Multi-Scale Digital Pathology Patch-Level Prostate Cancer Grading Using Deep Learning: Use Case Evaluation of DiagSet Dataset.

Prostate cancer remains a prevalent health concern, emphasizing the critical need for early diagnosis and precise treatment strategies to mitigate mortality rates. The accurate prediction of cancer grade is paramount for timely interventions. This paper introduces an approach to prostate cancer grading, framing it as a classification problem. Leveraging ResNet models on multi-scale patch-level digital pathology and the Diagset dataset, the proposed method demonstrates notable success, achieving an accuracy of 0.999 in identifying clinically significant prostate cancer. The study contributes to the evolving landscape of cancer diagnostics, offering a promising avenue for improved grading accuracy and, consequently, more effective treatment planning. By integrating innovative deep learning techniques with comprehensive datasets, our approach represents a step forward in the pursuit of personalized and targeted cancer care.

Ensemble Deep Learning-Based Image Classification for Breast Cancer Subtype and Invasiveness Diagnosis from Whole Slide Image Histopathology.

Cancer diagnosis and classification are pivotal for effective patient management and treatment planning. In this study, a comprehensive approach is presented utilizing ensemble deep learning techniques to analyze breast cancer histopathology images. Our datasets were based on two widely employed datasets from different centers for two different tasks: BACH and BreakHis. Within the BACH dataset, a proposed ensemble strategy was employed, incorporating VGG16 and ResNet50 architectures to achieve precise classification of breast cancer histopathology images. Introducing a novel image patching technique to preprocess a high-resolution image facilitated a focused analysis of localized regions of interest. The annotated BACH dataset encompassed 400 WSIs across four distinct classes: Normal, Benign, In Situ Carcinoma, and Invasive Carcinoma. In addition, the proposed ensemble was used on the BreakHis dataset, utilizing VGG16, ResNet34, and ResNet50 models to classify microscopic images into eight distinct categories (four benign and four malignant). For both datasets, a five-fold cross-validation approach was employed for rigorous training and testing. Preliminary experimental results indicated a patch classification accuracy of 95.31% (for the BACH dataset) and WSI image classification accuracy of 98.43% (BreakHis). This research significantly contributes to ongoing endeavors in harnessing artificial intelligence to advance breast cancer diagnosis, potentially fostering improved patient outcomes and alleviating healthcare burdens.

Edge IoT Prototyping Using Model-Driven Representations: A Use Case for Smart Agriculture.

Industry 4.0 is positioned at the junction of different disciplines, aiming to re-engineer processes and improve effectiveness and efficiency. It is taking over many industries whose traditional practices are being disrupted by advances in technology and inter-connectivity. In this context, enhanced agriculture systems incorporate new components that are capable of generating better decision making (humidity/temperature/soil sensors, drones for plague detection, smart irrigation, etc.) and also include novel processes for crop control (reproducible environmental conditions, proven strategies for water stress, etc.). At the same time, advances in model-driven development (MDD) simplify software development by introducing domain-specific abstractions of the code that makes application development feasible for domain experts who cannot code. XMDD (eXtreme MDD) makes this way to assemble software even more user-friendly and enables application domain experts who are not programmers to create complex solutions in a more straightforward way. Key to this approach is the introduction of high-level representations of domain-specific functionalities (called SIBs, service-independent building blocks) that encapsulate the programming code and their organisation in reusable libraries, and they are made available in the application development environment. This way, new domain-specific abstractions of the code become easily comprehensible and composable by domain experts. In this paper, we apply these concepts to a smart agriculture solution, producing a proof of concept for the new methodology in this application domain to be used as a portable demonstrator for MDD in IoT and agriculture in the Confirm Research Centre for Smart Manufacturing. Together with model-driven development tools, we leverage here the capabilities of the Nordic Thingy:53 as a multi-protocol IoT prototyping platform. It is an advanced sensing device that handles the data collection and distribution for decision making in the context of the agricultural system and supports edge computing. We demonstrate the importance of high-level abstraction when adopting a complex software development cycle within a multilayered heterogeneous IT ecosystem.

Clinical Trials and Climate Change: Doing Our Part While Pursuing Progress.

The escalating global climate crisis necessitates a critical examination of the environmental impact of various sectors, including health care. Ongoing efforts to establish standard methods for estimating emissions and tracking progress are needed to promote sustainable clinical research.

