Mortality related to the use of stapler devices and clip appliers: Analysis of the Food and Drug Administration Manufacturer and User Facility Device Experience database.

BACKGROUND: Surgical staplers and clip appliers are commonly used and have a potential to malfunction, which may result in serious injury or death. These events are self-reported to the Food and Drug Administration and compiled in the Food and Drug Administration's Manufacturer and User Facility Device Experience database. This study characterizes mortality related to surgical stapler and clip applier failure reported in the Food and Drug Administration's Manufacturer and User Facility Device Experience database. METHODS: The Food and Drug Administration's Manufacturer and User Facility Device Experience database was reviewed between 1992 and 2016 for medical device reports related to surgical staplers and clip appliers filed under the following product codes: GAG, FZP, GDO, GDW, KOG, and GCJ. Adverse events including death and the type of device failure were reviewed. Temporal trends in reported deaths related to device failure were analyzed and the Healthcare Cost and Utilization Project database was used to adjust for annual surgical case volume using linear regression analysis. RESULTS: A total of 75,415 malfunctions, 21,115 injuries, and 676 deaths were associated with the use of surgical stapler and clip applier devices. Most deaths occurred postoperatively (N = 516, 76.3%) and were due to infection/sepsis (N = 89, 17.2%) or vascular injuries (N = 110, 21.3%). Intraoperative mortality (N = 79, 11.7%) was primarily due to vascular injuries (N = 73, 92.4%). Device failures resulting in death were noted both intraoperatively (N = 268, 39.6%) and postoperatively (N = 325, 48.1%). In post hoc root cause analysis, a surgical stapler and clip applier device problem was the most common attributed cause of death (N = 238, 65.4%). In the linear regression analysis, there was a significant increase in the mortality from device failure in the study period after adjusting for annual surgical volume (P < .01). CONCLUSION: Mortality related to the use of surgical staplers and clip appliers is increasing. Most deaths occurred postoperatively, and an increased awareness of potential life-threatening complications is warranted when these devices are used.

Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) Versus the Standard of Care Imaging in the Diagnosis of Peritoneal Carcinomatosis.

OBJECTIVE: To compare positron emission tomography (PET)/magnetic resonance imaging (MRI) to the standard of care imaging (SCI) for the diagnosis of peritoneal carcinomatosis (PC) in primary abdominopelvic malignancies. SUMMARY BACKGROUND DATA: Identifying PC impacts prognosis and management of multiple cancer types. METHODS: Adult subjects were prospectively and consecutively enrolled from April 2019 to January 2021. Inclusion criteria were: 1) acquisition of whole-body contrast-enhanced (CE) 18F-fluorodeoxyglucose PET/MRI, 2) pathologically confirmed primary abdominopelvic malignancies. Exclusion criteria were: 1) greater than 4 weeks interval between SCI and PET/MRI, 2) unavailable follow-up. SCI consisted of whole-body CE PET/computed tomography (CT) with diagnostic quality CT, and/or CE-CT of the abdomen and pelvis, and/or CE-MRI of the abdomen±pelvis. If available, pathology or surgical findings served as the reference standard, otherwise, imaging followup was used. When SCI and PET/MRI results disagreed, medical records were checked for management changes. Follow-up data were collected until August 2021. RESULTS: One hundred sixty-four subjects were included, 85 (52%) were female, and the median age was 60 years (interquartile range 50-69). At a subject level, PET/MRI had higher sensitivity (0.97, 95% CI 0.86-1.00) than SCI (0.54, 95% CI 0.37-0.71), P < 0.001, without a difference in specificity, of 0.95 (95% CI 0.90-0.98) for PET/MRI and 0.98 (95% CI 0.93-1.00) for SCI, P » 0.250. PET/MRI and SCI results disagreed in 19 cases. In 5/19 (26%) of the discordant cases, PET/MRI findings consistent with PC missed on SCI led to management changes. CONCLUSION: PET/MRI improves detection of PC compared with SCI which frequently changes management.

Remediating Desmoplasia with EGFR-Targeted Photoactivable Multi-Inhibitor Liposomes Doubles Overall Survival in Pancreatic Cancer.

