Low-risk Lesions Research Articles

Comparing Raman Spectroscopy-Based Artificial Intelligence to High-Definition White Light Endoscopy for Endoscopic Diagnosis of Gastric Neoplasia: A Feasibility Proof-of-Concept Study

Background: Endoscopic assessment for the diagnosis of gastric cancer is limited by interoperator variability and lack of real-time capability. Recently, Raman spectroscopy-based artificial intelligence (AI) has been proposed as a solution to overcome these limitations. Objective: To compare the performance of the AI-enabled Raman spectroscopy with that of high-definition white light endoscopy (HD-WLE) for the risk classification of gastric lesions. Methods: This was a randomized double-arm feasibility proof-of-concept trial in which participants with suspected gastric neoplasia underwent endoscopic assessment using either the Raman spectroscopy-based AI (SPECTRA IMDx™) or HD-WLE performed by expert endoscopists. Identified lesions were classified in real time as having either low or high risk for neoplasia. Diagnostic outcomes were compared between the two groups using histopathology as the reference. Results: A total of 20 patients with 25 lesions were included in the study. SPECTRA, in real-time, performed at a statistically similar level to that of HD-WLE performed by expert endoscopists, achieving an overall sensitivity, specificity, and accuracy of 100%, 80%, and 89.0%, respectively, by patient; and 100%, 80%, and 92%, respectively, by lesion, while expert endoscopists using HD-WLE attained a sensitivity, specificity, and accuracy of 100%, 80%, and 90%, respectively, by patient; and 100%, 83.3%, and 91.7%, respectively, by lesion, in differentiating high-risk from low-risk gastric lesions. Conclusions: The SPECTRA’s comparable performance with that of HD-WLE suggests that it can potentially be a valuable adjunct for less experienced endoscopists to attain accurate and real-time diagnoses of gastric lesions. Larger-scale prospective randomized trials are recommended to validate these promising results further.

Spatial Transcriptomics of IPMN Reveals Divergent Indolent and Malignant Lineages.

Intraductal papillary mucinous neoplasms (IPMN) occur in 5-10% of the population, but only a small minority progress to pancreatic ductal adenocarcinoma (PDAC). The lack of accurate predictors of high-risk disease leads both to unnecessary operations for indolent neoplasms as well as missed diagnoses of PDAC. Digital spatial RNA profiling (DSP-RNA) provides an opportunity to define and associate transcriptomic states with cancer risk. Whole-transcriptome DSP-RNA profiling was performed on 10 IPMN specimens encompassing the spectrum of dysplastic changes from normal duct to cancer. Ductal epithelial regions within each tissue were annotated as normal duct (NL), low-grade dysplasia (LGD), high-grade dysplasia (HGD), or invasive carcinoma (INV). Gene expression count data was generated by Illumina sequencing and analyzed with R/Bioconductor. Dimension reduction analysis exposed three clusters reflecting IPMN transcriptomic states denoted "normal-like" ( cNL ), "low-risk" ( cLR ) and "high-risk" ( cHR ). In addition to specific marker genes, the three states exhibited significant enrichment for the exocrine, classical, and basal-like programs in PDAC. Specifically, exocrine function diminished in cHR , classical activation distinguished neoplasia from cNL , and basal-like genes were specifically upregulated in cHR . Intriguingly, markers of cHR were detected in NL and LGD regions from specimens with PDAC but not low-grade IPMN. DSP-RNA of IPMN revealed low-risk (indolent) and high-risk (malignant) expression programs that correlated with the activity of exocrine and basal-like PDAC signatures, respectively, and distinguished pathologically low-grade from malignant specimens. These findings contextualize IPMN pathogenesis and have the potential to transform existing risk stratification models. Current consensus guidelines for management of intraductal papillary mucinous neoplasms (IPMN) of the pancreas utilize clinical and radiographic criteria for risk stratification. Unfortunately, the estimated positive predictive value of these criteria for IPMN-associated pancreatic ductal adenocarcinoma (PDAC) is under 50%, indicating that over half of pancreatectomies are performed for benign disease. Moreover, nearly 15% of patients who were deemed "low risk" by the same criteria harbored PDAC. Surgical resection of IPMN has maximal benefit when performed prior to the development of PDAC, as evidence of carcinoma has been associated with a high rate of recurrence and poor overall survival. Thus, the development of molecular diagnostics that improve the accuracy of IPMN risk classification would have immediate relevance for patient care, both in terms of better selecting patients for potentially curative operations, as well as sparing patients with low-risk lesions from invasive procedures.

