High Community-Level Social Vulnerability is Associated with Worse Recurrence-Free Survival (RFS) After Resection of Extremity and Truncal Soft Tissue Sarcoma.

BACKGROUND: Although social vulnerability has been associated with worse postoperative and oncologic outcomes in other cancer types, these effects have not been characterized in patients with soft tissue sarcoma. This study evaluated the association of social vulnerability and oncologic outcomes. METHODS: The authors conducted a single-institution cohort study of adult patients with primary and locally recurrent extremity or truncal soft tissue sarcoma undergoing resection between January 2016 and December 2021. The social vulnerability index (SVI) was measured on a low (SVI 1-39%, least vulnerable) to high (60-100%, most vulnerable) SVI scale. The association of SVI with overall survival (OS) and recurrence-free survival (RFS) was evaluated by Kaplan-Meier analysis and Cox proportional hazard regression. RESULTS: The study identified 577 patients. The median SVI was 44 (interquartile range [IQR], 19-67), with 195 patients categorized as high SVI and 265 patients as low SVI. The median age, tumor size, histologic subtype, grade, comorbidities, stage, follow-up time, and perioperative chemotherapy and radiation utilization were similar between the high and low SVI cohorts. The patients with high SVI had worse OS (p = 0.07) and RFS (p = 0.016) than the patients with low SVI. High SVI was independently associated with shorter RFS in the multivariate analysis (hazard ratio, 1.64; 95% confidence interval, 1.06-2.54) but not with OS (HR, 1.47; 95% CI 0.84-2.56). CONCLUSION: High community-level social vulnerability appears to be independently associated with worse RFS for patients undergoing resection of extremity and truncal soft tissue sarcoma. The effect of patient and community-level social risk factors should be considered in the treatment of patients with extremity sarcoma.

Classification of Gastric Neuroendocrine Tumors and Associations With Survival.

BACKGROUND AND OBJECTIVES: Not all gastric neuroendocrine tumors (GNETs) may be classified into one of the three described clinicopathologic subtypes. The purpose of this study was to better characterize GNET subtypes and associated outcomes. METHODS: Patients treated for GNET at our institution (1995-2021) were identified. Pathologic specimens of tumors that could not be classified as type 1, 2, or 3 were further reviewed. GNETs were categorized as proton pump inhibitor (PPI)-associated based on changes in the background gastric mucosa consistent with PPI use. Distant metastasis at presentation (DM) and disease-specific survival (DSS) were evaluated. RESULTS: Among 246 patients, there were 164 (67%) type 1, 5 (2%) type 2, 52 (21%) type 3, and 18 (7%) PPI-associated GNETs. Seven (3%) tumors remained unclassified. DM was more frequent with type 3 GNETs (38%) than type 1 (1%), type 2 (20%), or PPI-associated tumors (11%, p < 0.001). Ten-year DSS rates were 100% for type 1, 53% (95% confidence interval [CI], 38%-75%) for type 3, and 80% (95% CI, 58%-100%) for PPI-associated tumors (p < 0.001). GNET subtype, race, and DM were independently associated with DSS. CONCLUSIONS: PPI-associated tumors may represent a distinct GNET subtype with intermediate outcomes. Other factors should also be considered in overall prognosis.

Effect of surgical approach on early return to intended oncologic therapy after resection for pancreatic ductal adenocarcinoma.

BACKGROUND: Although robotic pancreatectomy may facilitate an earlier functional recovery, the impact of a robotic pancreatectomy program during its early experience on the timing of return to intended oncologic therapy (RIOT) after surgery is unknown. METHODS: In this retrospective cohort study, we used propensity score matching with a 1:2 ratio to compare patients who underwent robotic or open surgery (distal pancreatectomy or pancreatoduodenectomy) for pancreatic ductal adenocarcinoma (PDAC) during the first 3 years of our robotic pancreatectomy experience (January 2018-December 2021). Generalized estimating equations modeling was used to evaluate the effect of surgical approach on early RIOT, defined as adjuvant chemotherapy initiation within 8 weeks after surgery, and late RIOT, defined as initiation within 12 weeks after surgery. RESULTS: The matched cohort included 26 patients who underwent robotic pancreatectomy and 52 patients who underwent open pancreatectomy. Rates of receipt of adjuvant chemotherapy were 96.2% and 78.9%, respectively. Rate of early RIOT in the robotic group (73.1% was higher than that in the open group (44.2%; P = 0.018). In multivariable analysis, a robotic approach was associated with early RIOT (odds ratio, 3.54; 95% confidence interval 1.08-11.62; P = 0.038). Surgical approach did not impact late RIOT (odds ratio, 3.21; 95% confidence interval 0.71-14.38; P = 0.128). CONCLUSIONS: Compared with open pancreatectomy, robotic pancreatectomy did not delay RIOT. In fact, odds of early RIOT were increased, which supports the oncological safety of our robotic pancreatectomy program during its implementation.