En kvinne i 60-årene som ikke lenger gjenkjente det hun så.

BACKGROUND: Neurological disorders can present with a vast array of visual disturbances. The constellation of symptoms and findings in this patient prompted workup for unusual causes of both stroke and neurodegenerative disorder. CASE PRESENTATION: A woman in her sixties presented with visual disturbances, followed by weakness in her right arm and aphasia three days later. Her close acquaintances had suspected progressive cognitive decline during the previous year. CT and MRI showed an occluded left posterior cerebral artery with a subacute occipito-temporal infarction. The finding of extensive white matter lesions and segmental arterial vasoconstriction necessitated further workup of vasculitis and hereditary small vessel disease, which were ruled out. The stroke aetiology was considered to be atherosclerotic intracranial large vessel disease. FDG-PET scan revealed decreased metabolism in the left hemisphere, and cerebrospinal biomarkers had slightly decreased beta-amyloid. The findings were suggestive of early Alzheimer's disease or primary progressive aphasia, but currently inconclusive. INTERPRETATION: Based on clinical-anatomical correlation, the patient's visual disturbances, in this case right hemianopsia and object agnosia, were solely related to the stroke and not to a neurodegenerative disorder. Knowledge and interpretation of visual agnosias can in many cases be clinically valuable.

Distance to Treatment With Radical Cystectomy in a Rural State: Long Car Rides, Equivalent Outcomes.

INTRODUCTION: Radical cystectomy is a complex surgery with better outcomes reported when performed at high-volume centers. This may lead to patients traveling farther for care. We examined the impact of travel distance on clinical outcomes. METHODS: A total of 220 patients undergoing radical cystectomy from 2015-2021 were retrospectively reviewed. Distance traveled to the treatment center by patient zip codes was classified as <12.5 miles, 12.5-49.9 miles, and ≥50 miles. Multivariable logistic regression was used to assess complications, readmissions, 90-day mortality, and length of stay by distance traveled. Time to treatment based on distance traveled was compared. RESULTS: A total of 220 patients underwent radical cystectomy with complete 90-day follow-up. Of the patients 38.6% (85/220) were readmitted; 62.5% (53/85) presented to the treatment center or were transferred. All patients readmitted to an outside hospital traveled ≥12.5 miles (P < .001). Patients with high-grade complications were likely to be transferred to the treatment center with only 23.7% (9/38) definitively managed by outside hospital. Patients traveling >12.5 miles with low-grade complications were more likely to be managed at an outside hospital (57.5%, P = .01). There was no difference in time to initiation of neoadjuvant chemotherapy (P = .99) or time to radical cystectomy following neoadjuvant chemotherapy (P = .23) by distance traveled. For 49 muscle-invasive bladder cancer patients proceeding directly to surgery without neoadjuvant chemotherapy, time from diagnosis to radical cystectomy was increased if traveling >12.5 miles (P = .04). CONCLUSIONS: Increased travel distance did not impact early postoperative outcomes. Distance traveled may impact access to care, such as time to surgery or location of readmission to the treatment center postoperatively.

Functional impact of augmentative and alternative communication scale: development of an outcome measure for educators of students with complex communication needs.

PURPOSE: The study aim was to develop and assess the measurement properties of the Functional Impact of Augmentative and Alternative Communication - Educator (FIAAC-E) scale - an educator-reported measure designed to detect change in factors associated with communicative participation in students who use augmentative and alternative communication (AAC). METHODS: The study had three phases. In phase 1 (content validity), 22 content specialists independently rated the relevancy of 22 dimensions proposed for the new scale. In phase 2 (item generation, face validity), 8 educators independently completed a preliminary version of the FIAAC-E scale and flagged items that were unclear. Next, these educators adjusted the wording of unclear items during consensus-building sessions. In phase 3 (item reduction, reliability, convergent validity), 62 educators completed an online survey that included the revised FIAAC-E scale. Survey data were used to shorten the scale, estimate its reliability, and evaluate support for its convergent validity. RESULTS: In phase 1, the 11 dimensions ranked most highly by content specialists were selected for inclusion in the preliminary scale. In phase 2, educators reviewed 113 items and revised 33 to improve clarity. In phase 3, correlational statistics informed the selection of 77 items for the shortened scale. Subsequent data analyses indicated acceptable levels of internal consistency and test-retest reliability and support for convergent validity of the preliminary measure. CONCLUSION: The study provides emerging evidence that supports the FIAAC-E scale as a reliable way to evaluate communicative participation in children and youth who use AAC systems at school.Implications for rehabilitationUsing a reliable means to measure the effectiveness of AAC for children and youth at school may reveal important factors that influence successful communicative, academic, and social participation in school.The FIAAC-E scale is a promising educator-reported questionnaire to inform the development of communication goals and monitor progress towards meeting these goals for students with complex communication needs.

