The prognostic impact of tumor deposits in colorectal cancer: More than just N1c.

BACKGROUND: The identification of tumor deposits (TD) currently plays a limited role in staging for colorectal cancer (CRC) aside from N1c lymph node designation. The objective of this study was to determine the prognostic impact, beyond American Joint Committee on Cancer N1c designation, of TDs among patients with primary CRC. METHODS: Patients who had resected stage I-III primary CRC diagnosed between 2010 and 2019 were identified from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Cancer-specific survival (CSS) stratified by TD status and lymph node (N) status was calculated using the Kaplan-Meier method and multivariable Cox proportional hazards regression analyses. RESULTS: In total, 147,783 patients with primary CRC were identified. TDs were present in 15,444 patients (10.5%). The presence of TDs was significantly associated with adverse tumor characteristics, including advanced pathologic stage, nodal status, and metastasis status. The presence of TDs was associated with worse CSS (hazard ratio [HR], 3.12; 95% confidence interval [CI], 3.02-3.22), as it was for each given N category (e.g., N2a and TD-negative [HR, 2.50; 95% CI, 2.37-2.64] vs. N2a and TD-positive [HR, 3.75; 95% CI, 3.49-4.03]). The presence of multiple TDs was also associated with decreased CSS for each given N category compared with a single TD (e.g. N2a with one TD [HR, 3.09; 95% CI, 2.65-3.61] vs. N2a with two or more TDs [HR, 4.32; 95% CI, 3.87-4.82]). CONCLUSIONS: TDs were identified as an independent predictor of a worse outcome in patients with CRC. The presence of TDs confers distinctly different CSS and provides important prognostic information among patients with CRC and warrants further investigation as a unique variable in future iterations of CRC staging.

Para-aortic Lymph Node Dissection for Colorectal Cancer: Predicting Pathologic Lymph Node Positivity and Optimizing Outcomes.

INTRODUCTION: In colorectal cancer, the presence of para-aortic lymph nodes (PALN) indicates extraregional disease. Appropriately selecting patients for whom PALN dissection will provide oncologic benefit remains challenging. This study identified factors to predict survival among patients undergoing PALN dissection for colorectal cancer. METHODS: An institutional database was queried for patients who underwent curative-intent resection of clinically positive PALN for colorectal cancer between 2007 and 2020. Preoperative radiologic images were reviewed, and patients who did and did not have positive PALN on final pathology were compared. Survival analysis was performed to evaluate the impact of pathologically positive PALN on recurrence-free (RFS) and overall survival (OS). RESULTS: Of 74 patients who underwent PALN dissection, 51 had PALN metastasis at the time of primary tumor diagnosis, whereas 23 had metachronous PALN disease. Preoperative chemotherapy ± radiotherapy was given in 60 cases (81.1%), and 28 (37.8%) had pathologically positive PALN. Independent factors associated with positive PALN pathology included metachronous PALN disease and pretreatment and posttreatment radiographically abnormal PALN. On multivariable analysis, pathologically positive PALN was significantly associated with decreased RFS (hazard ratio 3.90) and OS (HR 4.49). Among patients with pathologically positive PALN, well/moderately differentiated histology was associated with better OS, and metachronous disease trended toward an association with better OS. CONCLUSIONS: Pathologically positive PALN are associated with poorer RFS and OS after PALN dissection for colorectal cancer. Clinicopathologic factors may predict pathologic PALN positivity. Curative-intent surgery may provide benefit, especially in patients with well-to-moderately differentiated primary tumors and possibly metachronous PALN disease.

Repeat Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Recurrent Mucinous Appendiceal Adenocarcinoma: A Viable Treatment Strategy with Demonstrable Benefit.