Practice Pattern Variability in the Management of Regional Lymph Node Metastasis in Extremity and Trunk Soft Tissue Sarcoma: A Survey of the Society of Surgical Oncology and Musculoskeletal Tumor Society Membership.

BACKGROUND: Regional lymph node metastasis in extremity and trunk soft tissue sarcoma (ETSTS) is rare with no standardized management. We sought to determine management patterns for regional lymph node metastasis in ETSTS. METHODS: A survey regarding the management of ETSTS lymph node metastasis was distributed to the membership of the Musculoskeletal Tumor Society (MSTS) and the Society of Surgical Oncology (SSO) in January 2022. The survey queried the type of training (surgical oncology, orthopedic oncology), details of their practice setting, and management decisions of hypothetical ETSTS scenarios that involved potential or confirmed lymph node metastasis. RESULTS: The survey was distributed to 349 MSTS members (open rate of 63%, completion rate 21%) and 3026 SSO members (open rate of 55%, completion rate 4.7%) and was completed by 214 respondents, of whom 73 (34.1%) and 141 (65.9%) were orthopedic oncology and surgical oncology fellowship-trained, respectively. The majority of respondents practiced in an academic setting (n = 171, 79.9%) and treat >10 extremity sarcoma cases annually (n = 138, 62.2%). In scenarios with confirmed nodal disease for clear cell and epithelioid sarcoma, surgical oncologists were inclined to perform lymphadenectomy, while orthopedic oncologists were inclined to offer targeted lymph node excision with adjuvant radiation (p < 0.001). There was heterogeneity of responses regarding the management of nodal disease regardless of training background. CONCLUSION: Self-reported management of nodal disease in ETSTS was variable among respondent groups with differences and similarities based on training background. These data highlight the variability of practice for nodal disease management and the need for consensus-based guidelines.

Clinical Impact of External Beam Radiotherapy for Surgically Resected Primary Retroperitoneal Liposarcoma.

INTRODUCTION: EORTC-62092 (STRASS) was a phase 3, randomized study that compared surgery alone versus surgery plus neoadjuvant radiotherapy (RT) for retroperitoneal sarcomas. RT was not associated with improved abdominal recurrence-free survival, the primary outcome measure, although on subanalysis, there may have been benefit for well-differentiated (WD) liposarcoma. This study investigated the real-world use and outcomes of RT (neoadjuvant and adjuvant) for the management of retroperitoneal liposarcoma. METHODS: We queried the National Cancer Database (NCDB) (2004-2017) for patients with nonmetastatic, primary retroperitoneal liposarcoma treated with resection with or without RT (n = 3911). Patients were stratified by treatment type and histology [WD (n = 2252), dedifferentiated (DD) (n = 1659)]. Propensity score (PS) matching was used before comparison of treatment groups. Overall survival (OS) was the primary outcome measure. RESULTS: Median follow-up time was 4.1 years, and median OS was 10.7 years. There was no association between RT and OS for either WDLPS or DDLPS cohorts. We performed a subgroup analysis of neoadjuvant RT only, similar to STRASS. For WDLPS after PS matching (n = 208), neoadjuvant RT was not associated with OS (hazard ratio [HR] 1.01, p = 0.0523) but was associated with longer postoperative hospital stay (p = 0.012). For DDLPS after PS matching (n = 290), neoadjuvant RT was not associated with OS (HR 1.02, p = 0.889). For both WD-LPS and DD-LPS, utilization of neoadjuvant RT was associated with treatment at high-volume (≥ 10 cases/year) and academic/network facilities. CONCLUSIONS: For primary retroperitoneal liposarcoma treated with surgical resection, radiotherapy was not associated with an overall survival benefit in this propensity-matched, adjusted analysis of the NCDB.

Melanoma metastatic to the adrenal gland: An update on the role of adrenalectomy in multidisciplinary management.