Desmoplasia is characteristic of pancreatic ductal adenocarcinoma (PDAC), which exhibits 5-year survival rates of 3%. Desmoplasia presents physical and biochemical barriers that contribute to treatment resistance, yet depleting the stroma alone is unsuccessful and even detrimental to patient outcomes. This study is the first demonstration of targeted photoactivable multi-inhibitor liposomes (TPMILs) that induce both photodynamic and chemotherapeutic tumor insult, while simultaneously remediating desmoplasia in orthotopic PDAC. TPMILs targeted with cetuximab (anti-EGFR mAb) contain lipidated benzoporphyrin derivative (BPD-PC) photosensitizer and irinotecan. The desmoplastic tumors comprise human PDAC cells and patient-derived cancer-associated fibroblasts. Upon photoactivation, the TPMILs induce 90% tumor growth inhibition at only 8.1% of the patient equivalent dose of nanoliposomal irinotecan (nal-IRI). Without EGFR targeting, PMIL photoactivation is ineffective. TPMIL photoactivation is also sixfold more effective at inhibiting tumor growth than a cocktail of Visudyne-photodynamic therapy (PDT) and nal-IRI, and also doubles survival and extends progression-free survival by greater than fivefold. Second harmonic generation imaging reveals that TPMIL photoactivation reduces collagen density by >90% and increases collagen nonalignment by >103 -fold. Collagen nonalignment correlates with a reduction in tumor burden and survival. This single-construct phototoxic, chemotherapeutic, and desmoplasia-remediating regimen offers unprecedented opportunities to substantially extend survival in patients with otherwise dismal prognoses.

Myo-Inositol Levels Measured with MR Spectroscopy Can Help Predict Failure of Antiangiogenic Treatment in Recurrent Glioblastoma.

Background Patients with recurrent glioblastoma (GBM) are often treated with antiangiogenic agents, such as bevacizumab (BEV). Despite therapeutic promise, conventional MRI methods fail to help determine which patients may not benefit from this treatment. Purpose To use MR spectroscopic imaging (MRSI) with intermediate and short echo time to measure corrected myo-inositol (mI)normalized by contralateral creatine (hereafter, mI/c-Cr) in participants with recurrent GBM treated with BEV and to investigate whether such measurements can help predict survivorship before BEV initiation (baseline) and at 1 day, 4 weeks, and 8 weeks thereafter. Materials and Methods In this prospective longitudinal study (2016-2020), spectroscopic data on mI-a glial marker and osmoregulator within the brain-normalized by contralateral creatine in the intratumoral, contralateral, and peritumoral volumes of patients with recurrent GBM were evaluated. Area under the receiver operating characteristic curve (AUC) was calculated for all volumes at baseline and 1 day, 4 weeks, and 8 weeks after treatment to determine the ability of mI/c-Cr to help predict survivorship. Results Twenty-one participants (median age ± standard deviation, 62 years ± 12; 15 men) were evaluated. Lower mI/c-Cr in the tumor before and during BEV treatment was predictive of poor survivorship, with receiver operating characteristic analyses showing an AUC of 0.75 at baseline, 0.87 at 1 day after treatment, and 1 at 8 weeks after. A similar result was observed in contralateral normal-appearing tissue and the peritumoral volume, with shorter-term survivors having lower levels of mI/c-Cr. In the contralateral volume, a lower ratio of mI to creatine (hereafter, mI/Cr) predicted shorter-term survival at baseline and all other time points. Within the peritumoral volume, lower mI/c-Cr levels were predictive of shorter-term survival at baseline (AUC, 0.80), at 1 day after treatment (AUC, 0.93), and at 4 weeks after treatment (AUC, 0.68). Conclusion Lower levels of myo-inositol normalized by contralateral creatine within intratumoral, contralateral, and peritumoral volumes were predictive of poor survivorship and antiangiogenic treatment failure as early as before bevacizumab treatment. Adapting MR spectroscopic imaging alongside conventional MRI modalities conveys critical information regarding the biologic characteristics of tumors to help better treat individuals with recurrent glioblastoma. Clinical trial registration no. NCT02843230 © RSNA, 2021 Online supplemental material is available for this article.

Clinical impact of PET/MRI in oligometastatic colorectal cancer.