INTRODUCTION: Many patients with mucinous appendiceal adenocarcinoma experience peritoneal recurrence despite complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prior work has demonstrated that repeat CRS/HIPEC can prolong survival in select patients. We sought to validate these findings using outcomes from a high-volume center. PATIENTS AND METHODS: Patients with mucinous appendiceal adenocarcinoma who underwent CRS/HIPEC at MD Anderson Cancer Center between 2004 and 2021 were stratified by whether they underwent CRS/HIPEC for recurrent disease or as part of initial treatment. Only patients who underwent complete CRS/HIPEC were included. Initial and recurrent groups were compared. RESULTS: Of 437 CRS/HIPECs performed for mucinous appendiceal adenocarcinoma, 50 (11.4%) were for recurrent disease. Patients who underwent CRS/HIPEC for recurrent disease were more often treated with an oxaliplatin or cisplatin perfusion (35%/44% recurrent vs. 4%/1% initial, p < 0.001), had a longer operative time (median 629 min recurrent vs. 511 min initial, p = 0.002), and had a lower median length of stay (10 days repeat vs. 13 days initial, p < 0.001). Thirty-day complication and 90-day mortality rates did not differ between groups. Both cohorts enjoyed comparable recurrence free survival (p = 0.82). Compared with patients with recurrence treated with systemic chemotherapy alone, this select cohort of patients undergoing repeat CRS/HIPEC enjoyed better overall survival (p < 0.001). CONCLUSIONS: In appropriately selected patients with recurrent appendiceal mucinous adenocarcinoma, CRS/HIPEC can provide survival benefit equivalent to primary CRS/HIPEC and that may be superior to that conferred by systemic therapy alone in select patients. These patients should receive care at a high-volume center in the context of a multidisciplinary team.

The Impact of Intraoperative Anesthesiology Provider Handovers on Postoperative Complications After Hepatopancreatobiliary (HPB) Surgery.

BACKGROUND: The objective of this study is to assess the possible association between intraoperative anesthesia team handovers and increased 90-day major complications following HPB surgery. METHODS: This is a single-center retrospective cohort study of patients who underwent HPB surgery. Anesthesiologist handover (AH) occurred when a complete transfer of care to a receiving anesthesiologist. total anesthesia team handovers (TH) occurred when both anesthesiologist and supervised provider transferred care. The primary outcome was 90-day major complications, defined as an ACCORDION score of ≥ 3. RESULTS: Ninety-day major complications occurred in 35 (21.6%) of TH and 96 (21.9%) of AH patients. With adjustment of other covariates, no significant association was found between AH (OR, 1.358, 95% CI, 0.935-1.973, p = 0.1079) or TH (OR, 1.157, 95% CI, 0.706-1.894, p = 0.5633) and 90-day major complications. CONCLUSIONS: In a high-volume HPB center, anesthesia team handovers were not associated with an increased risk of patients having a major complication within 90 days after HPB surgery.

Treatment Variation and Long-Term Outcomes of Low-Grade Appendiceal Neoplasms.

BACKGROUND: Heterogenous nomenclature describing appendiceal neoplasms has added to uncertainty around their appropriate treatment. Although a recent consensus has established the term low-grade appendiceal neoplasm (LAMN), we hypothesize that significant variation remains in the treatment of LAMNs. METHODS: We retrospectively reviewed our prospectively maintained appendiceal registry, identifying patients with LAMNs from 2009 to 2019. We assessed variability in treatment, including whether patients underwent colectomy, spread of disease at presentation, and long-term outcomes. RESULTS: Of 136 patients with LAMNs, 88 (35%) presented with localized disease and 48 (35%) with disseminated peritoneal disease. Median follow-up was 2.9 years (IQR 1.9-4.4), and 120 (88%) patients underwent pre-referral surgery. Among 26 pre-referral colectomy patients, 23 (88%) were performed for perceived oncologic need/nodal evaluation; no nodal metastases were identified. In patients with resected LAMNs without radiographic evidence of disseminated disease, 41 (47%) underwent second look diagnostic laparoscopy (DL) to evaluate for occult metastases. No peritoneal metastases were identified. Patients with disseminated disease were treated with cytoreductive surgery/heated intraperitoneal chemotherapy (CRS/HIPEC). For patients undergoing CRS/HIPEC, 5-year recurrence-free survival was 94% (95% CI 81-98%). For patients with localized disease, 5-year RFS was 98% (95% CI 85-99%). CONCLUSIONS: Significant variation exists in treatment patterns for LAMNs, particularly prior to referral to a high-volume center. Patients frequently underwent colectomy without apparent oncologic benefit. In the current era of high-quality cross sectional imaging, routine use of DL has low yield and is not recommended. Recurrence in this population is rare, and low-intensity surveillance can be offered. Overall prognosis is excellent, even with peritoneal disease.