Prostate Specific Antigen Testing Behaviors for Prostate Cancer Screening Among U.S. Immigrants: A Cross-sectional Analysis Using the National Health Interview Survey.

PURPOSE: Immigrants constitute 14% of the U.S. population, and this group is especially vulnerable to poor health care access. Prior research demonstrates U.S. immigrants have low rates of guideline-concordant breast and colorectal screening, but prostate cancer screening has not previously been evaluated. We sought to characterize screening behaviors among U.S. immigrants and to consider possible mechanisms to enhance PSA-based screening for this population. MATERIALS AND METHODS: Data were obtained from the 2010, 2013, 2015, and 2018 National Health Interview Survey reports, which were the recent survey years that included questions about PSA testing. Complex samples logistic regression was performed to assess the relationship between immigrant-specific characteristics including region of birth, citizenship status, length of residence within the U.S., English language proficiency, and history of PSA testing. RESULTS: There were 22,997 survey respondents; 3,257 were foreign-born and 19,740 were U.S.-born. Rates of PSA testing were much lower among the foreign-born population compared to the U.S.-born population (43% vs 60%). Citizenship status, length of residence in the U.S. for more than 15 years, and English proficiency were directly linked to increased rates of PSA testing. There was significant variability in PSA testing among immigrant subgroups and Asian immigrants had the lowest rate of PSA testing. Annual physician visits and English language proficiency were associated with increased PSA testing among the U.S. immigrant population. CONCLUSIONS: Immigrants have relatively low rates of PSA testing. Improving health care utilization and language services may help to narrow the gap in guideline-concordant prostate cancer screening between immigrants and nonimmigrants.

PRState: Incorporating genetic ancestry in prostate cancer risk scores for men of African ancestry.

BACKGROUND: Prostate cancer (PrCa) is one of the most genetically driven solid cancers with heritability estimates as high as 57%. Men of African ancestry are at an increased risk of PrCa; however, current polygenic risk score (PRS) models are based on European ancestry groups and may not be broadly applicable. The objective of this study was to construct an African ancestry-specific PrCa PRS (PRState) and evaluate its performance. METHODS: African ancestry group of 4,533 individuals in ELLIPSE consortium was used for discovery of African ancestry-specific PrCa SNPs. PRState was constructed as weighted sum of genotypes and effect sizes from genome-wide association study (GWAS) of PrCa in African ancestry group. Performance was evaluated using ROC-AUC analysis. RESULTS: We identified African ancestry-specific PrCa risk loci on chromosomes 3, 8, and 11 and constructed a polygenic risk score (PRS) from 10 African ancestry-specific PrCa risk SNPs, achieving an AUC of 0.61 [0.60-0.63] and 0.65 [0.64-0.67], when combined with age and family history. Performance dropped significantly when using ancestry-mismatched PRS models but remained comparable when using trans-ancestry models. Importantly, we validated the PRState score in the Million Veteran Program (MVP), demonstrating improved prediction of PrCa and metastatic PrCa in individuals of African ancestry. CONCLUSIONS: African ancestry-specific PRState improves PrCa prediction in African ancestry groups in ELLIPSE consortium and MVP. This study underscores the need for inclusion of individuals of African ancestry in gene variant discovery to optimize PRSs and identifies African ancestry-specific variants for use in future studies.

On-Clamp vs. Off-Clamp Robot-Assisted Partial Nephrectomy for cT2 Renal Tumors: Retrospective Propensity-Score-Matched Multicenter Outcome Analysis.

