Faculty Bibliography

OBJECTIVE:Indeterminate lesions on prostate-specific membrane antigen (PSMA)-PET are challenging to address. We aimed to develop, implement, and evaluate a multidisciplinary consensus algorithm that integrates existing interpretation systems with multimodality imaging and clinicopathological information for interpreting indeterminate bone and lymph node lesions on PSMA-PET. MATERIALS AND METHODS/METHODS:This was a retrospective single-center study on a prospectively implemented algorithm. We included all consecutive prostate cancer patients whose PSMA-PET findings for indeterminate bone lesions or lymph nodes were discussed at a multidisciplinary tumor board (MDT) in 2024-2025. An algorithm determining the level of suspicion for metastasis was developed in a multidisciplinary fashion, incorporating lesion location, conventional imaging features, PSMA-PET characteristics, and clinicopathological information. The application of the algorithm and outcomes were documented, compared against a composite reference standard. Comparisons were made with PSMA-RADS and PROMISE V2 PSMA-expression scores. RESULTS:81 patients (median age 68, interquartile range 64-75) were included. Algorithm results were benign (48.1% [39/81]), equivocal (4.9% [4/81]), metastasis (40.7% [33/81]), and mixed (benign and metastatic lesions, 6.2% [5/81]). The algorithm was correct in 94.1% (64 of 68 patients with a sufficient reference standard). The algorithm was discordant with PSMA-RADS in 54.3% (44/81) and with PROMISE V2 PSMA-expression score in 71.6% (58/81). The frequency of equivocal lesions was lower using the algorithm (4.9% [4/81]) compared with PSMA-RADS (53.1% [43/81]) and PSMA-expression score (64.2% [52/81]). CONCLUSION/CONCLUSIONS:A multidisciplinary consensus algorithm for interpreting indeterminate bone lesions and lymph nodes on PSMA-PET was developed and implemented. Integrating clinicopathological information and multimodality imaging in an MDT setting reduced equivocal interpretations. KEY POINTS/CONCLUSIONS:Question While prostate-specific membrane antigen (PSMA)-PET has become essential in the management of prostate cancer, indeterminate bone lesions and lymph nodes remain challenging to address. Findings A multidisciplinary algorithm for interpreting indeterminate bone lesions and lymph nodes on PSMA-PET, incorporating clinicopathological information and multimodality imaging, reduced the frequency of equivocal interpretations. Clinical relevance An algorithm for interpreting indeterminate bone lesions and lymph nodes on PSMA-PET, incorporating clinicopathological information and multimodality imaging in a multidisciplinary tumor board setting, decreases the frequency of equivocal interpretations and can potentially help management decisions.

BACKGROUND:Although most adrenal incidentalomas are benign, many are identified by single-phase contrast-enhanced computed tomography, which is unreliable for excluding malignancy. Virtual noncontrast computed tomography is a newer modality with the potential to better characterize adrenal nodules. METHODS:Virtual noncontrast computed tomography of adrenal nodules with available reference standard of true noncontrast computed tomography were identified (2016-2024). Images were evaluated for nodule characteristics including Hounsfield unit attenuation and variability. Nodules were classified as benign (≤10 Hounsfield units) or indeterminate/suspicious (>10 Hounsfield units) by true noncontrast computed tomography. Hounsfield units were compared between virtual noncontrast computed tomography and true noncontrast computed tomography. Variability in attenuation measurements was compared by evaluating Hounsfield unit differences 1 slice up and down from the chosen mid-depth image. Receiver operating characteristic analysis was used to define optimal virtual noncontrast computed tomography accuracy thresholds. RESULTS:After excluding 5 adrenal nodules due to suboptimal imaging, 67 nodules were identified. Based on true noncontrast computed tomography Hounsfield units, 23 nodules (34.3%) were benign, and 44 (65.7%) were indeterminate/suspicious. Hounsfield unit measurements for each nodule exhibited wide variability by both virtual noncontrast computed tomography and true noncontrast computed tomography. Virtual noncontrast computed tomography and true noncontrast computed tomography were significantly correlated with moderate effect size (Pearson coefficient 0.69, P < .001). Conflicting impressions occurred for 6 nodules (9.0%). Overall, virtual noncontrast computed tomography exhibited outstanding discrimination between benign and indeterminate/suspicious nodules (area under the curve 0.94). Maintaining a threshold of ≤10 Hounsfield units achieved 93% sensitivity, 76% specificity, and 84% negative predictive value, whereas ≤7 Hounsfield units achieved 100% negative predictive value. The functional utility of virtual noncontrast computed tomography as a rule-out test applied to 16% of nodules. CONCLUSION/CONCLUSIONS:Despite wide variability in Hounsfield unit measurements, adrenal nodules are well defined by both virtual noncontrast computed tomography and true noncontrast computed tomography. Well-reconstructed virtual noncontrast computed tomography images can accurately rule out malignancy in selected patients, potentially obviating the need for additional imaging.

