Annals of surgery最新文献

Objective: To quantify the rate of progression in surveilled cysts and assess what factors should indicate delayed resection.

Background: Side-branch intraductal papillary mucinous neoplasms (SB-IPMNs) are increasingly discovered, making it challenging to identify which patients require resection, thus avoiding inappropriate treatment. Most incidental lesions are surveyed, yet the consequences of that decision remain uncertain.

Methods: A prospectively maintained database of pancreatic cystic neoplasms was queried for patients with SB-IPMN. Patients with ≥2 imaging studies >6 months apart were included. Clinically relevant progression (CR-progression) was defined by symptoms, worrisome/high-risk stigmata, or invasive cancer (IC). Growth ≥5 mm in 2 years is considered CR-progression; size ≥3 cm alone is not.

Results: Between 1997 and 2023, 1337 patients were diagnosed with SB-IPMN. Thirty-seven (2.7%) underwent up-front surgery; 1000 (75.0%) had >6 months of surveillance.The rate of CR-progression was 15.3% (n = 153) based on size increase (n = 63, 6.3%), main-duct involvement (n = 48, 4.8%), symptoms (n = 8, 5.0%), or other criteria (n = 34, 3.4%). At a median follow-up of 6.6 years (interquartile range: 3.0-10.26), 17 patients (1.7%) developed IC. Those with CR-progression developed IC in 11.1% (n = 17) and high-grade dysplasia (HGD) in 6.5% (n = 10). Nearly half of the cancers were not contiguous with the surveyed SB-IPMN.Size ≥3 cm was not associated with HGD/IC ( P = 0.232). HGD/IC was least common in CR-progression determined by size growth (6.3%) versus main-duct involvement (24%) or other (43%, P < 0.001)Patients with CR-progression demonstrated improved survival (overall survival) with resection on time-to-event ( P < 0.001) and multivariate Cox regression (hazard ratio = 0.205, 0.096-0.439, P < 0.001) analyses. Overall survival was not improved with resection in all patients ( P = 0.244).

Conclusions: CR-progression for SB-IPMNs is uncommon, with the development of cancer anywhere in the pancreas being rare. Initial size should not drive resection. Long-term and consistent nonoperative surveillance is warranted, with surgery currently reserved for CR-progression, knowing that the majority of these still harbor low-grade pathology.

Objective: To evaluate the optimal timing of thromboprophylaxis (TPX) initiation after hepatic angioembolization in trauma patients.

Background: TPX after hepatic trauma is complicated by the risk of bleeding, but the relative risk after hepatic angioembolization is unknown.

Methods: Patients who underwent hepatic angioembolization within 24 hours were retrospectively identified from the 2017 to 2019 American College of Surgeons Trauma Quality Improvement Project data sets. Cases with <24-hour length of stay and other serious injuries were excluded. Venous thromboembolism (VTE) included deep venous thrombosis and PE. Bleeding complications included hepatic surgery, additional angioembolization, or blood transfusion after TPX initiation. Differences were tested with univariate and multivariate analyses.

Results: Of 1550 patients, 1370 had initial angioembolization. Bleeding complications were higher in those with TPX initiation within 24 hours (20.0% vs 8.9%, P <0.001) and 48 hours (13.2% vs 8.4%, P =0.013). However, VTE was higher in those with TPX initiation after 48 hours (6.3% vs 3.3%, P =0.025). In the 180 patients with hepatic surgery before angioembolization, bleeding complications were higher in those with TPX initiation within 24 hours (72% vs 20%, P <0.001), 48 hours (50% vs 17%, P <0.001), and 72 hours (37% vs 14%, P =0.001). Moreover, deep venous thrombosis was higher in those with TPX initiation after 96 hours (14.3% vs 3.1%, P =0.023).

Conclusions: This is the first study to address the timing of TPX after hepatic angioembolization in a national sample of trauma patients. For these patients, initiation of TPX at 48 to 72 hours achieves the safest balance in minimizing bleeding while reducing the risk of VTE.

Level of evidence: Level III-retrospective cohort study.

Objective: Since introducing new and alternative treatment options may increase decisional conflict, we aimed to describe the use of the decision support tool (DST) and its impact on treatment preference and decisional conflict.

