The anatomy and pathology of the space of Retzius.

The space of Retzius is an important anatomic location for pathology. Pathology in the space of Retzius is more common than previously believed, especially as more cases are discovered with increased use of cross-sectional imaging. Knowledge of the anatomy of the Space of Retzius is crucial for identifying and distinguishing between benign and pathological findings. This paper uses several case examples to discuss benign etiologies, including normal tissue or a foreign body. The paper also demonstrates a case series with pathologic findings in the Space of Retzius under the broad categories of infection, neoplasm, hemorrhage, or urine extravasation. Understanding of the anatomy and these example cases can improve the diagnostic accuracy of radiologists.

The Mount Sinai Clinical Pathway for the Diagnosis and Management of Hypercortisolism due to Ectopic ACTH Syndrome.

Neoplasms that secrete ectopic adrenocorticotropin (ACTH) may cause severe, life-threatening hypercortisolism. These tumors are often difficult to localize and treat, requiring a comprehensive and systematic management plan orchestrated by a multidisciplinary team. The Mount Sinai Adrenal Center hosted an interdisciplinary retreat of experts in adrenal disorders and neuroendocrine tumors (NETs) with the aim of developing a clinical pathway for the management of Cushing syndrome due to ectopic ACTH production. The result was institutional recommendations for the diagnosis, localization, surgical approaches to intrathoracic tumors and bilateral adrenalectomy, and perioperative and postoperative medical management of hypercortisolism and its sequelae. Specific recommendations were made regarding the timing and selection of therapies based on the considerations of our team as well as a review of the current literature. Our clinical pathway can be applied by other institutions directly or serve as a guide for institution-specific management.

Impact of pathological response after neoadjuvant chemotherapy on adjuvant therapy decisions and patient outcomes in gastrointestinal cancers.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is frequently used in gastrointestinal cancers (GIC), and pathological, radiological, and tumor marker responses are assessed during and after NAC. AIM: To evaluate the relationship between pathologic, radiologic, tumor marker responses and recurrence-free survival (RFS), overall survival (OS), adjuvant chemotherapy (AC) decisions, and the impact of changing to a different AC regimen after poor response to NAC. METHODS AND RESULTS: Medical records of GIC patients treated with NAC at Mount Sinai between 1/2012 and 12/2018 were reviewed. One hundred fifty-six patients (58.3% male, mean age 63 years) were identified. Primary tumor sites were: 43 (27.7%) pancreas, 62 (39.7%) gastroesophageal, and 51 (32.7%) colorectal. After NAC, 31 (19.9%) patients had favorable pathologic response (FPR; defined as College of American Pathologists [CAP] score 0-1). Of 107 patients with radiological data, 59 (55.1%) had an objective response, and of 113 patients with tumor marker data, 61 (54.0%) had a ≥50% reduction post NAC. FPR, but not radiographic or serological responses, was associated with improved RFS (HR 0.28; 95% CI 0.11-0.72) and OS (HR 0.13; 95% CI 0.2-0.94). Changing to a different AC regimen from initial NAC, among all patients and specifically among those with unfavorable pathological response (UPR; defined as CAP score 2-3) after NAC, was not associated with improved RFS or OS. CONCLUSIONS: GIC patients with FPR after NAC experienced significant improvements in RFS and OS. Patients with UPR did not benefit from changing AC. Prospective studies to better understand the role of pathological response in AC decisions and outcomes in GIC patients are needed.

Characterization of solid renal neoplasms using MRI-based quantitative radiomics features.