Comparison of British Thyroid Association and TIRADS classifications and their impact on the radiological and surgical management of indeterminate thyroid nodules

BackgroundThe British Thyroid Association (BTA) Guidelines for the Management of Thyroid Cancer advocate for fine-needle aspiration cytology for all thyroid nodules graded indeterminate (U3) at ultrasound assessment. This approach raises concerns regarding potential over-diagnosis of low-risk lesions. Conversely, equivalent Thyroid Imaging Reporting and Data Systems (TIRADS) guidelines permit surveillance or discharge of indeterminate thyroid nodules of certain sizes. This service analysis analyses how guideline choice impacts the fine-needle aspiration cytology rate and subsequent surgical management of indeterminate thyroid nodules. MethodsAll patients with an indeterminate (U3) thyroid nodule identified on ultrasound over a 12-month period were included. Indeterminate thyroid nodules were retrospectively rescored using three equivalent TIRADS classifications by three independent reviewers, blinded to the histopathology. Hypothetical differences in fine-needle aspiration cytology rates and surgical activity were then compared. ResultsNinety-six nodules were identified. Retrospective application of TIRADS guidelines resulted in a hypothetical 44.8-55.2% reduction in fine-needle aspiration cytology performed for indeterminate thyroid nodules compared to BTA. A statistically significant increase in rates of surgical activity for indeterminate thyroid nodules was observed between BTA guidance and all retrospectively applied TIRADS guidelines (p<0.001). Of four confirmed thyroid cancers, three would have been unanimously removed. ConclusionUnder BTA guidance, increased fine-needle aspiration cytology rates for indeterminate thyroid nodules resulted in significantly increased surgical activity in our cohort compared to retrospectively applied TIRADS guidelines.

T2 Hyperintensities in Children with Neurofibromatosis Type 1

Areas of increased signal intensity, known as T2 hyperintensities (T2Hs), observed on T2-weighted magnetic resonance imaging (MRI) scans, are linked to a spectrum of brain abnormalities in children with neurofibromatosis type 1 (NF1). Defining the radiological characteristics that distinguish non-neoplastic from neoplastic T2Hs in children with NF1 is crucial. Then, we could identify lesions that were most likely to require oncologic surveillance. We conducted a single-center retrospective review of all available brain MRIs from 98 children with NF1 and 50 healthy pediatric controls. All T2Hs identified on MRI were characterized based on location, imaging features, and the presence of lesion-related symptoms. Subsequently, all T2Hs were classified using newly established criteria and categorized into 3 distinct groups: low-risk tumor lesions, medium-risk tumor lesions, and high-risk tumor lesions. Lesions deemed to be high-risk will be recommended for surgical treatment. T2Hs were present in 61 (62.2%) individuals of the NF1 cohort. T2Hs were a highly sensitive (100%; 95% confidence interval 92.9%-100.0%) and specific (62.2%; 95% confidence interval 51.9%-71.8%) marker for the diagnosis of NF1. In children aged 4-10, the detection rate of T2Hs is significantly higher than in children under 4years old and those aged between 10 and 18 (P < 0.05). T2Hs were most frequently located in basal ganglia, cerebellar hemispheres, and brainstem. During the follow-up process, none of the lesions categorized as low-risk or medium-risk tumor lesions progressed to high-risk tumor lesions. Seven patients had high-risk tumor lesions and underwent surgical treatment. The pathological assessment identified 5 cases of glioma among the 7 patients, along with 1 case of gliosis and 1 case of vascular dysplasia. Low-risk and medium-risk tumor lesions can both be classified as unidentified bright objects . Unidentified bright objects constituted the majority of T2Hs in children with NF1. High-risk tumor lesions should be considered as probable tumors. With the application of standardized radiologic criteria, a high prevalence of probable brain tumors will be identified in this at-risk population of children, which underscores the importance of vigilant and appropriate oncological surveillance to ensure timely detection and intervention for these tumors.