BACKGROUND: Oligometastatic colorectal cancer (CRC) is potentially curable and demands individualised strategies. METHODS: This single-centre retrospective study investigated if positron emission tomography (PET)/magnetic resonance imaging (MR) had a clinical impact on oligometastatic CRC relative to the standard of care imaging (SCI). Adult patients with oligometastatic CRC on SCI who also underwent PET/MR between 3/2016 and 3/2019 were included. The exclusion criterion was lack of confirmatory standard of reference, either surgical pathology, intraoperative gross confirmation or imaging follow-up. SCI consisted of contrast-enhanced (CE) computed tomography (CT) of the chest/abdomen/pelvis, abdominal/pelvic CE-MR, and/or CE whole-body PET/CT with diagnostic quality (i.e. standard radiation dose) CT. Follow-up was evaluated until 3/2020. RESULTS: Thirty-one patients constituted the cohort, 16 (52%) male, median patient age was 53 years (interquartile range: 49-65 years). PET/MR and SCI results were divergent in 19% (95% CI 9-37%) of the cases, with PET/MR leading to management changes in all of them. The diagnostic accuracy of PET/MR was 90 ± 5%, versus 71 ± 8% for SCI. In a pairwise analysis, PET/MR outperformed SCI when compared to the reference standard (p = 0.0412). CONCLUSIONS: These findings suggest the potential usefulness of PET/MR in the management of oligometastatic CRC.

MR spectroscopic imaging predicts early response to anti-angiogenic therapy in recurrent glioblastoma.

BACKGROUND: Determining failure to anti-angiogenic therapy in recurrent glioblastoma (GBM) (rGBM) remains a challenge. The purpose of the study was to assess treatment response to bevacizumab-based therapy in patients with rGBM using MR spectroscopy (MRS). METHODS: We performed longitudinal MRI/MRS in 33 patients with rGBM to investigate whether changes in N-acetylaspartate (NAA)/Choline (Cho) and Lactate (Lac)/NAA from baseline to subsequent time points after treatment can predict early failures to bevacizumab-based therapies. RESULTS: After stratifying based on 9-month survival, longer-term survivors had increased NAA/Cho and decreased Lac/NAA levels compared to shorter-term survivors. ROC analyses for intratumoral NAA/Cho correlated with survival at 1 day, 2 weeks, 8 weeks, and 16 weeks. Intratumoral Lac/NAA ROC analyses were predictive of survival at all time points tested. At the 8-week time point, 88% of patients with decreased NAA/Cho did not survive 9 months; furthermore, 90% of individuals with an increased Lac/NAA from baseline did not survive at 9 months. No other metabolic ratios tested significantly predicted survival. CONCLUSIONS: Changes in metabolic levels of tumoral NAA/Cho and Lac/NAA can serve as early biomarkers for predicting treatment failure to anti-angiogenic therapy as soon as 1 day after bevacizumab-based therapy. The addition of MRS to conventional MR methods can provide better insight into how anti-angiogenic therapy affects tumor microenvironment and predict patient outcomes.

PET/MRI assessment of lung nodules in primary abdominal malignancies: sensitivity and outcome analysis.

PURPOSE: To evaluate PET/MR lung nodule detection compared to PET/CT or CT, to determine growth of nodules missed by PET/MR, and to investigate the impact of missed nodules on clinical management in primary abdominal malignancies. METHODS: This retrospective IRB-approved study included [18F]-FDG PET/MR in 126 patients. All had standard of care chest imaging (SCI) with diagnostic chest CT or PET/CT within 6 weeks of PET/MR that served as standard of reference. Two radiologists assessed lung nodules (size, location, consistency, position, and [18F]-FDG avidity) on SCI and PET/MR. A side-by-side analysis of nodules on SCI and PET/MR was performed. The nodules missed on PET/MR were assessed on follow-up SCI to ascertain their growth (≥ 2 mm); their impact on management was also investigated. RESULTS: A total of 505 nodules (mean 4 mm, range 1-23 mm) were detected by SCI in 89/126 patients (66M:60F, mean age 60 years). PET/MR detected 61 nodules for a sensitivity of 28.1% for patient and 12.1% for nodule, with higher sensitivity for > 7 mm nodules (< 30% and > 70% respectively, p < 0.05). 75/337 (22.3%) of the nodules missed on PET/MR (follow-up mean 736 days) demonstrated growth. In patients positive for nodules at SCI and negative at PET/MR, missed nodules did not influence patients' management. CONCLUSIONS: Sensitivity of lung nodule detection on PET/MR is affected by nodule size and is lower than SCI. 22.3% of missed nodules increased on follow-up likely representing metastases. Although this did not impact clinical management in study group with primary abdominal malignancy, largely composed of extra-thoracic advanced stage cancers, with possible different implications in patients without extra-thoracic spread.