Background: For the treatment of appendicitis, antibiotics are an effective alternative to appendectomy, with both approaches associated with a different set of risks (eg, recurrence vs surgical complications) and benefits (eg, more rapid return to work vs decreased chance of readmission). Patients often have limited knowledge of these treatment options, and DSTs that include video-based educational materials and questions to elicit patient preferences about outcomes may be helpful. Concurrent with the Comparing Outcomes of Drugs and Appendectomy trials, our group developed a DST for appendicitis treatment ( www.appyornot.org ).

Methods: A retrospective cohort including people who self-reported current appendicitis and used the AppyOrNot DST between 2021 and 2023. Treatment preferences before and after the use of the DST, demographic information, and Ottawa Decisional Conflict Scale (DCS) were reported after completing the DST.

Results: A total of 8243 people from 66 countries and all 50 U.S. states accessed the DST. Before the DST, 14% had a strong preference for antibiotics and 31% for appendectomy, with 55% undecided. After using the DST, the proportion in the undecided category decreased to 49% ( P < 0.0001). Of those who completed the Ottawa Decisional Conflict Score (DCS; n = 356), 52% reported the lowest level of decisional conflict (<25) after using the DST; 43% had a DCS score of 25 to 50, 5.1% had a DCS score of >50 and 2.5% had and DCS score of >75.

Conclusions: The publicly available DST appyornot.org reduced the proportion that was undecided about which treatment they favored and had a modest influence on those with strong treatment preferences. Decisional conflict was not common after use. The use of this DST is now a component of a nationwide implementation program aimed at improving the way surgeons share information about appendicitis treatment options. If its use can be successfully implemented, this may be a model for improving communication about treatment for patients experiencing emergency health conditions.

Objective: To describe the evolution of pancreas transplantation, including improved outcomes and factors associated with improved outcomes over the past 5 decades.

Background: The world's first successful pancreas transplant was performed in December 1966 at the University of Minnesota. As new modalities for diabetes treatment mature, we must carefully assess the current state of pancreas transplantation to determine its ongoing role in patient care.

Methods: A single-center retrospective review of 2500 pancreas transplants was performed over >50 years in bivariate and multivariable models. Transplants were divided into 6 eras; outcomes are presented for the entire cohort and by era.

Results: All measures of patient and graft survival improved progressively through the 6 transplant eras. The overall death-censored pancreas graft half-lives were >35 years for simultaneous pancreas and kidney (SPK), 7.1 years for pancreas after kidney (PAK), and 3.3 years for pancreas transplants alone (PTA). The 10-year death-censored pancreas graft survival rate in the most recent era was 86.9% for SPK recipients, 58.2% for PAK recipients, and 47.6% for PTA. Overall, graft loss was most influenced by patient survival in SPK transplants, whereas graft loss in PAK and PTA recipients was more often due to graft failures. Predictors of improved pancreas graft survival were primary transplants, bladder drainage of exocrine secretions, younger donor age, and shorter preservation time.

Conclusions: Pancreas outcomes have significantly improved over time through sequential, but overlapping, advances in surgical technique, immunosuppressive protocols, reduced preservation time, and the more recent reduction of immune-mediated graft loss.

Objective: To evaluate prognostic differences between minimally invasive esophagectomy (MIE) and open esophagectomy (OE) in patients with surgery after a prolonged interval (>12 wk) following chemoradiotherapy (CRT).

Background: Previously, we established that a prolonged interval after CRT before esophagectomy was associated with poorer long-term survival.

Methods: This was an international multicenter cohort study involving 17 tertiary centers, including patients who received CRT followed by surgery between 2010 and 2020. Patients undergoing MIE were defined as thoracoscopic and laparoscopic approaches.

Results: A total of 428 patients (145 MIE and 283 OE) had surgery between 12 weeks and 2 years after CRT. Significant differences were observed in American Society of Anesthesiologists grade, radiation dose, clinical T stage, and histologic subtype. There were no significant differences between the groups in age, sex, body mass index, pathologic T or N stage, resection margin status, tumor location, surgical technique, or 90-day mortality. Survival analysis showed MIE was associated with improved survival in univariate ( P =0.014), multivariate analysis after adjustment for smoking, T and N stage, and histology (HR=1.69; 95% CI: 1.14-2.5) and propensity-matched analysis ( P =0.02). Further subgroup analyses by radiation dose and interval after CRT showed survival advantage for MIE in 40 to 50 Gy dose groups (HR=1.9; 95% CI: 1.2-3.0) and in patients having surgery within 6 months of CRT (HR=1.6; 95% CI: 1.1-2.2).