Black women with estrogen receptor-positive, HER2-negative (ER + /HER2-) breast cancer experience higher rates of distant recurrence and worse survival outcomes compared to White women. This may be due not only to disparities in social determinants of health, but also differences in the tumor microenvironment (TME), including TMEM (Tumor Microenvironment of Metastasis) doorway score. TMEM doorways serve as portals for cancer cell hematogenous dissemination to distant sites. While higher TMEM doorway scores have been observed in Black (compared to White) patients with residual ER + /HER2- breast cancer after neoadjuvant chemotherapy, this has not been evaluated in treatment-naïve primary breast cancers. Here, we report on a multi-institutional study to evaluate TMEM doorway score in 418 treatment-naïve archived human breast cancer samples, including 265 patients with ER + /HER2-, 102 with triple negative (TNBC), and 51 with HER2-positive breast cancer. In addition to analyzing TMEM doorway scores by race across breast cancer subtypes, we examined their association with distant recurrence and assessed whether the effect of TMEM doorway scores on recurrence differed by race. Black patients had significantly higher TMEM doorway score than White patients in the overall study population (median 29.9 vs 17.9, p < 0.001), in the ER + /HER2- (median 25.0 vs 16.8, p < 0.001) and the HER2-positive subset (median 37.2 vs 12.9, p = 0.003), but not in TNBC (median 36.2 vs 36.3, p = 0.86). Racial differences in macrophage density mirrored racial differences in the TMEM doorway score. In multivariate models including age, body mass index, tumor size, grade, lymph node status, and chemotherapy treatment, neither Black race nor TMEM doorway density was associated with a higher distant recurrence risk alone. However, there was a statistically significant interaction between race and high TMEM doorway score with respect to distant recurrence risk in ER + /HER2- patients; Black patients with high TMEM doorway score were 4.6-fold (95% CI 1.28-22.82, p = 0.03) and 4.2-fold (95% CI 1.17 - 18.23, p = 0.04) more likely to have a distant recurrence at 5-years and 10-years, respectively, while White patients with high TMEM doorway scores did not (p = 0.21, p = 0.11). Our study reveals racial disparities in the TME of women with ER + /HER2- breast cancer, which may play a critical role in driving disparities in breast cancer outcomes.

Primary effusion lymphoma (PEL) is a rare and aggressive B-cell non-Hodgkin lymphoma (NHL) that predominantly affects patients with human immunodeficiency virus infection and is strongly associated with human herpes virus 8 (HHV-8) infection. Due to its rarity, the current understanding of PEL's epidemiology and management is largely derived from case reports and small retrospective studies. Using the SEER-17 database, we conducted a retrospective analysis of adults with pathologically confirmed primary effusion lymphoma diagnosed between 2001-2021. Patients were stratified into two time periods (2001-2010 and 2011-2021) to assess temporal trends. Age-adjusted incidence rates, relative survival (RS), overall survival (OS), and lymphoma-specific survival (LSS) were calculated using flexible parametric survival models. Competing risk analysis was performed to evaluate cumulative incidence of lymphoma-specific death. Among 236 patients (median age 51 years, 88% male), 82 were diagnosed in 2001-2010 and 154 in 2011-2021. Age-adjusted incidence rates increased from 1.0 to 1.6 cases per 10,000,000 person-years between periods (p = 0.004). Five-year RS improved from 21% to 37%, with median OS increasing from 4 to 12 months. On multivariable analysis, the more recent period showed significant improvements in OS (HR = 0.65; 95% CI, 0.44-0.97) and LSS (HR = 0.56; 95% CI, 0.36-0.86), with reduced cumulative incidence of lymphoma-specific death (HR = 0.49; 95% CI, 0.33-0.74). In our population-level analysis of PEL, we report a significant improvement in survival outcomes between 2001-2021, likely reflecting advances in both lymphoma treatment and HIV management. However, despite these improvements, OS remains low underscoring the need for prioritizing these patients to clinical trials with novel therapies.