Impact of PET/MRI in the Treatment of Pancreatic Adenocarcinoma: a Retrospective Cohort Study.

PURPOSE: Imaging is central to the diagnosis and management of Pancreatic Ductal Adenocarcinoma (PDAC). This study evaluated if positron emission tomography (PET)/magnetic resonance imaging (MRI) elicited treatment modifications in PDAC when compared to standard of care imaging (SCI). PROCEDURES: This retrospective study included consecutive patients with PDAC who underwent 2-deoxy-2-[18F]fluoro-D-glucose ([18F]F-FDG) PET/MRI and SCI from May 2017 to January 2019. SCI included abdominal computed tomography (CT), MRI, and/or PET/CT. For patients who had more than one pair of PET/MRI and SCI, each management decision was independently evaluated. Treatment strategies based on each modality were extracted from electronic medical records. Follow-up was evaluated until January 2020. RESULTS: Twenty-five patients underwent 37 PET/MRI's, mean age was 65 ± 9 years and 13 (13/25, 52 %) were men. 49 % (18/37, 95 % CI 33-64 %) of the PET/MRI scans changed clinical management. Whether the SCI included a PET/CT or not did not significantly modify the probability of management change (OR = 0.9, 95 % CI 0.2-4, p = 1). One hundred percent (33/33) of the available follow-up data confirmed PET/MRI findings. CONCLUSIONS: PET/MRI significantly changed PDAC management, consistently across the different SCI modalities it was compared to. These findings suggest a role for PET/MRI in the management of PDAC.

Influence of feature calculating parameters on the reproducibility of CT radiomic features: a thoracic phantom study.

BACKGROUND: Existing studies have demonstrated that imaging parameters may affect radiomic features. However, the influence of feature calculating parameters has been overlooked. The purpose of this study is to investigate the influence of feature calculating parameters (gray-level range and bin size) on the reproducibility of CT radiomic features. METHODS: Thirty-six CT scans from an anthropomorphic thoracic phantom were acquired with different imaging parameters including effective dose, pitch, slice thicknesses and reconstruction kernels. The influence of feature calculating parameters was investigated in terms of three gray-level ranges and eleven gray-level bin sizes. Feature reproducibility was assessed by the intraclass correlation coefficient (ICC) with the cutoff value of 0.8 and the coefficient of variation (CV) with the cutoff value of 20%. The agreements of reproducible features in different ranges and bin sizes were analyzed by Kendall's W test and Kappa test. The proportions of reproducible features, in terms of two calculating, four imaging and two segmentation parameters, were evaluated using Cochran's Q test and Dunn's test. RESULTS: For the three gray-level ranges, 50% (44/88) of features were reproducible with a perfect agreement (Kendall's W coefficient 0.844, P<0.001). Of the 72 features that may be influenced by gray-level bin size, 33.3% (24/72) were reproducible for 11 bin sizes with a perfect agreement (Kendall's W coefficient 0.879, P<0.001). For the proportions of reproducible features, there was no statistically significant difference among three ranges (P=0.420), but there was among eleven bin sizes (P=0.013). The proportions of reproducible features in feature calculating parameters were statistically significantly lower than those in imaging parameters (adjusted P<0.05). CONCLUSIONS: Feature calculating parameters may have a greater influence than imaging parameters on the reproducibility of CT radiomic features, which should be given special attention in clinical applications.

PET/MRI Radiomics in Rectal Cancer: a Pilot Study on the Correlation Between PET- and MRI-Derived Image Features with a Clinical Interpretation.

PURPOSE: The aim of this study was to explore possible correlations among different imaging features from 2-deoxy-2-[18F]fluoro-D-Glucose positron emission tomography/magnetic resonance imaging (PET/MRI) in rectal cancer (RC). PROCEDURES: RC patients who underwent PET/MRI were enrolled. A region of interest (ROI) was drawn around each primary RC on PET/MRI images (PET, pelvic axial T2w, and apparent diffusion coefficient maps (ADC)). Multiple imaging features were assessed, and Pearson's correlation was used to explore possible correlations among them. RESULTS: A total of 13 patients were included, mean age 56.1 years old, 6 females. A strong inverse correlation was observed between SUVpeak and ADCmean values, MTV and T2 sphericity, MTV and ADC sphericity, MTV and T2 entropy, and TLG and ADC sphericity. There was also strong direct correlation between PET entropy and ADC sphericity. CONCLUSIONS: In conclusion, several clinically relevant correlations were observed between PET and MRI imaging features. These findings show how the use of both modalities provides complementary information.