We compared perioperative outcomes after on-clamp versus off-clamp robot-assisted partial nephrectomy (RAPN) for >7 cm renal masses. A multicenter dataset was queried for patients who had undergone RAPN for a cT2cN0cM0 kidney tumor from July 2007 to February 2022. The Trifecta achievement (negative surgical margins, no severe complications, and ≤ 30% postoperative estimated glomerular filtration rate (eGFR) reduction) was considered a surrogate of surgical quality. Overall, 316 cases were included in the analysis, and 58% achieved the Trifecta. A propensity-score-matched analysis generated two cohorts of 89 patients homogeneous for age, ASA score, preoperative eGFR, and RENAL score (all p > 0.21). Compared to the on-clamp approach, OT was significantly shorter in the off-clamp group (80 vs. 190 min; p < 0.001), the incidence of sRFD was lower (22% vs. 40%; p = 0.01), and the Trifecta rate higher (66% vs. 46%; p = 0.01). In a crude analysis, >20 min of hilar clamping was associated with a significantly higher risk of sRFD (OR: 2.30; 95%CI: 1.13−4.64; p = 0.02) and with reduced probabilities of achieving the Trifecta (OR: 0.46; 95%CI: 0.27−0.79; p = 0.004). Purely off-clamp RAPN seems to be a safe and viable option to treat cT2 renal masses and may outperform the on-clamp approach regarding perioperative surgical outcomes.

Case of a Man with Hemichorea and Behavioral Changes: "A Red Herring".

Background: Progressive supranuclear palsy (PSP)-pallido-nigro-luysian atrophy (PNLA) is a neuropathological entity thought to be a variant of classic PSP. Clinical features and pathologic hallmarks are the same in both conditions; however, age and order of symptom onset, disease duration and prognosis, and distribution and density of pathology differentiate the 2 entities. Objectives: This study presents a PSP-PNLA case confirmed pathologically with a clinical presentation of hemichorea/ballism, spasticity, progressive hemiparesis, and a frontal behavioral syndrome with relative cognitive sparing early in the disease course. Methods: We describe the clinical progression in this unique case supplemented with video and imaging findings in the form of magnetic resonance imaging and brain single photon emission computed tomography. Final diagnosis is via pathological analysis at autopsy. Results: We present an elderly gentleman who manifested a clinical syndrome consisting of subacute onset of chorea that at presentation was distinctly unilateral and a frontal behavioral syndrome in the setting of mild thrombocytopenia and elevated anticardiolipin antibodies. Positive antiphospholipid antibodies resulted in an initial antemortem diagnosis of primary antiphospholipid syndrome as a cause of his chorea. Longitudinal follow-up over 5 years demonstrated a progression of clinical features with hemi-motor impersistence/chorea, disinhibition and impulsivity, and eventually corticospinal distribution weakness on the initially affected side. He required nursing home care and falls necessitated wheelchair use. Postmortem neuropathological study revealed a diagnosis of frontotemporal lobar degeneration-tau, PSP-PNLA. Conclusions: This case broadens the phenotype of PSP-PNLA and to our knowledge is the only case presenting with unilateral chorea.

Clarifying the Trade-Offs of Risk-Stratified Screening for Prostate Cancer: A Cost-Effectiveness Study.

Cancer risk prediction is necessary for precision early detection, which matches screening intensity to risk. However, practical steps for translating risk predictions to risk-stratified screening policies are not well established. We used a validated population prostate-cancer model to simulate the outcomes of strategies that increase intensity for men at high risk and reduce intensity for men at low risk. We defined risk by the Prompt Prostate Genetic Score (PGS) (Stratify Genomics, San Diego, California), a germline genetic test. We first recalibrated the model to reflect the disease incidence observed within risk strata using data from a large prevention trial where some participants were tested with Prompt PGS. We then simulated risk-stratified strategies in a population with the same risk distribution as the trial and evaluated the cost-effectiveness of risk-stratified screening versus universal (risk-agnostic) screening. Prompt PGS risk-adapted screening was more cost-effective when universal screening was conservative. Risk-stratified strategies improved outcomes at a cost of less than $100,000 per quality-adjusted life year compared with biennial screening starting at age 55 years, but risk stratification was not cost-effective compared with biennial screening starting at age 45. Heterogeneity of risk and fraction of the population within each stratum were also important determinants of cost-effectiveness.

National Recommendations against Prostate Specific Antigen Screening versus Statewide Medicaid Expansion Initiatives: A Battle of the Titans.