BACKGROUND AND OBJECTIVES: Modern systemic therapy (immune checkpoint blockade [ICB], targeted therapy) has improved survival for patients with metastatic melanoma. The role of adrenal metastasectomy is not well characterized in this setting. METHODS: Consecutive patients treated with adrenalectomy 1/1/2007-1/1/2019 were retrospectively compared to patients treated with systemic therapy alone in the same time period. Overall survival and survival after adrenal metastasis were compared, prognostic factors associated with survival after adrenal metastasis development were evaluated. RESULTS: A total of 74 patients underwent adrenalectomy and were compared to 69 treated with systemic therapy alone. The most common indications for adrenalectomy were to render the patient disease-free in the setting of isolated adrenal metastasis (n = 32, 43.2%) or treatment of isolated progression in the setting of other stable/responding metastases (n = 32, 43.2%). Patients treated surgically had longer survival (116.9 vs. 11.0 months after adrenal metastasis diagnosis, p < 0.001). On multivariate analysis, receipt of ICB (hazard ratio [HR]: 0.62, 95% confidence interval [CI]: [0.40-0.95]) and selection for adrenalectomy (HR: 0.27, 95% CI: [0.17-0.42]) were the strongest factors associated with improved survival after adrenal metastasis diagnosis. CONCLUSIONS: Selective application of adrenal metastasectomy is associated with prolonged survival benefit and remains an important consideration in the multidisciplinary management of patients with metastatic melanoma.

Parathyroidectomy for Normocalcemic Primary Hyperparathyroidism is Associated with Improved Bone Mineral Density Regardless of Postoperative Parathyroid Hormone Levels.

BACKGROUND: Biochemical cure in normocalcemic primary hyperparathyroidism (nPHPT) is defined as parathyroid hormone (PTH) level normalization 6 months after parathyroidectomy. However, recent studies show that a significant number of nPHPT patients have persistent PTH elevation postoperatively. We sought to correlate changes in PTH levels with skeletal outcomes after parathyroidectomy in nPHPT patients. METHODS: Adult patients who underwent parathyroidectomy at a tertiary referral center for sporadic PHPT between 2010 and 2020 were reviewed. Pre- and postoperative (6 months, 18 months, and last follow-up) laboratory and bone mineral densities (BMD) were recorded. Primary outcome was 18-month postoperative BMD change in the lumbar spine (LS), total hip (TH) and femoral neck (FN) in normocalcemic and hypercalcemic PHPT (hPHPT) patients. RESULTS: Of 661 patients included, 68 had nPHPT. nPHPT patients frequently had multigland disease (31% vs. 18%, p = 0.014), more bilateral cervical explorations (22% vs. 13%, p = 0.042), and fewer achieved biochemical cure (76% vs. 95%, p < 0.001) than hPHPT patients. Twenty-eight nPHPT patients had BMD data for comparison. Overall, nPHPT patients had improvement in the LS (1.84%, p = 0.002) and TH (1.64%, p = 0.014). When stratified by postoperative PTH levels, nPHPT patients with persistent PTH elevation had more BMD improvement at the TH than those who normalized PTH (3.73% vs. - 0.83%, p = 0.017). There was no difference in improvement at the LS or FN (p = NS). CONCLUSION: Parathyroidectomy is associated with improved BMD in nPHPT patients with bone disease. Although one in four nPHPT patients had elevated postoperative PTH levels persisting throughout the study, BMD improvement was still seen regardless of postoperative PTH level normalization.

Prognostic significance of acellular mucin in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for appendiceal neoplasms.

INTRODUCTION: Appendiceal neoplasms have a propensity for peritoneal dissemination. The standard of care for select individuals is CRS/HIPEC. In the current 8th AJCC Staging system, a finding of only intraperitoneal acellular mucin (M1a) is classified as Stage IVa. There is concern that the current AJCC system may over-stage patients. METHODS: This was a single-institution retrospective review of 164 cases of mucinous appendiceal neoplasm. Patients undergoing CRS/HIPEC with M1a disease were compared to patients with peritoneal deposits containing tumor cells (well-differentiated adenocarcinoma; low-grade mucinous carcinoma peritonei-M1b,G1). Overall and recurrence-free survival were assessed. RESULTS: Median age was 51 years, 70% were female, and 75% White. Sixty-four patients had M1a disease and 100 M1b,G1 disease. M1a disease had a lower median PCI score (11 vs. 20, p = .0001) and a higher rate of complete CRS (62% vs. 50%, p = .021). Median follow-up was 7.6 years (IQR 5.6-10.5 years). For M1a disease, there were no recurrences and only one patient died during the study interval. In comparison, for M1b disease, 66/100 (66%) recurred with a 5-year RFS of 40.5% (HR 8.0, 95% CI 4.9-15.1, p < .0001), and 31/100 (31%) died with a 5-year OS of 84.8% (HR 4.5, 95% CI 2.2-9.2, p < .0001). CONCLUSIONS: Acellular mucin (M1a disease) after CRS/HIPEC for appendiceal neoplasm is associated with longer OS and RFS compared to M1b, G1 disease. Current AJCC staging does not accurately reflect the differing outcomes of these two patient populations. The presence of acellular mucin in the peritoneal cavity should not be perceived as a metastatic equivalent.

