Endoscopic Ultrasound-Guided Biliary Drainage of First Intent With a Lumen-Apposing Metal Stent vs Endoscopic Retrograde Cholangiopancreatography in Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Study (ELEMENT Trial).

BACKGROUND & AIMS: Endoscopic ultrasound-guided choledochoduodenostomy with a lumen-apposing metal stent (EUS-CDS) is a promising modality for management of malignant distal biliary obstruction (MDBO) with potential for better stent patency. We compared its outcomes with endoscopic retrograde cholangiopancreatography with metal stenting (ERCP-M). METHODS: In this multicenter randomized controlled trial, we recruited patients with MDBO secondary to borderline resectable, locally advanced, or unresectable peri-ampullary cancers across 10 Canadian institutions and 1 French institution. This was a superiority trial with a noninferiority assessment of technical success. Patients were randomized to EUS-CDS or ERCP-M. The primary end point was the rate of stent dysfunction at 1 year, considering competing risks of death, clinical failure, and surgical resection. Analyses were performed according to intention-to-treat principles. RESULTS: From February 2019 to February 2022, 144 patients were recruited; 73 were randomized to EUS-CDS and 71 were randomized to ERCP-M. The mean (SD) procedure time was 14.0 (11.4) minutes for EUS-CDS and 23.1 (15.6) minutes for ERCP-M (P < .01); 40% of the former was performed without fluoroscopy. Technical success was achieved in 90.4% (95% CI, 81.5% to 95.3%) of EUS-CDS and 83.1% (95% CI, 72.7% to 90.1%) of ERCP-M with a risk difference of 7.3% (95% CI, -4.0% to 18.8%) indicating noninferiority. Stent dysfunction occurred in 9.6% vs 9.9% of EUS-CDS and ERCP-M cases, respectively (P = .96). No differences in adverse events, pancreaticoduodenectomy and oncologic outcomes, or quality of life were noted. CONCLUSIONS: Although not superior in stent function, EUS-CDS is an efficient and safe alternative to ERCP-M in patients with MDBO. These findings provide evidence for greater adoption of EUS-CDS in clinical practice as a complementary and exchangeable first-line modality to ERCP in patients with MDBO. CLINICALTRIALS: gov, Number: NCT03870386.

Passive Versus Active Intra-Abdominal Drainage Following Pancreaticoduodenectomy: A Retrospective Study Using The American College of Surgeons NSQIP Database.

BACKGROUND: Prophylactic drainage following pancreaticoduodenectomy (PD) reduces morbidity and mortality. Little evidence exists to advise on whether passive gravity (PG) or active suction (AS) drainage systems result in superior outcomes. This study examines the relationship between drainage system and morbidity following PD. METHODS: All patients undergoing elective PD with an operatively placed drain in the 2016 ACS-NSQIP database were included. Pre- and intra-operative factors were examined. Multivariable logistic regression and coarsened exact matching (CEM) were used to assess for an association between drainage system (PG vs. AS) and morbidity. The primary outcome was postoperative pancreatic fistula (POPF). RESULTS: In total, 3430 patients were included: 563 (16.4%) with PG and 2867 (83.6%) with AS drainage system. On multivariable regression, 1787 patients were included. Drainage type was not associated with POPF, surgical site infection, delayed gastric emptying, or re-operation. AS drainage was protective against percutaneous drain insertion (OR 0.65, 95% CI 0.44-0.96, p = 0.033). In the CEM cohort (n = 268), superficial SSI was higher in the AS group (0.8% vs. 6.0%, p = 0.036). There was a trend toward higher rates of composite total SSI (PG 15.7%, AS 23.9%, p = 0.092) and organ space SSI (PG 14.2%, AS 20.2%, p = 0.195) in the AS group; this did not demonstrate statistical significance. CONCLUSIONS: The findings of this study suggest that AS drainage is protective against percutaneous drain insertion, but may be associated with increased risk of SSI. There was no relation between drainage type and POPF. A prospective, randomized controlled trial is warranted to further explore these findings.

Shorter Hospital Stay and Lower 30-Day Readmission After Unicondylar Knee Arthroplasty Compared to Total Knee Arthroplasty.

