosis, surface intraepithelial lymphocytosis, and subepithelial collagen thickness. The appropriateness of routine immunohistochemistry was uncertain. These expert recommendations will help standardize assessment of histological activity in patients with ICIC. The panel also identified the development and validation of an ICIC-specific histological index as a research priority.

Pyrite mega-analysis reveals modes of anoxia through geological time.

The redox structure of the water column in anoxic basins through geological time remains poorly resolved despite its importance to biological evolution/extinction and biogeochemical cycling. Here, we provide a temporal record of bottom and pore water redox conditions by analyzing the temporal distribution and chemistry of sedimentary pyrite. We combine machine-reading techniques, applied over a large library of published literature, with statistical analysis of element concentrations in databases of sedimentary pyrite and bulk sedimentary rocks to generate a scaled analysis spanning the majority of Earth's history. This analysis delineates the prevalent anoxic basin states from the Archaean to present day, which are associated with diagnostic combinations of five types of syngenetic pyrite. The underlying driver(s) for the pyrite types are unresolved but plausibly includes the ambient seawater inventory, precipitation kinetics, and the (co)location of organic matter degradation coupled to sulfate reduction, iron (oxyhydr)oxide dissolution, and pyrite precipitation.

Patient Satisfaction With Remote Consultations in a Primary Care Setting.

Introduction In recent years, the use of remote consultations has increased considerably. Many patient encounters in general practice are now conducted by phone or computer as opposed to traditional face-to-face appointments. The aim of this study was to measure patient satisfaction with remote consultations in a primary care setting. Aims To assess patient satisfaction with telephone consultations in a general practice setting and explore patient's experiences and attitudes toward remote consultations in general practice to formulate recommendations for potential telehealth improvements. Methods A total of 407 patients who had undergone primary care telephone consultations within the previous week were invited to provide feedback. Patient satisfaction was measured by a four-step questionnaire on patient experience, which was quantified on a Likert agreement scale, and the additional option of a comment section at the end of each questionnaire. The responses in the comment section were analysed according to the frequency of recurrent themes. Results The responses of 104 patients were included in the final analysis, and 44 patients used the comment section to provide additional information about their experience. Overall, the satisfaction with remote consultations was high while the rate of technical failure and the need for in-person follow-up were both low: 60 patients (58%) either agreed or strongly agreed that remote consultations are a convenient way of receiving health care and 26 patients (25%) would prefer to have remote consultations over face-to-face ones in the future while 42 patients (40%) would prefer face-to-face consultations in the future. Ninety-six (96) patients (92%) reported no technical problems affecting the consultation quality. Of all 104 face-to-face appointments, only 36 patients (35%) required in-person follow-up. Analyses of the comment section largely reflect the above findings but also highlight concerns from patients that remote consultations can generate additional anxiety, and symptoms might not be communicated effectively or even missed completely. Discussion The high satisfaction levels, low rates of technical failure and low need for a face-to-face follow-up show that in a primary care setting, remote consultations are an effective complement to face-to-face appointments. Nonetheless, the requirement for face-to-face contact goes beyond the need for physical examination alone, with many patients preferring face-to-face contact when discussing complex and sensitive health-related topics and symptoms.

Gastrointestinal Histoplasmosis Mimicking Crohn's Disease.

Disseminated histoplasmosis is a life-threatening disease usually seen in immunocompromised patients living in endemic areas. We present an apparently immunocompetent patient with gastrointestinal histoplasmosis who was initially diagnosed with biopsy-proven Crohn's disease. Following discontinuation of anti-inflammatory drugs and institution of antifungal therapy, his gastrointestinal illness completely improved. Specific fungal staining should be routinely included in histopathologic assessment of tissue specimens diagnosed as Crohn's disease.

A Case of Synchronous Malignant and Benign Granular Cell Tumor of the Vulva.

