Introduction
Recent classification of neuroendocrine neoplasms has defined well‐differentiated high‐grade neuroendocrine tumors (NET G3) as a distinct entity from poorly differentiated neuroendocrine ...carcinoma. The optimal treatment for NET G3 has not been well‐described. This study aimed to evaluate metastatic NET G3 response to different treatment regimens.
Materials and Methods
This was a retrospective study of patients with NET G3 within the Mayo Clinic database. Patients’ demographics along with treatment characteristics, responses, and survival were assessed. Primary endpoints were progression‐free survival (PFS) and overall survival. Secondary endpoints were objective response rate (ORR) and disease control rate (DCR).
Results
Treatment data was available in 30 patients with median age of 59.5 years at diagnosis. The primary tumor was mostly pancreatic (73.3%). Ki‐67 index was ≥55% in 26.7% of cases. Treatments included capecitabine + temozolomide (CAPTEM) (n = 20), lutetium 177 DOTATATE (PRRT; n = 10), Platinum‐etoposide (EP; n = 8), FOLFOX (n = 7), and everolimus (n = 2). CAPTEM exhibited ORR 35%, DCR 65%, and median PFS 9.4 months (95% confidence interval, 2.96–16.07). Both EP and FOLFOX showed similar radiographic response rates with ORR 25.0% and 28.6%; however, median PFS durations were quite distinct at 2.94 and 13.04 months, respectively. PRRT had ORR of 20%, DCR of 70%, and median PFS of 9.13 months.
Conclusion
Among patients with NET G3, CAPTEM was the most commonly used treatment with clinically meaningful efficacy and disease control. FOLFOX or PRRT are other potentially active treatment options. EP has some activity in NET G3, but responses appear to be short‐lived. Prospective studies evaluating different treatments effects in patients with NET G3 are needed to determine an optimal treatment strategy.
Implications for Practice
High‐grade well‐differentiated neuroendocrine tumors (NET G3) are considered a different entity from low‐grade NET and neuroendocrine carcinoma in terms of prognosis and management. The oral combination of capecitabine and temozolomide is considered a good option in the management of metastatic NET G3 and may be preferred. FOLFOX is another systemic option with reasonable efficacy. Similar to other well‐differentiated neuroendocrine tumors, peptide receptor radionuclide therapy seems to have some efficacy in these tumors.
This article evaluates the clinical outcomes of patients with well‐differentiated high‐grade neuroendocrine tumors treated with different cytotoxic regimens at Mayo Clinic.
Intravitreous injections of antivascular endothelial growth factor agents are effective for treating diabetic macular edema (DME) involving the center of the macula (center-involved DME CI-DME) with ...visual acuity impairment (20/32 or worse). The best approach to treating patients with CI-DME and good visual acuity (20/25 or better) is unknown.
To compare vision loss at 2 years among eyes initially managed with aflibercept, laser photocoagulation, or observation.
Randomized clinical trial conducted at 91 US and Canadian sites among 702 adults with type 1 or type 2 diabetes. Participants had 1 study eye with CI-DME and visual acuity of 20/25 or better. The first participant was randomized on November 8, 2013, and the final date of follow-up was September 11, 2018.
Eyes were randomly assigned to 2.0 mg of intravitreous aflibercept (n = 226) as frequently as every 4 weeks, focal/grid laser photocoagulation (n = 240), or observation (n = 236). Aflibercept was required for eyes in the laser photocoagulation or observation groups that had decreased visual acuity from baseline by at least 10 letters (≥ 2 lines on an eye chart) at any visit or by 5 to 9 letters (1-2 lines) at 2 consecutive visits.
The primary outcome was at least a 5-letter visual acuity decrease from baseline at 2 years. Antiplatelet Trialists' Collaboration adverse events (defined as myocardial infarction, stroke, or vascular or unknown death) were reported.