Evaluation of GARP immunohistochemical expression in papillary thyroid carcinoma

BackgroundGlycoprotein A repetitions predominant (GARP) is a novel transmembrane protein highly expressed on the surface of regulatory T cells (Tregs), which are a subset of immunosuppressive T lymphocytes that play a major role in inhibiting the antitumor immune response. Many studies documented increased GARP expression in various tumors, which is related to a poorer prognosis, and only one single paper investigated its expression in thyroid tumors.AimTo evaluate the immunohistochemical expression of GARP in differentiated thyroid carcinomas and their tumor-infiltrating lymphocytes (TILs) in comparison to its expression in other benign and low-risk lesions.MethodsSixty-nine cases of different thyroid lesions were subgrouped into 37 cases of malignant thyroid neoplasms, 25 cases of benign thyroid lesions, and 7 cases of low-risk neoplasms collected from the Pathology Department Laboratories of Ain Shams University Hospitals during the period from January 2017 to December 2021 and stained immunohistochemically for GARP. Immunohistochemical (IHC) results were evaluated in thyroid epithelial cells and TILs. The expression of GARP was correlated with the different clinicopathological parameters.ResultsGARP expression discloses a significant statistical difference between the three studied groups (P < 0.001). High GARP expression was detected in 89.19% of the malignant cases and in 28.57% of low-risk neoplasms, while all benign lesions exhibited low GARP expression. High GARP expression of TILs was detected in 60% of the malignant cases. Synchronous high GARP expression in tumor tissue and in the surrounding TILs was detected in 63.16% of the malignant cases, yet these results did not reach statistical significance.ConclusionGARP is a marker of Tregs, whose high expression is increased in malignant over benign and low-risk lesions. It might be a potential novel target for anticancer immunotherapy.

Melanoma in situ and low risk pT1a melanoma: Need for new diagnostic terminology

Melanoma incidence has risen rapidly, at least until recently, while mortality has changed only a little, a phenomenon suggestive of overdiagnosis, which can be defined as the diagnosis as “melanoma” of a lesion that would not have had the competence to cause death or symptoms even if it had not been excised. Overdiagnosis has been attributed to efforts at early diagnosis (“overdetection”), and to changes in criteria resulting in diagnosis as melanoma of lesions previously termed nevi (“overdefinition”). In terms of overdefinition, there is evidence that criteria for the histopathologic diagnosis of melanoma has changed over a period of approximately two decades. Specialization may play a role in overdefinition; research has shown that when pathologists interpret the same lesion, dermatopathologists are more likely to diagnose low stage (AJCC T1a) melanomas and general/surgical pathologists are more likely to diagnose atypical nevi. An important subset that contributes to overdiagnosis is those melanomas that lack the property of tumorigenic vertical growth phase, thus lacking metastatic competence, and perhaps not warranting diagnosis as overt melanomas. Studies have defined subsets of patients with very low stage lesions diagnosed as melanomas in which observed survival has been 100%. In the past, many of these lesions would have been diagnosed as nevi, constituting overdefinition. Other key characteristics for very low risk (or no risk) lesions that are currently termed invasive “melanomas” include low Breslow thickness, Clark's level II invasion, absence of mitoses, and clinically, lack of observed or experienced dynamic changes. We propose a provisional terminology for diagnosing extremely low risk subgroups as “Melanocytic neoplasms of low malignant potential”, aimed at reducing the negative personal and social effects of a cancer diagnosis for patients whose health and wellbeing are in reality not affected by an overdiagnosed “melanoma”. With additional confirmation and appropriate consensus, it is likely that some of these subgroups can be reclassified as atypical or dysplastic nevi.

Recurrence following successful eradication of neoplasia with endoscopic mucosal resection compared with endoscopic submucosal dissection in Barrett's esophagus: a retrospective comparison.

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are effective treatments for Barrett's neoplasia. However, little is known about recurrence rates following these techniques. We compared long-term neoplasia recurrence rates following EMR and ESD. This study included patients with Barrett's neoplasia (high grade dysplasia/adenocarcinoma) treated between July 2019 and December 2023 at a tertiary referral center in Canada. Outcomes were residual neoplasia at first follow-up, complete remission of neoplasia (CRN), and neoplasia recurrence following CRN. 157 patients were included (87 EMR, 70 ESD). Compared with EMR, the ESD group had larger lesions (median 2 vs. 3 cm, P<0.05), more adenocarcinoma (85.1% vs. 94.3%, P = 0.07), and deeper submucosal invasion (T1a: 71.6% vs. 75.8%; T1b-SM1: 25.7% vs. 6.1%; T1b≥SM2: 2.7% vs. 18.2%; P<0.05). Among 124 patients with follow-up (71 EMR, 53 ESD), 84.9% of ESD-treated patients had curative resections (i.e. R0 resection with low risk for lymph node metastasis), whereas 94.4% of EMR-treated patients had deep margin R0 resection of low risk lesions. At first follow-up, residual neoplasia (14.1% vs. 11.3%) and CRN (97.2% vs. 100%) were similar in the EMR and ESD groups, but neoplasia recurrence following CRN was significantly higher with EMR (13% vs. 1.9%, P<0.05), with cumulative probability of recurrence at 3 years of 18.3% vs. 4.2%, respectively. Neoplasia recurrence following CRN was significantly higher following EMR compared with ESD, suggesting that ESD may be superior to EMR in preventing neoplasia recurrence in Barrett's esophagus.

Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: How to Select the Most Suitable?

Rectal cancer shows specific characteristics in terms of pattern of recurrence, which occurs commonly at both local and distant sites. The standard of care for locally advanced rectal cancer (LARC) including neoadjuvant chemoradiotherapy, followed by surgery based on the total mesorectal excision principles leads to a reduction in the rates of local recurrences to 6-7% at 5 years. However, the outcomes among those with high-risk lesions remain unsatisfactory. On the contrary, neoadjuvant chemoradiotherapy results in long-term morbidities among those with low-risk lesions. Furthermore, the overall survival benefit of neoadjuvant therapy is still a subject to be debated, except for patients with complete or near-complete response to neoadjuvant therapy. Total neoadjuvant therapy (TNT) is a new paradigm of management of high-risk rectal cancer that includes early administration of the most effective systemic therapy either before or after neoadjuvant radiotherapy with or without chemotherapy prior to surgery with or without adjuvant chemotherapy. TNT potentially improves disease-free survival, even though whether it can prolong survival has been debatable. Recently, neoadjuvant chemotherapy only has been proved to be non-inferior to neoadjuvant chemoradiotherapy in patients with low-risk lesions. This review intends to review the current evidences of neoadjuvant therapy and propose a more customized paradigm of management of LARC.

Impact of the diagnostic label for a low-risk prostate lesion: protocol for two online factorial randomised experiments

IntroductionMany types of prostate cancer present minimal risk to a man’s lifespan or well-being, but existing terminology makes it difficult for men to distinguish these from high-risk prostate cancers. This...

Clinical features and outcomes of paediatric Spitz-type lesions

Introduction and ObjectivesNo definitive management guidelines exist for Spitz-type lesions; recommendations in the UK favour a “safe” approach, with a low threshold for excision. We aim to describe Spitz-type lesions in children to further clarify clinical features and outcomes. MethodsWe conducted a retrospective cohort study in Addenbrooke’s Hospital, Cambridge, UK, reviewing all patients with age ≤18 years with histologically confirmed Spitz-type lesions from November 2014-September 2020. Information collected included patient demographics, lesion details, follow-up, outcomes, and recurrence. Results91 children (male:female 42:49, mean age at diagnosis: 9.4 years, SD: 4.6 years) were identified, consisting of 64 (70.3%) Classic Spitz or Spitzoid naevi, 26 (28.6%) Atypical Spitz Tumours (AST), and one (1.1%) Spitzoid malignant melanoma based on histological features. Assessing clinical features where documented, we found 22.0% (20/91) showed amelanosis, 44.0% (40/91) had a raised bump, 12.1% (11/91) displayed bleeding, 25.0% (20/80) had non-uniform colour, 96.7% (88/91) were de novo lesions, 55.1% (43/78) were evolving in size, and 35.9% (28/78) were evolving in colour. 59 patients (64.8%) were discharged without requiring follow-up, and the other 32 had a median follow-up time of 4 months. We have found no incidences of local recurrence after confirmed excision, no distant metastases, and no mortality in all patients to date. ConclusionsOutcomes for paediatric Spitz-type lesions continue to be exceptionally good, remaining a low-risk lesion which is more likely to be benign in children. Hence, we do not advocate aggressive management policies for paediatric patients with clinically banal Spitz-type lesions.

Early Detection of Cancer and Precancerous Lesions in Persons with HIV through a Comprehensive Cancer Screening Protocol.