BACKGROUND: Reducing hospital stay and unplanned hospital readmission of arthroplasty patients has been a topic of recent interest. The aim of the present study was to query the National Surgical Quality Improvement Program database to compare the length of hospital stay (LOS) and the subsequent 30-day hospital readmission rates in patients undergoing primary unicondylar knee arthroplasty (UKA) and total knee arthroplasty (TKA). METHODS: We identified 1340 UKAs and 36,274 TKAs over a 2-year period (2011-2012). Patient demographics, comorbidities, LOS, 30-day postoperative complications, and readmission rates were compared between the groups. Multivariate regression analysis was used to determine the effect of procedure type on LOS and readmission rates. RESULTS: Unicondylar knee arthroplasty patients had a median LOS of 2 days compared to 3 days for TKAs (P < .001). The readmission rate in the TKA group was nearly double that of the UKA group (4.1% vs 2.2%) (P < .0001). Multivariate regression analysis identified that undergoing a UKA was predictive for a shorter LOS (coefficient -1 day) and was protective for 30-day readmission (odds ratio, 0.60; 95% confidence interval, 0.41-0.88). CONCLUSION: Patients undergoing UKA had a shorter LOS and a lower 30-day readmission rate compared to TKA patients. After adjusting for selected cofounders, we demonstrated that undergoing a UKA is a protective factor for 30-day readmission.

Blood transfusion in primary total hip and knee arthroplasty. Incidence, risk factors, and thirty-day complication rates.

BACKGROUND: The aim of this study was to analyze NSQIP (National Surgical Quality Improvement Program) data to better understand the incidence, risk factors, and thirty-day complication rates associated with transfusions in primary total hip and knee arthroplasty. METHODS: We identified 9362 total hip and 13,662 total knee arthroplasty procedures from the database and separated those in which any red blood-cell transfusion was performed within seventy-two hours after surgery from those with no transfusion. Patient demographics, comorbidities, preoperative laboratory values, intraoperative variables, and postoperative complications were compared between patients who received a transfusion and those who did not. Multivariate logistic regression was used to identify independent risk factors for receiving a transfusion as well as for associated postoperative complications (thirty-day incidences of infection, venous thromboembolism, and mortality). RESULTS: The transfusion rate after total hip arthroplasty was 22.2%. Significant risk factors for receiving a transfusion were age (OR [odds ratio] per ten years = 10.1), preoperative anemia (OR = 3.6), female sex (OR = 2.0), BMI (body mass index) of <30 kg/m(2) (OR = 1.4), and ASA (American Society of Anesthesiologists) class of >2 (OR = 1.3). Multivariate logistic regression analysis indicated that adjusted odds of infection, venous thromboembolism, and mortality did not differ significantly between patients who received a transfusion and those who did not. The transfusion rate after total knee arthroplasty was 18.3%. Risk factors for receiving a transfusion were age (OR per ten years = 10.2), preoperative anemia (OR = 3.8), BMI of <30 kg/m(2) (OR = 1.4), female sex (OR = 1.3), and ASA class of >2 (OR = 1.3). Multivariate logistic regression indicated that a transfusion was significantly associated with mortality (OR = 2.7) but not with infection or venous thromboembolism. CONCLUSIONS: We did not find a strong association between perioperative red blood-cell transfusion and thirty-day incidences of infection, venous thromboembolism, or mortality; however, the odds of mortality were higher in patients who received a transfusion during total knee arthroplasty. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Osteoclast precursors acquire sensitivity to breast cancer derived factors early in differentiation.

The development of osteolytic breast cancer bone metastases relies on the ability of tumor cells to stimulate the formation of bone-resorbing osteoclasts. We have studied the effects of soluble factors produced by MDA-MB-231 breast carcinoma cells on osteoclast formation from human monocytic precursors and RAW 264.7 monocytic cells. Although factors produced by breast cancer cells were ineffective in inducing osteoclast formation from monocytes, priming with RANKL for 1-3 days dramatically increased receptiveness of osteoclast precursors to cancer-derived factors, which enhanced osteoclast formation 2-3 fold in the absence of supporting cell types. Osteoclasts formed by exposure to cancer factors expressed proteases critical for bone resorption, cathepsin K and matrix metalloproteinase 9, and were capable of resorbing calcified matrices. Expression of key osteoclastogenic transcription factor NFATc1 in osteoclast precursors was dramatically increased by short treatment with RANKL. NFATc1 was localized in the nuclei of primed osteoclast precursors when RANKL was present; however removal of RANKL led to rapid nuclear export of NFATc1. Cancer-derived factors were able to substitute for RANKL in supporting nuclear localization of NFATc1. Using neutralizing antibodies against TGFbeta, and a kinase inhibitor targeting the TGFbeta type I receptor, we identified TGFbeta as a permissive factor, required for the effects of breast cancer cells on NFATc1 nuclear accumulation and osteoclast formation. Our data suggest that, during differentiation, osteoclast precursors acquire the competency to respond to factors secreted by breast cancer cells, which may serve to promote tumor growth at skeletal sites undergoing active bone turnover.