PURPOSE: Medicaid expansion under the Patient Protection and Affordable Care Act occurred almost concurrently with 2012 U.S. Preventive Services Task Force recommendations against prostate specific antigen screening. Here the relative influence on prostate specific antigen screening rates by 2 concurrent and opposing system-level policy initiatives is investigated: improved access to care and change in clinical practice guidelines. MATERIALS AND METHODS: Behavioral Risk Factor Surveillance System data from years 2012 to 2018 were analyzed for trends in self-reported prostate specific antigen screening and insurance coverage. Subanalyses included state Medicaid expansion status and respondent federal poverty level. Multivariable logistic regression was performed to evaluate factors associated with prostate specific antigen screening. RESULTS: From 2012 to 2018 prostate specific antigen screening predominantly declined with a notable exception of an increase of 7.3% for men at <138% federal poverty level between 2011 and 2013 in early expansion states. Initial increases did not continue, and screening trends mirrored those of nonexpansion states by 2018. Notably, 2014 planned expansions states did not follow this trend with minimal change between 2015 and 2017 compared to declines in early expansion states and nonexpansion states (-0.4% vs -6.7% and -8.6%, respectively). CONCLUSIONS: Medicaid expansion was associated with increased rates of insured men at <138% federal poverty level from 2012 to 2018 in early expansion states. In this group, initial increases in prostate specific antigen screening were not durable and followed the trend of reduced screening seen across the United States. In planned expansions states the global drop in prostate specific antigen screening from 2016 to 2018 was offset in men at <138% federal poverty level by expanding access to care. Nonexpansion states showed a steady decline in prostate specific antigen screening rates. This suggests that policy such as U.S. Preventive Services Task Force recommendations against screening competes with and often outmatches access to care.

Meditative and mind-body practice among patients with genitourinary malignancy.

INTRODUCTION AND OBJECTIVE: Research on the utility of meditative and mind-body (MB) practices has increased dramatically in the last two decades and both have been suggested as useful adjuncts in coping with stressors associated with cancer survivorship. There exists little data on use among genitourinary (GU) cancer survivors. This study seeks to describe meditative and MB utilization among GU cancer survivors. METHODS: Analysis of data from the 2012 and 2017 National Health Interview Survey was conducted. Patients aged 40 and older reporting a history of any cancer diagnosis (including 3 GU cancers) were included in the analysis. We explored questions about meditative and MB practices in the past 12 months. Complex Samples Logistic regression was performed to compare the relationship between cancer status and use of these practices. RESULTS: Self-reported meditative practices were more prevalent in 2017 (17%) than in 2012 (5%). Patients who self-reported a cancer diagnosis of any kind were significantly more likely to utilize meditative practices. Patients with kidney cancer were significantly more likely to meditate and trended towards higher MB utilization. In contrast, bladder cancer patients were less likely to meditate and use MB practices. Increases in meditation were greater than those seen for MB in all groups. CONCLUSIONS: Meditative and MB practices increased in prevalence between 2012 and 2017 with notable heterogeneity between cancer types. Given the potential benefit, more broad incorporation into survivorship programs may be warranted. Future work should explore the significance of this heterogeneity and the utility of these practices to patients with urologic malignancy.

Evaluation of the multidimensional effects of adaptive seating interventions for young children with non-ambulatory cerebral palsy.

PURPOSE: To investigate the short-term effectiveness of the first adaptive seating system received by children with non-ambulatory cerebral palsy (CP) who are classified as level IV or V according to the Gross Motor Function Classification System. MATERIALS AND METHODS: A trained clinical assessor examined 20 children with non-ambulatory CP (mean age: 4.5 years) for their trunk control ability in static, active, and reactive tasks using the Segmental Assessment of Trunk Control. Their primary caregivers were also interviewed about their child's activity and participation using the Paediatric Evaluation of Disability Inventory Computer - Adaptive Test in daily activity and social/cognitive domains and Family Impact of Assistive Technology Scale for Adaptive Seating in child and family functioning domains. Data for each measure were collected 3 times: at baseline (pre-intervention) and then 6 weeks and 3 months after children received their first adaptive seating system. RESULTS AND CONCLUSION: The static and active trunk control scores between baseline and 6 weeks, and baseline and 3 months significantly improved. Daily activity scaled scores significantly improved between baseline and 3 months, and 6 weeks and 3 months. Significant, large gains in child and family functioning overall were detected between baseline and 6 weeks, and baseline and 3 months. These findings provide emerging evidence of multidimensional effects associated with the introduction of a first adaptive seating system into the lives of young children with non-ambulatory CPIMPLICATIONS FOR REHABILITATIONThe introduction of an adaptive seating system into the wheelchair of children with non-ambulatory cerebral palsy may be associated with short-term gains in body function, activities, participation and aspects of the child's environment.

