Pockaj, Barbara A.

AbstractBackgroundMerkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy that usually occurs in the head/neck or extremities. However, there are reports of MCC developing in the lymph nodes or parotid gland without evidence of a primary cutaneous lesion.MethodsWe reviewed 415 patients with biopsy‐proven MCC. Patients with MCC of unknown primary (n = 37, 9%, MCCUP) made up the study cohort. The primary endpoints of the study were rate of recurrence, disease‐free survival, and overall survival.ResultsPatients with MCCUP presented with tumors in lymph nodes (n = 34) or parotid gland (n = 3). Nodal disease was most commonly detected in the inguinal/external iliac (n = 15) or axillary (n = 14) regions. The mean age at diagnosis was 70 years and 24% were female. Patients presented with distant metastases in 24.3% of cases. Patients with stage IIIA disease treated with regional lymph node dissection (RLND) had a lower risk of disease recurrence (hazard ratio 0.26, p = 0.046). Recurrence‐free survival was 59.3% at 5 years. Disease‐specific survival was 63.3% at 5 years.ConclusionPatients with MCCUP have a high risk of recurrence and mortality. The optimal treatment for MCCUP has yet to be elucidated, although therapeutic RLND appears beneficial for these patients.

Ultrasound is commonly used as an imaging tool in the medical sector. Compared to standard ultrasound imaging, quantitative ultrasound analysis can provide more details about a material microstructure. In this study, quantitative ultrasound analysis was conducted through computational modeling to detect various breast duct pathologies in the surgical margin tissue. Both pulse-echo and pitch-catch methods were evaluated for a high-frequency (22–41 MHz) ultrasound analysis. The computational surgical margin modeling was based on various conditions of breast ducts, such as normal duct, ductal hyperplasia, DCIS, and calcification. In each model, ultrasound pressure magnitude variation in the frequency spectrum was analyzed through peak density and mean-peak-to-valley distance (MPVD) values. Furthermore, the spectral patterns of all the margin models were compared to extract more pathology-based information. For the pitch-catch mode, only peak density provided a trend in relation to different duct pathologies. For the pulse-echo mode, only the MPVD was able to do that. From the spectral comparison, it was found that overall pressure magnitude, spectral variation, peak pressure magnitude, and corresponding frequency level provided helpful information to differentiate various pathologies in the surgical margin.

BackgroundThe significance of tumor‐infiltrating lymphocytes (TILs) in melanoma is debated. This article presents a multicenter, retrospective study assessing the predictive and prognostic value of TILs.MethodsThe Sentinel Lymph Node Working Group database was queried from 1993 to 2018 for cases with known TIL data. TILs were categorized as absent or present, which included nonbrisk (NB), brisk (B), and present but unspecified TIL levels. Clinicopathologic factors were correlated with TILs, sentinel lymph node (SLN) status, and melanoma‐specific survival (MSS).ResultsOverall, 3203 patients were included. The median thickness was 1.5 mm, and 469 cases had SLN metastases. TILs were present in 2458 cases (76.7%), with NB, B, and unspecified TILs seen in 1691 (68.8%), 691 (28.1%), and 76 (3.1%), respectively. Multivariable analysis showed that the presence of TILs significantly predicted a negative SLN biopsy (P < .05). The median follow‐up was 25.2 months. MSS was significantly better for cases with TILs than cases without TILs (P < .001). According to multivariable analysis, age, gender, thickness, mitotic rate, ulceration, lymphovascular invasion, and SLN status were significantly prognostic of MSS (all P values < .05). Although TILs were not prognostic of MSS, when multiple imputation was used and the SLN status was excluded, the presence of TILs was significantly prognostic of improved MSS (hazard ratio, 0.78; 95% confidence interval, 0.64‐0.95; P = .0154).ConclusionsTILs are a favorable marker because their presence significantly predicts a negative SLN, and the absence of TILs may be a prognostic marker of worse survival in patients with a positive SLN but not a negative SLN. TILs may also serve as a prognostic marker of survival when the SLN status is not considered.