Granular cell tumors (GCT) are rare soft tissue neoplasms, which seldom occur in the vulva. They are more commonly benign, but malignant GCT do occur. We report a case of a 50-yr-old postmenopausal woman who presented with a vulvar lesion that was diagnosed as GCT on biopsy. Imaging and clinical examination revealed an enlarged, likely positive lymph node. Pathology of the subsequently resected total deep vulvectomy specimen showed 2 histologically distinct GCTs. The larger lesion met criteria for malignancy and histologically corresponded to metastatic deposits seen in the pelvic lymph nodes. The separate smaller lesion was histologically benign. This case illustrates a malignant GCT with a synchronous, likely benign GCT both occurring in the vulva. Our case demonstrates the application of histologic criteria in the diagnosis of malignant and benign GCT with discussion on the diagnosis and treatment of this rare tumor.

Infliximab-induced autoimmune hepatitis requiring liver transplantation.

Autoimmune hepatitis is an infrequent but significant side effect of infliximab treatment. Diagnosis of autoimmune hepatitis is based on clinical, laboratory, and histological findings. Initial treatment involves cessation of infliximab and trial of prednisone. We present a rare case of infliximab-induced autoimmune hepatitis leading to liver failure requiring transplantation.

A prospective feasibility study evaluating the role of multimodality imaging and liquid biopsy for response assessment in locally advanced rectal carcinoma.

PURPOSE: Colorectal cancer is a commonly encountered disease that poses several diagnostic and therapeutic challenges. The inherent heterogeneity of tumor biology and propensity to relapse despite "curative" resection pose significant challenges with regard to response assessment. Although MR imaging already plays a key role in primary staging of patients with rectal carcinoma, its reliability in restaging after neoadjuvant therapy is debatable (Van der broek et al. in Dis Colon Rectum 60(3):274-283, 2017). Therefore, there is significant interest in developing additional methods which may improve diagnostic accuracy. This study aims to evaluate the role of multimodality imaging and liquid biopsy in therapeutic response assessment. METHODS: Seventeen patients were enrolled into the study over a span of 24 months. All underwent hybrid PET-MRI and CT-perfusion (CT-P), prior to and following neoadjuvant therapy for locally advanced rectal carcinoma. Twelve of the 17 patients also underwent liquid biopsy, which consisted of blood sampling and analysis of circulating tumor cells (CTCs) and extracellular vesicles (EVs), including cell fragments and microparticles (MPs), using the Cell Search System (Menarini Silicon Biosystems). SUV, DWI, and ADC were calculated during PET-MRI, and several parameters were evaluated during CT-perfusion, including average perfusion, blood flow (BF), blood volume (BV), mean transit time (MTT), permeability-surface area product (PS), contrast extraction efficiency (E), and K-trans (K). Changes observed pre- and post-neoadjuvant therapy in each modality were compared to tumor response at histopathology using a modified Ryan tumor regression grading system. RESULTS: Of the 17 patients included in the study, 14 were classified as non-responders, and 3 were classified as responders as determined by the modified Ryan Tumor Regression Grade (TRG) scoring system (Van der broek et al. in Dis Colon Rectum 60(3):274-283, 2017). When combined, blood markers and CT-P parameters (mean transit time (MTT), K-trans, and permeability-surface area product (PS)) produced the strongest models (p < 0.01). PET (SUV measurement) combined with CT-P-derived K-trans produced a marginally significant (p = 0.057) model for predicting response. MRI-derived ADC value did not provide a significant model for response prediction. CONCLUSION: A model of CT-P parameters plus liquid biopsy more accurately predicts tumor response than PET-MRI, CT-P alone, or liquid biopsy alone. These results suggest that in the evaluation of treatment response, liquid biopsy could provide additional information to functional imaging modalities such as CT-P and should therefore be explored further in a trial with larger sample size.

CDX2 and Muc2 immunohistochemistry as prognostic markers in stage II colon cancer.

