Pancreatic Cancer-Associated Diabetes is Clinically Distinguishable From Conventional Diabetes.

BACKGROUND: Type 3c diabetes mellitus (T3cDM) is diabetes secondary to other pancreatic diseases such as chronic pancreatitis, pancreatic resection, cystic fibrosis, and pancreatic ductal adenocarcinoma (PDA). Clinically, it may easily be confused with conventional type 2 diabetes mellitus (T2DM). A delay in pancreatic cancer diagnosis and treatment leads to a worse outcome. Therefore, early recognition of PDA-associated T3cDM and distinction from conventional T2DM represents an opportunity improve survival in patients with PDA. METHODS: Six hundred and sixty four patients with PDA underwent pancreatic resection. Patients were classified as per whether or not they had diabetes. The specific type of diabetes was determined. T3cDM surgical patients (n = 127) were compared with a control group of medical patients with T2DM who did not have PDA (n = 127). RESULTS: Patients with T3cDM were older (66 versus 61 y, P < 0.001), had lower body mass indices (25.9 versus 32.1, P < 0.001), more favorable hemoglobin A1c levels (7.0 versus 8.8, P < 0.001), higher alanine aminotransferase levels (39 versus 20, P < 0.001), and lower creatinine levels (0.8 versus 0.9 mg/dL, P < 0.001). In addition, they were more likely to be insulin dependent. In a subgroup analysis of surgical patients, T3cDM (versus surgical patients with T2DM and no diabetes) was not associated with surrogate markers of main pancreatic duct obstruction and glandular atrophy. CONCLUSIONS: PDA-associated T3cDM has a distinctive presenting phenotype compared with medical patients with conventional T2DM. Greater attention to associated signs, symptoms, and biochemical data could identify patients at risk for harboring an underlying pancreatic malignancy and trigger diagnostic pathways leading to earlier PDA diagnosis and treatment.

Uveal metastasis in 1111 patients: Interval to metastasis and overall survival based on timing of primary cancer diagnosis.

PURPOSE: To evaluate interval between primary cancer diagnosis and uveal metastasis and assess survival outcomes based on whether the primary cancer was diagnosed before or after uveal metastasis. METHODS: In this retrospective analysis, all patients with uveal metastasis evaluated on the Ocular Oncology Service, Wills Eye Hospital, Philadelphia, PA, USA between February 1, 1974 and June 1, 2017 were included. Features and outcomes based on timing of primary cancer diagnosis, whether before or after diagnosis of uveal metastasis, were assessed. RESULTS: A total of 2214 uveal metastases were diagnosed in 1310 eyes of 1111 consecutive patients. Primary cancer was known prior to uveal metastasis in 742 patients (67%) and not known in 369 (33%). Of those not known, the primary cancer was later found in 192 patients (17%) and never found in 177 patients (16%). For those with known primary cancer, mean interval from primary cancer diagnosis to uveal metastasis was 5.2 years with differences in primary sites of gastrointestinal (2.1 years, p = 0.003), lung (2.2 years, p < 0.001), breast (6.5 years, p < 0.001), and thyroid (13 years, p < 0.001). By Kaplan-Meier analysis, the 5-year overall survival showed no difference between patients with primary cancer found before (28%) vs after (20%) vs never found (33%), relative to uveal metastasis. CONCLUSION: Of 1111 patients with uveal metastasis, early-onset uveal metastases were found with lung and gastrointestinal tract cancers, whereas late-onset metastases were found with breast and thyroid cancers. Overall survival did not vary on whether the primary tumor was diagnosed before, after, or never found, relative to uveal metastasis.

CHOROIDAL NEVUS TRANSFORMATION INTO MELANOMA PER MILLIMETER INCREMENT IN THICKNESS USING MULTIMODAL IMAGING IN 2355 CASES: The 2019 Wendell L. Hughes Lecture.

