Travel Time to a High Volume Center Negatively Impacts Timing of Care in Rectal Cancer.

BACKGROUND: Regionalization of rectal cancer surgery may lead to worse disease free survival owing to longer travel time to reach a high volume center yet no study has evaluated this relationship at a single high volume center volume center. MATERIALS AND METHODS: This was a retrospective review of rectal cancer patients undergoing surgery from 2009 to 2019 at a single high volume center. Patients were divided into two groups based on travel time. The primary outcome was disease-free survival (DFS). Additional outcomes included treatment within 60 d of diagnosis, completeness of preoperative staging, and evaluation by a colorectal surgeon prior to initiation of treatment. RESULTS: A lower proportion of patients with long travel time began definitive treatment within 60 d of diagnosis (74.0% versus 84.0%, P= 0.01) or were seen by the treating colorectal surgeon before beginning definitive treatment (74.8% versus 85.4%, P < 0.01). On multivariable logistic regression analysis, patients with long travel time were significantly less likely to begin definitive treatment within 60 d of diagnosis (OR = 0.54; 95% CI = 0.31-0.93) or to be evaluated by a colorectal surgeon prior to initiating treatment (OR = 0.45; 95% CI = 0.25-0.80). There were no significant differences in DFS based on travel time. CONCLUSIONS: Although patients with long travel times may be vulnerable to delayed, lower quality rectal cancer care, there is no difference in DFS when definitive surgery is performed at a high volume canter. Ongoing research is needed to identify explanations for delays in treatment to ensure all patients receive the highest quality care.

A Multicenter Study of Nutritional Adequacy in Neonatal and Pediatric Extracorporeal Life Support.

BACKGROUND: Malnutrition in critically ill patients is common in neonates and children, including those that receive extracorporeal life support (ECLS). We hypothesize that nutritional adequacy is highly variable, overall nutritional adequacy is poor, and enteral nutrition is underutilized in this population. MATERIALS AND METHODS: A retrospective study of neonates and children (age<18 y) receiving ECLS at 5 centers from 2012 to 2014 was performed. Demographic, clinical, and outcome data were analyzed. Continuous variables are presented as median [IQR]. Adequate nutrition was defined as meeting 66% of daily caloric goals during ECLS support. RESULTS: Two hundred and eighty three patients received ECLS; the median age was 12 d [3 d, 16.4 y] and 47% were male. ECLS categories were neonatal pulmonary 33.9%, neonatal cardiac 25.1%, pediatric pulmonary 17.7%, and pediatric cardiac 23.3%. The predominant mode was venoarterial (70%). Mortality was 41%. Pre-ECLS enteral and parenteral nutrition was present in 80% and 71.5% of patients, respectively. The median percentage days of adequate caloric and protein nutrition were 50% [0, 78] and 67% [22, 86], respectively. The median percentage days with adequate caloric and protein nutrition by the enteral route alone was 22% [0, 65] and 0 [0, 50], respectively. Gastrointestinal complications occurred in 19.7% of patients including hemorrhage (4.2%), enterocolitis (2.5%), intra-abdominal hypertension or compartment syndrome (0.7%), and perforation (0.4%). CONCLUSIONS: Although nutritional delivery during ECLS is adequate, the use of enteral nutrition is low despite relatively infrequent observed gastrointestinal complications.

Interferon-based chemoradiation followed by gemcitabine for resected pancreatic adenocarcinoma: long-term follow-up.

To report long-term follow up of a phase II, single-arm trial of resectable pancreatic ductal adenocarcinoma (PDAC) treated with adjuvant interferon-based chemoradiation followed by gemcitabine to determine survival, recurrence, and complications. METHODS: From 2002 to 2005, 53 patients with PDAC underwent pancreaticoduodenectomy and received adjuvant interferon-based chemoradiation consisting of external-beam irradiation and simultaneous 3-drug chemotherapy of continuous daily 5-fluorouracil infusion, weekly intravenous bolus cisplatin, and subcutaneous interferon-α, followed by two months of weekly intravenous gemcitabine. RESULTS: Actual overall survival for the 5- and 10-year periods were 26% and 10%, respectively, with a median overall survival of 25 months (95% CI: 16.4-38.5). Adverse prognostic factors on multivariate analysis were positive tumor margin (p < 0.035), lymphovascular invasion (p < 0.015), and perineural invasion (p < 0.026). Median time to recurrence was 11 months. Positive tumor margin was associated with lymph node involvement (p < 0.005), portal vein resection (p < 0.038), and metastases (p < 0.018). Late complications were frequent and predominated by gastrointestinal and infectious complications. CONCLUSIONS: Adjuvant interferon-based chemoradiation for PDAC improves long-term survival compared to standard therapy. However, recurrence rates and long-term complications remain high, thus further studies are indicated to assess patient characteristics that indicate a favorable treatment profile.