Correlation between NF1 genotype and imaging phenotype on whole-body MRI: NF1 radiogenomics.

OBJECTIVE: To investigate the genotype-phenotype correlation between neurofibromatosis 1 (NF1) germline mutations and imaging features of neurofibromas on whole-body MRI (WBMRI) by using radiomics image analysis techniques. MATERIALS AND METHODS: Twenty-nine patients with NF1 who had known germline mutations determined by targeted next-generation sequencing were selected from a previous WBMRI study using coronal short tau inversion recovery sequence. Each tumor was segmented in WBMRI and a set of 59 imaging features was calculated using our in-house volumetric image analysis platform, 3DQI. A radiomics heatmap of 59 imaging features was analyzed to investigate the per-tumor and per-patient associations between the imaging features and mutation domains and mutation types. Linear mixed-effect models and one-way analysis of variance tests were performed to assess the similarity of tumor imaging features within mutation groups, between mutation groups, and between randomly selected groups. RESULTS: A total of 218 neurofibromas (97 discrete neurofibromas and 121 plexiform neurofibromas) were identified in 19 of the 29 patients. The unsupervised hierarchical clustering in heatmap analysis revealed 6 major image feature patterns that were significantly correlated with gene mutation domains and types with strong to very strong associations of genotype-phenotype correlations in both per-tumor and per-patient studies (p < 0.05, Cramer V > 0.5), whereas tumor size and locations showed no correlations with imaging features (p = 0.79 and p = 0.42, respectively). The statistical analyses revealed that the number of significantly different features (SDFs) within mutation groups were significantly lower than those between mutation groups (mutation domains: 10.9 ± 9.5% vs 31.9 ± 23.8% and mutation types: 31.8 ± 30.7% vs 52.6 ± 29.3%). The first and second quartile p values of within-patient groups were more than 2 times higher than those between-patient groups. However, the numbers of SDFs between randomly selected groups were much lower (approximately 5.2%). CONCLUSION: This preliminary study identified the NF1 radiogenomics linkage between NF1 causative mutations and MRI radiomic features, i.e., the correlation between NF1 genotype and imaging phenotype on WBMRI.

Preoperative functional MRI use in neurooncology patients: a clinician survey.

OBJECTIVE: Functional MRI (fMRI) is increasingly being investigated for use in neurosurgical patient care. In the current study, the authors characterize the clinical use of fMRI by surveying neurosurgeons' use of and attitudes toward fMRI as a surgical planning tool in neurooncology patients. METHODS: A survey was developed to inquire about clinicians' use of and experiences with preoperative fMRI in the neurooncology patient population, including example case images. The survey was distributed to all neurosurgical departments with a residency program in the US. RESULTS: After excluding incomplete surveys and responders that do not use fMRI (n = 11), 50 complete responses were included in the final analysis. Responders were predominantly from academic programs (88%), with 20 years or more in practice (40%), with a main area of practice in neurooncology (48%) and treating an adult population (90%). All 50 responders currently use fMRI in neurooncology patients, mostly for low- (94%) and high-grade glioma (82%). The leading decision factors for ordering fMRI were location of mass in dominant hemisphere, location in a functional area, motor symptoms, and aphasia. Across 10 cases, language fMRI yielded the highest interrater reliability agreement (Fleiss' kappa 0.437). The most common reasons for ordering fMRI were to identify language laterality, plan extent of resection, and discuss neurological risks with patients. Clinicians reported that fMRI results were not obtained when ordered a median 10% of the time and were suboptimal a median 27% of the time. Of responders, 70% reported that they had ever resected an fMRI-positive functional site, of whom 77% did so because the site was "cleared" by cortical stimulation. Responders reported disagreement between fMRI and awake surgery 30% of the time. Overall, 98% of responders reported that if results of fMRI and intraoperative mapping disagreed, they would rely on intraoperative mapping. CONCLUSIONS: Although fMRI is increasingly being adopted as a practical preoperative planning tool for brain tumor resection, there remains a substantial degree of discrepancy with regard to its current use and presumed utility. There is a need for further research to evaluate the use of preoperative fMRI in neurooncology patients. As fMRI continues to gain prominence, it will be important for clinicians to collectively share best practices and develop guidelines for the use of fMRI in the preoperative planning phase of brain tumor patients.

