Standardizing Prostaglandin Initiation in Prenatally Diagnosed Ductal-Dependent Neonates; A Quality Initiative.

Prostaglandin E1 (PGE) is used in patients with ductal-dependent congenital heart disease (CHD). Side effects of apnea and fever are often dose dependent and occur within 48 h after initiation. We initiated a standardized approach to PGE initiation after our institution recognized a high incidence of side effects and a wide variety of starting doses of PGE. Neonates with prenatally diagnosed ductal-dependent CHD were identified, started on a standardized protocol that started PGE at 0.01 mcg/kg/min, and evaluated for PGE related side effects. Compliance, outcomes and dose adjustments during the first 48 h post-PGE initiation were evaluated. Fifty patients were identified (25 pre-intervention; 25 post-intervention). After intervention, compliance with the protocol was 96%, and apnea or fever occurred in 28% (compared to 63% pre-intervention, p = 0.015). Dose adjustments (either increase or decrease) prior to cardiac surgery were similar in both cohorts (60%, 52%, p = 0.569). There were no mortalities or emergent procedures performed due to ductus arteriosus closure. Standardizing a protocol for initiating PGE in prenatally diagnosed ductal-dependent CHD was successful and reduced the incidence of apnea, fever, and sepsis evaluations. A starting dose of 0.01 mcg/kg/min did not cause increased adverse effects.

Gastrostomy tube placement in congenital cardiac surgery: a multi-institutional database study.

INTRODUCTION: Neonates and infants who undergo congenital cardiac surgery frequently have difficulty with feeding. The factors that predispose these patients to require a gastrostomy tube have not been well defined. We aimed to report the incidence and describe hospital outcomes and characteristics in neonates and infants undergoing congenital cardiac surgery who required gastrostomy tube placement. MATERIALS AND METHOD: A retrospective review was performed on patients undergoing congenital cardiac surgery between October 2015 and December 2020. Patients were identified by International Classification of Diseases 10th Revision codes, utilising the performance improvement database Vizient® Clinical Data Base, and stratified by age at admission: neonates (<1 month) and infants (1-12 months). Outcomes were compared and comparative analysis performed between admissions with and without gastrostomy tube placement. RESULTS: There were 11,793 admissions, 3519 (29.8%) neonates and 8274 (70.2%) infants. We found an increased incidence of gastrostomy tube placement in neonates as compared to infants following congenital cardiac surgery (23.1% versus 6%, p = <0.001). Outcomes in neonates and infants were similar with increased length of stay and cost in those requiring a gastrostomy tube. Gastrostomy tube placement was noted to be more likely in neonates and infants with upper airway anomalies, congenital abnormalities, hospital infections, and genetic abnormalities. DISCUSSION: Age at hospitalisation for congenital cardiac surgery is a definable risk factor for gastrostomy tube requirement. Additional factors contribute to gastrostomy tube placement and should be used when counselling families regarding the potential requirement of a gastrostomy tube.

Does Diffusely Infiltrating Lobular Carcinoma of the Breast Arise from Epithelial-Mesenchymal Hybrid Cells?

Classic diffusely infiltrating lobular carcinoma has imaging features divergent from the breast cancers originating from the terminal ductal lobular units and from the major lactiferous ducts. Although the term "invasive lobular carcinoma" implies a site of origin within the breast lobular epithelium, we were unable to find evidence supporting this assumption. Exceptional excess of fibrous connective tissue and the unique cell architecture combined with the aberrant features at breast imaging suggest that this breast malignancy has not originated from cells lining the breast ducts and lobules. The only remaining relevant component of the fibroglandular tissue is the mesenchyme. The cells freshly isolated and cultured from diffusely infiltrating lobular carcinoma cases contained epithelial-mesenchymal hybrid cells with both epithelial and mesenchymal properties. The radiologic and histopathologic features of the tumours and expression of the mesenchymal stem cell positive markers CD73, CD90, and CD105 all suggest development in the direction of mesenchymal transition. These hybrid cells have tumour-initiating potential and have been shown to have poor prognosis and resistance to therapy targeted for malignancies of breast epithelial origin. Our work emphasizes the need for new approaches to the diagnosis and therapy of this highly fatal breast cancer subtype.

