Nonlinear microscopy for detection of prostate cancer: analysis of sensitivity and specificity in radical prostatectomies.

Intraoperative evaluation of specimens during radical prostatectomy using frozen sections can be time and labor intensive. Nonlinear microscopy (NLM) is a fluorescence microscopy technique that can rapidly generate images that closely resemble H&E histology in freshly excised tissue, without requiring freezing or microtome sectioning. Specimens are stained with nuclear and cytoplasmic/stromal fluorophores, and NLM evaluation can begin within 3 min of grossing. Fluorescence signals can be displayed using an H&E color scale, facilitating pathologist interpretation. This study evaluates the accuracy of prostate cancer detection in a blinded reading of NLM images compared with the gold standard of formalin-fixed, paraffin-embedded H&E histology. A total of 122 freshly excised prostate specimens were obtained from 40 patients undergoing radical prostatectomy. The prostates were grossed, dissected into specimens of ~10 × 10 mm with 1-4 mm thickness, stained for 2 min for nuclear and cytoplasmic/stromal contrast, and then rinsed with saline for 30 s. NLM images were acquired and multiple images were stitched together to generate large field of view, centimeter-scale digital images suitable for reading. Specimens were then processed for standard paraffin H&E. The study protocol consisted of training, pretesting, and blinded reading phases. After a washout period, pathologists read corresponding paraffin H&E slides. Three pathologists achieved a 95% or greater sensitivity with 100% specificity for detecting cancer on NLM compared with paraffin H&E. Pooled sensitivity and specificity was 97.3% (93.7-99.1%; 95% confidence interval) and 100.0% (97.0-100.0%), respectively. Interobserver agreement for NLM reading had a Fleiss κ = 0.95. The high cancer detection accuracy and rapid specimen preparation suggest that NLM may be useful for intraoperative evaluation in radical prostatectomy.

Temporal profile of diabetic nephropathy pathologic changes.

Diabetic nephropathy, by far, is the most common cause of end stage renal disease in the US and many other countries. In type 1 diabetes, the natural history of diabetic nephropathy is tightly linked to evolution of classic lesions of the disease, namely glomerular basement membrane thickening, increased mesangial matrix, and reduced glomerular filtration surface density. These lesions progress in parallel and correlate with increased albumin excretion rate and reduced glomerular filtration rate across a wide range of renal function. In fact, the vast majority of the variances of albumin excretion and glomerular filtration rates can be explained by these glomerular lesions alone in type 1 diabetic patients. Although, classic lesions of diabetic nephropathy, indistinguishable from those of type 1 diabetes, also occur in type 2 diabetes, renal lesions are more heterogeneous in type 2 diabetic patients with some patients developing more advanced vascular or chronic tubulointerstitial lesions than diabetic glomerulopathy. More research biopsy longitudinal studies, especially in type 2 diabetic patients, are needed to better understand various pathways of renal injury in diabetic nephropathy.

Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: Epidemiology and Long-Term Outcomes in a Strictly Defined Cohort.

Background: A subset of encapsulated/circumscribed follicular variant of papillary thyroid carcinoma (FVPTC) was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in 2016 to reduce overtreatment of a low-risk tumor. Study objectives were to describe the epidemiology and long-term outcomes of NIFTP in a high-volume, urban, tertiary referral center. Methods: Among patients enrolled in the Boston Medical Center (BMC) Thyroid Cancer Registry, 110 cases of FVPTC underwent index thyroid surgery at BMC between 2000 and 2016. Historically, BMC pathologists assess all malignant nodules using sections ≤0.3 cm with evaluation of the entire nodule and capsule. After review of pathology reports to identify potential NIFTPs, slides were rereviewed using criteria established by the NIFTP Working Group in 2016 and 2018. We evaluated interobserver reliability using Cohen's Kappa coefficient. Results: Among 110 FVPTCs, 15 (13%) met NIFTP criteria; 11 women and 4 men, age range 31-64 (mean 47.5) years. Mean tumor diameter was 1.7 cm (compared with 2.2 cm for FVPTC). Among NIFTP cases, there were no lymph node metastases, distant metastases, or tumor recurrences. All NIFTP cases were American Thyroid Association (ATA) low risk compared with only 68% of FVPTC (p = 0.011). Among FVPTCs, 14% had positive lymph nodes at index operation. Four patients (4%) had distant metastases. Mean follow-up time was 46 and 69 months for FVPTC and NIFTP, respectively. Among FVPTCs with an excellent response to therapy (2015 ATA guidelines), there were no recurrences. Just over half (n = 8) of patients with NIFTP received postoperative radioactive iodine (RAI) therapy. Concordance between pathologists was high for ruling out NIFTP (75%), but only 36% for ruling in NIFTP. Overall, for NIFTP designation, Cohen's Kappa was 0.39, which is considered fair. Conclusions: Although this is a relatively small cohort, all NIFTP specimens underwent updated pathology review consistent with current guidelines; mean follow-up was nearly 6 years. NIFTP represents a small fraction of the total papillary neoplasia diagnosed at this tertiary referral center (2.3%). None of the NIFTP cohort experienced an adverse oncologic event, and there were no regional or distant metastases. Over 50% of patients with NIFTP received RAI. Thus, the NIFTP reclassification may substantially reduce the number of patients who require adjuvant therapies, such as completion surgery or RAI.

Surgical management in acute diverticulitis and its association with multi-detector CT, modified Hinchey classification, and clinical parameters.

PURPOSE: To assess whether CT findings, clinical parameters, and modified Hinchey classification are predictive of management outcomes of patients with acute diverticulitis. MATERIALS AND METHODS: Data were accrued between January 2014 and December 2015. A total of 301 adult subjects were identified from radiology reports, of which six who did not met the inclusion criteria were excluded, thus yielding 295 subjects. Subjects were 43.1% (n = 127) male and 56.9% female (n = 168), with mean age 51.9 years (range 18-90). Two independent abdominal radiologists reviewed all scans; imaging features and a modified Hinchey classification were scored. Descriptive statistics compared the relationships between imaging findings, clinical parameters obtained from medical record review, and modified Hinchey classification with management outcomes. RESULTS: CT findings associated with surgical management include the presence of a pericolonic fluid collection (36.8% vs. 8.2%, P = 0.0001), colonic fistula (13.2% vs. 0.4%, P = 0.0002), extraluminal air (26.4% vs. 9.3%, P = 0.0052), bowel obstruction (5.2% vs. 0.0%, P = 0.0162), and a modified Hinchey score of Ib or higher (55.3% vs. 11.7%, P = 0.0001). Slightly lower systolic blood pressure was also associated with operative management (137.2 mmHg vs. 128.2 mmHg, P = 0.0220). CONCLUSION: Specific CT imaging features and modified Hinchey classification are associated with subsequent surgical management in patients with acute diverticulitis.

Pancreatic Neuroendocrine Tumor in the Setting of Dorsal Agenesis of the Pancreas.

Dorsal agenesis of the pancreas (DAP) is an uncommon embryological abnormality where there is absence of the distal pancreas. DAP is mostly asymptomatic, but common presenting symptoms include diabetes mellitus, abdominal pain, pancreatitis, enlarged pancreatic head, and, in a few cases, polysplenia. MRCP and ERCP are the gold standard imaging techniques to demonstrate the absence of the dorsal pancreatic duct. The literature on the association of pancreatic neoplasia and DAP is limited. We present the case of a pancreatic neuroendocrine tumor in a patient with dorsal agenesis of the pancreas, with a review of the related literature.