A practical framework for the targeted use of total neoadjuvant therapy for rectal cancer.

Total neoadjuvant therapy (TNT) for rectal cancer is the preoperative delivery of radiation or chemoradiotherapy as well as systemic chemotherapy for the purpose of improving treatment completion rates and decreasing toxicity, maximizing the primary tumor response, and improving survival for patients with rectal cancer. This review summarizes the data surrounding TNT, including several recent randomized controlled trials. Moreover, it reviews the literature regarding high-quality surgery and the role of radiation and chemotherapy in the treatment of rectal cancer in the modern era. Finally, it presents an evidence-based protocol for the selective use of TNT in the treatment of patients with rectal cancer.

Effect of the Ductal Carcinoma In Situ Margin Consensus Guideline Implementation on Re-Excision Rates, Satisfaction, and Cost.

INTRODUCTION: The 2016 consensus guideline on margins for breast-conserving surgery (BCS) with whole-breast irradiation (WBI) for ductal carcinoma in situ (DCIS) recommended 2 mm margins to decrease local recurrence rates. We examined re-excision rates, cost, and patient satisfaction before and after guideline implementation. METHODS: From an Institutional Review Board-approved database, patients with DCIS who underwent BCS with over 1 year of follow-up at one academic institution and one community cancer center were evaluated. Two groups were compared based on when they received treatment, i.e. before (pre-consensus [PRE]) and after November 2016 (post consensus [POST]), with respect to outcome and cost parameters. RESULTS: After consensus guideline implementation, re-excision rate (32.1% vs. 20.0%) and mastectomy conversion (8.3% vs. 2.3%) significantly increased, although total resection volume, operative cost per patient, and satisfaction with breast scores did not differ. Not all patients with <2 mm margins were re-excised, although the re-excision rate among this subset significantly increased (62.4% vs. 31.3%). On multivariable analysis controlling for age, estrogen receptor status, WBI use, and margin status, surgery after consensus guideline publication was independently associated with a higher re-excision rate (odds ratio [OR] 1.97, 95% confidence interval [CI] 1.08-3.59, p = 0.03) and a higher rate of conversion to mastectomy (OR 6.84, 95% CI 1.67-28.00, p = 0.007). CONCLUSIONS: Implementation of the 2016 margin consensus guideline for DCIS resulted in an increase in re-excisions and mastectomy conversions at two institutions. Research is needed for operative tools and strategies to decrease DCIS re-excision rates.

Evaluating the effect of neoadjuvant chemotherapy on surgical outcomes after breast conserving surgery.

BACKGROUND: Neoadjuvant chemotherapy (NAC) increases breast-conserving surgery (BCS) rates with comparable locoregional control and survival outcomes to adjuvant therapy. More women are receiving NAC and achieving pathologic complete responses (pCR). This study sought to evaluate the effect of NAC on surgical outcomes after the adoption of a "no-ink-on-tumor" margin policy in patients undergoing primary BCS (PBSC). METHODS: An IRB approved database was queried for women undergoing BCS for invasive breast cancer after March 2014. We compared patients who underwent NAC followed by BCS versus PBCS. Demographic, tumor, treatment, and outcome variables were compared using both univariate and multivariable analysis. RESULTS: A total of 162 patients were evaluated. NAC patients had significantly lower re-excision rates (0% NAC vs. 9% PBCS, p = .03), margin positivity (0% NAC vs. 5% PBCS, p = .01), and greater patient satisfaction with breast cosmesis (97 NAC vs. 77 PBCS, p = .01). On multivariable analysis, NAC was not an independent predictor of lower final resection volume, total complications, or greater satisfaction with breasts when controlling for age and T category at diagnosis. CONCLUSION: NAC followed by BCS may offer less margin positivity, lower re-excision rates, and greater patient satisfaction when compared to a contemporary PBCS cohort in the "no-ink-on-tumor" era.