Sentinel Lymph Node Biopsy and Formal Lymphadenectomy for Soft Tissue Sarcoma: A Single Center Experience of 86 Consecutive Cases.

BACKGROUND: Lymph node metastases (LNMs) are rare in patients with soft tissue sarcoma (STS), and there is limited evidence to guide clinical management. We describe our experience with sentinel lymph node biopsy (SLNB) and lymphadenectomy in STS patients. METHODS: A single-center, retrospective review was performed for patients with STS treated with SLNB and/or lymphadenectomy from 1994 to 2018. Clinicopathologic characteristics, multimodality treatment, regional/distant recurrence-free survival (RFS), and overall survival (OS) were examined. RESULTS: Eighty-six patients underwent SLNB (n = 34) and/or lymphadenectomy (n = 60) for STS. The most frequent histologic subtypes were epithelioid, clear cell, and undifferentiated pleomorphic sarcoma. Eight of 34 (23.5%) patients had a positive SLNB with 5-year OS of 71.4% compared with 71.9% for those with a negative SLNB. Eight of the 26 SLN-negative patients (30.8%) eventually developed nodal recurrence (n = 2) and/or (n = 6) distant metastasis with an estimated 5-year OS of 50%. Of patients undergoing lymphadenectomy, estimated 5-year OS was 44.6% and median RFS was 12 months. Eight (13.3%) had distant disease at time of lymphadenectomy, 20 (33.3%) developed distant recurrence after lymphadenectomy, and 6 (10%) developed regional-only recurrence. Patients with regional-only recurrence after lymphadenectomy had an estimated 5-year OS of 66.7% compared with 29.1% for those who recurred distantly. CONCLUSIONS: Patients with positive SLNB had similar survival to those with negative SLNB. Lymphadenectomy for isolated nodal disease is associated with poor RFS but reasonable 5-year OS when recurrence is regional-only. In STS, regional disease appears clinically distinct from distant metastatic disease and has better outcomes.

Sarculator is a Good Model to Predict Survival in Resected Extremity and Trunk Sarcomas in US Patients.

BACKGROUND: Sarculator is an online validated nomogram that predicts overall survival of patients with resected, primary extremity sarcomas. However, its ability to accurately predict outcomes in US patients with sarcoma is unknown. PATIENTS AND METHODS: Patients from the National Cancer Data Base (NCDB) (2006-2016) with resected stage I-III primary extremity or trunk sarcoma were included. Predicted overall survival (pOS) was calculated using the Sarculator algorithm, which includes patient age, tumor size (cm), grade (1-3), and histology, and compared with actual overall survival (aOS). Harrell's C-index was calculated to determine the discriminatory ability of Sarculator (0.7 = good, 0.8 = strong, 1.0 = perfect model), and calibration plots were created. RESULTS: In total, 9738 patients were included. Five-year pOS was 73.7% compared with aOS of 68.9%. The C-index for the entire cohort was 0.726. By stage, the C-index was 0.730 for stage I, 0.708 for stage II, and 0.679 for stage III. By histology, C-indices were highest for leiomyosarcoma (0.745), myxofibrosarcoma (0.722), and other histologies (0.721). By sociodemographic variables, Sarculator performed better for patients < 50 years (C-index 0.722), of other/unknown race (C-index 0.781), with private insurance (C-index 0.715), treated at a center other than a community cancer programs (C-index > 0.7), and with no comorbidities (C-index 0.716). Outcomes by zip code educational attainment and income were not markedly different (all C-indices > 0.7). CONCLUSIONS: Sarculator is overall a good predictor of aOS and useful tool for clinicians to aid in survival prognostication. However, clinicians should be aware of populations for whom Sarculator's predictions may be less accurate. Future work could focus on enhancing the Sarculator algorithm specifically for US patients by including demographic variables.