PURPOSE: To assess the diagnostic value of magnetic resonance imaging (MRI)-based radiomics features using machine learning (ML) models in characterizing solid renal neoplasms, in comparison/combination with qualitative radiologic evaluation. METHODS: Retrospective analysis of 125 patients (mean age 59 years, 67% males) with solid renal neoplasms that underwent MRI before surgery. Qualitative (signal and enhancement characteristics) and quantitative radiomics analyses (histogram and texture features) were performed on T2-weighted imaging (WI), T1-WI pre- and post-contrast, and DWI. Mann-Whitney U test and receiver-operating characteristic analysis were used in a training set (n = 88) to evaluate diagnostic performance of qualitative and radiomics features for differentiation of renal cell carcinomas (RCCs) from benign lesions, and characterization of RCC subtypes (clear cell RCC [ccRCC] and papillary RCC [pRCC]). Random forest ML models were developed for discrimination between tumor types on the training set, and validated on an independent set (n = 37). RESULTS: We assessed 104 RCCs (51 ccRCC, 29 pRCC, and 24 other subtypes) and 21 benign lesions in 125 patients. Significant qualitative and quantitative radiomics features (area under the curve [AUC] between 0.62 and 0.90) were included for ML analysis. Models with best diagnostic performance on validation sets showed AUC of 0.73 (confidence interval [CI] 0.5-0.96) for differentiating RCC from benign lesions (using combination of qualitative and radiomics features); AUC of 0.77 (CI 0.62-0.92) for diagnosing ccRCC (using radiomics features), and AUC of 0.74 (CI 0.53-0.95) for diagnosing pRCC (using qualitative features). CONCLUSION: ML models incorporating MRI-based radiomics features and qualitative radiologic assessment can help characterize renal masses.

Metabolic Effects of JAK1/2 Inhibition in Patients with Myeloproliferative Neoplasms.

Ruxolitinib is an FDA approved janus kinase (JAK)1/2 inhibitor used to treat myeloproliferative neoplasms (MPNs), including myelofibrosis and polycythemia vera. We aimed to determine the metabolic consequences of ruxolitinib treatment in patients with MPNs. We performed a retrospective single-center cohort study utilizing an electronic medical record based database of patients who began treatment with ruxolitinib for MPNs from January 2010 to March 2017. We also examined the effects of ruxolitinib on adipose tissue JAK/STAT signaling in a mouse model. 127 patients were identified, of which 69 had data available for weight, and at least one other parameter of interest before, and 72 weeks after starting ruxolitinib. Mean baseline weight was 73.9 ± 17.0 kg, and 78.54 ± 19.1 kg at 72 weeks (p < 0.001). 50% of patients gained >5% body weight. Baseline body mass index (BMI) was 25.8 ± 4.8 kg/m2, and 27.5 ± 5.5 kg/m2 at 72 weeks (p < 0.001). Patients treated with ruxolitinib had a higher systolic blood pressure, serum AST, and ALT at 72 weeks, compared with baseline (p = 0.03, p = 0.01, p = 0.04, respectively). In mice, ruxolitinib decreased basal and GH-stimulated STAT5 phosphorylation in adipose tissue. As pharmacological JAK1/2 inhibitors are being developed and used in clinical practice, it is important to understand their long-term metabolic consequences.

A personalized platform identifies trametinib plus zoledronate for a patient with KRAS-mutant metastatic colorectal cancer.

Colorectal cancer remains a leading source of cancer mortality worldwide. Initial response is often followed by emergent resistance that is poorly responsive to targeted therapies, reflecting currently undruggable cancer drivers such as KRAS and overall genomic complexity. Here, we report a novel approach to developing a personalized therapy for a patient with treatment-resistant metastatic KRAS-mutant colorectal cancer. An extensive genomic analysis of the tumor's genomic landscape identified nine key drivers. A transgenic model that altered orthologs of these nine genes in the Drosophila hindgut was developed; a robotics-based screen using this platform identified trametinib plus zoledronate as a candidate treatment combination. Treating the patient led to a significant response: Target and nontarget lesions displayed a strong partial response and remained stable for 11 months. By addressing a disease's genomic complexity, this personalized approach may provide an alternative treatment option for recalcitrant disease such as KRAS-mutant colorectal cancer.

Anatomy and pathology of the canal of Nuck.