Non-AIDS defining malignancies present a growing challenge for persons with HIV (PWH), yet tailored interventions for timely cancer diagnosis are lacking. The Spanish IMPAC-Neo protocol was designed to compare two comprehensive cancer screening strategies integrated into routine HIV care. This study reports baseline data on the prevalence and types of precancerous lesions and early-stage cancer among participants at enrolment. Acceptability of the procedure was additionally assessed. Cross-sectional analysis of a comprehensive screening protocol to detect precancer and cancer. The readiness of healthcare providers to implement the protocol was evaluated using a validated 4-item survey. Among the 1430 enrolled PWH, 1172 underwent 3181 screening tests, with positive findings in 29.4% of cases, leading to further investigation in 20.7%. Adherence to the protocol was 84%, with HIV providers expressing high acceptability (97.1%), appropriateness (91.4%), and feasibility (77.1%). A total of 145 lesions were identified in 109 participants, including 60 precancerous lesions in 35 patients (3.0%), 9 early-stage cancers in 9 patients (0.8%), and 76 low-risk lesions in 65 subjects (5.5%). Adverse events related to screening occurred in 0.8% of participants, all mild. The overall prevalence of cancer precursors or early-stage cancer was 3.8% (95% CI, 2.74%-5.01%), with highest rates observed in individuals screened for anal and colorectal cancers. The baseline comprehensive cancer screening protocol of the IMPAC-Neo study successfully identified a significant proportion of PWH with precancerous lesions and early-stage cancer. High adherence rates and positive feedback from providers suggest effective implementation potential in real-world healthcare settings.

Early Surveillance Endoscopy Should Be Performed Selectively After Transanal Endoscopic Microsurgery for Rectal Lesions.

Introduction Local recurrence (LR) rates after transanal endoscopic microsurgery (TEM) are unclear, and the utility of early postoperative surveillance for low-risk lesions is unknown. This study aimed to define LR after TEM for benign polyps and invasive adenocarcinoma, describe risk factors for LR, and evaluate the utility of early surveillance endoscopy. Methods This retrospective cohort study was conducted at two hospitals in Winnipeg, Manitoba, Canada. Adult patients who underwent TEM between 2009 and 2020 were evaluated for inclusion. The primary outcome was the rate of LR on surveillance endoscopy. Other outcomes included risk factors for LR and diagnostic yield of surveillance endoscopy. Results Among 357 patients who underwent TEM for benign polyps, LR was 10.5% (95% confidence interval (CI) 5.8-15.2) at three years. Positive margin was correlated with LR on multivariate analysis (hazard ratio (HR) 8.01, 95% CI 2.78-23.08). TEM defect closure was associated with lower LR on multivariate analysis (HR 0.19, 95% CI 0.06-0.59). Among 124 patients who underwent TEM for rectal adenocarcinoma, LR was 15.0% (95% CI 6.0-24.0) at three years. The first surveillance endoscopy had a 1.4% yield for low-risk patients (benign lesion, negative margins, and closed TEM defect) and 6.9% for all others. Conclusions LR at three years after TEM was 10.5% for benign polyps and 15.0% for adenocarcinomas. Early surveillance endoscopy can be considered low yield in some patients after TEM, which can be informative for shared decision-making regarding whether to proceed with early endoscopy in a low-risk subgroup of patients.

Safety of first surveillance colonoscopy at 12 months after piecemeal EMR of large nonpedunculated colorectal lesions

After piecemeal EMR (pEMR) of nonpedunculated colorectal lesions≥20mm, guidelines recommend first endoscopic surveillance at 6 months. However, initial surveillance at 12 months may be adequate for selected low-risk lesions and could save the cost, risk, and inconvenience of 1 surveillance examination. This study retrospectively examined a prospectively collected database of all colorectal lesions referred to our center for endoscopic resection between August 2019 and April 2023. We report recurrence rates of patients with colorectal lesions≥20mm removed by pEMR who were assigned to 6-month first surveillance or to 12-month first surveillance (or assigned to a 6-month surveillance visit but did not return until after 10 months). There were 561 nonpedunculated lesions≥20mm that underwent first follow-up, including 490 lesions in 443 patients assigned to 6-month surveillance and 71 lesions in 65 patients assigned to 12-month surveillance. Lesions assigned to 12-month surveillance were smaller (mean size, 25.9 ± 6.1mm vs 37.0 ± 17.4mm), more likely serrated (63.4% vs 9.6%), and more often removed by cold pEMR (74.6% vs 20.4%). Twenty-nine lesions in 24 patients assigned to 6-month surveillance presented after 10 months, and their recurrence data were included in the group assigned to 12-month surveillance. Overall recurrence rates at 6 months and 12 months were 10.0% (46 of 461) and 10.0% (10 of 100), respectively. Mean recurrence sizes at 6 and 12 months were 10.9 ± 6.2mm and 5.0 ± 3.1mm, respectively. One patient in the 6-month surveillance group had cancer at the pEMR site, but no other recurrences at 6 or 12 months had either cancer or high-grade dysplasia. Twelve-month surveillance seems acceptable for selected colorectal lesions≥20mm removed by pEMR. A randomized trial comparing initial 6-month versus 12-month surveillance is warranted for selected lesions.