Differences in Clinicopathologic Behavior of Oncocytic Adrenocortical Neoplasms and Conventional Adrenocortical Carcinomas.

BACKGROUND: Oncocytic adrenocortical neoplasms (OANs) are rare endocrine tumors that present as a spectrum from benign to malignant. The outcomes after surgical resection of the oncocytic variant of adrenocortical carcinoma remain poorly understood. We sought to characterize the clinicopathologic features of OAN and compare oncocytic adrenocortical carcinoma (OAC) with conventional adrenocortical carcinoma (ACC). PATIENTS AND METHODS: Adult patients who underwent adrenalectomy for OAN or ACC between January 1990 and September 2020 were identified. Demographics, clinicopathologic factors, American Joint Committee on Cancer stage, and cancer-related outcomes were reviewed. A matched cohort analysis of disease-free survival (DFS) and overall survival (OS) was performed between patients with OACs and those with ACCs. RESULTS: Forty-one patients with OAN and 214 patients with ACC were included. The OAN cohort median age was 45.2 years [interquartile ratio (IQR) 38.5-54.0 years], and 61.0% were female. OANs were benign (n = 11), of uncertain malignant potential (UMP, n = 9), or OAC (n = 21). Disease recurrence occurred in 12 (57.1%) patients with OAC compared with 1 (11.1%) and 0 patients with UMP or benign OAN, respectively (p < 0.001). Seven (33.3%) patients with OAC died during follow-up compared with 0 patients with UMP or benign OAN (p = 0.020). Kaplan-Meier survival analysis found no difference in DFS between ACC and OAC groups before (p = 0.218) and after 2:1 matching (p = 0.417). Overall survival was shorter for patients who had ACC compared with those who had OAC (p = 0.031), but the difference was not evident with matched analysis (p = 0.200). CONCLUSIONS: OAN presents as a spectrum from benign indolent tumors to aggressive carcinomas. OACs demonstrate similar clinicopathologic behavior and recurrence-free and overall survival when matched to conventional ACCs.

Outcomes of Mixed Pathologic Response in Patients with Multiple Colorectal Liver Metastases Treated with Neoadjuvant Chemotherapy and Liver Resection.

BACKGROUND: Pathologic response to preoperative chemotherapy predicts survival in patients with colorectal liver metastases (CLMs) who undergo hepatectomy. In multiple CLMs, mixed pathologic response, wherein tumors exhibit different degrees of treatment response, is possible. We sought to evaluate survival outcomes of mixed response in patients with multiple CLMs. METHODS: We conducted a retrospective cohort study using a single-institution database of patients with two or more CLMs who underwent preoperative chemotherapy and hepatectomy (2010-2018). Pathologic response of each tumor was measured on pathology. Patients were stratified by pathologic response as complete (pCR) = 0-1% viability; major (pMajR) = 2-49% viability; minor (pMinR) = 50-99% viability; or mixed (pMixR) = at least one pCR/MajR tumor and one pMinR. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and adjusted risk of death was evaluated using Cox regression. RESULTS: Among 444 patients, 6% had pCR, 34% had pMajR, 36% had pMinR, and 24% had pMixR. Median and 5-year RFS for patients with pMixR was 10.4 months and 16%, respectively, compared with pMajR (11.3 months and 18%, respectively), pMinR (7.7 months and 13%, respectively), and pCR (23.1 months and 38%, respectively) [log-rank p < 0.001]. Median and 5-year OS for patients with pMixR was 77.4 months and 60%, respectively, compared with pMajR (80.5 months and 63%, respectively), pMinR (49.9 months and 39%, respectively), and pCR (median OS not reached; median follow-up of 37.1 months and 5-year OS of 65%) [log-rank p = 0.002]. pMixR was associated with a 52% risk of death reduction (hazard ratio 0.48, 95% confidence interval 0.30-0.78 vs. pMinR). CONCLUSIONS: One-quarter of patients with multiple CLMs have pMixR following preoperative chemotherapy and hepatectomy. OS and RFS for patients with pMixR mirror those of pMajR rather than pMinR, suggesting the greatest response achieved in any metastasis best predicts survival.