Among 702 randomized participants (mean age, 59 years; 38% female n=264), 625 of 681 (92% excluding deaths) completed the 2-year visit. For eyes with visual acuity that decreased from baseline, aflibercept was initiated in 25% (60/240) and 34% (80/236) in the laser photocoagulation and observation groups, respectively. At 2 years, the percentage of eyes with at least a 5-letter visual acuity decrease was 16% (33/205), 17% (36/212), and 19% (39/208) in the aflibercept, laser photocoagulation, and observation groups, respectively (aflibercept vs laser photocoagulation risk difference, -2% 95% CI, -9% to 5%; relative risk, 0.88 95% CI, 0.57-1.35; P = .79; aflibercept vs observation risk difference, -3% 95% CI, -11% to 4%; relative risk, 0.83 95% CI, 0.55-1.27; P = .79; laser photocoagulation vs observation risk difference, -1% 95% CI, -9% to 6%; relative risk, 0.95 95% CI, 0.64-1.41; P = .79). Antiplatelet Trialists' Collaboration vascular events occurred in 15 (7%), 13 (5%), and 8 (3%) participants in the aflibercept, laser photocoagulation, and observation groups.
Among eyes with CI-DME and good visual acuity, there was no significant difference in vision loss at 2 years whether eyes were initially managed with aflibercept or with laser photocoagulation or observation and given aflibercept only if visual acuity worsened. Observation without treatment unless visual acuity worsens may be a reasonable strategy for CI-DME.
ClinicalTrials.gov Identifier: NCT01909791.
ABSTRACT
Introduction
Trauma surgery skills sustainment and maintenance of combat readiness present a major problem for military general surgeons. The Military Health System (MHS) utilizes the ...knowledge, skills, and abilities (KSA) threshold score of 14,000 as a measure of annual deployment readiness. Only 9% of military surgeons meet this threshold. Most military–civilian partnerships (MCPs) utilize just-in-time training models before deployment rather than clinical experiences in trauma at regular intervals (skills sustainment model). Our aim is to evaluate an established skills sustainment MCP utilizing KSAs and established military metrics.
Materials and Methods
Three U.S. Navy active duty general surgeons were embedded into an urban level-1 trauma center taking supervised trauma call at regular intervals prior to deployment. Operative density (procedures/call), KSA scores, trauma resuscitation exposure, and combat casualty care relevant cases (CCC-RCs) were reviewed.
Results
During call shifts with a Navy surgeon present an average 16.4 trauma activations occurred; 32.1% were category-1, 27.6% were penetrating, 72.4% were blunt, and 33.8% were admitted to the intensive care unit. Over 24 call shifts of 24 hours in length, 3 surgeons performed 39 operative trauma cases (operative density of 1.625), generating 11,683 total KSA points. Surgeons 1, 2, and 3 generated 5109, 3167, and 3407 KSA points, respectively. The three surgeons produced a total of 11,683 KSA points, yielding an average of 3,894 KSA points/surgeon. In total, 64.1% of operations fulfilled CCC-RC criteria.
Conclusions
Based on this initial evaluation, a military surgeon taking two calls/month over 12 months through our regional skills sustainment MCP can generate more than 80% of the KSA points required to meet the MHS KSA threshold for deployment readiness, with the majority being CCC-RCs. Intangible advantages of this model include exposure to multiple trauma resuscitations while possibly eliminating just-in-time training and decreasing pre-deployment requirements.
We test whether measures of the retinal vasculature are associated with cognitive functioning and cognitive change.
Retinal images from a narrow-age cohort were analyzed using Vessel Assessment and ...Measurement Platform for Images of the Retina, producing a comprehensive range of quantitative measurements of the retinal vasculature, at mean age 72.5 years (SD = 0.7). Cognitive ability and change were measured using a battery of multiple measures of memory, visuospatial, processing speed, and crystallized cognitive abilities at mean ages 73, 76, and 79 years. We applied multivariate growth curve models to test the association between retinal vascular measurements with cognitive abilities and their changes.
Almost all associations were nonsignificant. In our most parsimonious model, venular asymmetry factor was associated with speed at age 73.
Our null findings suggest that the quantitative retinal parameters applied in this study are not significantly associated with cognitive functioning or cognitive change.
Continuous infusion of β-lactam antibiotics may improve outcomes because of time-dependent antibacterial activity compared with intermittent dosing.
To evaluate the efficacy of continuous versus ...intermittent infusion in patients with severe sepsis.
We conducted a randomized controlled trial in 25 intensive care units (ICUs). Participants commenced on piperacillin-tazobactam, ticarcillin-clavulanate, or meropenem were randomized to receive the prescribed antibiotic via continuous or 30-minute intermittent infusion for the remainder of the treatment course or until ICU discharge. The primary outcome was the number of alive ICU-free days at Day 28. Secondary outcomes were 90-day survival, clinical cure 14 days post antibiotic cessation, alive organ failure-free days at Day 14, and duration of bacteremia.