Discovery and technical validation of high-performance methylated DNA markers for the detection of cervical lesions at risk of malignant progression in low- and middle-income countries

BackgroundCervical cancer remains a leading cause of death, particularly in developing countries. WHO screening guidelines recommend human papilloma virus (HPV) detection as a means to identify women at risk of developing cervical cancer. While HPV testing identifies those at risk, it does not specifically distinguish individuals with neoplasia. We investigated whether a quantitative molecular test that measures methylated DNA markers could identify high-risk lesions in the cervix with accuracy.ResultsMarker discovery was performed in TCGA-CESC Infinium Methylation 450 K Array database and verified in three other public datasets. The panel was technically validated using Quantitative Multiplex-Methylation-Specific PCR in tissue sections (N = 252) and cervical smears (N = 244) from the USA, South Africa, and Vietnam. The gene panel consisted of FMN2, EDNRB, ZNF671, TBXT, and MOS. Cervical tissue samples from all three countries showed highly significant differential methylation in squamous cell carcinoma (SCC) with a sensitivity of 100% [95% CI 74.12–100.00], and specificity of 91% [95% CI 62.26–99.53] to 96% [95% CI 79.01–99.78], and receiver operating characteristic area under the curve (ROC AUC) = 1.000 [95% CI 1.00–1.00] compared to benign cervical tissue, and cervical intraepithelial neoplasia 2/3 with sensitivity of 55% [95% CI 37.77–70.84] to 89% [95% CI 67.20–98.03], specificity of 93% [95% CI 84.07–97.38] to 96% [95% CI 79.01–99.78], and a ROC AUC ranging from 0.793 [95% CI 0.68–0.89] to 0.99 [95% CI 0.97–1.00] compared to CIN1. In cervical smears, the marker panel detected SCC with a sensitivity of 87% [95% CI 77.45–92.69], specificity 95% [95% CI 88.64–98.18], and ROC AUC = 0.925 [95% CI 0.878–0.974] compared to normal, and high-grade squamous intraepithelial lesion (HSIL) at a sensitivity of 70% (95% CI 58.11–80.44), specificity of 94% (95% CI 88.30–97.40), and ROC AUC = 0.884 (95% CI 0.822–0.945) compared to low-grade intraepithelial lesion (LSIL)/normal in an analysis of pooled data from the three countries. Similar to HPV-positive, HPV-negative cervical carcinomas were frequently hypermethylated for these markers.ConclusionsThis 5-marker panel detected SCC and HSIL in cervical smears with a high level of sensitivity and specificity. Molecular tests with the ability to rapidly detect high-risk HSIL will lead to timely treatment for those in need and prevent unnecessary procedures in women with low-risk lesions throughout the world. Validation of these markers in prospectively collected cervical smear cells followed by the development of a hypermethylated marker-based cervical cancer detection test is warranted.

Comprehensive evaluation of cytomorphologic, histologic, and molecular features of DICER1-altered thyroid lesions on FNA: A multipractice experience.

DICER1 mutations, though infrequent, are encountered on preoperative molecular testing of indeterminate adult and pediatric thyroid fine-needle aspiration (FNA) specimens. Yet, published cytomorphologic features of DICER1-altered thyroid lesions are limited. Cytomorphological features of DICER1-altered thyroid lesions were examined in a multipractice FNA cohort with clinical, radiological, and histologic data. The cohort comprised 18 DICER1-altered thyroid FNAs, with 14 having slides available and eight having corresponding surgical resections. Smears, ThinPrep, and formalin-fixed cell block slides were reviewed and correlated with histology, when available. Clinical and radiologic data were obtained from the medical record. Most DICER1-altered FNAs were classified as atypia of undetermined significance (94.4%). DICER1 mutations occurred in codons 1709 (50%), 1810 (27.8%), and 1813 (22.2%). One patient had an additional DICER1 p.D1822N variant in both of their FNAs. Lesions were often hypoechoic (35.3%) and solid (47.1%) on ultrasound. Notable cytomorphologic features include mixed but prominent microfollicular or crowded component, variable colloid, and insignificant nuclear atypia. On resection (n=10), histologic diagnoses ranged from benign follicular adenoma and low-risk follicular thyroid carcinoma to high-grade follicular-derived nonanaplastic thyroid carcinoma. Subcapsular infarct-type change was the most common histologic change. There was no evidence of recurrence or metastasis in eight patients on limited follow-up. DICER1-altered thyroid lesions occurred frequently in young females and FNAs show RAS-like cytomorphology including crowded, mixed macro-/microfollicular pattern, and bland nuclear features. On resection, DICER1-altered thyroid lesions include benign (50%), low-risk lesions (30%), or high-risk malignancies (20%).