Lymphadenectomy and margin-negative resection for biliary tract cancer surgery in the United States-Differential technical performance by approach.

BACKGROUND: As minimally invasive surgery (MIS) approaches to biliary tract cancers become more commonplace, understanding the adequacy of their oncologic performance is key. METHODS: The National Cancer Database 2010-2016 was queried for patients who underwent hepatectomy for intrahepatic cholangiocarcinoma (IHC) and T1b or more advanced gallbladder cancer (GBC). Patients were grouped by approach: open (OA), laparoscopic (LA), and robotic (RA). Margin status, rate of lymph node (LN) dissection, and yield of LN dissection were evaluated. RESULTS: This cohort of 8612 patients, including 4034 patients with IHC (OA: 3281, LA: 675, RA: 78) and 4578 patients with GBC (OA: 1893, LA: 2588, RA: 97), MIS was used 40% of the time. R0 resection was achieved in 82% OA, 84% LA, and 91% RA, p = 0.004. Rate of LN dissection was 53% (OA: 60%, LA: 42%, RA: 51%, p < 0.001). Among patients who underwent lymphadenectomy, 6 + LN were retrieved less commonly with a LA (OA: 27%, LA: 20%, and RA: 30%, p < 0.001). High-volume MIS hepatectomy centers were more likely to perform a lymphadenectomy (odds ratio [OR]: 1.41) and a sampling of 6 + LN (OR: 1.18). CONCLUSION: Regardless of approach, lymphadenectomy is underperformed nationwide for biliary tract tumors, particularly with LA. As the use of MIS grows for the treatment of biliary tract cancers, scrutiny of oncologic outcomes is required.

Utilization and evolving prescribing practice of opioid and non-opioid analgesics in patients undergoing lymphadenectomy for cutaneous malignancy.

BACKGROUND AND OBJECTIVES: Opioids are commonly prescribed following surgery and can lead to persistent opioid use. We assessed changes in prescribing practices following an opioid education initiative for patients undergoing lymphadenectomy for cutaneous malignancy. METHODS: A single-institution retrospective study of all eligible patients (3/2016-3/2020) was performed. RESULTS: Indications for lymphadenectomy in 328 patients were metastatic melanoma (84%), squamous cell carcinoma (10%), and Merkel cell carcinoma (5%). At discharge, non-opioid analgesics were increasingly utilized over the 4-year study period, with dramatic increases after education initiatives (32%, 42%, 59%, and 79% of pts, respectively each year; p < 0.001). Median oral morphine equivalents (OMEs) prescribed also decreased dramatically starting in year 3 (250, 238, 150, and 100 mg, respectively; p < 0.001). Patients discharged with 200 mg OMEs were less likely to also be discharged with non-opioid analgesics (40% vs. 64%. respectively, p < 0.001). CONCLUSIONS: Analgesic prescribing practices following lymphadenectomy for cutaneous malignancy improved significantly over a 4-year period, with use of non-opioids more than doubling and a 60% reduction in median OME. Opportunities exist to further increase non-opioid use and decrease opioid dissemination after lymphadenectomy for cutaneous malignancy.

National Utilization of Imatinib in the Management of Resected Gastrointestinal Stromal Tumors.

BACKGROUND: Imatinib decreases recurrence risk and improves overall survival (OS) in localized gastrointestinal stromal tumors (GISTs); however, the extent to which patients receive appropriate treatment in the US has not been well characterized. METHODS: Patients with non-metastatic, resectable GIST were included in this study (National Cancer Database, 2010-2015). Those with a low-risk of recurrence were classified as receiving overtreatment or guideline-concordant treatment, while those with a high-risk of recurrence were classified as receiving undertreatment or guideline-concordant treatment. Multivariable logistic regression was used to determine factors associated with non-concordant treatment. The association between non-concordant treatment and OS was evaluated using multivariable Cox regression and propensity score matching. RESULTS: Among 3088 patients with high-risk GIST, 41% were undertreated, and among 3908 patients with low-risk GIST, 18.8% were overtreated. For patients with high-risk GIST, age > 60 years, African American race, and treatment at a community or comprehensive cancer program were associated with undertreatment. Among low-risk patients, small bowel primary, tumor size > 2 cm, and tumors with > 1 mitotic figure per 50 high-power fields were more likely to be overtreated. After propensity score matching, guideline-concordant therapy was associated with an 8.8% improvement in 5-year OS (81.9% vs. 73.1%, p = 0.002) for those with high-risk GIST and decreased risk of death (hazard ratio 0.63, 95% confidence interval 0.47-0.84). There was no statistically significant difference in survival for patients with low-risk GIST with the addition of imatinib overtreatment (overtreatment 93.9% vs. 89.6%, p = 0.053). CONCLUSIONS: Nearly 30% of GIST patients do not receive guideline-concordant treatment and future work is needed to understand the factors driving non-concordant treatment.