Use of Simulation For Training Advanced Colorectal Procedures.

OBJECTIVE: Simulation training for minimally invasive colorectal procedures is in developing stages. This study aims to assess the impact of simulation on procedural knowledge and simulated performance in laparoscopic low anterior resection (LLAR) and robotic right colectomy (RRC). DESIGN: LLAR and RRC simulation procedures were designed using human cadaveric models. Resident case experience and simulation selfassessments scores for operative ability and knowledge were collected before and after the simulation. Colorectal faculty assessed resident simulation performance using validated assessment scales (OSATS-GRS, GEARS). Paired t-tests, unpaired t-tests, Pearson's correlation, and descriptive statistics were applied in analyses. SETTING: Barnes-Jewish Hospital/Washington University School of Medicine in St. Louis, Missouri. PARTICIPANTS: Senior general surgery residents at large academic surgery program. RESULTS: Fifteen PGY4/PGY5 general surgery residents participated in each simulation. Mean LLAR knowledge score increased overall from 10.0 ±  2.0 to 11.5  ±  1.6 of 15 points (p = 0.0018); when stratified, this increase remained significant for the PGY4 cohort only. Mean confidence in ability to complete LLAR increased overall from 2.0 ±  0.8 to 2.8  ± 0.9 on a 5-point rating scale (p = 0.0013); when stratified, this increase remained significant for the PGY4 cohort only. Mean total OSATS GRS score was 28  ±  6.3 of 35 and had strong positive correlation with previous laparoscopic colorectal experience (r = 0.64, p = 0.0092). Mean RRC knowledge score increased from 9.4 ±  2.2 to 11.1 ±  1.5 of 15 points (p = 0.0030); when stratified, this increase again remained significant for the PGY4 cohort only. Mean confidence in ability to complete RRC increased from 1.9 ±  0.9 to 3.2  ±  1.1 (p = 0.0002) and was significant for both cohorts. CONCLUSIONS: Surgical trainees require opportunities to practice advanced minimally invasive colorectal procedures. Our simulation approach promotes increased procedural knowledge and resident confidence and offers a safe complement to live operative experience for trainee development. In the future, simulations will target trainees on the earlier part of the learning curve and be paired with live operative assessments to characterize longitudinal skill progression.

Fragmented Care in the Treatment of Rectal Cancer and Time to Definitive Therapy.

BACKGROUND: The National Accreditation Program for Rectal Cancer (NAPRC) emphasizes a multidisciplinary approach for treating rectal cancer and has developed performance measures to ensure that patients receive standardized care. We hypothesized that rectal cancer patients receiving care at multiple centers would be less likely to receive timely and appropriate care. STUDY DESIGN: A single institution retrospective review of a prospectively maintained database was performed. All patients undergoing proctectomy and ≤1 other treatment modality (eg radiation and/or chemotherapy) for Stage II/III rectal adenocarcinoma were included. Unified care was defined as receiving all modalities of care at our institution, and fragmented care was defined as having at least 1 treatment modality at another institution. RESULTS: From 2009 to 2019, 415 patients met inclusion criteria, with 197 (47.5%) receiving fragmented care and 218 (52.5%) receiving unified care. The unified cohort patients were more likely to see a colorectal surgeon before starting treatment (89.0% vs 78.7%, p < 0.01) and start definitive treatment within 60 days of diagnosis (89.0% vs 79.7%, p = 0.01). On adjusted analysis, unified care patients were 2.78 times more likely to see a surgeon before starting treatment (95% CI 1.47-5.24) and 2.63 times more likely to start treatment within 60 days (95% CI 1.35-5.13). There was no difference in 90-day mortality or 5-year disease-free survival. CONCLUSIONS: This retrospective cohort study suggests patients with rectal cancer receiving fragmented care are at an increased risk of delays in care without any impact on disease-free survival. These findings need to be considered within the context of ongoing regionalization of rectal cancer care to ensure all patients receive optimal care, irrespective of whether care is delivered across multiple institutions.

Surgeon Variation in Intraoperative Supply Cost for Pancreaticoduodenectomy: Is Intraoperative Supply Cost Associated with Outcomes?