Association Between Pulsatility Index and the Development of Necrotizing Enterocolitis in Infants with Congenital Heart Disease.

Infants with congenital heart disease are known to have higher rates of necrotizing enterocolitis (NEC) which is associated with poorer outcomes. Although the etiology is recognized as distinct from the premature neonatal population, there is not a universal consensus regarding etiology or specific risk factors. In this retrospective single-institution case-control study, we assessed whether aortic pulsatility index (PI) as detected via ultrasound might be associated with NEC in neonates undergoing cardiac surgical repair within the first month of life. The study identified 30 participants who developed NEC and 50 matched controls. Baseline demographic and surgical characteristics were similar between groups. Patients who developed NEC had higher mortality (26% vs 4%, p < 0.01). Standard PI and the modified pulsatility values were calculated manually and underwent logistic regression. The median log PI of the NEC cohort was higher compared to the lowest control PI (0.68 vs 0.48, p = 0.03); the median log PI of the NEC cohort was significantly lower than the highest PI of the control cohort (0.61 vs 0.98, p = 0.05). The modified pulsatility index demonstrated similar trends with the median log MODPI of the NEC cohort being significantly greater than that of the control cohort (3.9 vs. 3.1, p = 0.01). Infants with congenital heart disease who develop NEC have a higher PI and MODPI when compared to the lowest control PI. This suggests that infants with a higher baseline PI may be at increased risk for developing NEC.

Beneficial Effect of Consecutive Screening Mammography Examinations on Mortality from Breast Cancer: A Prospective Study.

Background Previously, the risk of death from breast cancer was analyzed for women participating versus those not participating in the last screening examination before breast cancer diagnosis. Consecutive attendance patterns may further refine estimates. Purpose To estimate the effect of participation in successive mammographic screening examinations on breast cancer mortality. Materials and Methods Participation data for Swedish women eligible for screening mammography in nine counties from 1992 to 2016 were linked with data from registries and regional cancer centers for breast cancer diagnosis, cause, and date of death (Uppsala University ethics committee registration number: 2017/147). Incidence-based breast cancer mortality was calculated by whether the women had participated in the most recent screening examination prior to diagnosis only (intermittent participants), the penultimate screening examination only (lapsed participants), both examinations (serial participants), or neither examination (serial nonparticipants). Rates were analyzed with Poisson regression. We also analyzed incidence of breast cancers proving fatal within 10 years. Results Data were available for a total average population of 549 091 women (average age, 58.9 years ± 6.7 [standard deviation]). The numbers of participants in the four groups were as follows: serial participants, 392 135; intermittent participants, 41 746; lapsed participants, 30 945; and serial nonparticipants, 84 265. Serial participants had a 49% lower risk of breast cancer mortality (relative risk [RR], 0.51; 95% CI: 0.48, 0.55; P < .001) and a 50% lower risk of death from breast cancer within 10 years of diagnosis (RR, 0.50; 95% CI: 0.46, 0.55; P < .001) than serial nonparticipants. Lapsed and intermittent participants had a smaller reduction. Serial participants had significantly lower risk of both outcomes than lapsed or intermittent participants. Analyses correcting for potential biases made little difference to the results. Conclusion Women participating in the last two breast cancer screening examinations prior to breast cancer diagnosis had the largest reduction in breast cancer death. Missing either one of the last two examinations conferred a significantly higher risk. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Stephen A. Feig in this issue.

Prospective comparison of 18F-PSMA-1007 PET/CT, whole-body MRI and CT in primary nodal staging of unfavourable intermediate- and high-risk prostate cancer.