We enrolled 432 eligible participants with a median age of 64 years and an Acute Physiology and Chronic Health Evaluation II score of 20. There was no difference in ICU-free days: 18 days (interquartile range, 2-24) and 20 days (interquartile range, 3-24) in the continuous and intermittent groups (P = 0.38). There was no difference in 90-day survival: 74.3% (156 of 210) and 72.5% (158 of 218); hazard ratio, 0.91 (95% confidence interval, 0.63-1.31; P = 0.61). Clinical cure was 52.4% (111 of 212) and 49.5% (109 of 220); odds ratio, 1.12 (95% confidence interval, 0.77-1.63; P = 0.56). There was no difference in organ failure-free days (6 d; P = 0.27) and duration of bacteremia (0 d; P = 0.24).
In critically ill patients with severe sepsis, there was no difference in outcomes between β-lactam antibiotic administration by continuous and intermittent infusion. Australian New Zealand Clinical Trials Registry number (ACT RN12612000138886).
Syringomatous adenoma of the nipple is a very rare benign tumor, with radiographic and clinical characteristics that are difficult to differentiate from malignant tumors. Less than 60 cases have been ...identified thus far and most studies have not included radiographic findings. As such, the neoplasm requires more characterization within the literature. The usual clinical presentation of syringomatous adenoma of the nipple is symptomatic with a solitary, unilateral nipple mass within the subareolar region which may be tender and/or painful and may cause nipple inversion or discharge. We present a case of a 43-year-old woman that is unique, as the patient was asymptomatic and only presented following standard screening mammography. Moreover, we offer further characterization of the neoplasm through documented imaging and histologic findings.
Anorectal neuroendocrine carcinomas (NECs) are uncommon malignancies with poor prognosis. Consensus guidelines exist for treating extrapulmonary NEC. However, limited data is available to guide ...treatment for anorectal NEC. In this study, we sought to review the clinical characteristics and outcomes of patients with NEC of the rectum and/or anus at Mayo Clinic.
This is a retrospective study of all patients with the diagnosis of NEC of the anus and/or rectum treated across Mayo Clinic sites since 2000. Baseline patient characteristics, tumor pathology, imaging profiles, treatment strategies utilized, and survival outcomes were analyzed. Kaplan-Meier analysis was used with a significance level of P < .05.
The study included a total of 38 patients with primary NEC of the anus and/or rectum. The median age at diagnosis was 55.5 years. The median follow-up was 18.8 months. Fifteen patients had locoregional disease (LRD) at diagnosis. The remaining 23 had metastatic disease. Overall survival was significantly shorter in patients with LRD compared with those with metastatic disease at diagnosis (18.1 vs. 13.8 months; P = .039). The majority (n = 11) of patients with LRD were treated with concurrent chemoradiation therapy, and 10 underwent surgical resection of the primary tumor. The majority (13/15) of patients with LRD progressed, with the majority (11/15) of progressions being distant. The median progression-free survival for patients with LRD was 5.7 months (1-year progression-free survival, 26.7%).
Anorectal NEC is an aggressive malignancy with poor prognosis requiring multidisciplinary discussion. In addition, the systemic nature of anorectal NEC with distant recurrences in LRD and poor outcomes in metastatic disease emphasizes the need to further develop better systemic treatment options that can potentially improve outcomes in NEC.
Anorectal neuroendocrine carcinoma is a rare, aggressive malignancy. The median overall survival of patients with locoregional disease in this study was 18 months, with significantly shorter overall survival of 14 months in patients with metastatic disease. The median progression-free survival was 6 months in patients with metastatic disease treated with chemotherapy (either etoposide/platinum or fluoropyrimidine regimens) with or without radiation therapy. Further study is warranted to determine the optimal multidisciplinary approach to treatment.
A common task in microscopy is to fit an image of a fluorescent probe to a point spread function (PSF) in order to estimate the position of the probe. The PSF is often approximated as a Gaussian for ...mathematical simplicity. We show that the separable property of the Gaussian PSF enables a reduction of computational time from O(L2) to O(L), where L is the width (in pixels) of the image. When tested on realistic simulated data, our algorithm is able to localize the probes with precision close to the Cramér-Rao lower bound.
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