AbstractBackground and ObjectivesThe prognostic significance of regression in predicting melanoma recurrences is unknown. We present a large multicenter study correlating regression with recurrence.MethodsThe Sentinel Lymph Node Working Group database was queried from 1993 to 2018 for cases with regression data. Clinicopathologic factors were correlated with overall and first‐site of recurrence and with recurrence‐free survival (RFS).ResultsThere were 4790 patients and the median follow‐up was 39.6 months. Regression and recurrences were seen in 1081 (22.6%) and 773 (16.1%) cases, respectively. First‐site locoregional and distant recurrences were seen in 412 (8.6%) and 352 (7.3%) patients, respectively. Regression was seen in 15.8% and 24.7% of all cases with and without recurrences (p < 0.0001), respectively, while regression was seen in 14.3% and 17.9% of first‐site locoregional and distant recurrent cases, respectively, compared with 23.3% and 22.9% of patients with regression and without first‐site locoregional and distant recurrences, respectively (p = 0.29). On multivariable analysis, after controlling for age, gender, thickness, ulceration, lymphovascular invasion, and sentinel lymph node status, regression significantly predicted improved RFS (p = 0.004) and fewer first‐site regional recurrences (p = 0.017).ConclusionOur data suggest that regression is a favorable prognostic marker in melanoma and predicts significantly better RFS and decreased first‐site regional recurrences.

Abstract Purpose:Quantify in vivo biomechanical tissue properties in various breast densities and in normal risk and high risk women using Magnetic Resonance Imaging (MRI)/MRE and examine the association between breast biomechanical properties and cancer risk.Methods: Patients with normal risk or high risk of breast cancer underent 3.0 T breast MR imaging and elastography. Breast parenchymal enhancement (BPE), density (from most recent mammogram), stiffness, elasticity, and viscosity were recorded. Within each breast density group (non-dense versus dense), stiffness, elasticity, and viscosity were compared across risk groups (normal versus high). A multivariable logistic regression model was used to evaluate whether the MRE parameters (separately for stiffness, elasticity, and viscosity) predicted risk status after controlling for clinical factors.Results: 50 normal risk and 86 high risk patients were included. Risk groups were similar on age, density, and menopausal status. Among patients with dense breasts, mean stiffness, elasticity, and viscosity were significantly higher in high risk patients (N = 55) compared to normal risk patients (N = 34; all p < 0.001). Stiffness remained a significant predictor of risk status (OR=4.26, 95% CI [1.96, 9.25]) even after controlling for breast density, BPE, age, and menopausal status. Similar results were seen for elasticity and viscosity.Conclusion: A structurally-based, quantitative biomarker of tissue stiffness obtained from MRE is associated with differences in breast cancer risk in dense breasts. Tissue stiffness could provide a novel prognostic marker to help identify high risk women with dense breasts who would benefit from increased surveillance and/or risk reduction measures.

11033 Background: Breast enhanced recovery after surgery (ERAS) protocols emphasize multimodal analgesia to decrease pain and expedite home recovery, but variability remains for same-day discharge and pain management. The purpose of this qualitative study is to examine how residents learn and apply breast surgery ERAS protocols, how they conceptualize pain management for breast surgery patients, and what influences their decision to discharge a patient home on the day of surgery. Methods: A semi-structured interview guide was adapted from existing instruments in the pain management qualitative literature. Surgical residents who rotated on the breast surgery service within the previous 12 months were interviewed by a single researcher. Interviews were recorded, transcribed, de-identified, and independently inductively coded by two researchers. A codebook was developed and refined using the constant comparative method until interrater reliability (Cohen’s kappa) reached greater than 0.9. Codes were grouped into coding categories and explored for thematic analysis. Results: Twelve interviews were completed with plastic and general surgery residents. Participants spanned post-graduate years 1-4. Preferred discharge narcotic regimens for mastectomy patients ranged from 5-30 tablets of 5mg oxycodone and participants rarely reported the same quantity. Ultimately, 365 primary codes were collapsed into 26 parent codes, with a Cohen’s kappa of 0.93. Six emerging themes were identified. Three themes describe how participants learned through a mixture of templated care, formal education, and informal experiential learning. Two themes delineate how residents would teach breast surgery ERAS protocols: by emphasizing buy-in and by connecting the impetus behind ERAS with the implementation in daily workflow. One theme illustrates the patient-centered culture and how that impacts postoperative management and same-day discharges. Conclusions: Residents learn breast surgery ERAS and postoperative pain management from imitating their seniors, observing patient encounters, completing templated orders, and translating concepts from other ERAS services, more so than from a formal lecture. When implementing new same-day discharge protocols for mastectomy patients, it is important to consider how informal learning and local culture influence postoperative pain management and discharge rates.