Protocol for a prospective evaluation of postpartum engagement in HIV care among women living with HIV in South Africa.

INTRODUCTION: KwaZulu-Natal (KZN), South Africa (SA) has the highest prevalence of pregnant women living with HIV in the world. Pregnancy and the postpartum period offer opportunities to engage women in HIV care, to prevent perinatal transmission and to optimise maternal and infant well-being. However, research suggests that remaining engaged in HIV care during this time can be challenging. METHODS AND ANALYSIS: We are conducting a 5-year prospective cohort study among pregnant women living with HIV in KZN to estimate the rates and factors associated with attrition from HIV care during this critical period. To determine who is most likely to fall out of care, we are examining a range of relevant variables informed by a socioecological model of HIV care, including individual, relational, community and healthcare system variables. We are enrolling 18-45-year-old women, at 28 weeks or more of pregnancy, who are living with HIV and currently taking antiretroviral therapies. Participants complete quantitative assessments at baseline (pregnancy) and at 6, 12, 18 and 24 months postpartum. A subset of women and their partners are invited to complete qualitative interviews to further explore their experiences in HIV care. The main study outcomes are suppressed HIV RNA and retention in care at each study assessment. Our understanding of the factors that drive postpartum attrition from HIV care will ultimately inform the development of interventions to facilitate continued engagement in postpartum HIV care. ETHICS AND DISSEMINATION: This protocol has been approved by the Human Research Ethics Committee (Medical) at The University of the Witwatersrand (Johannesburg, SA) and the Partners Human Research Committee at Partners HealthCare (Boston, Massachusetts, USA). Site support and approval were obtained from the District Hospital and the KZN Provincial Department of Health. Results will be disseminated through peer-reviewed manuscripts, reports and both local and international presentations (Ethics Registration #170 212).

Differences in Weeklong Ambulatory Vocal Behavior Between Female Patients With Phonotraumatic Lesions and Matched Controls.

Purpose Previous work using ambulatory voice recordings has shown no differences in average vocal behavior between patients with phonotraumatic vocal hyperfunction and matched controls. This study used larger groups to replicate these results and expanded the analysis to include distributional characteristics of ambulatory voice use and measures indicative of glottal closure. Method Subjects included 180 adult women: 90 diagnosed with vocal fold nodules or polyps and 90 age-, sex-, and occupation-matched controls with no history of voice disorders. Weeklong summary statistics (average, variability, skewness, kurtosis) of voice use were computed from neck-surface acceleration recorded using an ambulatory voice monitor. Voice measures included estimates of sound pressure level (SPL), fundamental frequency (f o), cepstral peak prominence, and the difference between the first and second harmonic magnitudes (H1-H2). Results Statistical comparisons resulted in medium-large differences (Cohen's d ≥ 0.5) between groups for SPL skewness, f o variability, and H1-H2 variability. Two logistic regressions (theory-based and stepwise) found SPL skewness and H1-H2 variability to classify patients and controls based on their weekly voice data, with an area under the receiver operating characteristic curve of 0.85 and 0.82 on training and test sets, respectively. Conclusion Compared to controls, the weekly voice use of patients with phonotraumatic vocal hyperfunction reflected higher SPL tendencies (negatively skewed SPL) with more abrupt glottal closure (reduced H1-H2 variability, especially toward higher values). Further work could examine posttreatment data (e.g., after surgery and/or therapy) to determine the extent to which these differences are associated with the etiology and pathophysiology of phonotraumatic vocal fold lesions.

Validation of a Comprehensive Clinical Algorithm for the Assessment and Treatment of Microbial Keratitis.