Comparing patterns of care and outcomes after operative management of complications after bariatric surgery at MBSAQIP accredited bariatric centers and non-bariatric facilities.

BACKGROUND: Many operations for complications after bariatric surgery are performed by surgeons without bariatric expertise at centers without teams who routinely care for bariatric patients. This study sought to evaluate whether bariatric expertise affects patterns of care and perioperative outcomes among patients undergoing operative intervention for complications after bariatric surgery. METHODS: Administrative claims data from the Kentucky Office of Health Policy were queried for inpatients undergoing operative intervention for complications related to bariatric surgery between 2015 and 2018. Patients were stratified with respect to whether or not they underwent surgery at a Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) accredited bariatric surgery center (BCE) or not (non-BCE). Groups were compared with respect to demographic, procedural, and outcome variables. RESULTS: BCE patients were more often Caucasian than non-BCE patients (p < 0.001) and have either private insurance or Medicare coverage (p = 0.02). Regarding operative approach, operations were more likely to be performed laparoscopically in BCE (88.5% BCE vs. 80.9% non-BCE, p = 0.007). Length of stay was significantly shorter for BCE patients (median 2 days BCE vs. 3 days non-BCE, p < 0.001), and BCE patients were more likely to be discharged home (85.4% BCE vs. 78.5% non-BCE, p = 0.02). Inpatient mortality and average total charges per patient did not differ significantly between the two groups CONCLUSIONS: Surgical management of complications after bariatric surgery at BCE is associated with greater utilization of minimally invasive techniques, shorter hospital stay, and increased likelihood of routine home discharge. These findings should prompt a review and standardization of care patterns for patients with complications after bariatric surgery aimed at optimizing outcomes and improving value.

Intraoperative Esophagogastroduodenoscopy During Heller Myotomy: Evaluating Guidelines.

BACKGROUND: National guidelines suggest routine intraoperative esophagogastroduodenoscopy (EGD) during laparoscopic Heller myotomy (LHM) to assess for mucosal perforation and myotomy adequacy, but the utility of this is unknown. This study aimed to evaluate the effect of intraoperative EGD on outcomes after LHM. METHODS: Patients who underwent LHM in a single center were retrospectively identified. Outcomes were compared between patients who did and did not undergo intraoperative EGD. RESULTS: Sixty-one patients were reviewed: 46 (75%) underwent intraoperative EGD and 15 (25%) did not. Mucosal perforations occurred in 2 (4%) of the EGD group and 3 (20%) of the non-EGD group (p = 0.06). All perforations, regardless of EGD use, were recognized laparoscopically. There were no postoperative leaks. Failed myotomy occurred in 5 (11%) who underwent EGD and 1 (7%) who did not (p = 0.64). CONCLUSIONS: Because EGD does not appear to improve outcomes after LHM, we emphasize its selective, rather than routine, use.

Temporospatial shifts within commercial laboratory mouse gut microbiota impact experimental reproducibility.

