Evaluation of a Combinatorial Immunotherapy Regimen That Can Cure Mice Bearing MYCN-Driven High-Risk Neuroblastoma That Resists Current Clinical Therapy.

Background: Incorporating GD2-targeting monoclonal antibody into post-consolidation maintenance therapy has improved survival for children with high-risk neuroblastoma. However, ~50% of patients do not respond to, or relapse following, initial treatment. Here, we evaluated additional anti-GD2-based immunotherapy to better treat high-risk neuroblastoma in mice to develop a regimen for patients with therapy-resistant neuroblastoma. Methods: We determined the components of a combined regimen needed to cure mice of established MYCN-amplified, GD2-expressing, murine 9464D-GD2 neuroblastomas. Results: First, we demonstrate that 9464D-GD2 is nonresponsive to a preferred salvage regimen: anti-GD2 with temozolomide and irinotecan. Second, we have previously shown that adding agonist anti-CD40 mAb and CpG to a regimen of radiotherapy, anti-GD2/IL2 immunocytokine and anti-CTLA-4, cured a substantial fraction of mice bearing small 9464D-GD2 tumors; here, we further characterize this regimen by showing that radiotherapy and hu14.18-IL2 are necessary components, while anti-CTLA-4, anti-CD40, or CpG can individually be removed, and CpG and anti-CTLA-4 can be removed together, while maintaining efficacy. Conclusions: We have developed and characterized a regimen that can cure mice of a high-risk neuroblastoma that is refractory to the current clinical regimen for relapsed/refractory disease. Ongoing preclinical work is directed towards ways to potentially translate these findings to a regimen appropriate for clinical testing.

Venous thromboembolism prophylaxis following colorectal surgery: a survey of American Society of Colon and Rectal Surgery (ASCRS) member surgeons.

BACKGROUND: Postoperative venous thromboembolism (VTE) is associated with significant morbidity. Evidence from other surgical specialties demonstrate inadequate use of extended VTE prophylaxis following cancer surgery. While guidelines recommend extended VTE prophylaxis for patients undergoing surgery for colorectal cancer (CRC), it is unknown to what extent colon and rectal surgeons adhere to these recommendations. METHODS: An 18-question online survey was distributed to all surgeon members of the American Society of Colon and Rectal Surgeons (ASCRS). The survey was designed to capture knowledge, attitudes, and practices regarding ASCRS VTE prevention guidelines. Questions were also designed to elucidate barriers to adopting these guidelines. RESULTS: The survey was distributed to 2,316 ASCRS-member surgeons and there were 201 complete responses (8.7% response rate). Most respondents (136/201, 68%) reported that they were familiar with ASCRS VTE prevention guidelines and used them to guide their practice. Extended VTE prophylaxis was reported to be routinely prescribed by the majority of surgeons following CRC resection (109/201, 54%), with an additional 27% reporting selective prescribing (55/201). The most frequently reported reasons for not prescribing extended VTE chemoprophylaxis following CRC resection included patient compliance and insurance/copay issues. CONCLUSION: Most ASCRS-member surgeon respondents reported that they are familiar with ASCRS VTE prevention guidelines, though only 54% surgeons reported routinely prescribing extended VTE prophylaxis following CRC surgery. Patient compliance and insurance issues were identified as the most common barriers. Targeted interventions at the surgeon, patient, and payer level are required to increase the use of extended VTE prophylaxis following CRC resection.

Peritoneal recurrence after resection for Stage I-III colorectal cancer: A population analysis.

BACKGROUND: Colorectal cancer (CRC) often recurs in the peritoneum, although the pattern of peritoneal recurrence (PR) has received less attention. We sought to describe the presentation and risk factors for PR following CRC resection. METHODS: We performed a cohort study of patients undergoing resection of Stage I-III CRC from 2006 to 2007 using merged data from a Commission on Cancer Special Study and the National Cancer Database. We estimated the timing, method of detection, and risk factors for isolated PR. RESULTS: Here, 8991 patients were included and isolate PR occurred in 77 (0.9%) patients. The median time to PR was 16.2 months (intrquartile range = 9.3-28.0 months) and most patients were identified via new symptoms (36.4%). Pathologic factors associated with increased odds of PR included higher T stage (T3 vs. T2, odds ratio [OR] = 4.8, 95% confidence interval [CI] = 1.5-15.7), N stage (N1 vs. N0, OR = 2.00, CI = 1.1-3.7), and signet ring (OR = 8.2, CI = 3.0-22.3) or mucinous histology (OR = 2.6, CI = 1.5-4.7). CONCLUSIONS: The majority of PR was detected within 18 months and few were identified by surveillance. Advanced T/N stage and signet ring/mucinous histology were associated with increased odds of PR.

