Adequacy of lymph node harvest following colectomy for obstructed and nonobstructed colon cancer.

BACKGROUND: Technical and clinical differences in resection of obstructed and non-obstructed colon cancers may result in differences in lymph node retrieval. The objective of this study is to compare the lymph node harvest following resection of obstructed and nonobstructed colon cancer patients. METHODS: A retrospective analysis utilizing the 2014-2018 NSQIP colectomy targeted data set was conducted. One-to-one coarsened exact matching (CEM) was utilized between patients undergoing resection for obstructed and non-obstructed colon cancer. The primary outcome was the adequacy of lymph node retrieval (LNR, ≥12 nodes). RESULTS: CEM resulted in 9412 patients. Patients with obstructed tumors were more likely to have inadequate LNR (13.3% vs 8.2%, p < .001) compared to those with nonobstructed tumors. Multivariate analysis demonstrated that patients with obstructing tumors had worse LNR compared to non-obstructed tumors (odds ratio [OR]: 0.74, 95% confidence interval [CI]: 0.62-0.87; p < .005). Increased age (OR: 0.99, 95% CI: 0.098-0.99), presence of preoperative sepsis (OR: 0.70, 95% CI: 0.055-0.90), left-sided and sigmoid tumors compared to right-sided (OR: 0.64, 95% CI: 0.51-0.81; OR: 0.69, 95% CI: 0.58-0.82, respectively), and open surgical resection compared to an minimally invasive surgical approach were associated with inadequate LNR (p < .05). CONCLUSION: This study demonstrated that resection for obstructing colon cancer compared to non-obstructed colon cancer is associated with increased odds of inadequate lymph node harvest.

Machine learning based local recurrence prediction in colorectal cancer using polarized light imaging.

Significance: Current treatment for stage III colorectal cancer (CRC) patients involves surgery that may not be sufficient in many cases, requiring additional adjuvant systemic therapy. Identification of this latter cohort that is likely to recur following surgery is key to better personalized therapy selection, but there is a lack of proper quantitative assessment tools for potential clinical adoption. Aim: The purpose of this study is to employ Mueller matrix (MM) polarized light microscopy in combination with supervised machine learning (ML) to quantitatively analyze the prognostic value of peri-tumoral collagen in CRC in relation to 5-year local recurrence (LR). Approach: A simple MM microscope setup was used to image surgical resection samples acquired from stage III CRC patients. Various potential biomarkers of LR were derived from MM elements via decomposition and transformation operations. These were used as features by different supervised ML models to distinguish samples from patients that locally recurred 5 years later from those that did not. Results: Using the top five most prognostic polarimetric biomarkers ranked by their relevant feature importances, the best-performing XGBoost model achieved a patient-level accuracy of 86%. When the patient pool was further stratified, 96% accuracy was achieved within a tumor-stage-III sub-cohort. Conclusions: ML-aided polarimetric analysis of collagenous stroma may provide prognostic value toward improving the clinical management of CRC patients.

Mueller matrix polarization parameters correlate with local recurrence in patients with stage III colorectal cancer.

The peri-tumoural stroma has been explored as a useful source of prognostic information in colorectal cancer. Using Mueller matrix (MM) polarized light microscopy for quantification of unstained histology slides, the current study assesses the prognostic potential of polarimetric characteristics of peri-tumoural collagenous stroma architecture in 38 human stage III colorectal cancer (CRC) patient samples. Specifically, Mueller matrix transformation and polar decomposition parameters were tested for association with 5-year patient local recurrence outcomes. The results show that some of these polarimetric parameters were significantly different (p value < 0.05) for the recurrence versus the no-recurrence patient cohorts (Mann-Whitney U test). MM parameters may thus be prognostically valuable towards improving clinical management/treatment stratification in CRC patients.

Polarimetric biomarkers of peri-tumoral stroma can correlate with 5-year survival in patients with left-sided colorectal cancer.