PURPOSE: To prospectively compare 18F-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/CT, whole-body magnetic resonance imaging (WBMRI) including diffusion-weighted imaging (DWI) and standard computed tomography (CT), in primary nodal staging of prostate cancer (PCa). METHODS: Men with newly diagnosed unfavourable intermediate- or high-risk PCa prospectively underwent 18F-PSMA-1007 PET/CT, WBMRI with DWI and contrast-enhanced CT within a median of 8 days. Six readers (two for each modality) independently reported pelvic lymph nodes as malignant, equivocal or benign while blinded to the other imaging modalities. Sensitivity, specificity and accuracy were reported according to optimistic (equivocal lesions interpreted as benign) and pessimistic (equivocal lesions interpreted as malignant) analyses. The reference standard diagnosis was based on multidisciplinary consensus meetings where available histopathology, clinical and follow-up data were used. RESULTS: Seventy-nine patients completed all the imaging modalities, except for one case of interrupted WBMRI. Thirty-one (39%) patients had pelvic lymph node metastases, which were detected in 27/31 (87%), 14/31 (45%) and 8/31 (26%) patients by 18F-PSMA-1007 PET/CT, WBMRI with DWI and CT, respectively (optimistic analysis). In 8/31 (26%) patients, only 18F-PSMA-1007 PET/CT detected malignant lymph nodes, while the other two imaging modalities were reported as negative. At the patient level, sensitivity and specificity values for 18F-PSMA-1007 PET/CT, WBMRI with DWI and CT in optimistic analysis were 0.87 (95%CI 0.71-0.95) and 0.98 (95%CI 0.89-1.00), 0.37 (95%CI 0.22-0.55) and 0.98 (95%CI 0.89-1.00) and 0.26 (95%CI 0.14-0.43) and 1.00 (95%CI 0.93-1.00), respectively. CONCLUSION: 18F-PSMA-1007 PET/CT showed significantly greater sensitivity in nodal staging of primary PCa than did WBMRI with DWI or CT, while maintaining high specificity. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT03537391.

Hospital Survival After Surgical Repair of Truncus Arteriosus with Interrupted Aortic Arch: Results from a Multi-institutional Database.

Truncus arteriosus (TA) is a major congenital cardiac malformation that requires surgical repair in the first few weeks of life. Interrupted aortic arch (IAA) is an associated malformation that significantly impacts the complexity of the TA operation. The aim of this study was to (1) define the comorbid conditions associated with TA and (2) determine the hospital survival and morbidity of patients with TA with and without an IAA. Data was collected from the Vizient Clinical Database/Resource Manager, formerly University HealthSystem Consortium, which encompasses more than 160 academic medical centers in the United States. The database was queried for patients admitted from 2002 to 2016 who were ≤ 4 months of age at initial admission, diagnosed with TA, and underwent complete surgical repair during that hospitalization. Of the 645 patients with TA who underwent surgery, 98 (15%) had TA with an interrupted aortic arch (TA-IAA). Both TA and TA-IAA were associated with a high prevalence of comorbidities, including DiGeorge syndrome, prematurity, and other congenital malformations. There was no difference in mortality between TA and TA-IAA (13.7-18.4%, p value = 0.227). No comorbid conditions were associated with an increased mortality in either group. However, patients with TA-IAA had a longer post-operative length of stay (LOS) compared to those without IAA (30 versus 40.3 days, p value = 0.001) and this effect was additive with each additional comorbid condition. In conclusion, the addition of IAA to TA is associated with an increased post-operative LOS, but does not increase in-hospital mortality.

Mammography screening reduces rates of advanced and fatal breast cancers: Results in 549,091 women.

BACKGROUND: It is of paramount importance to evaluate the impact of participation in organized mammography service screening independently from changes in breast cancer treatment. This can be done by measuring the incidence of fatal breast cancer, which is based on the date of diagnosis and not on the date of death. METHODS: Among 549,091 women, covering approximately 30% of the Swedish screening-eligible population, the authors calculated the incidence rates of 2473 breast cancers that were fatal within 10 years after diagnosis and the incidence rates of 9737 advanced breast cancers. Data regarding each breast cancer diagnosis and the cause and date of death of each breast cancer case were gathered from national Swedish registries. Tumor characteristics were collected from regional cancer centers. Aggregated data concerning invitation and participation were provided by Sectra Medical Systems AB. Incidence rates were analyzed using Poisson regression. RESULTS: Women who participated in mammography screening had a statistically significant 41% reduction in their risk of dying of breast cancer within 10 years (relative risk, 0.59; 95% CI, 0.51-0.68 [P < .001]) and a 25% reduction in the rate of advanced breast cancers (relative risk, 0.75; 95% CI, 0.66-0.84 [P < .001]). CONCLUSIONS: Substantial reductions in the incidence rate of breast cancers that were fatal within 10 years after diagnosis and in the advanced breast cancer rate were found in this contemporaneous comparison of women participating versus those not participating in screening. These benefits appeared to be independent of recent changes in treatment regimens.