Mechanism of effective combination radio-immunotherapy against 9464D-GD2, an immunologically cold murine neuroblastoma.

BACKGROUND: Most pediatric cancers are considered immunologically cold with relatively few responding to immune checkpoint inhibition. We recently described an effective combination radio-immunotherapy treatment regimen ( c ombination a daptive- i nnate immunotherapy r egimen (CAIR)) targeting adaptive and innate immunity in 9464D-GD2, an immunologically cold model of neuroblastoma. Here, we characterize the mechanism of CAIR and the role of major histocompatibility complex class I (MHC-I) in the treatment response. METHODS: Mice bearing GD2-expressing 9464D-GD2 tumors were treated with CAIR (external beam radiotherapy, hu14.18-IL2 immunocytokine, CpG, anti-CD40, and anti-CTLA4) and tumor growth and survival were tracked. Depletion of specific immune cell lineages, as well as testing in immunodeficient R2G2 mice, were used to determine the populations necessary for treatment efficacy. Induction of MHC-I expression in 9464D-GD2 cells in response to interferon-γ (IFN-γ) and CAIR was measured in vitro and in vivo, respectively, by flow cytometry and quantitative real-time PCR. A cell line with IFN-γ-inducible MHC-I expression (9464D-GD2-I) was generated by transfecting a subclone of the parental cell line capable of expressing MHC-I with GD2 synthase and was used in vivo to assess the impact of MHC-I expression on responsiveness to CAIR. RESULTS: CAIR cures some mice bearing small (50 mm3) but not larger (100 mm3) 9464D-GD2 tumors and these cured mice develop weak memory responses against tumor rechallenge. Early suppression of 9464D-GD2 tumors by CAIR does not require T or natural killer (NK) cells, but eventual tumor cures are NK cell dependent. Unlike the parental 9464D cell line, 9464D-GD2 cells have uniformly very low MHC-I expression at baseline and fail to upregulate expression in response to IFN-γ. In contrast, 9464D-GD2-I upregulates MHC-I in response to IFN-γ and is less responsive to CAIR. CONCLUSION: Treatment with CAIR cures 9464D-GD2 tumors in a NK cell dependent manner and induction of MHC-I by tumors cells was associated with decreased efficacy. These results demonstrate that the early tumor response to this regimen is T and NK cell independent, but that NK cells have a role in generating lasting cures in the absence of MHC-I expression by tumor cells. Further strategies to better inhibit tumor outgrowth in this setting may require further NK activation or the ability to engage alternative immune effector cells.

Short-course neoadjuvant in situ vaccination for murine melanoma.

BACKGROUND: Surgical resection remains an important component of multimodality treatment for most solid tumors. Neoadjuvant immunotherapy has several potential advantages, including in-situ tumor vaccination and pathologic assessment of response in the surgical specimen. We previously described an in-situ tumor vaccination strategy in melanoma using local radiation (RT) and an intratumoral injection of tumor-specific anti-GD2 immunocytokine (IT-IC). Here we tested whether neoadjuvant in-situ tumor vaccination using anti-GD2 immunocytokine and surgical resection, without RT, could generate immunologic memory capable of preventing recurrence or distant metastasis. METHODS: Mice bearing GD2 expressing B78 melanoma tumors were treated with neoadjuvant radiation, IT-IC, or combined RT + IT-IC. Surgical resection was performed following neoadjuvant immunotherapy. Immune infiltrate was assessed in the resection specimens. Mice were rechallenged with either B78 contralateral flank tumors or pulmonary seeding of non-GD2 expressing B16 melanoma metastasis induced experimentally. Rejection of rechallenge in mice treated with the various treatment regimens was considered evidence of immunologic memory. RESULTS: Neoadjuvant IT-IC and surgical resection resulted in increased CD8 T cell infiltration, a higher CD8:regulatory T cell ratio, and immunologic memory against contralateral flank rechallenge. The timing of resection did not significantly impact the development of memory, which was present as early as the day of surgery. There was less local wound toxicity with neoadjuvant IT-IC compared with neoadjuvant RT +IT IC. Neoadjuvant IT-IC and resection resulted in the rejection of B16 lung metastasis in a CD4 T cell dependent manner. CONCLUSIONS: Neoadjuvant IT-IC generates immunologic memory capable of preventing distant metastasis despite limited efficacy against large primary melanoma tumors. By combining neoadjuvant tumor vaccination and surgery, the toxicity of local RT was avoided. These preclinical data support further investigation regarding the use of neoadjuvant IT-IC in patients with melanoma at high risk for occult distant disease.