BACKGROUND: With increased scrutiny on the quality and cost of health care, surgeons must be mindful of their outcomes and resource use. We evaluated surgeon-specific intraoperative supply cost (ISC) for pancreaticoduodenectomy and examined whether ISC was associated with patient outcomes. STUDY DESIGN: Patients undergoing open pancreaticoduodenectomy between January 2012 and March 2015 were included. Outcomes were tracked prospectively through postoperative day 90, and ISC was defined as the facility cost of single-use surgical items and instruments, plus facility charges for multiuse equipment. Multivariate logistic regression was used to test associations between ISC and patient outcomes using repeated measures at the surgeon level. RESULTS: There were 249 patients who met inclusion criteria. Median ISC was $1,882 (interquartile range [IQR] $1,497 to $2,281). Case volume for 6 surgeons ranged from 18 to 66. Median surgeon-specific ISC ranged from $1,496 to $2,371. Greater case volume was associated with decreased ISC (p < 0.001). Overall, ISC was not predictive of postoperative complications (p = 0.702) or total hospitalization expenditures (p = 0.195). At the surgeon level, surgeon-specific ISC was not associated with the surgeon-specific incidence of severe complication or any wound infection (p > 0.227 for both), but was associated with delayed gastric emptying (p = 0.004) and postoperative pancreatic fistula (p < 0.001). CONCLUSIONS: In a single-institution cohort of 249 pancreaticoduodenectomies, high-volume surgeons tended to be low-cost surgeons. Across the cohort, ISC was not associated with outcomes. At the surgeon level, associations were noted between ISC and complications, but these may be attributable to unmeasured differences in the postoperative management of patients. These findings suggest that quality improvement efforts to restructure resource use toward more cost-effective practice may not affect patient outcomes, although prospective monitoring of safety and effectiveness must be of the utmost concern.

Combination of Oral Antibiotics and Mechanical Bowel Preparation Reduces Surgical Site Infection in Colorectal Surgery.

BACKGROUND: Surgical site infections (SSI) are a common complication after colorectal surgery. An infection prevention bundle (IPB) was implemented to improve outcomes. STUDY DESIGN: A standardized IPB that included the administration of oral antibiotics with a mechanical bowel preparation, preoperative shower with chlorhexidine, hair removal and skin preparation in holding, antibiotic wound irrigation, and a "clean-closure" protocol was implemented in January 2013. Data from the American College of Surgeons NSQIP were analyzed at a single academic institution to compare pre-IPB and post-IPB SSI rates. In January 2014, a prospective database was implemented to determine compliance with individual IPB elements and their effect on outcomes. RESULTS: For the 24 months pre-IPB, the overall SSI rate was 19.7%. During the 30 months after IPB implementation, the SSI rate decreased to 8.2% (p < 0.0001). A subset of 307 patients was identified in both NSQIP and our prospective compliance databases. Elements of IPB associated with decreased SSI rates included preoperative shower with chlorhexidine (4.6% vs 16.2%; p = 0.005), oral antibiotics (3.4% vs 15.4%; p < 0.001), and mechanical bowel preparation (4.4% vs 14.3%; p = 0.008). Patients who received a full bowel preparation of both oral antibiotics and a mechanical bowel preparation had a 2.7% SSI rate compared with 15.8% for all others (p < 0.001). On multivariate analysis, full bowel preparation was independently associated with significantly fewer SSI (adjusted odds ratio 0.2; 95% CI 0.1 to 0.9; p = 0.006). CONCLUSIONS: Implementation of an IPB was successful in decreasing SSI rates in colorectal surgery patients. The combination of oral antibiotics with a mechanical bowel preparation was the strongest predictor of decreased SSI.

Conjugation to the sigma-2 ligand SV119 overcomes uptake blockade and converts dm-Erastin into a potent pancreatic cancer therapeutic.

Cancer-selective drug delivery is an important concept in improving treatment while minimizing off-site toxicities, and sigma-2 receptors, which are overexpressed in solid tumors, represent attractive pharmacologic targets. Select sigma-2 ligands have been shown to be rapidly internalized selectively into cancer cells while retaining the capacity to deliver small molecules as drug cargoes. We utilized the sigma-2-based drug delivery concept to convert Erastin, a clinically underperforming drug, into a potent pancreatic cancer therapeutic. The Erastin derivative des-methyl Erastin (dm-Erastin) was chemically linked to sigma-2 ligand SV119 to create SW V-49. Conjugation increased the killing capacity of dm-Erastin by nearly 35-fold in vitro and reduced the size of established tumors and doubled the median survival in syngeneic and patient-derived xenograft models when compared to non-targeted dm-Erastin. Mechanistic analyses demonstrated that cell death was associated with robust reactive oxygen species production and could be efficiently antagonized with antioxidants. Mass spectrometry was employed to demonstrate selective uptake into pancreatic cancer cells. Thus, targeted delivery of dm-Erastin via conjugation to the sigma-2 ligand SV119 produced efficient tumor control and prolonged animal survival with minimal off-target toxicities, and SW V-49 represents a promising new therapeutic with the potential to advance the fight against pancreatic cancer.