The treatment for colorectal cancer is largely surgical followed by adjuvant chemotherapy in high-risk cases. In patients with stage II cancer, there is no clear benefit for chemotherapy, and the current tools for assessment of risk are inadequate. A recent study identified that colorectal cancer with a gene signature similar to undifferentiated colonic stem cells was associated with a worse outcome. It was later shown that loss of CDX2 detected by immunohistochemistry (IHC) alone resulted in a worse prognosis and that this could be used to predict patients who would benefit from chemotherapy. Having observed that CDX2 expression can be patchy, we elected to validate these prior results for clinical practice using whole-slide IHC. The pathology of all cases was reviewed, and 3 blocks were selected for CDX2 IHC. We also expanded the panel beyond CDX2 to assess whether other markers in the gene signature including CDX1, Muc2, GPX2, and villin could better predict outcome. Among 210 cases, CDX2 expression was diffusely lost in 11% and focally lost in 23% of cases. There was no difference in survival based on CDX2 expression, but Muc2 loss was associated with reduced survival (hazard ratio, 3.32; 95% confidence interval, 1.20 to 9.20). No significant differences in outcome were identified based on CDX1, GPX2, or villin expression. In keeping with this, assessment of The Cancer Genome Atlas gene expression data demonstrated that decreased Muc2 expression was associated with reduced overall survival. Our results with whole-slide IHC are different from the previous studies and caution against the use of CDX2 in isolation as a prognostic marker in clinical practice. We have identified that loss of Muc2 is associated with reduced survival. This supports the use of the colonic differentiation gene expression signature to identify high-risk patients but cautions against the use of any one IHC-based marker in isolation.

Intradepartmental consultations in surgical pathology: Review of a standardized process and factors influencing consultation rates and practices in an academic and community hospital setting.

Intradepartmental consultations (ICs) are important for quality assurance (QA) and ensuring diagnostic accuracy in surgical pathology. Few studies have reviewed pathologist factors that influence IC rates. Our study reviews IC data and factors that influence both formal (written) and informal (verbal) consultation practices among pathologists in academic and community hospital settings. Formal IC records from the academic hospital were collected and academic and community pathologists were invited to complete a survey about their IC practices. All centers had a formalized process for documenting ICs; however, 92% of academic and 90% of community pathologists also requested informal IC. The top reasons for selecting a particular colleague for IC was perceived level of expertise; however, interpersonal relationships and office proximity had a greater impact on informal IC practice. Top reasons for requesting a formal IC were mandatory (subspecialty defined) consultation and uncertainty regarding pathological findings. Advice on wording was a common reason for informal IC. Written documentation of IC aids in QA and determination of IC metrics; however, informal, undocumented ICs still occur. Reasons for IC and choice of consulting pathologist are multifactorial, and identifying these can help target quality improvement initiatives.

Is focal active colitis of greater clinical significance in pediatric patients? A retrospective review of 68 cases with clinical correlation.

Focal active colitis (FAC) is a histopathologic finding of uncertain clinical significance in individual patients. In adults, infection accounts for approximately 50%, Crohn's disease (CD) for 0-13%, and 20%-30% are idiopathic. One previous study of 29 cases of pediatric FAC showed a 28% rate of CD. This study reviewed a larger cohort of pediatric patients to determine what proportion had IBD, and whether an amount or pattern of inflammation could predict IBD. Sixty-eight patients aged ≤18years with FAC were identified and reviewed. Patients with a prior diagnosis of IBD or chronic colitis in the index biopsies were excluded. Slides were assessed for a number of inflammatory criteria. Clinical data and final diagnoses were recorded. Data were analyzed using Pearson correlations and Fisher's exact χ2 analyses. Sixteen patients (24%) had a final diagnosis of IBD. When cases with terminal ileal (TI) inflammation were excluded, 6 of 54 patients had a final diagnosis of IBD (11%). A final diagnosis of IBD was significantly associated with crypt abscesses and elevated serum inflammatory markers. IBD was significantly associated with TI inflammation. An amount or pattern of inflammation that could be used to predict IBD was not determined. This study demonstrated a 24% rate of IBD in pediatric patients with FAC; however, when patients with associated TI inflammation were excluded, the rate was 11%, similar to reported rates in adults. FAC in pediatric patients without terminal ileal inflammation does not appear to warrant more aggressive follow-up.