Readmissions From Venous Thromboembolism After Complex Cancer Surgery.

IMPORTANCE: Venous thromboembolism (VTE) is a major cause of preventable morbidity and mortality after cancer surgery. Venous thromboembolism events that are significant enough to require hospital readmission are potentially life threatening, yet data regarding the frequency of these events beyond the 30-day postoperative period remain limited. OBJECTIVE: To determine the rates, outcomes, and predictive factors of readmissions owing to VTE up to 180 days after complex cancer operations, using a national data set. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of the 2016 Nationwide Readmissions Database was performed to study adult patients readmitted with a primary VTE diagnosis. Data obtained from 197 510 visits for 126 104 patients were analyzed. This was a multicenter, population-based, nationally representative study of patients who underwent a complex cancer operation (defined as cystectomy, colectomy, esophagectomy, gastrectomy, liver/biliary resection, lung/bronchus resection, pancreatectomy, proctectomy, prostatectomy, or hysterectomy) from January 1 through September 30, 2016, for a corresponding cancer diagnosis. EXPOSURES: Readmission with a primary diagnosis of VTE. MAIN OUTCOMES AND MEASURES: Proportion of 30-, 90-, and 180-day VTE readmissions after complex cancer surgery, factors associated with readmissions, and outcomes observed during readmission visit, including mortality, length of stay, hospital cost, and readmission to index vs nonindex hospital. RESULTS: For the 126 104 patients included in the study, 30-, 90-, and 180-day VTE-associated readmission rates were 0.6% (767 patients), 1.1% (1331 patients), and 1.7% (1449 of 83 337 patients), respectively. A majority of patients were men (58.7%), and the mean age was 65 years (SD, 11.5 years). For the 1331 patients readmitted for VTE within 90 days, 456 initial readmissions (34.3%) were to a different hospital than the index surgery hospital, median length of stay was 5 days (IQR, 3-7 days), median cost was $8102 (IQR, $5311-$10 982), and 122 patients died (9.2%). Independent factors associated with readmission included type of operation, scores for severity and risk of mortality, age of 75 to 84 years (odds ratio [OR], 1.30; 95% CI, 1.02-1.78), female sex (OR, 1.23; 95% CI, 1.11-1.37), nonelective index admission (OR, 1.31; 95% CI, 1.03-1.68), higher number of comorbidities (OR, 1.30; 95% CI, 1.06-1.60), and experiencing a major postoperative complication during the index admission (OR, 2.08; 95% CI, 1.85-2.33). CONCLUSIONS AND RELEVANCE: In this cohort study, VTE-related readmissions after complex cancer surgery continued to increase well beyond 30 days after surgery. Quality improvement efforts to decrease the burden of VTE in postoperative patients should measure and account for these late VTE-related readmissions.

Gender Differences in Entrustable Professional Activity Evaluations of General Surgery Residents.

OBJECTIVE: To determine differences in entrustable professional activity (EPA) assessments between male and female general surgery residents. SUMMARY BACKGROUND DATA: Evaluations play a critical role in career advancement for physicians. However, female physicians in training receive lower evaluations and underrate their own performance. Competency-based assessment frameworks, such as EPAs, may help address gender bias in surgery by linking evaluations to specific, observable behaviors. METHODS: In this cohort study, EPA assessments were collected from July 2018 to May 2020. The effect of resident sex on EPA entrustment levels was analyzed using multiple linear and ordered logistic regressions. Narrative comments were analyzed using latent dirichlet allocation to identify topics correlated with resident sex. RESULTS: Of the 2480 EPAs, 1230 EPAs were submitted by faculty and 1250 were submitted by residents. After controlling for confounding factors, faculty evaluations of residents were not impacted by resident sex (estimate = 0.09, P = 0.08). However, female residents rated themselves lower by 0.29 (on a 0-4 scale) compared to their male counterparts (P < 0.001). Within narrative assessments, topics associated with resident sex demonstrated that female residents focus on the "guidance" and "supervision" they received while performing an EPA, while male residents were more likely to report "independent" action. CONCLUSIONS: Faculty assessments showed no difference in EPA levels between male and female residents. Female residents rate themselves lower by nearly an entire post graduate year (PGY) level compared to male residents. Latent dirichlet allocation -identified topics suggest this difference in self-assessment is related to differences in perception of autonomy.