Time to Rethink Upfront Surgery for Resectable Intrahepatic Cholangiocarcinoma? Implications from the Neoadjuvant Experience.

BACKGROUND: While surgery is a mainstay of curative-intent treatment for patients with intrahepatic cholangiocarcinoma (IHC), the role of neoadjuvant therapy (NT) has not been well-established. We sought to describe trends in NT utilization, characterize associated factors, and evaluate association with overall survival (OS). METHODS: Retrospective cohort study of 4456 surgically resected IHC patients within National Cancer Data Base (2006-2016). NT included chemotherapy alone and/or (chemo)radiation. Descriptive statistics used to describe the cohort. Multivariable hierarchical logistic regression models were used to examine factors associated with NT administration. Analyses conducted comparing OS among upfront surgery patients and NT patients using propensity matching using nearest-neighbor methodology and adjustment using inverse probability of treatment weighting (IPTW). Association between NT and risk of death evaluated using multivariable Cox shared frailty modeling. RESULTS: Utilization of NT did not significantly increase over time (11%-2006 to 16%-2016, trend test p = 0.07) but did increase among patients with clinical nodal involvement (cN+, 13% to 36%, p = 0.002). Factors associated with NT use include cN+ disease (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.31-2.15) and advanced clinical T stage: T2 (OR 1.65, 95% CI 1.33-2.06); T3 (OR 1.51, 95% CI 1.13-2.02). After propensity matching, NT associated with a 23% decreased risk of death relative to upfront surgery (hazard ratio [HR] 0.77, 95% CI 0.61-0.97). Findings were similar after IPTW (HR 0.83, 95% CI 0.78-0.88). CONCLUSIONS: NT is increasingly used for the management of IHC patients with characteristics indicating aggressive tumor biology and is associated with decreased risk of death. These data suggest need for prospective studies of NT in management of patients with potentially resectable IHC.

Incidence of Lymph Node Metastases and Impact of Radical Surgery for Duodenal Neuroendocrine Tumors.

BACKGROUND: Despite the high frequency of regional lymph node (LN) metastases associated with duodenal neuroendocrine tumors (D-NETs), the impact of these metastases on survival and the ideal extent of LN dissection are unknown. We used the National Cancer Database (NCDB) to investigate factors associated with survival, including LN metastases and types of surgery, in patients with D-NETs. METHODS: All patients with D-NETs recorded in the NCDB between 2004 and 2016 were included in the study. We applied a multivariate Cox regression model to assess the relationship between the clinicopathological characteristics and overall survival (OS). RESULTS: We identified 7613 patients, among whom 4886 local excisions and 233 radical surgeries had been performed. Among patients with at least 1 LN pathologically examined, the overall incidence of LN metastasis was 41.2%. For all patients, the median OS was 10.6 years. Univariate analyses showed equivalent OS in N0 and N1 groups (HR,0.83; 95% CI,0.64-1.09) and diminished OS in those who had undergone radical surgery compared with those who had undergone local resection (HR,1.35; 95% CI,1.02-1.8). In multivariable analyses, tumor size >50 mm and having more than 9 positive LNs were associated with diminished OS (HR,1.64 and 5.2; 95% CI,1.25-2.16 and 1.91-14.18), whereas the type of surgery did not remain in the model. CONCLUSION: Our study revealed that the presence of regional LN metastases and extent of surgery did not affect OS among patients with D-NETs. Radical resection to clear occult LN metastases for nonfunctioning, sporadic D-NETs was not supported by the current study.

Sustained reduction in discharge opioid volumes through provider education: Results of 1168 cancer surgery patients over 2 years.