The incidence of fatal breast cancer measures the increased effectiveness of therapy in women participating in mammography screening.

BACKGROUND: Women and their health care providers need a reliable answer to this important question: If a woman chooses to participate in regular mammography screening, then how much will this choice improve her chances of avoiding a death from breast cancer compared with women who choose not to participate? METHODS: To answer this question, we used comprehensive registries for population, screening history, breast cancer incidence, and disease-specific death data in a defined population in Dalarna County, Sweden. The annual incidence of breast cancer was calculated along with the annual incidence of breast cancers that were fatal within 10 and within 11 to 20 years of diagnosis among women aged 40 to 69 years who either did or did not participate in mammography screening during a 39-year period (1977-2015). For an additional comparison, corresponding data are presented from 19 years of the prescreening period (1958-1976). All patients received stage-specific therapy according to the latest national guidelines, irrespective of the mode of detection. RESULTS: The benefit for women who chose to participate in an organized breast cancer screening program was a 60% lower risk of dying from breast cancer within 10 years after diagnosis (relative risk, 0.40; 95% confidence interval, 0.34-0.48) and a 47% lower risk of dying from breast cancer within 20 years after diagnosis (relative risk, 0.53; 95% confidence interval, 0.44-0.63) compared with the corresponding risks for nonparticipants. CONCLUSIONS: Although all patients with breast cancer stand to benefit from advances in breast cancer therapy, the current results demonstrate that women who have participated in mammography screening obtain a significantly greater benefit from the therapy available at the time of diagnosis than do those who have not participated.

Novel biparametric MRI and targeted biopsy improves risk stratification in men with a clinical suspicion of prostate cancer (IMPROD Trial).

PURPOSE: To evaluate the role of a 3T biparametric magnetic resonance imaging (bpMRI), T2 -weighted imaging, and three separate diffusion-weighted imaging acquisitions combined with targeted biopsy (TB) for improving risk stratification of men with elevated prostate-specific antigen (PSA). MATERIALS AND METHODS: Between March 2013 and February 2015, 175 men with a clinical suspicion of prostate cancer (PCa) were offered bpMRI (NCT01864135) based on a suspicion of PCa (two repeated PSA measurements in the range 2.5-20.0 ng/ml and/or abnormal digital rectal examination). Men with an equivocal to high suspicion of PCa had two TBs of the dominant lesion using cognitive ultrasound guidance, followed by systematic biopsy (SB). Men with a low to very low suspicion had only SB. In total, 161 (161/175, 92%) prospectively enrolled men completed the trial and were included in the final analyses. The primary endpoint of the trial was the cancer detection rate (CDR) of TB and SB. Clinically significant cancer (SPCa) was defined as Gleason score ≥3 + 4. RESULTS: TB compared with SB had higher CDR for SPCa (45%, 72/161 vs. 39%, 63/161, respectively; P > 0.05) and a lower CDR for Gleason score 3 + 3 (8%, 15/161 vs. 16%, 30/161; P < 0.05). Restricting biopsy to men with equivocal to highly suspicious bpMRI findings would have resulted in a 24% (38/161) reduction in the number of men undergoing biopsy, while missing 4 (2%) with SPCa. All anonymized datasets, including bpMRI reports and follow up information, are freely available on the trial server. CONCLUSION: Prebiopsy bpMRI and TB in men with a clinical suspicion of PCa improved risk stratification. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:1089-1095.

Preparticipation Cardiac Evaluation from the Pediatric Perspective.

Each year millions of children and adolescents undergo sports preparticipation evaluations (PPEs) before participating in organized sports. A primary aim of the PPE is to screen for risk factors associated with sudden cardiac death. This article is designed to summarize the current thoughts on the PPE with a specific slant toward the pediatric and early adolescent evaluation and how these evaluations may differ from those in adults.

Beneficial effect of repeated participation in breast cancer screening upon survival.