BACKGROUND: Experimental reproducibility in mouse models is impacted by both genetics and environment. The generation of reproducible data is critical for the biomedical enterprise and has become a major concern for the scientific community and funding agencies alike. Among the factors that impact reproducibility in experimental mouse models is the variable composition of the microbiota in mice supplied by different commercial vendors. Less attention has been paid to how the microbiota of mice supplied by a particular vendor might change over time. RESULTS: In the course of conducting a series of experiments in a mouse model of malaria, we observed a profound and lasting change in the severity of malaria in mice infected with Plasmodium yoelii; while for several years mice obtained from a specific production suite of a specific commercial vendor were able to clear the parasites effectively in a relatively short time, mice subsequently shipped from the same unit suffered much more severe disease. Gut microbiota analysis of frozen cecal samples identified a distinct and lasting shift in bacteria populations that coincided with the altered response of the later shipments of mice to infection with malaria parasites. Germ-free mice colonized with cecal microbiota from mice within the same production suite before and after this change followed by Plasmodium infection provided a direct demonstration that the change in gut microbiota profoundly impacted the severity of malaria. Moreover, spatial changes in gut microbiota composition were also shown to alter the acute bacterial burden following Salmonella infection, and tumor burden in a lung tumorigenesis model. CONCLUSION: These changes in gut bacteria may have impacted the experimental reproducibility of diverse research groups and highlight the need for both laboratory animal providers and researchers to collaborate in determining the methods and criteria needed to stabilize the gut microbiota of animal breeding colonies and research cohorts, and to develop a microbiota solution to increase experimental rigor and reproducibility.

A literature-based treatment algorithm for low-grade neuroendocrine liver metastases.

BACKGROUND: The optimal timing of treatment of liver metastases from low-grade neuroendocrine tumors (LG-NELM) varies significantly due to numerous treatment modalities and the literature supporting various treatment(s). This study sought to create and validate a literature-based treatment algorithm for LG-NELM. METHODS: A treatment algorithm to maximize overall survival (OS) was designed using peer-reviewed articles evaluating treatment of LG-NELM. This algorithm was retrospectively applied to patients treated for LG-NELM at our institution. Deviation was determined based on whether or not a patient received treatment consistent with that recommended by the algorithm. Patients who did and did not deviate from the algorithm were compared with respect to OS and number of treatments. RESULTS: Applying our algorithm to a 149-patient cohort, 57 (38%) deviated from recommended treatment. Deviation occurred in the form of alternative (28, 49%) versus additional procedures (29, 51%). Algorithm deviators underwent significantly more procedures than non-deviators (median 1 vs. 2, p < 0.001). Cox model indicated no difference in OS associated with algorithm deviation (HR 1.19, p = 0.58) when controlling for age and tumor characteristics. CONCLUSION: This literature-based algorithm helps standardize treatment protocols in patients with LG-NELM and can reduce cost and risk by minimizing unnecessary procedures. Prospective implementation and validation is required.

Identifying Factors Predicting Prolonged Opioid Use After Mastectomy.

BACKGROUND: Women who undergo mastectomy for breast cancer may be prone to prolonged opioid use (POU). However, risk factors for long-term opioid use after mastectomy remain unclear. This study seeks to identify risk factors for POU after mastectomy. PATIENTS AND METHODS: A single-institution database was queried for women who underwent mastectomy for breast cancer between January 2016 and December 2017. Patients were stratified based on opioid use < 90 or ≥ 90 days after mastectomy or completion of their reconstruction. Clinicopathologic and operative parameters as well as preoperative and postoperative opioid usage were compared. RESULTS: Patients with opioid use ≥ 90 days after last procedure (POU) had a history of preoperative opioid use (29.3% vs 8.2%, p = 0.002), were more likely to have concomitant psychiatric illness (70% vs 35.6%, p < 0.001), and had received adjuvant chemotherapy (43.1% vs 24.7%, p = 0.03). Patients with POU also had greater daily opioid doses prescribed upon discharge (59.6 mg vs 44.6 mg, p < 0.001). On multivariable analysis, preoperative opioid use (OR 3.61, 95% CI 1.16-11.22, p = 0.03), daily oral morphine equivalents prescribed at discharge (OME-D) (OR 1.02, 95% CI 1.01-1.05, p = 0.003), and psychiatric illness (OR 4.48, 95% CI 1.85-10.89, p < 0.001) were independently associated with POU. Among opioid-naïve patients, 37% were found to have POU. Among these patients, OME at discharge (OR 1.02, 95% CI 1.003-1.04, p = 0.02) and psychiatric illness (OR 3.23, 95% CI 1.25-8.31, p = 0.02) independently predicted POU. CONCLUSIONS: Preoperative opioid use, psychiatric illness, and daily OME at discharge independently predict POU after mastectomy.