Peripheral nerve blocks with liposomal bupivacaine are associated with increased opioid use compared to thoracic epidural in patients with an epigastric incision.

BACKGROUND: Thoracic epidurals are commonly recommended in enhanced recovery protocols, though they may cause hypotension and urinary retention. Peripheral nerve blocks using liposomal bupivacaine are a potential alternative, though they have not been extensively studied in major cancer operations with an epigastric incision. METHODS: We conducted a retrospective review of prospectively collected data following the transition from thoracic epidural to liposomal peripheral nerve blocks in patients undergoing major oncologic surgery. Patients receiving peripheral nerve blocks were compared to those receiving thoracic epidural. Outcome variables included postoperative opioid use (milligram morphine equivalents [MME]), severe pain, and postoperative complications. RESULTS: Forty-seven of 102 patients studied (46%) received peripheral nerve blocks. Opioid use was higher in the peripheral nerve block group during the 0-24 h (116 vs. 94 MME, p = 0.04) and 24-48 h postoperative period (94 vs. 23 MME, p < 0.01). There was no significant difference in severe pain, hypotension, urinary retention, or ileus. Peripheral nerve blocks were associated with earlier ambulation (1 vs. 2 days, p = 0.04), though other milestones were similar. CONCLUSIONS: Liposomal peripheral nerve blocks were associated with increased opioid use compared to thoracic epidural. On the basis of our results, thoracic epidural might be preferred in surgical oncology patients with an epigastric incision.

Clinical and Cost Profile of Controlled Grade B Postoperative Pancreatic Fistula: Rationale for Their Consideration as Low Risk.

BACKGROUND: Despite standardization, the 2016 ISGPF criteria are limited by their wider applicability and oversimplification of grade B POPF. This work applied the 2016 ISGPF grading criteria within a US academic cancer center to verify clinical and fiscal distinctions and sought to improve grading criteria for grade B POPF. METHODS: The 2008-2018 cost and NSQIP data from pancreaticoduodenectomy to postoperative day 90 were merged. All POPFs were coded by 2016 ISGPF criteria. The Clavien-Dindo Classification (CD) defined complication severity. On sub-analyses, grade B POPFs were divided into those with adequate drainage and those requiring additional drainage. Chi-square, ANOVA, and Fisher's least significant difference test were employed. RESULTS: Two hundred thirty-two patients were in the final analyses, 72 (31%) of whom had POPFs: 16 (7%) biochemical leaks, 54 (23%) grade B (28% required additional drainage), and 2 (1%) grade C. There was no significant difference in length of stay, CD, readmission, or cost in patients without a POPF, with biochemical leak or grade B POPF. On sub-analyses, 92% of adequately drained grade B POPFs had CD 1-2 and readmission equivalent to patients without POPF (p > 0.05). One hundred percent of grade B POPF requiring drainage had CD 3-4a, and 67% were readmitted. Cost was significantly increased in grade B POPF requiring additional drainage (p = 0.02) and grade C POPF (p < 0.01). CONCLUSIONS: This analysis did not confirm an incremental increase in morbidity and cost with POPF grade. Sub-analyses enabled accurate clinical and cost distinctions in grade B POPF; adequately drained grade B POPF are low risk and clinically insignificant.

Sentinel lymph node biopsy is associated with increased cost in higher risk thin melanoma.

