Management of primary graft dysfunction after lung transplantation with extracorporeal life support: an evidence-based review.

Primary graft dysfunction (PGD) is a complex inflammatory syndrome that can lead to respiratory failure after lung transplantation (LTx). The pathogenesis of PGD is multifactorial and can be driven by attributes of both the donor and recipient, perioperative characteristics, and technical handling of the graft. Despite significant advancements in patient and donor selection, perioperative management and surgical technique, PGD is still a major contributor to morbidity and mortality after lung transplant. Although there are no known durable treatment options for PGD after LTx, an increasing body of evidence and experience in high-volume lung transplant centers show that extracorporeal life support (ECLS) is a reliable option for both preventing PGD and supporting critically ill patients with PGD. Both veno-venous (V-V) ECLS and veno-arterial (V-A) ECLS are proven and feasible strategies for mitigating the morbidity and mortality associated with post-LTx PGD. In this evidence-based review, we provide an overview of the epidemiology and physiology of PGD as well as a growing body of data that supports ECLS as a major tool to manage PGD. We describe the role of ECMO in PGD prevention and management, worldwide outcomes of LTx with ECLS support, and outline our step-wise approach to managing this complex respiratory syndrome leading up to institution of ECLS.

Assessment of Surgeon Performance of Advanced Open Surgical Skills Using a Microskills-Based Novel Curriculum.

Importance: The increase in minimally invasive surgical procedures has eroded exposure of general surgery residents to open operations. High-fidelity simulation, together with deliberate instruction, is needed for advanced open surgical skill (AOSS) development. Objective: To collect validity evidence for AOSS tools to support a shared model for instruction. Design, Setting, and Participants: This prospective cohort study included postresidency surgeons (PRSs) and second-year general surgery residents (R2s) at a single academic medical center who completed simulated tasks taught within the AOSS curriculum between June 1 and October 31, 2021. Exposures: The AOSS curriculum includes 6 fine-suture and needle handling tasks, including deep suture tying (with and without needles) and continuous suturing using the pitch-and-catch and push-push-pull techniques (both superficial and deep). Teaching and assessment are based on specific microskills using a 3-dimensional printed iliac fossa model. Main Outcomes and Measures: The PRS group was timed and scored (5-point Likert scale) on 10 repetitions of each task. Six months after receiving instruction on the AOSS tasks, the R2 group was similarly timed and scored. Results: The PRS group included 14 surgeons (11 male [79%]; 8 [57%] attending surgeons) who completed the simulation; the R2 group, 9 surgeons (5 female [55%]) who completed the simulation. Score and time variability were greater for the R2s compared with the PRSs for all tasks. The R2s scored lower and took longer on (1) deep pitch-and-catch suturing (69% of maximum points for a mean [SD] of 142.0 [31.7] seconds vs 77% for a mean [SD] of 95.9 [29.4] seconds) and deep push-push-pull suturing (63% of maximum points for a mean [SD] of 284.0 [72.9] seconds vs 85% for a mean [SD] of 141.4 [29.1] seconds) relative to the corresponding superficial tasks; (2) suture tying with a needle vs suture tying without a needle (74% of maximum points for a mean [SD] of 64.6 [19.8] seconds vs 90% for a mean [SD] of 54.4 [15.6] seconds); and (3) the deep push-push-pull vs pitch-and-catch techniques (63% of maximum points for a mean [SD] of 284.0 [72.9] seconds vs 69% of maximum points for a mean [SD] of 142.0 [31.7] seconds). For the PRS group, time was negatively associated with score for the 3 hardest tasks: superficial push-push-pull (ρ = 0.60; P = .02), deep pitch-and-catch (ρ = 0.73; P = .003), and deep push-push-pull (ρ = 0.81; P < .001). For the R2 group, time was negatively associated with score for the 2 easiest tasks: suture tying without a needle (ρ = 0.78; P = .01) and superficial pitch-and-catch (ρ = 0.79; P = .01). Conclusions and Relevance: The findings of this cohort study offer validity evidence for a novel AOSS curriculum; reveal differential difficulty of tasks that can be attributed to specific microskills; and suggest that position on the surgical learning curve may dictate the association between competency and speed. Together these findings suggest specific, actionable opportunities to guide instruction of AOSS, including which microskills to focus on, when individual rehearsal vs guided instruction is more appropriate, and when to focus on speed.