Current considerations on intraductal papillary neoplasms of the bile duct and pancreatic duct

Pancreatobiliary intraductal papillary neoplasms (IPNs) represent precursors of pancreatic cancer or bile duct cholangiocarcinoma that can be detected and treated. Despite advances in diagnostic methods, identifying these premalignant lesions is still challenging for treatment providers. Modern imaging, biomarkers and molecular tests for genomic alterations can be used for diagnosis and follow-up. Surgical intervention in combination with new chemotherapeutic agents is considered the optimal treatment for malignant cases. The balance between the risk of malignancy and any risk of resection guides management policy; therefore, treatment should be individualized based on a meticulous preoperative assessment of high-risk stigmata. IPN of the bile duct is more aggressive; thus, early diagnosis and surgery are crucial. The conservative management of low-risk pancreatic branch-duct lesions is safe and effective.

Deep-learning model to improve histological grading and predict upstaging of atypical ductal hyperplasia / ductal carcinoma in situ on breast biopsy.

Risk stratification of atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS), diagnosed using breast biopsy, has great clinical significance. Clinical trials are currently exploring the possibility of active surveillance for low-risk lesions, whereas axillary lymph node staging may be considered during surgical planning for high-risk lesions. We aimed to develop a machine-learning algorithm based on whole-slide images of breast biopsy specimens and clinical information to predict the risk of upstaging to invasive breast cancer after wide excision. Patients diagnosed with ADH/DCIS on breast biopsy were included in this study, comprising 592 (740 slides) and 141 (198 slides) patients in the development and independent testing cohorts, respectively. Histological grading of the lesions was independently evaluated by two pathologists. Clinical information, including biopsy method, lesion size, and Breast Imaging Reporting and Data System (BI-RADS) classification of ultrasound and mammograms, were collected. Deep DCIS consisted of three deep neural networks to evaluate nuclear grade, necrosis, and stromal reactivity. Deep DCIS output comprised five parameters: total patches, lesion extent, Deep Grade, Deep Necrosis, and Deep Stroma. Deep DCIS highly correlated with the pathologists' evaluations of both slide- and patient-level labels. All five parameters of Deep DCIS were significantly associated with upstaging to invasive carcinoma in subsequent wide excisional specimens. Using multivariate logistic regression, Deep DCIS predicted upstaging to invasive carcinoma with an area under the curve (AUC) of 0.81, outperforming pathologists' evaluation (AUC, 0.71 and 0.69). After including clinical and hormone receptor status information, performance further improved (AUC, 0.87). This combined model retained its predictive power in two subgroup analyses: the first subgroup included unequivocal DCIS (excluding cases of ADH and DCIS suspicious for microinvasion) (AUC, 0.83), while the second excluded cases of high-grade DCIS (AUC, 0.81). The model was validated in an independent testing cohort (AUC, 0.81). This study demonstrated that deep-learning models can refine histological evaluation of ADH and DCIS on breast biopsies, which may help guide future treatment planning.

Pancreatic cysts: can surveillance interval for small low-risk lesions be lengthened?

Surveillance of pancreatic cysts are necessary due to risk of malignant transformation. However, reported progression rates to advanced neoplasia are variable and the high frequency of surveillance scans may pose a considerable burden on healthcare resources. To validate the effectiveness of the Fukuoka Guidelines surveillance regime and determine if a longer surveillance interval can be established. All magnetic resonance imaging (MRI) studies of the pancreas performed at our institution between January 2014 and December 2016 with at least one pancreatic cystic lesion and follow-up MRI or computed tomography (CT) over at least two years were reviewed for size, worrisome feature (WF), and high-risk stigmata (HRS) at diagnosis and follow-up imaging (up to year 6). Reference standards for advanced neoplasia were based on endoscopic ultrasound, fine needle aspiration cytology, or the presence of ≥2 WF or ≥1 HRS on imaging. Comparison of MRI features of progression and outcomes of diagnostic endpoints between lesions <20 mm and ≥20 mm was performed. A total of 270 patients were included (201 cysts <20 mm, 69 cysts ≥20 mm). Compared with cysts <20 mm, cysts ≥20 mm were more likely to be associated with WF or HRS (40.6% vs. 12.4%; P ≤0.00001), demonstrate increase in size of ≥5 mm in two years (20.3% vs. 10.9%; P = 0.049), and develop advanced neoplasia (24.6% vs. 0.5%; P <0.00001). Pancreatic cysts <20 mm have a low risk of developing WF and HRS and surveillance interval may be lengthened.