Electrochemotherapy with Irreversible Electroporation and FOLFIRINOX Improves Survival in Murine Models of Pancreatic Adenocarcinoma.

BACKGROUND: Previously published work has demonstrated that combining gemcitabine with irreversible electroporation (IRE) results in increased drug delivery to pancreatic adenocarcinoma cells in vivo. This study assessed the efficacy of IRE + gemcitabine and IRE + FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin), the impact of the superior regimen on survival, and the safety of electrochemotherapy in human subjects. METHODS: Histologic analysis was performed after in vitro and in vivo treatment of S2013 and Panc-1 pancreatic cancer cells and S2013 orthotopic tumors, respectively, and levels of apoptotic machinery and cell cycle proteins were evaluated using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot. RESULTS: Electrochemotherapy (ECT) with IRE and FOLFIRINOX resulted in increased tumor cells apoptosis compared with gemcitabine, gemcitabine + IRE, and FOLFIRINOX alone, and significantly improved overall survival when compared with mice treated with IRE or FOLFIRINOX. Increased tumor cell apoptosis, caspase-3 mRNA, active caspase-3 protein, and decreased cell proliferation were noted at the time of death or euthanasia in the ECT group compared with folinic acid alone. In five patients, ECT with either FOLFIRINOX or gemcitabine was well-tolerated and resulted in no dose-limiting toxicities. CONCLUSIONS: ECT thus results in synergistic antitumor activity compared with either treatment modality used alone, resulting in increased tumor cell apoptosis as well as decreased tumor cell proliferation and improved overall survival. Pilot data suggest that ECT represents a promising modality for the treatment of patients with locally advanced pancreatic cancer. TRIAL REGISTRATION: The human subject portion of this work was conducted as part of an investigator-initiated clinical trial at the University of Louisville (NCT03484299).

Identifying factors impacting the efficacy of postmastectomy radiotherapy in patients with early-stage breast cancer and one to two positive lymph nodes.

INTRODUCTION: In women with T1-2 breast cancer and one to two positive axillary lymph nodes (LN) at low risk for recurrence, postmastectomy radiation therapy (PMRT) may provide insufficient benefit to justify its toxicity. This study evaluated the interaction of factors associated with overall survival (OS) after PMRT in these patients. METHODS: The National Cancer Database was queried for women with T1-2 breast cancer undergoing mastectomy with one to two positive LN identified on lymphadenectomy. Patients were grouped according to number of positive LN and then stratified by PMRT use. Differences in OS were evaluated. RESULTS: Multivariable modeling demonstrated an interaction effect of age on the efficacy of PMRT. In patients more than or equal to 60 years old, PMRT was associated with improved survival when adjusting for age and tumor grade in patients with 1 to 2 positive LN (risk ratio = 0.62, 95% confidence interval = 0.40-0.93, P = .018). In patients less than 60 years old, tumor size and grade, but not PMRT, were associated with improved OS. CONCLUSION: For women with T1-2 breast cancer and one to two positive LN, PMRT's association with OS is influenced by age, tumor grade, and number of positive LN. PMRT appears to be associated with improvements in OS in older patients, but not younger patients, regardless of tumor size or nodal status.

Identifying factors influencing delays in breast cancer treatment in Kentucky following the 2014 Medicaid expansion.