Ileal "carcinoid" tumors-small size belies deadly intent: high rate of nodal metastasis in tumors ≤1 cm in size.

Neuroendocrine tumors (NETs) account for 2% of tumors of the gastrointestinal tract, most occurring in the small intestine. A size of 2 cm is generally regarded as a cut-off point for risk of lymph node metastasis in intestinal neuroendocrine tumors in the absence of other high-risk features; however, metastatic disease has been reported in 12% of tumors of the jejunum and ileum measuring 1 cm or less. Archives from 2 institutions were searched for ileal NETs measuring 1 cm or less, and selected data were recorded. Twenty-one ileal NETs were identified measuring ≤1 cm. Six (29%) were multifocal and 7 (33%) had distant metastasis at diagnosis. Regional lymph nodes were examined in 14 cases (67%), and 10 of these cases (71%) showed lymph node metastasis. Mean primary tumor size in cases with nodal metastasis was 7.3 mm. In this series of ileal NETs ≤1 cm in size, the rate of lymph node metastasis was 48% overall and 71% for cases with regional lymph node resections. In addition, 33% showed distant metastasis at the time of diagnosis. Tumors as small as 3 mm and those confined to the submucosa can give rise to nodal metastasis, emphasizing the need for consideration of local resection with regional lymphadenectomy, even for subcentimeter ileal NETs.

Mitotically Active Sclerosing Stromal Tumor of the Ovary: Report of a Case Series With Parallels to Mitotically Active Cellular Fibroma.

Sclerosing stromal tumor of the ovary is a rare neoplasm that typically occurs in the second and third decades of life. To date, all reported cases have behaved in a benign manner. In their usual form, these neoplasms exhibit scant, if any, mitotic activity. Herein, we report a case series of 6 sclerosing stromal tumors with increased mitotic activity (between 7 and 12 mitoses per 10 high-power fields in the most mitotically active areas). Follow-up is available in 4 of 6 cases (ranging from 3 wk to 68 mo) and 1 tumor recurred within the pelvis. We suggest that the term mitotically active sclerosing stromal tumor is used for such neoplasms and draw parallels with mitotically active cellular fibroma, another benign ovarian stromal neoplasm which occasionally recurs locally, but which does not metastasize.

Intraepithelial lymphocytosis is a frequent finding in biopsies from ileal pouch-anal anastomoses.

Following restorative proctocolectomy with an ileal pouch-anal anastomosis, the small bowel mucosa undergoes several specific histologic adaptions, which may be unrelated to the underlying disease or symptoms of pouchitis. An increase in intraepithelial lymphocytes (IELs) has not been described as part of this spectrum. Mucosal biopsies of the ileal pouch and afferent limb of 230 patients (mean age: 45.7y [18.3-74.7], gender [female/male]: 117/113) with a functioning ileal pouch-anal anastomosis (mean time since ileostomy closure: 10.8months) and associated clinically annotated outcome data were assessed for IELs/100 enterocytes. Forty-two patients (18.3%) showed an increase in IELs (≥20 IELs/100 enterocytes [range 20-39]), in pouch and/or afferent limb biopsies. Intraepithelial lymphocytosis was more commonly observed in afferent limb compared to pouch biopsies (18.8% vs 8.3%; P = .42) and in familial adenomatous polyposis compared to ulcerative colitis patients (16% vs 8%; P = 0.36), but neither difference reached statistical significance. No cases with increased IELs displayed severe villous blunting. Increased IELs were not significantly associated with age, sex, ethnicity, smoking history, time since ileostomy, use of antibiotics, biologic agents, anti-diarrheal agents or probiotics, C-reactive protein levels or differential white cell count. None of the 42 patients with increased IELs had positive celiac serology (anti-human tissue transglutaminase IgA [ELISA] with corresponding total serum IgA). Intraepithelial lymphocytosis in pouch biopsies may represent a subclinical response to an altered bacterial microenvironment. Pathologists should be aware that intraepithelial lymphocytosis is part of the spectrum of changes in pouch biopsies, and only rarely is due to celiac disease.