PURPOSE: To analyze risk of nevus transformation into melanoma per millimeter increment. METHODS: Retrospective analysis of 3,806 choroidal nevi for transformation into melanoma per incremental millimeter thickness (flat [≤1.0 mm], thin [1.1-2.0 mm], thicker [2.1-3.0 mm], and thickest [>3.0 mm]) RESULTS:: The median nevus thickness was 1.4 mm, and nevi were categorized (flat, thin, thicker, and thickest) in 1,140 (30%), 2052 (54%), 555 (15%), and 59 (<1%), respectively. There were differences in tumor diameter (2.5, 4.8, 7.5, and 9.3 mm; P < 0.01), optical coherence tomography detection of overlying subretinal fluid (<1, 4, 15, and 11%; P < 0.01), overlying retinal edema (<1, 3, 14, and 25%; P < 0.01), overlying drusen (23, 49, 64, and 64%; P < 0.01), overlying retinal pigment epithelial detachment (1, 4, 4, and 9%; P < 0.01), and overlying lipofuscin hyperautofluoresence (<1, 3, 6, and 7%; P < 0.01). Choroidal nevus transformation into melanoma (n = 90/2,355 cases, 3.8%) was found by Kaplan-Meier 7-year estimates (2.2, 6.1, 31.7, and 34.5%; P < 0.0001) and by hazard ratio (HR) compared with nevus ≤1.0 mm (not available, 4.7 [P = 0.01], 35.7 [P < 0.0001], and 52.0 [P < 0.0001]). For all thicknesses, those with growth displayed increase in mean basal diameter of 2.4 mm and thickness of 1.1 mm, optical coherence tomography increase in subretinal fluid (65%), autofluorescence increase in lipofuscin (40%), and ultrasonography increase in hollowness (30%). Multivariable risk factors, recalled by the mnemonic "To Find Small Ocular Melanoma Doing IMaging" (TFSOM-DIM) representing Thickness >2 mm (ultrasonography), Fluid subretinal (optical coherence tomography), Symptom vision loss (Va), Orange pigment (autofluorescence), Melanoma hollow (ultrasonography), and DIaMeter >5 mm, revealed factors per incremental thickness category (compared with flat) including thin (Fluid overlying, HR 6.1; DIaMeter >5 mm, HR 3.3), thicker (Fluid subretinal ≤3 mm from nevus, HR 5.7; Melanoma acoustic hollowness, HR 2.7), and thickest (Orange pigment, HR 9.1). CONCLUSION: Each incremental increase in choroidal nevus thickness demonstrated risk of growth into melanoma with HR (compared with flat) 4.7 for thin, 35.7 for thicker, and 52.0 for thickest. The increase from ≤2.0 mm to >2.0 mm thickness conferred the greatest rise for transformation.

CHOROIDAL NEVUS IMAGING FEATURES IN 3,806 CASES AND RISK FACTORS FOR TRANSFORMATION INTO MELANOMA IN 2,355 CASES: The 2020 Taylor R. Smith and Victor T. Curtin Lecture.

PURPOSE: To use multimodal imaging for identification of risk factors for choroidal nevus transformation into melanoma. METHODS: Retrospective chart review of 3806 consecutive choroidal nevi with imaging and 2355 choroidal nevi with additional follow up to identify factors predictive of transformation of choroidal nevus into melanoma. RESULTS: The median patient age was 62.5 years and Caucasian race in 3167 (95%). The choroidal nevus demonstrated median basal diameter of 4.0 mm and thickness of 1.4 mm. Imaging included optical coherence tomography (OCT) showing subretinal fluid (SRF) in 312 (9%), ultrasonography (US) with acoustic hollowness in 309 (9%), and hyper-autofluorescence (AF) in 100 (3%). Of those 2355 choroidal nevi with follow up, Kaplan-Meier estimates of nevus transformation into melanoma at 1, 5, and 10 years were 1.2%, 5.8%, and 13.9%, respectively. Multivariate analysis, using multimodal imaging for detection of factors predictive of nevus transformation into melanoma, included thickness >2 mm on US (hazard ratio (HR) 3.80, p < 0.0001), SRF on OCT as cap over nevus (HR 3.00, p < 0.0001) or SRF ≤3 mm from nevus margin (HR 3.56, p = 0.0003), symptomatic vision loss ≤20/50 on Snellen visual acuity (VA) (HR 2.28, p = 0.005), orange pigment (lipofuscin) hyperautofluorescence on AF (HR 3.07, p = 0.0004), acoustic hollowness on US (HR 2.10, p = 0.0020), and tumor diameter >5 mm on photography (HR 1.84, p = 0.0275). These factors can be recalled by the mnemonic "To Find Small Ocular Melanoma Doing IMaging" (TFSOM-DIM) representing Thickness >2 mm (US), Fluid subretinal (OCT), Symptoms vision loss (VA), Orange pigment (AF), Melanoma hollow (US), and DIaMeter >5mm (photography). The mean 5-year estimates of nevus growth into melanoma were 1% (HR 0.8) for those with 0 risk factor, 11% (HR 3.09) with 1 factor, 22% (HR 10.6) with 2 factors, 34% (HR 15.1) with 3 factors, 51% (HR 15.2) with 4 factors, 55% (HR 26.4) with 5 risk factors, and not-estimable with all 6 risk factors. CONCLUSION: In this analysis, multimodal imaging was capable of detecting risk factors for nevus transformation into melanoma, including thickness >2 mm (US), fluid subretinal (OCT), symptoms vision loss (Snellen acuity), orange pigment (AF), melanoma hollowness (US), and diameter >5 mm (photography). Increasing number of risk factors imparts greater risk for nevus transformation into melanoma, including thickness >2 mm (US), fluid subretinal (OCT), symptoms vision loss (Snellen acuity), orange pigment (AF), melanoma hollowness (US), and diameter >5 mm (photography). Increasing number of risk factors imparts greater risk for transformation.