OBJECTIVES: The benefit of mammography screening in reducing population mortality from breast cancer is well established. In this paper, we estimate the effect of repeated participation at scheduled screens on case survival. METHODS: We analysed incidence and survival data on 37,079 women from nine Swedish counties who had at least one to five invitation(s) to screening prior to diagnosis, and were diagnosed with breast cancer between 1992 and 2016. Of these, 4564 subsequently died of breast cancer. We estimated the association of survival with participation in up to the most recent five screens before diagnosis. We used proportional hazards regression to estimate the effect on survival of the number of scheduled screens in which subjects participated prior to the diagnosis of breast cancer. RESULTS: There was successively better survival with an increasing number of screens in which the subject participated. For a woman with five previous screening invitations who participated in all five, the hazard ratio was 0.28 (95% confidence interval (CI) 0.25-0.33, p < 0.0001) compared to a woman attending none (86.9% vs 68.9% 20-year survival). Following a conservative adjustment for potential self-selection factors, the hazard ratio was 0.34 (95% CI 0.26-0.43, p < 0.0001), an approximate three-fold reduction in the hazard of dying from breast cancer. CONCLUSION: For those women who develop breast cancer, regular prior participation in mammography screening confers significantly better survival.

Racial Disparities in Sports Cardiology: A Review.

Importance: Racial disparities in cardiovascular health, including sudden cardiac death (SCD), exist among both the general and athlete populations. Among competitive athletes, disparities in health outcomes potentially influenced by social determinants of health (SDOH) and structural racism remain inadequately understood. This narrative review centers on race in sports cardiology, addressing racial disparities in SCD risk, false-positive cardiac screening rates among athletes, and the prevalence of left ventricular hypertrophy, and encourages a reexamination of race-based practices in sports cardiology, such as the interpretation of screening 12-lead electrocardiogram findings. Observations: Drawing from an array of sources, including epidemiological data and broader medical literature, this narrative review discusses racial disparities in sports cardiology and calls for a paradigm shift in approach that encompasses 3 key principles: race-conscious awareness, clinical inclusivity, and research-driven refinement of clinical practice. These proposed principles call for a shift away from race-based assumptions towards individualized, health-focused care in sports cardiology. This shift would include fostering awareness of sociopolitical constructs, diversifying the medical team workforce, and conducting diverse, evidence-based research to better understand disparities and address inequities in sports cardiology care. Conclusions and Relevance: In sports cardiology, inadequate consideration of the impact of structural racism and SDOH on racial disparities in health outcomes among athletes has resulted in potential biases in current normative standards and in the clinical approach to the cardiovascular care of athletes. An evidence-based approach to successfully address disparities requires pivoting from outdated race-based practices to a race-conscious framework to better understand and improve health care outcomes for diverse athletic populations.

Stent angioplasty to relieve left pulmonary artery obstruction caused by patent ductus arteriosus device occlusion: bipartisan teamwork by two interventional devices.

A 7-month-old patient in congestive heart failure due to a moderate sized patent ductus arteriosus (PDA) underwent uncomplicated implantation of an Amplatzer Ductal Occluder (ADO1). Two months after percutaneous device PDA closure, left pulmonary artery (LPA) stenosis was discovered. Rather than spontaneous improvement as reported in previous cases, our patient's LPA stenosis progressed in severity 7 months after ADO1 placement. A catheterization demonstrated a 32 mm Hg peak gradient from her main pulmonary artery to her LPA. She underwent successful stent angioplasty of her LPA with an excellent result and preserved PDA closure. This case demonstrates that stent angioplasty is a feasible an effective method of relieving LPA obstruction caused by a PDA occluder device. Additionally, despite slight deflection by the stent, the ADO1 device continued to provide complete ductal closure. Stent angioplasty should be considered in patients who have LPA stenosis caused by ADO1 occluder device that does not improve over time.

Effects of race, ethnicity, and gender on surgical mortality in hypoplastic left heart syndrome.