Pathologic nodal downstaging in men with clinically involved lymph nodes undergoing radical prostatectomy: Implications for definitive locoregional therapy.

A prostate cancer (CaP) patient with nonmetastatic but clinical positive lymph nodes (cN+) represents a difficult clinical scenario. We compare overall survival (OS) between cN+ men that underwent radical prostatectomy (RP) and were found to have negative node status (pN) with those found to have positive nodal status (pN+), and assess predictors of discordant nodal status. We queried the National Cancer Data Base between 2004 and 2015 for patients that were cT1-3 cN+ cM0 CaP treated with RP. Patients with 0 nodes, cT4, or cM1 disease were excluded. We compared groups based on pathologic nodal status: Discordant (cN+ -> pN) & Concordant (cN+ -> pN+). Kaplan Meier estimations were used to compare OS. Logistic regression was used to determine possible predictors of nodal status. We find that of 6470 cN+ patients, 1,367 (21.1%) underwent RP, 866 (13.4%) had confirmed nodal status. Discordant status was found in 159 (18.4%) and concordant staging in 707 (81.6%). Differences exist in PSA at diagnosis (7.3 vs. 11.2), biopsy group, # of nodes examined (7 vs. 10), race, and Charlson index. Discordant staging had longer OS compared to Concordant staging (P = 0.007) and similar OS to a 3:1 matched cohort of high risk localized CaP patients used as reference (P = 0.46). Lower Gleason Score (GG1-3) was associated with an increased likelihood of discordant staging. Clinical nodal staging is associated with a substantial false positive rate. Discordant status had better OS than Concordant status and similar OS to matched patients with localized CaP. Clinical nodal staging may inappropriately lead to noncurative therapy in a substantial number of men with potentially curable disease.

Impact of positive surgical margins on survival after partial nephrectomy in localized kidney cancer: analysis of the National Cancer Database.

BACKGROUND: The impact of positive surgical margins (PSM) on outcomes in partial nephrectomy (PN) is controversial. We investigated impact of PSM for patients undergoing PN on overall survival (OS) in different stages of renal cell carcinoma (RCC). METHODS: Retrospective analysis of patients from the US National Cancer Database who underwent PN for cT1a-cT2b N0M0 RCC between 2004-13. Patients were stratified by pathological stage (pT1a, pT1b, pT2a, pT2b, and pT3a [upstaged]) and analyzed by margin status. Cox Regression multivariable analysis (MVA) was performed to investigate associations of PSM and covariates on all-cause mortality (ACM). Kaplan-Meier analysis (KMA) of OS was performed for PSM versus negative margin (NSM) by pathological stage. Sub-analysis of Charlson Comorbidity Index 0 (CCI=0) subgroup was conducted to reduce bias from comorbidities. RESULTS: We analyzed 42,113 PN (pT1a: 33,341 [79.2%]; pT1a, pT1b: 6689 [15.9%]; pT2a: 757 [1.8%]; pT2b: 165 [0.4%]; and pT3a: upstaged 1161 [2.8%]). PSM occurred in 6.7% (2823) (pT1a: 6.5%, pT1b: 6.3%, pT2a: 5.9%, pT2b: 6.1%, pT3a: 14.1%, P<0.001). On MVA, PSM was associated with 31% increase in ACM (HR 1.31, P<0.001), which persisted in CCI=0 sub-analysis (HR: 1.25, P<0.001). KMA revealed negative impact of PSM vs. NSM on 5-year OS: pT1 (87.3% vs. 90.9%, P<0.001), pT2 (86.7% vs. 82.5%, P=0.48), and upstaged pT3a (69% vs. 84.2%, P<0.001). CONCLUSIONS: PSM after PN was independently associated with across-the-board decrement in OS, which worsened in pT3a disease and persisted in sub-analysis of patients with CCI=0. PSM should prompt more aggressive surveillance or definitive resection strategies.