PURPOSE: To validate a comprehensive clinical algorithm for the assessment and treatment of microbial keratitis (MK). DESIGN: Retrospective cohort study. METHODS: The "1, 2, 3 Rule" for the initial management of MK was conceived by Vital and associates in 2007 to inform the decision as to when to perform corneal cultures. The rule is invoked when any 1 of 3 clinical parameters is met: ≥1+ anterior chamber cells, ≥2 mm infiltrate, or infiltrate ≤3 mm distance from the corneal center. When the rule is met, we added the mandatory use of fortified topical antibiotics after cultures are obtained. We compared outcomes of cases presenting to Massachusetts Eye and Ear 2 years before (Group I, n = 665) and after (Group II, n = 767) algorithm implementation. The primary composite outcome was a vision-threatening complication, such as corneal perforation. RESULTS: At a median follow-up of 67.0 and 60.0 days, respectively, 172 patients experienced a vision-threatening complication (Group I, 12.9% vs Group II, 11.2%, P = .51). While the algorithm codified conventional management practice at either end of disease severity, the effect of algorithm-augmented care was best appreciated in patients with lesions satisfying only 1 criterion. In this group, there was an increase in the proportion of patients undergoing culture at presentation (54.6% vs 67.7%, P = .006), fortified antibiotic prescription (29.7% vs 53.9%, P < .001), and reduction in vision-threatening complications (9.7% vs 1.8%, P = .001). The proportion of patients who were not cultured at presentation but later required culturing decreased (13.4% vs 5.1%, P = .001), as did patients who did not meet any criteria but were nonetheless cultured (23.9% vs 8.5%, P < .001). Multiple logistic regression showed that all algorithm parameters were independently associated with outcome: ≥1+ anterior chamber cells (odds ratio [OR] 1.66, 95% confidence interval 1.09-2.52); ≥2 mm infiltrate (OR 4.74, 2.68-8.40); and ≤3 mm from corneal center (OR 2.82, 1.85-4.31), confirmed with comparison to a bootstrapped sample (n = 10,000). CONCLUSIONS: The implementation of this algorithm reduced vision-threatening complications for patients with lesions satisfying only 1 criterion, arguably the most difficult patients in whom to judge disease severity. Implementation also led to a decrease in patients receiving unnecessary care.

Performance of 18F-fluciclovine PET/MR in the evaluation of osseous metastases from castration-resistant prostate cancer.

PURPOSE: 18F-Fluciclovine is indicated for evaluation of suspected prostate cancer (PCa) biochemical recurrence. There are few studies investigating fluciclovine with PET/MR and none evaluated osseous metastases. Our aim was to assess the performance of 18F-fluciclovine PET/MR (fluciclovine-PET/MR) for detecting osseous metastases in patients with castration-resistant prostate cancer (CRPC). We also investigated possible correlations between SUVmax and ADCmean. METHODS: We evaluated 8 patients with CRPC metastatic to bones, some before and some after radium therapy, who underwent 13 fluciclovine-PET/MR studies. We analyzed the performance of radionuclide bone scan (RBS), MR alone, fluciclovine-PET alone, and fluciclovine-PET/MR in detecting osseous metastases. Lesion size, characteristics (early sclerotic, late sclerotic, mixed, lytic), SUVmax, and ADCmean were assessed. The reference standard was a combination of clinical information and correlation with both prior and follow-up imaging. RESULTS: Of 347 metastatic bony lesions in 13 studies, 238/347 (68%) were detected by fluciclovine-PET alone, 286/347 (82%) by RBS, 344/347 (99%) by MR alone, and 347/347 (100%) by fluciclovine-PET/MR. Fluciclovine-PET/MR and MR had the best performance (p < 0.001). There was no statistically significant difference between fluciclovine-PET/MR and MR alone (p = 0.25). Fluciclovine-PET had a lower detection rate especially with late sclerotic lesions (p < 0.001). There was a moderate inverse correlation between lesion SUVmax and ADCmean (r = - 0.49; p < 0.001). CONCLUSIONS: This study suggests that fluciclovine-PET/MR and MR have high sensitivity for detecting osseous metastases in CRPC. Fluciclovine-PET alone underperformed in detecting late sclerotic lesions. The inverse correlation between SUVmax and ADCmean suggests a possible relationship between tumor metabolism and cellularity.

Management implications of fluorodeoxyglucose positron emission tomography/magnetic resonance in untreated intrahepatic cholangiocarcinoma.