INTRODUCTION: National Comprehensive Cancer Network guidelines recommend that sentinel lymph node biopsy (SLNB) be discussed with patients with thin melanoma at higher risk for lymph node metastasis (T1b or T1a with positive deep margins, lymphovascular invasion, or high mitotic index). We examined the association between SLNB and resource utilization in this cohort. METHODS: We conducted a retrospective cohort study of patients that underwent wide local excision for higher risk thin melanomas from 2009 to 2018 at a tertiary care center. Patients who underwent SLNB were compared to those who did not undergo SLNB with regard to resource utilization, including total hospital cost. RESULTS: A total of 70 patients were included in the analysis and 50 patients (71.4%) underwent SLNB. SLNB was associated with increased hospital costs ($6700 vs. $3767; p < .01) and increased operative time (68.5 vs. 36.0 min; p < .01). This cost difference persisted in multivariable regression (p < .01). Of patients who underwent successful SLN mapping, 3 out of 49 patients had a positive SLN (6.1%). The cost to identify a single positive sentinel lymph node (SLN) was $47,906. CONCLUSION: In patients with a higher risk of thin melanoma, SLNB is associated with increased cost despite a low likelihood of SLN positivity. These data better inform patient-provider discussions as the role of SLNB in thin melanoma evolves.

Surgeon Variability Impacts Costs in Laparoscopic Cholecystectomy: the Volume-Cost Relationship.

BACKGROUND: Physician variation in adherence to best practices contributes to the high costs of health care. Understanding surgeon-specific cost variation in common surgical procedures may inform strategies to improve the value of surgical care. METHODS: Laparoscopic cholecystectomies at a single institution were identified over a 5-year period and linked to an institutional cost database. Multiple linear regression was used to control for patient-, case-, and hospital-specific factors while assessing the impact of surgeon variability on cost. RESULTS: The final dataset contained 1686 patients. Higher surgeon volume (reported in tertiles) was associated with decreased costs ($5354 vs. $6301 vs. $7156, p < 0.01) and OR times (66 min vs. 85 min vs. 95 min, p < 0.01). After controlling for patient-, case-, and hospital-specific factors, non-MIS fellowship training type (p < 0.01) and low surgeon volume (p < 0.01) were associated with increased costs, while time in practice did not contribute to cost variation (p = NS). CONCLUSIONS: Surgeon variability contributes to costs in laparoscopic cholecystectomy. Some of this variability is associated with operative volume and fellowship training. Collaboration to limit this cost variability may reduce surgical resource utilization.

Early vs Late Readmissions in Pancreaticoduodenectomy Patients: Recognizing Comprehensive Episodic Cost to Help Guide Bundled Payment Plans and Hospital Resource Allocation.

INTRODUCTION: Previous studies on readmission cost in pancreaticoduodenectomy patients use estimated cost data and do not delineate etiology or cost differences between early and late readmissions. We sought to identify relationships between postoperative complication type and readmission timing and cost in pancreaticoduodenectomy patients. METHODS: Hospital cost data from date of discharge to postoperative day 90 were merged with 2008-2018 NSQIP data. Early readmission was within 30 days of surgery, and late readmission was 30 to 90 days from surgery. Regression analyses for readmission controlled for patient comorbidities, complications, and surgeon. RESULTS: Of 230 patients included, 58 (25%) were readmitted. The mean early and late readmission costs were $18,365 ± $20,262 and $24,965 ± $34,435, respectively. Early readmission was associated with index stay deep vein thrombosis (p < 0.01), delayed gastric emptying (p < 0.01), and grade B pancreatic fistula (p < 0.01). High-cost early readmission had long hospital stays or invasive procedures. Common late readmission diagnoses were grade B pancreatic fistula requiring drainage (n = 5, 14%), failure to thrive (n = 4, 14%), and bowel obstruction requiring operation (n = 3, 11%). High-cost late readmissions were associated with chronic complications requiring reoperation. CONCLUSION: Early and late readmissions following pancreaticoduodenectomy differ in both etiology and cost. Early readmission and cost are driven by common complications requiring percutaneous intervention while late readmission and cost are driven by chronic complications and reoperation. Late readmissions are frequent and a significant source of resource utilization. Negotiations of bundled care payment plans should account for significant late readmission resource utilization.

Intercostal nerve cryoablation is associated with lower hospital cost during minimally invasive Nuss procedure for pectus excavatum.