10541 Background: Biomechanical tissue properties may vary in the breasts of patients at elevated risk for breast cancer. We aim to quantify in vivo biomechanical tissue properties in various breast densities and in both normal risk and high risk women using Magnetic Resonance Imaging (MRI)/MRE and examine the association of biomechanical properties of the breast with cancer risk. Methods: In this IRB–approved prospective single-institution study, we recruited two groups of women differing by breast cancer risk to undergo a 3.0 T dynamic contrast enhanced MRI/MRE of the breast. Low-average risk women were defined as having no personal or significant family history of breast cancer, no prior high risk breast biopsies and a negative mammography within 12 months. High-risk breast cancer patients were recruited from those patients who underwent standard of care breast MR. Within each breast density group (non-dense versus dense), two-sample t-tests were used to compare breast stiffness, elasticity, and viscosity across risk groups (low-average vs high). Results: There were 50 low-average risk and 86 high-risk patients recruited to the study. The risk groups were similar on age (mean age = 55.6 and 53.6 years), density (68% vs. 64% dense breasts) and menopausal status (66.0% vs. 69.8%). Among patients with dense breasts, mean stiffness, elasticity, and viscosity were significantly higher in high risk patients ( N = 55) compared to low-average risk patients ( N = 34; all p < 0.001). In the multivariate logistic regression model, breast stiffness remained a significant predictor of risk status (OR=4.26, 95% CI [1.96, 9.25]) even after controlling for breast density, MRI BPE, age, and menopausal status. Similar results were seen for breast elasticity (OR=4.88, 95% CI [2.08, 11.43]) and viscosity (OR=11.49, 95% CI [1.15, 114.89]). Conclusions: Structurally-based, quantitative biomarker of tissue stiffness obtained from global 3D breast MRE is associated with differences in breast cancer risk in dense breasts. As such, tissue stiffness could provide a novel prognostic marker to help identify the subset of high-risk women with dense breasts who would benefit from increased surveillance.[Table: see text]

Ultrasound measurement is a relatively inexpensive and commonly used imaging tool in the health sector. The through-transmission process of ultrasound measurement has been extensively evaluated for detecting abnormalities in tissue pathology. Compared to standard imaging parameters such as amplitude and time of flight, quantitative ultrasound parameters in the frequency domain can provide additional details regarding tissue microstructures. In this study, pressure magnitude or amplitude variation in the frequency spectrum of the received signal was evaluated as a potential imaging technique using the spectral peak density parameter. Computational C-scan imaging analysis was developed through a finite element model. The magnitude variation in the received signal showed different patterns while interacting with and without inclusions. Images were reconstructed based on peak density values that varied with the presence of solid structure. The computational results were verified with the experimental C-scan imaging results from the literature. It was found that magnitude variation can be an effective parameter for C-scan imaging of thin structures. The feasibility of the study was further extended to identify the structure’s relative position along with the sample depth during C-scan imaging. While moving the structure in the direction of the sample depth, the pressure magnitude variation strongly followed a second-degree polynomial trend.

Abstract Background Appendiceal cancers represent a diverse group of malignancies with varying biological behavior. The significance of lymph node metastases in relation to long‐term survival and chemotherapy response is poorly defined. Methods The National Cancer Database was queried to find patients diagnosed with appendiceal cancer from 1998 to 2012. Kaplan–Meier curves and multivariable Cox regression analyses were used to study the association between lymph node status and overall survival. Stage IV patients were excluded. Results The rate of nodal positivity of the 9841 patients with known node status was: signet ring 47.4%, carcinoid 42.3%, nonmucinous adenocarcinoma 28.8%, goblet cell 21.9%, and mucinous adenocarcinoma 20.4%. Node‐positive patients had worse long‐term survival for all subtypes with the exception of carcinoid tumors ( p < 0.001). The strongest association was for signet cell and goblet cell. Adjuvant chemotherapy in node‐positive patients improved survival for mucinous, nonmucinous, and signet ring cell histology ( p < 0.01), but not for goblet cell. Conclusions Nodal involvement in patients with appendiceal cancer varies in incidence, association with adverse survival, and response to systemic therapy. Individualized treatment algorithms for the management of the subtypes of appendiceal cancer are needed.