BACKGROUND AND OBJECTIVES: A previous analysis of breast cancer care after the 2014 Medicaid expansion in Kentucky demonstrated delays in treatment despite a 12% increase in insurance coverage. This study sought to identify factors associated with treatment delays to better focus efforts for improved breast cancer care. METHODS: The Kentucky Cancer Registry was queried for adult women diagnosed with invasive breast cancer between 2010 and 2016 who underwent up-front surgery. Demographic, tumor, and treatment characteristics were assessed to identify factors independently associated with treatment delays. RESULTS: Among 6225 patients, treatment after Medicaid expansion (odds ratio [OR] = 2.18, 95% confidence interval [CI] = 1.874-2.535, P < .001), urban residence (OR = 1.362, 95% CI = 1.163-1.594, P < .001), treatment at an academic center (OR = 1.988, 95% CI = 1.610-2.455, P < .001), and breast reconstruction (OR = 3.748, 95% CI = 2.780-5.053, P < .001) were associated with delay from diagnosis to surgery. Delay in postoperative chemotherapy was associated with older age (OR = 1.155,95% CI = 1.002-1.332, P = .0469), low education level (OR = 1.324, 95% CI = 1.164-1.506, P < .001), hormone receptor positivity (OR = 1.375, 95% CI = 1.187-1.593, P < .001), and mastectomy (OR = 1.312, 95% CI = 1.138-1.513, P < .001). Delay in postoperative radiation was associated with younger age (OR = 1.376, 95% CI = 1.370-1.382, P < .001), urban residence (OR = 1.741, 95% CI = 1.732-1.751, P < .001), treatment after Medicaid expansion (OR = 2.007, 95% CI = 1.994-2.021, P < .001), early stage disease (OR = 5.661, 95% CI = 5.640-5.682, P < .001), and mastectomy (OR = 1.884, 95% CI = 1.870-1.898, P < .001). CONCLUSIONS: Patient, tumor, and socioeconomic factors influence the timing of breast cancer treatment. Improving timeliness of treatment will likely require improvements in outreach, education, and healthcare infrastructure.

Primitive neuroectodermal tumor incidence, treatment patterns, and outcome: An analysis of the National Cancer Database.

BACKGROUND: Primitive neuroectodermal tumors (PNETs) comprise less than 1% of all sarcomas. The rarity of this disease has resulted in a paucity of information about disease process and management. This study sought to evaluate the incidence, treatment patterns, and outcomes among patients with PNET. METHODS: The National Cancer Database was queried for diagnoses of PNET between 2004 and 2014. Patients were dichotomized based on tumor type (central [cPNET] vs peripheral [pPNET]). Demographic, tumor, treatment, and outcome variables were analyzed for the entire patient cohort and by type of PNET. RESULTS: White (86.4%) males (56.6%) represented the majority of patients. The incidence of PNET remained stable over the study period (r2 = 0.0821). A total of 70.7% underwent surgical resection of the primary site, 50.3% received radiation, and 74.7% received systemic chemotherapy. Compared to those with pPNET, patients with cPNET more often received radiation treatment (P < .001), primary tumor resection (P < .001), and experienced increased 90-day mortality (P < .014). CONCLUSION: cPNET and pPNET are rare and aggressive malignancies that tend to arise in White males. Multimodal treatment including surgery, chemotherapy, and radiation is conventional. Patients with cPNET more often receive radiation and primary tumor resection with increased 90-day mortality.

Adverse outcomes and short-term cost implications of bile duct injury during cholecystectomy.

BACKGROUND: Bile duct injury (BDI) is an uncommon but major complication of cholecystectomy that has a poorly defined magnitude of effect on hospital costs. This study sought to calculate the healthcare costs, length of stay, and discharge status associated with bile duct injury in patients undergoing cholecystectomy in the United States. METHODS: The Premier Healthcare Database, which comprises hospital-billing records from over 700 hospitals in the United States, was queried for all patients undergoing cholecystectomy between January 2010 and March 2018. BDI was defined by ICD-9-CM and ICD-10-CM codes. Patient demographics, clinical characteristics, and operative information were extracted. Hospital costs, length of stay, and discharge status were compared between BDI and non-BDI patients. Propensity score matching was used to minimize confounding factors. Multivariable regression models were used to estimate the association between BDI and the outcomes variables. RESULTS: A total of 1,168,288 cholecystectomies were identified. BDI occurred in 878 patients (0.08%). Laparoscopy was the most common approach (> 95%). The majority of BDI occurred during inpatient admissions (71.0%). BDI patients had higher index admission hospital costs ($18,771 vs. $12,345, p < 0.0001), increased rate of discharge to an institutional post-acute care facility (odds ratio 3.89, 95% CI 2.92-5.19, p < 0.0001), and increased risk of readmission within 30 days after discharge (odds ratio 1.86, 95% CI 1.52-2.28, p < 0.0001), compared to patients without BDI. Among inpatient cholecystectomies, BDI was associated with increased length of stay (8.6 days vs. 4.8 days, p < 0.0001). CONCLUSION: BDI is associated with significantly increased hospital costs, length of stay, 30-day readmission, and discharge to an institutional post-acute care facility.