Ecological variables such as climate and habitat composition can impact the infection patterns of gastrointestinal parasites in animal host populations by affecting host behavior and parasite survivability and distribution in the external environment. Data from wild primate populations provide insights into these processes. To contribute new insights from a well-characterized population, we collected 200 fecal samples from five groups of Costa Rican capuchin monkeys from August 2020 to August 2021 and screened them for gastrointestinal parasites. We estimated annual home range sizes for the groups and used satellite imagery to measure forest productivity (via Normalized Difference Vegetation Index) and forest cover within their home ranges. We also measured total monthly rainfall and average monthly temperature at the field site to explore the effects of local climate on parasitism. We used Bayesian regression models to examine the effects of these ecological variables on parasite richness, fecal parasite density, and parasite presence. We found that rainfall, and to a lesser extent, temperature, affected the presence and fecal density of certain parasitic taxa. The presence of the soil-transmitted helminth Strongyloides decreased in both hotter and rainier months, and hosts shed fewer Strongyloides eggs during hotter months. Infections with indirectly transmitted parasites (e.g., Prosthenorchis sp., Hymenolepis sp.) were more common during drier months. This corresponds with times when fruit availability is lower and invertebrate consumption is higher at this site. These findings highlight the relationship between climate and patterns of parasitic infection in hosts, likely reflecting changes in host diet, behavior, and parasite abundance.

The early resuscitation of patients with mild to moderate non-exsanguinating trauma has shifted from the conventional use of one to two liters of crystalloids to the use of one to two units of PRBC. This evolution assumes that the transfusion of PRBC is superior to the administration of any volume of crystalloids because of the propensity of crystalloids to migrate from the intravascular to the interstitial space leading to organ dysfunction, organ failure, and worse outcomes. However, the premise of the fluid migration relies on Starling original model of fluid exchange between the hydrostatic and oncotic pressure without considering whether the endothelial surface glycocalyx (ESG) is affected by the degree of traumatic insult and by the duration and depth of hypotension. It fails to account for the changes that occur to the PRBC during storage from the standpoint of off-loading of oxygen and the ability to negotiate the microcirculation. This review explores the impact of the burden of trauma and hemorrhage on the ESG, the changes to the RBCs that occur during storage, particularly their diminished capacity to offload oxygen and to negotiate low-shear microvascular districts, leading to failure to improve oxygen consumption despite the increase in oxygen delivery. We argue that the recent trend toward early resuscitation with one to two units of PRBC rather that low-volume crystalloids, in patients with non-exsanguinating mild to moderate trauma lacks sufficient justification.

BACKGROUND AND AIMS/OBJECTIVE:Piecemeal endoscopic mucosal resection (EMR) is the standard of care for large, nonpedunculated colon polyps but is associated with recurrence rates of 9% to 31%. Current guidelines recommend 6-month surveillance for all patients, although this may not be necessary for lower-risk cases. METHODS:We retrospectively reviewed patients who underwent piecemeal EMR of ≥20-mm colon polyps between 2018 and 2021. Patients were stratified into 6- or 12-month surveillance groups based on polyp features. Recurrence rates and associated factors were compared. RESULTS:Among 193 patients, recurrence was higher in the 6-month (31.5%) than in the 12-month group (14.3%, P < .05). Among patients with recurrence, the 6-month follow-up group had more tubulovillous adenomas (P < .05) on index colonoscopy. Tubulovillous histology in the initial polyp was the only factor associated with recurrence. CONCLUSIONS:A risk-stratified approach may safely extend surveillance to 12 months for lower-risk patients after piecemeal EMR, reducing unnecessary procedures without compromising care.