Conclusions: MIE was associated with improved overall survival compared with OE in patients with a prolonged interval from CRT to surgery. The mechanism for this observed improvement in survival remains unknown, with potential hypotheses including a reduction in complications and improved functional recovery after MIE.

Objective: To test the efficacy of metformin (MET) during the induction of coronary ischemia on myocardial performance in a large animal model of coronary artery disease (CAD) and metabolic syndrome (MS), with or without concomitant extracellular vesicular (EV) therapy.

Background: Although surgical and endovascular revascularization are durably efficacious for many patients with CAD, up to one-third are poor candidates for standard therapies. For these patients, many of whom have comorbid MS, adjunctive strategies are needed. EV therapy has shown promise in this context, but its efficacy is attenuated by MS. We investigated whether MET pretreatment could ameliorate therapeutic decrements associated with MS.

Methods: Yorkshire swine (n = 29) were provided a high-fat diet to induce MS, whereupon an ameroid constrictor was placed to induce CAD. Animals were initiated on 1000 mg oral MET or placebo; all then underwent repeat thoracotomy for intramyocardial injection of EVs or saline. Swine were maintained for 5 weeks before the acquisition of functional and perfusion data immediately before terminal myocardial harvest. Immunoblotting and immunofluorescence were performed on the most ischemic tissue from all groups.

Results: Regardless of EV administration, animals that received MET exhibited significantly improved ejection fraction, cardiac index, and contractility at rest and during rapid myocardial pacing, improved perfusion to the most ischemic myocardial region at rest and during pacing, and markedly reduced apoptosis.

Conclusions: MET administration reduced apoptotic cell death, improved perfusion, and augmented both intrinsic and load-dependent myocardial performance in a highly translatable large animal model of chronic myocardial ischemia and MS.

Objective: This large database study assessed whether extended pharmacologic prophylaxis for venous thromboembolism after colon cancer resection was associated with improved oncologic survival.

Background: Heparin derivatives may confer an antineoplastic effect via a variety of mechanisms (eg, inhibiting angiogenesis in the tumor microenvironment). Studies evaluating the oncologic benefit of heparin and its derivatives have been limited in postsurgical patients. Multiple society guidelines recommend consideration of 30-day treatment with low molecular weight heparin to reduce venous thromboembolism risk after abdominopelvic cancer surgery. However, utilization of extended prophylaxis remains low.

Methods: Surveillance, Epidemiology, and End Results-Medicare data were used to identify patients (age 65+) undergoing resection for nonmetastatic colon cancer from 2016 to 2017. The primary outcomes were overall and cancer-specific survival. Log-rank testing and multivariable Cox regression compared survival in patients who received extended prophylaxis versus those who did not in an inverse propensity treatment weighted cohort.

Results: A total of 20,102 patients were included in propensity-weighting and analyzed. Eight hundred (3.98%) received extended pharmacologic prophylaxis. Overall survival and cancer-specific survival were significantly higher in patients receiving prophylaxis on log-rank tests ( P =0.0017 overall, P =0.0200 cancer-specific). Multivariable Cox regression showed improved overall survival [adjusted hazard ratio 0.66 (0.56-0.78)] and cancer-specific survival [adjusted hazard ratio 0.56 (0.39-0.81)] with prophylaxis after controlling for patient, treatment, and hospital factors.

Conclusions: Extended pharmacologic prophylaxis after colon cancer resection was independently associated with improved overall and cancer-specific survival. These results suggest a potential antineoplastic effect from heparin derivatives when used in the context of preventing postsurgical venous thromboembolism.

Objective: To assess the effect of a practice-level preoperative frailty screening and optimization toolkit (OPTI-Surg) on postoperative functional recovery and complications in elderly cancer patients undergoing major surgery.

Background: Frailty is common in older adults. It increases the risk of poor postoperative functional recovery and complications. The potential for a practice-level screening/optimization intervention to improve outcomes is unknown.

Methods: Thoracic, gastrointestinal, and urologic oncological surgery practices within the National Cancer Institute Community Oncology Research Program (NCORP) were randomized 1:1:1 to usual care (UC), OPTI-Surg, or OPTI-Surg with an implementation coach. OPTI-Surg consisted of the Edmonton Frail Scale and guided recommendations for referral interventions. Patients 70 years old or above undergoing curative intent surgery were eligible. The primary outcome was 8 weeks postoperative function (kcal/wk). The key secondary outcome was complications within 90 days. Mixed models were used to compare UC to the 2 OPTI-Surg arms combined.