The canal of Nuck is the female equivalent of the processus vaginalis in the male but is less well known than its male counterpart. It is a rare entity not commonly encountered by radiologists, particularly in the adult population. Knowledge of the embryology and anatomy of the canal of Nuck is essential for identification of the various pathologic conditions that may occur in this location. Moreover, radiologists should be familiar with this entity to compose an appropriate and thorough differential diagnosis of a labial mass/swelling. In this review, we discuss both the anatomy and the more common pathology that can be encountered within it.

The Mount Sinai clinical pathway for the management of pheochromocytoma.

OBJECTIVE: Pheochromocytomas are complex tumors that require a comprehensive and systematic management plan orchestrated by a multidisciplinary team. METHODS: To achieve these ends, The Mount Sinai Adrenal Center hosted an interdisciplinary retreat where experts in adrenal disorders assembled with the aim of developing a clinical pathway for the management of pheochromocytomas. RESULTS: The result was a consensus for the diagnosis, perioperative management, and postoperative management of pheochromocytomas, with specific recommendations from our team of adrenal experts, as well as a review of the current literature. CONCLUSION: Our clinical pathway can be applied by other institutions directly or may serve as a guide for institution-specific management.

Implementation and evaluation of a performance improvement intervention to address physician documentation deficiencies in abdominal ultrasound.

PURPOSE: For ultrasound reports to meet criteria for coding as abdomen complete (USABC), 8 elements are required: liver, bile ducts, gallbladder, spleen, kidneys, pancreas, inferior vena cava (IVC), and aorta. Failure to document all 8 results in coding as ultrasound abdomen limited. The purposes of our study were to identify deficiencies in documentation, implement a performance improvement intervention to address deficiencies, and evaluate the intervention. METHODS: In the first phase, 50 consecutive USABC reports performed as part of routine medical care were retrospectively analyzed for the presence or absence of the 8 elements required for USABC coding. Subsequently, education regarding current procedural terminology coding in abdominal ultrasound and standardized macros was provided to radiologists. In the second, postintervention phase, an additional 50 consecutive USABC reports were analyzed for the presence or absence of the 8 elements. RESULTS: In the first phase, none (0%) of 50 reports met criteria for USABC. The most commonly omitted elements were IVC (present in 2% of reports) and aorta (present in 6%). After intervention, there was an increase to 37 reports (74%) meeting criteria for USABC. The most commonly omitted elements were IVC (present in 76%) and aorta (present in 86%). Lack of 100% compliance was secondary to failure to update a macro and inaccurately scheduled studies (focused right lower quadrant/appendicitis study scheduled as USABC). CONCLUSIONS: We improved USABC documentation from 0% to 74%. Our compliance rate after intervention was similar to the 75.1% of previously published larger studies. Our study illustrates the efficacy of simple performance improvement interventions to improve abdominal ultrasound documentation.

Phase 1 study of intravenous rigosertib (ON 01910.Na), a novel benzyl styryl sulfone structure producing G2/M arrest and apoptosis, in adult patients with advanced cancer.

Rigosertib (ON 01910.Na), a synthetic novel benzyl styryl sulfone, was administered to 28 patients with advanced cancer in a Phase I trial in order to characterize its pharmacokinetic profile, determine the dose-limiting toxicities (DLT), define the recommended phase II dose (RPTD) and to document any antitumor activity. Patients with advanced malignant neoplasms refractory to standard therapy were given escalating doses of rigosertib (50, 100, 150, 250, 325, 400, 650, 850, 1,050, 1,375, 1,700 mg/m(2)/24h) as a 3-day continuous infusion (CI) every 2 weeks. An accelerated Fibonacci titration schedule with specified decreases for toxicities was used for escalation until grade ≥2 toxicity occurred. Intrapatient dose escalation was allowed if toxicity was grade ≤2 and the disease remained stable. Plasma pharmacokinetics (PK) and urinary PK assessments were studied in the 1st and 4th cycles. Twenty-nine patients (12 men and 17 women; age 36-87 y with a median of 63 y) were registered, but one died before study drug was given. Twenty-eight patients received a median of 3 cycles of therapy. Most common grade ≥2 toxicities attributable to rigosertib included fatigue, anorexia, vomiting and constipation. DLTs included muscular weakness, hyponatremia, neutropenia, delirium and confusional state. Risk factors for severe toxicities include pre-existing neurological dysfunction or advanced gynecologic cancer after pelvic surgery. Rigosertib pharmacokinetics showed rapid plasma distribution phases and urinary excretion. Elevations in plasma Cmax and AUC due to decreases in plasma clearance were associated with acute grade ≥3 toxicities. Of 22 evaluable patients, 9 (41%) achieved a best overall response of stable disease; all other patients (n=13; 59%) progressed. The median progression-free survival time was 50 days (95% confidence interval [CI]: 37-80 days). Nine (41%) patients survived for over 1 y. In summary, prolonged IV infusions of rigosertib were generally well tolerated. Nine (41%) patients achieved stable disease and 9 (41%) patients survived for over 1 year. The RPTD appears to be 850 mg/m(2)/24hr CI x 3 days. (ClinicalTrials.gov identifier: NCT01538537).