Minimally invasive repair of pectus excavatum (Nuss procedure) is associated with significant pain, and efforts to control pain impact resource utilization. Bilateral thoracic intercostal nerve cryoablation has been proposed as a novel technique to improve post-operative pain control, though the impact on hospital cost is unknown. METHODS: We conducted a retrospective study of patients undergoing a Nuss procedure from 2016 to 2019. Patients who received cryoablation were compared to those that received traditional pain control (patient-controlled analgesia or epidural). Outcome variables included postoperative opioid usage (milligram morphine equivalents, MME), length of stay (LOS), and hospital cost. RESULTS: Thirty-five of 73 patients studied (48%) received intercostal nerve cryoablation. LOS (1.0 vs 4.0 days, p < 0.01) and total hospital cost ($21,924 versus $23,694, p = 0.04) were decreased in the cryoablation cohort, despite longer operative time (152 vs 74 min, p < 0.01). Cryoablation was associated with decreased opioid usage (15.0 versus 148.6 MME, p < 0.01) during the 24 h following surgery and this persisted over the entire postoperative period, including discharge opioid prescription (112.5 vs 300.0 MME, p < 0.01). CONCLUSION: Bilateral intercostal nerve cryoablation is associated with decreased postoperative opioid usage and decreased resource utilization in pediatric patients undergoing a minimally invasive Nuss procedure for pectus excavatum. LEVEL OF EVIDENCE: Retrospective comparative study, level III.

Overprescription of Opioids Following Outpatient Anorectal Surgery: A Single-Institution Study.

BACKGROUND: Surgeons contribute to the opioid epidemic by overprescribing opioids for postoperative pain. Excess, unused opioids may be diverted for misuse/abuse. OBJECTIVE: This study aimed to characterize opioid prescribing and use among patients undergoing outpatient anorectal procedures and to assess the adequacy of postoperative pain management. DESIGN: This is a retrospective cohort study, prospective cross-sectional survey. SETTINGS: Patients were treated by colorectal surgeons in an academic medical center between January 2018 and September 2019. PATIENTS: Six hundred twenty-seven patients undergoing an outpatient anorectal procedure were included. MAIN OUTCOME MEASURES: The primary outcomes measured were the opioids prescribed at discharge, opioid prescription refills, patient-reported outcomes regarding opioid use, and the adequacy of postoperative pain management in terms of pain intensity and pain interference. Opioids were standardized to 5-mg oxycodone pills. Patient-reported outcomes were assessed by using previously validated instruments. RESULTS: The majority of patients underwent fistula surgery (n = 234) followed by examination under anesthesia (n = 183), hemorrhoidectomy (n = 131), incision and drainage (n = 51), and pilonidal excision (n = 28). Most patients received opioids (78% fistula, 49% examination under anesthesia, 87% hemorrhoidectomy, 71% incision and drainage, 96% pilonidal). Patients undergoing examination under anesthesia received the fewest opioid pills (median 10; range 3-50) followed by patients undergoing fistula surgery (median13, range 1-50), incision and drainage (median 15, range 3-120), pilonidal excisions (median 15, range 3-60), and hemorrhoidectomies (median 28, range 3-60). Regardless of procedure, the majority of patients used fewer than 5 opioid pills postoperatively. Patients undergoing pilonidal excisions had the largest number of excess unused pills (median 14, range 0-30) followed by patients undergoing fistula surgery and incision and drainage (median 7, ranges 0-30 and 5-17), hemorrhoidectomy (median 6, range 0-50), and examination under anesthesia (median 2, range 0-23). Whereas patients undergoing hemorrhoidectomy reported higher pain levels following discharge, most reported minimal interference with day-to-day activities due to pain regardless of the procedure performed. LIMITATIONS: The limitations of this study included recall bias and sample bias. CONCLUSIONS: The majority of patients do not need more than five to ten 5-mg oxycodone equivalents to achieve adequate pain management after outpatient anorectal surgical procedures. See Video Abstract at http://links.lww.com/DCR/B347. EXCESO DE PRESCRIPCIÓN DE OPIOIDES DESPUÉS DE UNA CIRUGÍA ANORRECTAL AMBULATORIA: UN ESTUDIO DE UNA SOLA INSTITUCIÓN: Cirujanos contribuyen a la epidemia de opioides al recetar en exceso opioides para el dolor postoperatorio. El exceso de opioides no utilizados puede ser desviado por para mal uso o abuso.Caracterizar la prescripción y el uso de opioides entre pacientes sometidos a procedimientos anorrectales ambulatorios y evaluar la efectividad del tratamiento del dolor postoperatorio.Estudio de cohorte retrospectivo, encuesta transversal prospectiva.pacientes tratados por cirujanos colorrectales en un centro médico académico entre enero de 2018 y septiembre de 2019.se incluyeron 627 pacientes que se sometieron a un procedimiento anorrectal ambulatorio.Opioides recetados al alta, reabastecimientos de prescripción de opioides, resultados informados por el paciente con respecto al uso de opioides y efectividad del manejo del dolor postoperatorio en términos de intensidad del dolor y trastornos secundarios a dolor. Los opioides se estandarizaron con píldoras de oxicodona de 5 mg. Los resultados informados por los pacientes se evaluaron utilizando instrumentos previamente validados.La mayoría de los pacientes fueron sometidos a cirugía de fístula (n = 234) seguida de un examen bajo anestesia (EUA; n = 183), hemorroidectomía (n = 131), incisión y drenaje (I&D) (n = 51) y escisión pilonidal (n = 28). La mayoría de los pacientes recibieron opioides (78% fístula, 49% EUA, 87% hemorroidectomía, 71% I&D, 96% pilonidal). Las EUA recibieron la menor cantidad de píldoras opioides (mediana 10, rango 3-50) seguidas de fístula (mediana 13, rango 1-50), I y D (mediana 15, rango 3-120), pilonidales (mediana 15, rango 3-60) y hemorroides. (mediana 28, rango 3-60). Independientemente del procedimiento, la mayoría de los pacientes usaron menos de cinco píldoras opioides después de la operación. Los pacientes pilonidales tuvieron el mayor número de píldoras no utilizadas en exceso (mediana 14, rango 0-30) seguido de fístula e I&D (mediana 7, rangos 0-30 y 5-17, respectivamente), hemorroidectomía (mediana 6, rango 0-50) y EUA (mediana 2, rango 0-23). Si bien los pacientes con hemorroidectomía informaron niveles de dolor más altos después del alta, la mayoría de pacientes informaron un mínimo de interferencia con las actividades diarias debido al dolor, independientemente del procedimiento realizado.Sesgo de recuerdo autoinformado, sesgo de muestra.La mayoría de los pacientes no necesitan más de cinco a diez equivalentes de oxicodona de 5 mg para lograr un manejo adecuado del dolor después de procedimientos quirúrgicos anorrectales ambulatorios. Consulte Video Resumen en http://links.lww.com/DCR/B347. (Traducción-Dr. Adrian Ortega).