The differential effects of low birth weight and Western diet consumption upon early life hepatic fibrosis development in guinea pig.

Postnatal intake of an energy dense diet, the Western diet (WD), is a strong risk factor for liver fibrosis. Recently, adverse in utero conditions resulting in low birth weight (LBW) have also been associated with postnatal fibrosis development. We assessed the independent and possible synergistic effects of placental insufficiency-induced LBW and postnatal WD consumption on liver fibrosis in early adulthood, with a specific focus on changes in inflammation and apoptosis pathways in association with fibrogenesis. Male LBW (uterine artery ablation) and normal birth weight (NBW) guinea pig pups were fed either a control diet (CD) or WD from weaning to 150 days. Significant steatosis, mild lobular inflammation, apoptosis and mild stage 1 fibrosis (perisinusoidal or portal) were evident in WD-fed offspring (NBW/WD and LBW/WD). In LBW/CD versus NBW/CD offspring, increased transforming growth factor-beta 1 and matrix metallopeptidase mRNA and sma- and Mad-related protein 4 (SMAD4) were present in conjunction with minimal stage 1 portal fibrosis. Further, connective tissue growth factor mRNA was increased and miR-146a expression decreased in LBW offspring, irrespective of diet. Independent of birth weight, WD-fed offspring exhibited increased expression of fibrotic genes as well as elevated inflammatory and apoptotic markers. Moreover, the augmented expression of collagen, type III, alpha 1 and tumor necrosis factor-alpha was associated with increased recruitment of RNA polymerase II and enhanced histone acetylation (K9) to their respective promoters. These data support a role for both LBW and postnatal WD as factors contributing to hepatic fibrosis development in offspring through distinct pathways.

Interobserver variability in assessing dysplasia and architecture in colorectal adenomas: a multicentre Canadian study.

AIMS: Following the introduction of colorectal cancer screening programmes throughout Canada, it became necessary to standardise the diagnosis of colorectal adenomas. Canadian guidelines for standardised reporting of adenomas were developed in 2011. The aims of the present study were (a) to assess interobserver variability in the classification of dysplasia and architecture in adenomas and (b) to determine if interobserver variability could be improved by the adoption of criteria specified in the national guidelines. METHODS: An a priori power analysis was used to determine an adequate number of cases and participants. Twelve pathologists independently classified 40 whole-slide images of adenomas according to architecture and dysplasia grade. Following a wash-out period, participants were provided with the national guidelines and asked to reclassify the study set. RESULTS: At baseline, there was moderate interobserver agreement for architecture (K=0.4700; 95% CI 0.4427 to 0.4972) and dysplasia grade (K=0.5680; 95% CI 0.5299 to 0.6062). Following distribution of the guidelines, there was improved interobserver agreement in assessing architecture (K=0.5403; 95% CI 0.5133 to 0.5674)). For dysplasia grade, overall interobserver agreement remained moderate but decreased significantly (K=0.4833; 95% CI 0.4452 to 0.5215). Half of the cases contained high-grade dysplasia (HGD). Two pathologists diagnosed HGD in ≥75% of cases. CONCLUSIONS: The improvement in interobserver agreement in classifying adenoma architecture suggests that national guidelines can be useful in disseminating knowledge, however, the variability in the diagnosis of HGD, even following guideline review suggests the need for ongoing knowledge-transfer exercises.