Delay in post-endoscopic refeeding in patients with upper GI bleeding leads to increased hospital length of stay

BackgroundPatients with acute upper gastrointestinal bleeding (UGIB) are made NPO prior to endoscopy. It is standard practice in those found to have low risk lesions to immediately resume a usual diet. Here, we evaluated refeeding practices in hospitalized patients with UGIB after endoscopy. MethodsIn this retrospective single-center cross-sectional study, we examined patients over the age of 18 with acute UGIB and low risk or no endoscopic lesion(s). Appropriate refeeding was categorically defined as resuming normal diet ≤ 4 h post-endoscopy. ResultsOf 230 patients (mean age, 62 years; 57% female) with acute UGIB and low-risk lesions or no lesion(s), 96 [41% (95% CI: 35% to 48%)] received their usual diet within 4 h after EGD. For the remaining 134 patients, refeeding was delayed on average from 13 (NPO until regular diet) to 31 (NPO until liquid diet, then regular diet) hours. Baseline clinical features were identical in patients who received their regular diet within 4 h after EGD and those who did not. Hospital length of stay was shorter in patients receiving usual diets promptly (5.3 days vs. 6.4 days, p = 0.03). Patients in an ICU at the time of their endoscopy had a statistically significantly higher probability of not being refed appropriately [OR 2.371, 95% CI 1.191-4.722). ConclusionsInappropriate dietary restrictions are frequent in patients with UGIB caused by low risk lesions. This delay in refeeding leads to increased length of hospital stay - suggesting that appropriate refeeding is an opportunity to improve patient care.

Prediction of Pathological Risk Stratification using Computed Tomography Features in Gastrointestinal Stromal Tumours: A Retrospective observational Study

Introduction: Gastrointestinal Stromal Tumours (GISTs) are the most common mesenchymal tumours of gastrointestinal tract. A high postsurgical recurrence and metastatic rate have created a need for a presurgical risk profile identification system. Aim: To assess the association between morphological Computed Tomography (CT) parameters with the pathological risk profile and analyse which CT features can predict the risk grading of GISTs. Materials and Methods: This was a retrospective cohort study based on imaging and histopathological data of 26 patients with pathologically proven GISTs presenting to the Department of Radiodiagnosis of a tertiary hospital in the northern Indian Himalayan foothills over a period of five years from July 2018 to June 2023. CT imaging features including size, growth pattern, margins, enhancement, calcifications, necrosis, intralesional haemorrhage, enlarged feeding vessels, direct organ invasion, and associations such as ascites and lymphadenopathy were studied. All lesions were classified as per Miettinen risk classification into no risk, very low-risk, low, moderate, and high-risk lesions. Analysis was done by the Chi-square test. Predictive analysis was carried out by computing the odds ratio and performing regression analysis on significantly associated imaging features. Results: Out of 26 patients, the study group comprised 16 males (61.54%) and 10 females (38.46%). The most common decade of presentation was the 6th decade with the mean age of presentation being 55.81±4.23 years. Twelve patients were grouped under intermediate to high-risk grading. Lesion size &gt;5 cm (p-value=0.0171, OR=19.12), ill-defined margins (p-value=0.0048, OR=18.33), intralesional necrosis (p-value=0.0053, OR=19.8), and enlarged feeding vessels (p-value=0.012, OR=21.27) were identified as imaging features with significant association and predictive ability for high-risk lesions. The strongest predictive ability for a high-risk profile was shown by ill-defined margins (R2 =0.381) and intralesional necrosis (R2 =0.3287). Conclusion: A preoperative Contrast Enhanced Computed Tomography (CECT) assessment provides a comprehensive imaging profile for GISTs as well as a fair accuracy of risk profile prediction via various singular and clustered morphological parameters.