Information is limited regarding the effect of race, ethnicity, and gender on the outcomes of the three palliative procedures for hypoplastic left heart syndrome (HLHS). This study examined the effects of race, ethnicity, gender, type of admission, and surgical volume on in-hospital mortality associated with palliative procedures for HLHS between 1998 and 2007 using data from the University HealthSystem Consortium. According to the data, 1,949 patients underwent stage 1 palliation (S1P) with a mortality rate of 29 %, 1,279 patients underwent stage 2 palliations (S2P) with a mortality rate of 5.4 %, and 1,084 patients underwent stage 3 palliation (S3P) with a mortality rate of 4.1 %. The risk factors for increased mortality with S1P were black and "other" race, smaller surgical volume, and early surgical era. The only risk factors for increased mortality with S2P were black race (11 % mortality; odds ratio [OR], 3.19; 95 % confidence interval [CI] 1.69-6.02) and Hispanic ethnicity (11 % mortality; OR 3.30; 95 % CI 1.64-6.64). For S2P, no racial differences were seen in the top five surgical volume institutions, but racial differences were seen in the non-top-five surgical volume institutions. Mortality with S1P was significantly higher for patients discharged after birth (37 vs 24 %; p = 0.004), and blacks were more likely to be discharged after birth (12 vs 5 % for all other races; p < 0.001). No racial differences with S3P were observed. The risk factors for increased mortality at S1P were black and "other" race, smaller surgical volume, and early surgical era. The risk factors for increased in-hospital mortality with S2P were black race and Hispanic ethnicity.

Preparticipation Cardiac Evaluation from the Pediatric Perspective.

Each year millions of children and adolescents undergo sports preparticipation evaluations (PPEs) before participating in organized sports. A primary aim of the PPE is to screen for risk factors associated with sudden cardiac death. This article is designed to summarize the current thoughts on the PPE with a specific slant toward the pediatric and early adolescent evaluation and how these evaluations may differ from those in adults.

Can we improve breast cancer management using an image-guided histopathology workup supported by larger histopathology sections?

PURPOSE: Breast radiologists examine the entire breast in full-size images, while breast pathologists examine small tissue samples at high magnification. The diagnostic information from these complementary imaging approaches can be difficult to integrate for a more clinically relevant evaluation of malignancies spanning several centimetres. We have explored the advantages and disadvantages of imaging guided larger section pathology techniques compared with the standard 2 × 2.5 cm. small section technique. METHODS: We compared the ability of conventional small section histopathology with larger section histopathology techniques to examine surgical resection margins and full disease extent. We evaluated the pre-surgical imaging workup and use of microfocus magnification radiography of sliced surgical specimens in the histopathologic evaluation of disease extent and status of surgical margins. RESULTS: Image assisted large section histopathology of excised breast tissue enables comprehensive examination of an approximately tenfold larger contiguous tissue area than is provided by conventional small section technology. Attempting to cover the full area of each consecutive slice of resected tissue is more labour-intensive and expensive with the small section approach and poses challenges in reconstituting three-dimensional tumour architecture after morcellation and sectioning. Restricting histopathologic examination to a limited number of samples provides an incomplete evaluation of surgical margins. CONCLUSIONS: A considerably improved documentation of breast cancer and a more reliable assessment of tissue margins is provided by using larger sized histopathology samples to correlate with breast imaging findings. These in turn can enable more appropriate treatment planning, improved surgical performance, fewer recurrences, and better patient outcome. Uncertainty of surgical margin evaluation inherent to the standard small section technique can lead to inappropriate decisions in surgical management and adjunctive therapy. Progress in breast diagnosis and treatment will largely depend on whether histopathology terminology and technique will undergo a revolution similar to the one that has already occurred in breast imaging.

Multifocal and diffusely infiltrating breast cancers are highly fatal subgroups needing further improvement in diagnostic and therapeutic strategies.

Physicians treating breast cancer patients often wonder why this dreaded disease is still fatal in some women despite our best diagnostic and therapeutic efforts. Our own studies on prospectively documented cases spanning several decades have given us new insights for approaching this problem. By using imaging biomarkers to classify breast cancer subtypes according to their apparent site of origin, we found that a majority of breast cancer deaths (71%) occur in a minority of breast cancers (45%). Breast cancer deaths are significantly more likely to occur in women with multifocal acinar adenocarcinoma of the breast, AAB (13.1%), diffusely invasive breast cancers of ductal origin, DAB (24 %) and breast malignancies of mesenchymal hybrid cell origin, BCMO (33.7%) compared with women having unifocal invasive breast cancers (6.1%). Preventing more of these fatal events will require a re-evaluation of the current imperfect histopathologic terminology of breast cancer with special attention to the diffuse breast cancer subtypes, intensification of multimodality imaging and multidisciplinary management, as well as application of image guided large format histopathology.