Radiographic findings of anastomotic leaks.

Although computed tomography (CT) scans play an important role in the diagnosis and management of anastomotic leaks (AL), there is no consensus on what radiographic findings are associated with AL. The purpose of this study is to identify the most common CT scan findings associated with AL and whether the amount of extraluminal air or the density of extraluminal fluid can be correlated with the presence of an AL. A retrospective chart review of 210 patients with anastomotic leaks from 2003 to 2010 at Mount Sinai Medical Center was performed. Eighty-six patients fit our criteria and were included. All CT scans were reread by an independent radiologist not involved with patient care. Our study included 59 per cent men and 41 per cent women with a mean age of 51 years. Diagnoses included inflammatory bowel disease (53%), malignancy (21%), and diverticulitis (12%). One hundred per cent of the patients had one of three findings: extraluminal air (92%), extraluminal fluid (88%), or extravasation of contrast (32%). Eighty-one per cent (70/86) had both fluid and air simultaneously. Extraluminal air was seen in 79 patients. The estimated amounts of extraluminal air were as follows: 0 to 25 mL (49%), 26 to 500 mL (41%), 500 to 1000 mL (5%), and more than 1000 mL (5%). The Hounsfield unit (HU) measurements of the fluid ranged from 3 to 633 HUs. The most common CT findings associated with AL are pneumoperitoneum and extraluminal fluid, including extravasation of contrast, which can be seen in up to 100 per cent of patients. The amount of estimated extraluminal air and density of fluid collection have no prognostic value in predicting AL.

Intraductal polypoid lipid-rich neuroendocrine tumor of the pancreas with entrapped ductules: case report and review of the literature.

Pancreatic neuroendocrine tumors of the main pancreatic duct are rare and usually small due to symptoms of pancreatic duct obstruction. We present a case of a large (3 cm), well-differentiated (G1) lipid-rich polypoid neuroendocrine tumor of the pancreas completely occluding the main pancreatic duct with non-neoplastic-entrapped ductules and CK19 positivity. Clinical, radiological, gross, microscopic, immunohistochemical, and ultrastructural findings are discussed. The literature pertaining to the unique features of this case is reviewed including clinical and pathologic pitfalls and the possible etiologic and prognostic significance of these findings.

Hepatic imaging in the 21st century.

Imaging of the liver has progressed rapidly during the past decade with continued advancement of current ultrasound, computed tomography, and magnetic resonance imaging (MRI). Each modality not only has seen refinement enabling better anatomic characterization of disease but also has received strength from the addition of new techniques to its resources. New contrast agents have become available for all modalities and some agents, particularly for MRI, have opened the way for better functional assessment. MRI continues to see an elaboration of sequences (including spectroscopy and diffusion) that also open imaging to the microscopic structure of disease and normal function. The further development of workstations have improved both analysis and depiction of disease. In the 21st century imaging will continue to shift from a simple source of anatomic information to a more functional problem-solving tool.