What Drives High Costs of Cytoreductive Surgery and HIPEC: Patient, Provider or Tumor?

INTRODUCTION: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is utilized for peritoneal malignancies and is associated with significant resource use. To address potentially modifiable factors contributing to excessive cost, we sought to determine predictors of high cost of care for patients undergoing CRS/HIPEC. METHODS: An institutional CRS/HIPEC database was queried for adult patients from 2014 to 2018. Cost was defined as cost for the index hospitalization, and high-cost cases were defined as > 75th percentile for cost. Bivariate analyses for cost were performed, and all significant tumor, patient, and surgeon-specific variables were entered in a linear regression for cost. A separate linear regression was performed for length of stay (LOS). RESULTS: In total, 59 patients underwent 61 CRS/HIPEC procedures. The median direct variable cost was $20,509 (16,395-25,240). Median length of stay (LOS) was 8 (7-11.5) days and ICU stay was 1 (1-1.5) day. LOS, length of ICU stay and operative time were predictive of cost. Factors associated with increased LOS were Clavien-Dindo grade II complications and ostomy creation. Patient-related factors, including age and BMI, tumor-related factors, such as PCI and CCR, and surgeon were not predictive of cost nor LOS. DISCUSSION: Our results, the first to identify predictors of high cost of CRS/HIPEC-related care in the US, reveal cost was largely related to length and intensity of care. In turn, these drivers were influenced by complications and operative factors. Future work will focus on identifying an appropriate ERAS protocol following CRS/HIPEC and selection of those patients that may avoid routine ICU admission.

Operative Delay in Adults with Appendicitis: Time is Money.