PURPOSE: Intrahepatic cholangiocarcinoma (ICC) is associated with a poor prognosis with surgical resection offering the best chance for long-term survival and potential cure. However, in up to 36% of patients who undergo surgery, more extensive disease is found at time of operation requiring cancellation of surgery. PET/MR is a novel hybrid technology that might improve local and whole-body staging in ICC patients, potentially influencing clinical management. This study was aimed to investigate the possible management implications of PET/MR, relative to conventional imaging, in patients affected by untreated intrahepatic cholangiocarcinoma. METHODS: Retrospective review of the clinicopathologic features of 37 patients with iCCC, who underwent PET/MR between September 2015 and August 2018, was performed to investigate the management implications that PET/MR had exerted on the affected patients, relative to conventional imaging. RESULTS: Of the 37 patients enrolled, median age 63.5 years, 20 (54%) were female. The same day PET/CT was performed in 26 patients. All patients were iCCC-treatment-naïve. Conventional imaging obtained as part of routine clinical care demonstrated early-stage resectable disease for 15 patients and advanced stage disease beyond the scope of surgical resection for 22. PET/MR modified the clinical management of 11/37 (29.7%) patients: for 5 patients (13.5%), the operation was cancelled due to identification of additional disease, while 4 "inoperable" patients (10.8%) underwent an operation. An additional 2 patients (5.4%) had a significant change in their operative plan based on PET/MR. CONCLUSIONS: When compared with standard imaging, PET/MR significantly influenced the treatment plan in 29.7% of patients with iCCC. TRIAL REGISTRATION: 2018P001334.

Multiparametric MRI as a Biomarker of Response to Neoadjuvant Therapy for Localized Prostate Cancer-A Pilot Study.

RATIONALE AND OBJECTIVES: To explore a role for multiparametric MRI (mpMRI) as a biomarker of response to neoadjuvant androgen deprivation therapy (ADT) for prostate cancer (PCa). MATERIALS AND METHODS: This prospective study was approved by the institutional review board and was HIPAA compliant. Eight patients with localized PCa had a baseline mpMRI, repeated after 6-months of ADT, followed by prostatectomy. mpMRI indices were extracted from tumor and normal regions of interest (TROI/NROI). Residual cancer burden (RCB) was measured on mpMRI and on the prostatectomy specimen. Paired t-tests compared TROI/NROI mpMRI indices and pre/post-treatment TROI mpMRI indices. Spearman's rank tested for correlations between MRI/pathology-based RCB, and between pathological RCB and mpMRI indices. RESULTS: At baseline, TROI apparent diffusion coefficient (ADC) was lower and dynamic contrast enhanced (DCE) metrics were higher, compared to NROI (ADC: 806 ± 137 × 10-6 vs. 1277 ± 213 × 10-6 mm2/sec, p = 0.0005; Ktrans: 0.346 ± 0.16 vs. 0.144 ± 0.06 min-1, p = 0.002; AUC90: 0.213 ± 0.08 vs. 0.11 ± 0.03, p = 0.002). Post-treatment, there was no change in TROI ADC, but a decrease in TROI Ktrans (0.346 ± 0.16 to 0.188 ± 0.08 min-1; p = 0.02) and AUC90 (0.213 ± 0.08 to 0.13 ± 0.06; p = 0.02). Tumor volume decreased with ADT. There was no difference between mpMRI-based and pathology-based RCB, which positively correlated (⍴ = 0.74-0.81, p < 0.05). Pathology-based RCB positively correlated with post-treatment DCE metrics (⍴ = 0.76-0.70, p < 0.05) and negatively with ADC (⍴ = -0.79, p = 0.03). CONCLUSION: Given the heterogeneity of PCa, an individualized approach to ADT may maximize potential benefit. This pilot study suggests that mpMRI may serve as a biomarker of ADT response and as a surrogate for RCB at prostatectomy.

Repeatability of Multiparametric Prostate MRI Radiomics Features.

In this study we assessed the repeatability of radiomics features on small prostate tumors using test-retest Multiparametric Magnetic Resonance Imaging (mpMRI). The premise of radiomics is that quantitative image-based features can serve as biomarkers for detecting and characterizing disease. For such biomarkers to be useful, repeatability is a basic requirement, meaning its value must remain stable between two scans, if the conditions remain stable. We investigated repeatability of radiomics features under various preprocessing and extraction configurations including various image normalization schemes, different image pre-filtering, and different bin widths for image discretization. Although we found many radiomics features and preprocessing combinations with high repeatability (Intraclass Correlation Coefficient > 0.85), our results indicate that overall the repeatability is highly sensitive to the processing parameters. Neither image normalization, using a variety of approaches, nor the use of pre-filtering options resulted in consistent improvements in repeatability. We urge caution when interpreting radiomics features and advise paying close attention to the processing configuration details of reported results. Furthermore, we advocate reporting all processing details in radiomics studies and strongly recommend the use of open source implementations.