BACKGROUND: An opioid reduction education program to decrease discharge opioid prescriptions was initiated in our Department of Surgical Oncology. The study's aim was to measure the results and sustainability of these interventions 1 year later. METHODS: This prospective quality improvement project identified patients undergoing resection in five index tumor sites (peritoneal surface, sarcoma, stomach, pancreas, liver) at a high-volume cancer center. Patients were grouped into pre-education (PRE: July 2017-July 2018) and posteducation (POST: September 2018-July 2019) periods, before and after departmental education talks and videos in August 2018. Opioids were converted to oral morphine equivalents (OME) to compare the groups. RESULTS: Of 1168 evaluable patients (PRE 646, 55%; POST 522, 45%), the median last-24-h inpatient OME was 15 mg in PRE patients and 10 mg in POST patients (p < .001). Median discharge OME decreased from 200 mg in PRE to 100 mg in POST patients (p < .001). The frequency of patients with zero discharge opioids increased from 11% to 19% (p < .001). This discharge OME reduction amounted to 52,200 mg OME saved, or the equivalent of 6960 5-mg oxycodone pills not disseminated. CONCLUSIONS: A perioperative opioid reduction education program targeted to providers halved discharge OME, with sustained reductions 1 year later.

Cortisol, inflammatory biomarkers and neurotrophins in children and adolescents with attention deficit hyperactivity disorder (ADHD) in Taiwan.

BACKGROUND: Hypothalamus-Pituitary-Adrenal (HPA) axis dysregulation, inflammation and imbalance of neurotrophins have been suggested in attention deficit hyperactivity disorder (ADHD), but the results have not been conclusive. The aim of this study is to investigate the levels of salivary cortisol across 4-time points during the day, and of morning plasma inflammatory biomarkers and neurotrophins, in youth with ADHD and in typically developing youth (TD), with stratification by age, ADHD subtypes and oppositional defiant disorder (ODD) comorbidity in Taiwan. METHODS: We conducted a case-control study measuring saliva cortisol levels at 4 different time points during the day (at awakening, noon, 1800 h and bedtime) and morning plasma levels of inflammatory and neurotrophins biomarkers in youth with ADHD (n = 98, age 6-18 years old with mean age 9.32 ± 3.05 years) and TD (n = 21, age 6-18 years old with mean age 9.19 ± 2.96 years) in Taiwan. RESULTS: Our study showed that youth with ADHD had lower levels of bedtime salivary cortisol (effects size (ES) = -0.04, p = .023), with children with the combined form of the disorder (with inattention, hyperactivity and impulsivity all present) having the lowest awakening salivary cortisol levels. ADHD youth also had higher levels of plasma high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 (ES = 0.85-1.20, p < .0001), and lower plasma tumor necrosis factor-alpha (ES = -0.69, p = .009) and brain-derived neurotrophic factors (BDNF) (ES = -1.13, p < .0001). Both ADHD groups regardless of ODD comorbidity had higher levels of IL-6 (p < .0001) and lower levels BDNF (p < .0001). CONCLUSION: The lower bedtime salivary cortisol levels and higher levels of inflammatory biomarkers in youth with ADHD further support the role of abnormal HPA axis and inflammation in ADHD. Moreover, the lower levels of BDNF in ADHD also indicate that BDNF may be a potential biomarker in this disorder that is part of a broader biological dysfunction.

Management and outcomes of ruptured, perforated or fistulized tumors of mesenchymal origin.

BACKGROUND: Patients with ruptured, perforated or fistulized (RPF) sarcomas commonly have issues such as sepsis and malnutrition and are usually unsuitable for oncologic resection in the emergency setting. We present our approach for managing a series of patients and the outcomes which were achieved with multidisciplinary care. METHODS: We reviewed records of patients referred to the section of sarcoma surgical oncology. Clinicopathologic factors, preoperative and operative interventions as well as short-term oncologic outcomes were assessed. RESULTS: Sixteen patients were identified between 1 January 1998 to 31 December 2018. Median age was 42.8 years. Histologies were; Gastrointestinal stromal tumors (7), desmoid (4), spindle cell tumor (2), dedifferentiated liposarcoma (2), and nonseminomatous germ cell tumor (1). Five patients had preoperative sepsis, 8 received antimicrobials, and 50% required hospitalization with a median stay of 21 days. Total parenteral nutrition was administered to 5 (31.3%) patients. Median tumor size and estimated blood loss were 13.1 cm and 350 mL respectively. No perioperative mortality occurred. Two patients have expired at a median follow-up of 16.1 months. CONCLUSION: Preoperative optimization, including the use of percutaneous drains, and antibiotics to control sepsis, where necessary, can lead to eventual oncologic resection with acceptable morbidity and no short-term mortality for patients with RPF sarcomas.