Results: From July 2019 to September 2022, 325 patients were enrolled in 29 practices. One hundred ninety-nine (64 UC, 135 OPTI-Surg) and 279 (78 UC, 201 OPTI-Surg) were evaluable for primary and secondary analysis, respectively. UC and OPTI-Surg patients did not significantly differ in total caloric expenditure (2.2 UC, 2.0 OPTI-Surg) after adjusting for baseline function ( P =0.53). UC and OPTI-Surg patients did not significantly differ in postoperative complications (25.6% UC, 35.3% OPTI-Surg, P =0.5).

Conclusions: Frailty assessment was successfully performed, but the OPTI-Surg intervention did not improve postoperative function nor reduce postoperative complications compared with UC. Future analysis will explore practice-level factors associated with toolkit implementation and the differences between the coaching and noncoaching arms.

Objective: We sought to determine the premium associated with a career in academic surgery, as measured by compensation normalized to the work relative value unit (wRVU).

Background: An academic surgical career embodying innovation and mentorship offers intrinsic rewards but is not well monetized. We know compensation for academic surgeons is less than their nonacademic counterparts, but the value of clinical effort, as normalized to the wRVU, between academic and nonacademic surgeons has not been well characterized. Thus, we analyzed the variations in the valuation of academic and nonacademic surgical work from 2010 to 2022.

Methods: We utilized Medical Group Management Association Provider Compensation data from 2010, 2014, 2018, and 2022 to compare academic and nonacademic surgeons. We analyzed raw total cash compensation (TCC), wRVU, TCC per wRVU (TCC/wRVU), and TCC to collections (TCCtColl). We calculated collections per wRVU (Coll/wRVU). We adjusted TCC and TCCtColl for inflation using the Consumer Price Index. Linear modeling for trend analysis was performed.

Results: Compared with nonacademic, academic surgeons had lower TCC (2010: $500,415.0±23,666 vs $631,515.5±23,948.2, -21%; 2022: $564,789.8±23,993.9 vs $628,247.4±15,753.2, -10%), despite higher wRVUs (2022: 9109.4±474.9 vs 8062.7±252.7) and higher Coll/wRVU (2022: 76.68±8.15 vs 71.80±6.10). Trend analysis indicated that TCC will converge in 2038 at an estimated $660,931.

Conclusions: In 2022, academic surgeons had more clinical activity and superior organizational revenue capture, despite less total and normalized clinical compensation. On the basis of TCC/wRVUs, academia charges a premium of 16% over nonacademic surgery. However, trend analysis suggests that TCC will converge within the next 20 years.

Objective: This study focuses on dose-response investigation using a codon-optimized and de novo-synthesized E-Selectin/AAV2 (E-Sel/AAV2) vector in preparation for Investigational New Drug enabling of subsequent clinical studies.

Background: Gene therapy is a potential solution for patients suffering from chronic limb-threatening ischemia. Understanding the dose for effective gene delivery is crucial for future Investigational New Drug-enabling studies.

Methods: Expression of the codon-optimized E-Selectin gene was assessed by flow cytometry following in vitro cell transfection assay and RT-qPCR for murine limbs injected in vivo with AAV-m-E-Selectin (E-Sel/AAV2). Dose-response studies involved 3 cohorts of FVB/NJ mice (n=6/group) with escalating log doses of E-Selectin/AAV2 injected intramuscularly in divided aliquots, ranging from 2 × 10 9 VG to 2 × 10 11 VG, into ischemic limbs created by left femoral artery/vein ligation/excision and administration of nitric oxide synthase inhibitor, L-NAME. Limb perfusion, extent of gangrene free limb, functional limb recovery, and therapeutic angiogenesis were assessed.

Results: Codon-optimized E-Sel/AAV2 gene therapy exhibits a superior expression level than WT E-Sel/AAV2 gene therapy both in vitro and in vivo. Mice treated with a high dose (2 × 10 11 VG) of E-Sel/AAV2 showed significantly improved perfusion indices, lower Faber scores, increased running stamina, and neovascularization compared with lower doses tested with control groups, indicating a distinct dose-dependent response. No toxicity was detected in any of the animal groups studied.

Conclusions: E-Sel/AAV2 Vascular Regeneration Gene Therapy holds promise for enhancing the recovery of ischemic hindlimb perfusion and function, with the effective dose identified in this study as 2 × 10 11 VG aliquots injected intramuscularly.