Using a novel variant of polarized light microscopy for high-contrast imaging and quantification of unstained histology slides, the current study assesses the prognostic potential of peri-tumoral collagenous stroma architecture in 32 human stage III colorectal cancer (CRC) patient samples. We analyze three distinct polarimetrically-derived images and their associated texture features, explore different unsupervised clustering algorithm models to group the data, and compare the resultant groupings with patient survival. The results demonstrate an appreciable total accuracy of ~ 78% with significant separation (p < 0.05) across all approaches for the binary classification of 5-year patient survival outcomes. Surviving patients preferentially belonged to Cluster 1 irrespective of model approach, suggesting similar stromal microstructural characteristics in this sub-population. The results suggest that polarimetrically-derived stromal biomarkers may possess prognostic value that could improve clinical management/treatment stratification in CRC patients.

A Case Series of Metastatic Malignant Gastrointestinal Neuroectodermal Tumors and Comprehensive Genomic Profiling Analysis of 20 Cases.

Malignant gastrointestinal neuroectodermal tumor (GNET) is an ultra-rare soft tissue sarcoma, therefore often misdiagnosed and has no available standard treatment. Here, we report 3 cases of metastatic GNET with variable clinical courses. Our small case series as well as extensive literature review, further support that GNET is a spectrum of diseases with variable inherent biology and prognosis. Surgical management in the setting of recurrent/metastatic disease may be appropriate for GNET with indolent nature. Response to systemic treatments including chemotherapy and targeted treatments is variable, likely related to heterogenous biology as well. Furthermore, we retrospectively identified 20 additional GNET cases from Foundation Medicine's genomic database and expanded on their clinicopathological and genomic features. Comprehensive genomic profiling (CGP) with DNA and RNA sequencing of this cohort, in the course of clinical care, demonstrated recurrent EWSR1 chromosomal rearrangements and a sparsity of additional recurrent or driver genomic alterations. All cases had low tumor mutational burden (TMB) and were microsatellite stable.

Toward a quantitative method for estimating tumour-stroma ratio in breast cancer using polarized light microscopy.

The tumour-stroma ratio (TSR) has been explored as a useful source of prognostic information in various cancers, including colorectal, breast, and gastric. Despite research showing potential prognostic utility, its uptake into the clinic has been limited, in part due to challenges associated with subjectivity, reproducibility, and quantification. We have recently proposed a simple, robust, and quantifiable high-contrast method of imaging intra- and peri-tumoural stroma based on polarized light microscopy. Here we report on its use to quantify TSR in human breast cancer using unstained slides from 40 patient samples of invasive ductal carcinoma (IDC). Polarimetric results based on a stromal abundance metric correlated well with pathology designations, showing a statistically significant difference between high- and low-stroma samples as scored by two clinical pathologists. The described polarized light imaging methodology shows promise for use as a quantitative, automatic, and standardizable tool for quantifying TSR, potentially addressing some of the challenges associated with its current estimation.

Novel quantitative signature of tumor stromal architecture: polarized light imaging differentiates between myxoid and sclerotic human breast cancer stroma.

As a leading cause of death in women, breast cancer is a global health concern for which personalized therapy remains largely unrealized, resulting in over- or under-treatment. Recently, tumor stroma has been shown to carry important prognostic information, both in its relative abundance and morphology, but its current assessment methods are few and suboptimal. Herein, we present a novel stromal architecture signature (SAS) methodology based on polarized light imaging that quantifies patterns of tumor connective tissue. We demonstrate its ability to differentiate between myxoid and sclerotic stroma, two pathology-derived categories associated with significantly different patient outcomes. The results demonstrate a 97% sensitivity and 88% specificity for myxoid stroma identification in a pilot study of 102 regions of interest from human invasive ductal carcinoma breast cancer surgical specimens (20 patients). Additionally, the SAS numerical score is indicative of the wide range of stromal characteristics within these binary classes and highlights ambiguous mixed-morphology regions prone to misclassification. The enabling polarized light microscopy technique is inexpensive, fast, fully automatable, applicable to fresh or embedded tissue without the need for staining and thus potentially translatable into research and/or clinical settings. The SAS metric yields quantifiable and objective stromal characterization with promise for prognosis in many types of cancers beyond breast carcinoma, enabling researchers and clinicians to further investigate the emerging and important role of stromal architectural patterns in solid tumors.

Peri-tumoural stroma collagen organization of invasive ductal carcinoma assessed by polarized light microscopy differs between OncotypeDX risk group.