Correlating serum alpha-fetoprotein in hepatocellular carcinoma with response to Yttrium-90 transarterial radioembolization with glass microspheres (TheraSphere™).

BACKGROUND: Few studies have assessed the relationship between serum alpha-fetoprotein (AFP) and yttrium-90 (Y-90) radioembolization response in hepatocellular carcinoma (HCC). The objective of the study was to evaluate whether peri-procedural serum AFP was correlated with Y-90 therapy response in HCC. METHODS: Patients undergoing Y-90 radioembolization with glass microspheres (TheraSphere™) for HCC between 2006 and 2013 at a single center were evaluated. The relationship between AFP and 6-month radiographic improvement (complete or partial response by modified RECIST criteria), overall (OS), and disease-specific survival (DSS) were analyzed. RESULTS: Seventy-four patients underwent a total of 124 Y-90 infusions. Median age was 65 years, median AFP was 37 ng/mL (range: 2-112,593 ng/mL) and median model for end-stage liver disease score was 6.2 (range:1.8-11.2). Increased AFP was not associated with radiographic improvement (odds ratio (OR) = 0.99, 95% confidence interval (CI) = 0.75-1.30, p = 0.92). Median OS was 15.2 months and was increased in patients with low AFP compared to high AFP (30.8 months vs. 7.8 months, p < 0.001). On multivariable regression analysis, increased AFP was associated with worse OS (OR = 1.11, 95%CI = 1.01-1.22, p = 0.034) and DSS (OR = 1.13, 95%CI = 1.03-1.25, p = 0.018). CONCLUSION: Pre-infusion AFP independently predicted survival after Y-90 treatment for HCC, but not radiographic response, and can help guide treatment decisions.

Age and Lymphovascular Invasion Accurately Predict Sentinel Lymph Node Metastasis in T2 Melanoma Patients.

BACKGROUND: The risk of sentinel lymph node (SLN) metastasis in melanoma is related directly to tumor thickness and inversely to age. The authors hypothesized that for T2 (thickness 1.1-2.0 mm) melanoma, age, and other factors may be able to identify a cohort of patients with a low risk of SLN metastases. METHODS: The authors developed logistic regression models to predict positive SLNs in patients undergoing SLN biopsy for T2 melanoma using the National Cancer Database. Classification and regression-tree analysis were used to identify groups of patients with high and low risk for SLN metastases. The prediction model then was applied to a separate data set from a multicenter randomized clinical trial. RESULTS: The study identified 12,918 patients with T2 melanoma undergoing SLN biopsy with clinically node-negative melanoma. In the multivariable analysis, increasing thickness, younger age, lymphovascular invasion (LVI), mitotic rate of 1/mm2 or more, axial location, and Clark level of 4 or 5 were independent risk factors for SLN metastases. A cohort based on age (> 56 years) and no LVI was identified with a relatively low risk (7.8%; 95% confidence interval 7.2-8.4%) of SLN metastases. The independent data set of 1531 patients with T2 melanoma confirmed these findings. Among elderly patients (age > 75 years) with melanoma 1.2 mm or smaller and no LVI, the risk of a positive SLN was 4.9% (95% confidence interval 3.3-7.1%). CONCLUSIONS: Younger age and LVI are powerful predictors of SLN metastases for patients with T2 melanoma. This prediction model can inform shared decision-making regarding whether to perform SLN biopsy for older patients with otherwise low-risk T2 melanoma.