Combination of multimodal imaging features predictive of choroidal nevus transformation into melanoma.

AIM: To characterise combinations of multimodal imaging risk factors and predictive value for choroidal nevus transformation into melanoma. METHODS: This is a retrospective review of multimodal imaging features for 3806 choroidal nevi from 1 January 2007 through 1 January 2017. Kaplan-Meier estimates and Cox regression analyses were used to calculate 5-year percentages of growth to melanoma and HR. RESULTS: Using multimodal imaging, six risk factors predictive of choroidal nevus transformation into melanoma were identified, namely tumour thickness >2 mm, subretinal fluid, symptoms of visual acuity loss to 20/50 or worse, orange pigment, hollow acoustic density and tumour largest basal diameter >5 mm. Kaplan-Meier 5-year estimated tumour growth was found in 1% of nevi with no risk factors, 11% (range 9%-37%) with one factor, 22% (12%-68%) with two factors, 34% (21%-100%) with three factors, 51% (0%-100%) with four factors and 55% (0%-100%) with five factors. HR for growth was 0.1 with no factor, 2.1-7.8 with one factor, 1.8-12.1 with two factors, 4.0-24.4 with three factors, 4.6-170.0 with four factors and 12.0-595.0 with five factors. The highest HR with each combination of two, three, four or five risk factors always included symptoms of visual acuity loss and orange pigment. CONCLUSION: Six risk factors for choroidal nevus transformation into melanoma by multimodal imaging have been identified. Risk for transformation into melanoma is 1% when no factors are present, and approaches 100% with specific combinations of three or more risk factors. Understanding how combinations of factors influence risk of transformation into melanoma can guide counselling and treatment decisions.

Plaque Radiotherapy for Medulloepithelioma in 6 Cases From a Single Center.

PURPOSE: To describe outcomes of 6 patients treated with plaque radiotherapy for medulloepithelioma. DESIGN: Retrospective review. METHODS: Computerized medical records were reviewed for patients with cytopathologically confirmed medulloepithelioma and treated with plaque radiotherapy from January 1970 to December 2017. Clinical and radiotherapy parameters along with outcomes of tumor regression, globe salvage, and metastatic disease were recorded. RESULTS: Of 6 patients with medulloepithelioma, plaque radiotherapy was primary (n = 5) or secondary (n = 1) treatment. The median patient age at diagnosis was 41 months (mean, 145; range, 10-624 months). Patient demographics included white race (n = 6) and female sex (n = 5). Patients presented with strabismus (n = 1), decreased vision (n = 1), ocular pain (n = 1), hyphema (n = 1), corectopia (n = 1), and visible iris lesion (n = 1). The mean tumor basal diameter was 11.2 mm (median, 10.0; range, 7.0-16.0 mm), and mean tumor thickness was 6.8 mm (median, 6.4; range, 3.1-11.0 mm). Related findings included cataract (n = 2), iris neovascularization (n = 5), secondary glaucoma (n = 2), and ectropion uveae (n = 2). The mean radiation dose to tumor apex was 44 Gy (median, 38; range, 35-70 Gy). At a mean follow-up of 59 months (range, 12-210 months), tumor control was achieved in 5 eyes (83%) with globe salvage in 4 eyes (67%). No patient had evidence of metastases or death at the last follow-up visit. CONCLUSIONS: Plaque radiotherapy is a reasonable alternative treatment for localized, small- to medium-size medulloepithelioma. Tumors larger than 11.0 mm, with retrolental cyclitic membrane or extrascelral extension, might still require enucleation.