A commercially available genomic test, OncotypeDX has emerged as a useful postsurgical treatment guide for early stage breast cancer. Despite widespread clinical adoption, there remain logistical issues with its implementation. Collagenous stromal architecture has been shown to hold prognostic value that may complement OncotypeDX. Polarimetric analysis of breast cancer surgical samples allows for the quantification of collagenous stroma abundance and organization. We examine intratumoural collagen abundance and alignment along the tumor-host interface for 45 human samples of invasive ductal carcinoma categorized as low or higher risk by OncotypeDX. Furthermore, we probe the separatory power of collagen alignment patterns to classify unlabeled samples as low or higher OncotypeDX risk group using a linear discriminant (LD) model. No significant difference in mean collagen abundance was found between the two risk groups. However, collagen alignment along the tumor boundary was found to be significantly lower in higher risk samples. The LD model achieved a 71% total accuracy and 81% sensitivity to higher risk samples. Prognostic information extracted from the stromal morphology has potential to complement OncotypeDX as an easy-to-implement prescreening methodology.

Correction to: A multiscale Mueller polarimetry module for a stereo zoom microscope.

[This corrects the article DOI: 10.1007/s13534-019-00116-w.].

Novel methodology to image stromal tissue and assess its morphological features with polarized light: towards a tumour microenvironment prognostic signature.

The amount and organization details of peri-tumoural stroma have been linked to patient outcomes in various cancers. In this study, we propose a novel and relatively simple methodology using polarized light microscopy (PLM) to image fibrillar structures within a tumour microenvironment, using only linear crossed polarizers. We demonstrate the technique's ability to image and extract measurement-geometry-independent quantitative morphological metrics related to stromal density and alignment in human invasive breast cancer samples. The findings are promising towards quantitative characterization of peri-tumoural stroma, with potential to develop a PLM signature of tumour microenvironment for providing clinically important information such as breast cancer behaviour or treatment outcome prognosis.

A multiscale Mueller polarimetry module for a stereo zoom microscope.

Mueller polarimetry is a quantitative polarized light imaging modality that is capable of label-free visualization of tissue pathology, does not require extensive sample preparation, and is suitable for wide-field tissue analysis. It holds promise for selected applications in biomedicine, but polarimetry systems are often constrained by limited end-user accessibility and/or long-imaging times. In order to address these needs, we designed a multiscale-polarimetry module that easily couples to a commercially available stereo zoom microscope. This paper describes the module design and provides initial polarimetry imaging results from a murine preclinical breast cancer model and human breast cancer samples. The resultant polarimetry module has variable resolution and field of view, is low-cost, and is simple to switch in or out of a commercial microscope. The module can reduce long imaging times by adopting the main imaging approach used in pathology: scanning at low resolution to identify regions of interest, then at high resolution to inspect the regions in detail. Preliminary results show how the system can aid in region of interest identification for pathology, but also highlight that more work is needed to understand how tissue structures of pathological interest appear in Mueller polarimetry images across varying spatial zoom scales.

The treatment of abdominoscrotal hydrocele: Is there a role for nonoperative management?

BACKGROUND/PURPOSE: Abdominoscrotal hydrocele (ASH) is an uncommon entity. Until now, the recommended treatment has been surgical. There is only one successful case of nonoperative management reported in literature. We report the largest series of children with ASH, and provide evidence in support of an initial nonoperative approach. METHODS: This study is a retrospective chart review of patients treated from 1994 to 2015 with ASH at a single institution. RESULTS: Thirty patients were identified with ASH, with 29 included in the analysis. Nine patients (30%) had operative management with an 80% complication rate. Twenty out of 29 patients (70%) were initially managed expectantly. Sixteen (80%) had resolution of their abdominal component, twelve (60%) of which went on to have full resolution of ASH. Four patients (20%) in this group required operative management of ASH. CONCLUSIONS: ASH should be included in the differential diagnosis of pediatric scrotal swelling. The "Springing Back Ball Sign" should be used as a screening tool. If it is positive, a dynamic ultrasound should be performed to confirm the diagnosis. We recommend observation as the first step in the management of uncomplicated ASH. It can result in avoidance of operation or at least lower the complication risk significantly if operation is required. LEVEL OF EVIDENCE: 4.