BACKGROUND: Evidence suggests that operative delay of up to 24 h is not associated with adverse outcomes among patients undergoing emergent appendectomy. However, the fiscal implication of operative delay is not well described in adults. We sought to examine the effect of delayed appendectomy on clinical outcomes and hospital cost. METHODS: We conducted a retrospective cohort study of patients undergoing nonelective laparoscopic appendectomy from 2014 to 2018 at both a tertiary care center and an affiliated short-stay hospital. Using a unique data set constructed from merged electronic health record and patient-level hospital financial data, patients with delayed surgery, defined as >12 h from emergency department (ED) arrival to operation, were compared with patients who underwent surgery within 12 h. Patient-specific variables were analyzed for their association with resource utilization, and subsequent multivariable linear regression was performed for total hospital cost. RESULTS: 1372 patients underwent laparoscopic appendectomy during the study period. 938 patients (68.3%) underwent surgery within 12 h of ED arrival, and 434 patients (31.6%) underwent delayed surgery. Delayed cases had longer length of stay (44.6 ± 42.5 versus 34.5 ± 36.5 h, P < 0.01) and increased total hospital cost ($9326 ± 4691 versus $8440 ± 3404, P < 0.01). The cost difference persisted on multivariable analysis (P < 0.01). There were no significant differences between delayed cases and nondelayed cases for operative time, intraoperative findings, including rate of perforation, or postoperative complications. CONCLUSIONS: Although safe, delayed appendectomy is associated with an increased length of stay and increased total hospital costs compared with appendectomy within 12 h of reaching the ED.

Summary perioperative risk metrics within the electronic medical record predict patient-level cost variation in pancreaticoduodenectomy.

BACKGROUND: Automated data extraction from the electronic medical record is fast, scalable, and inexpensive compared with manual abstraction. However, concerns regarding data quality and control for underlying patient variation when performing retrospective analyses exist. This study assesses the ability of summary electronic medical record metrics to control for patient-level variation in cost outcomes in pancreaticoduodenectomy. METHODS: Patients that underwent pancreaticoduodenectomy from 2014 to 2018 at a single institution were identified within the electronic medical record and linked with the National Surgical Quality Improvement Program. Variables in both data sets were compared using interrater reliability. Logistic and linear regression modelling of complications and costs were performed using combinations of comorbidities/summary metrics. Models were compared using the adjusted R2 and Akaike information criterion. RESULTS: A total of 117 patients populated the final data set. A total of 31 (26.5%) patients experienced a complication identified by the National Surgical Quality Improvement Program. The median direct variable cost for the encounter was US$14,314. Agreement between variables present in the electronic medical record and the National Surgical Quality Improvement Program was excellent. Stepwise linear regression models of costs, using only electronic medical record-extractable variables, were non-inferior to those created with manually abstracted individual comorbidities (R2 = 0.67 vs 0.30, Akaike information criterion 2,095 vs 2,216). Model performance statistics were minimally impacted by the addition of comorbidities to models containing electronic medical record summary metrics (R2 = 0.67 vs 0.70, Akaike information criterion 2,095 vs 2,088). CONCLUSION: Summary electronic medical record perioperative risk metrics predict patient-level cost variation as effectively as individual comorbidities in the pancreaticoduodenectomy population. Automated electronic medical record data extraction can expand the patient population available for retrospective analysis without the associated increase in human and fiscal resources that manual data abstraction requires.

Mannose receptor (CD206) activation in tumor-associated macrophages enhances adaptive and innate antitumor immune responses.

Solid tumors elicit a detectable immune response including the infiltration of tumor-associated macrophages (TAMs). Unfortunately, this immune response is co-opted into contributing toward tumor growth instead of preventing its progression. We seek to reestablish an antitumor immune response by selectively targeting surface receptors and endogenous signaling processes of the macrophage subtypes driving cancer progression. RP-182 is a synthetic 10-mer amphipathic analog of host defense peptides that selectively induces a conformational switch of the mannose receptor CD206 expressed on TAMs displaying an M2-like phenotype. RP-182-mediated activation of this receptor in human and murine M2-like macrophages elicits a program of endocytosis, phagosome-lysosome formation, and autophagy and reprograms M2-like TAMs to an antitumor M1-like phenotype. In syngeneic and autochthonous murine cancer models, RP-182 suppressed tumor growth, extended survival, and was an effective combination partner with chemo- or immune checkpoint therapy. Antitumor activity of RP-182 was also observed in CD206high patient-derived xenotransplantation models. Mechanistically, via selective reduction of immunosuppressive M2-like TAMs, RP-182 improved adaptive and innate antitumor immune responses, including increased cancer cell phagocytosis by reprogrammed TAMs.