Contemporary Management of Hepatic Cyst Disease: Techniques and Outcomes at a Tertiary Hepatobiliary Center.

BACKGROUND: Hepatic cyst disease is often asymptomatic, but treatment is warranted if patients experience symptoms. We describe our management approach to these patients and review the technical nuances of the laparoscopic approach. METHODS: Medical records were reviewed for operative management of hepatic cysts from 2012 to 2019 at a single, tertiary academic medical center. RESULTS: Fifty-three patients (39 female) met the inclusion criteria with median age at presentation of 65 years. Fifty cases (94.3%) were performed laparoscopically. Fourteen patients carried diagnosis of polycystic liver disease. Dominant cyst diameter was median 129 mm and located within the right lobe (30), left lobe (17), caudate (2), or was bilobar (4). Pre-operative concern for biliary cystadenoma/cystadenocarcinoma existed for 7 patients. Operative techniques included fenestration (40), fenestration with decapitation (7), decapitation alone (3), and excision (2). Partial hepatectomy was performed in conjunction with fenestration/decapitation for 15 cases: right sided (7), left sided (7), and central (1). One formal left hepatectomy was performed in a polycystic liver disease patient. Final pathology yielded simple cyst (52) and one biliary cystadenoma. Post-operative complications included bile leak (2), perihepatic fluid collection (1), pleural effusion (1), and ascites (1). At median 7.1-month follow-up, complete resolution of symptoms occurred for 34/49 patients (69.4%) who had symptoms preoperatively. Reintervention for cyst recurrence occurred for 5 cases (9.4%). CONCLUSIONS: Outcomes for hepatic cyst disease are described with predominantly laparoscopic approach, approach with minimal morbidity, and excellent clinical results.

Surgical management of middle aortic syndrome in an adult.

Middle aortic syndrome (MAS), a coarctation of the lower thoracic and/or abdominal aorta, is typically diagnosed and treated in the pediatric population. We present a 48-year-old patient with a long-standing history of hypertension who was lost to follow-up owing to a lack of insurance coverage. After two myocardial infarcts owing to severe hypertension, a vascular workup including a computed tomography angiogram revealed a diagnosis of MAS. He underwent open vascular reconstruction with a thoracoabdominal Dacron bypass graft. He was discharged within 1 week with no hypertension or claudication. Adult patients diagnosed with MAS should undergo open or endovascular surgical repair with close follow-up.

Predictors and Outcomes of Paramedian Incisional Hernia After Anterior Spine Exposure.

BACKGROUND: Anterior exposures for lumbar spine surgery are increasingly common for treating various spinal pathologies. A retroperitoneal approach via a paramedian incision has grown rapidly in popularity, but little is known about the risk of incisional hernia development with this technique. We sought to assess the incidence of paramedian incisional hernia development and identify risk factors that are associated with occurrence. MATERIALS AND METHODS: We conducted a retrospective review of all patients who underwent anterior lumbar spine exposure by a paramedian approach between 2012 and 2017 at a single, tertiary medical center. The primary outcome was the development of postoperative paramedian incisional hernia. RESULTS: Of the 735 patients included in the study, 445 (60.5%) were women, and the mean (standard deviation) age of all patients was 60 y (12.4). Nearly all (97.4%) paramedian approaches were performed with a vascular surgeon present. Median follow-up time was 10 mo (interquartile range 3.5-19.9). Postoperative paramedian hernia developed in 20 patients (2.7%), of which 14 underwent repair. The mean (standard deviation) size of the hernia was 13.5 cm (5.5); 9 of 14 (64%) were repaired with synthetic mesh, whereas 3 of 14 (21%) required bowel resection. On multivariate analysis, risk factors associated with hernia development were male gender (0.045), higher American Society of Anesthesiologists class (0.039), history of abdominal surgery (P = 0.013), and postoperative intensive care unit admission (P = 0.02). CONCLUSIONS: A paramedian approach for anterior lumbar spine exposure resulted in a low rate of incisional hernia with minimal morbidity. Surgeons involved in these collaborative procedures should consider the risk factors that predispose patients to develop these hernias.

Broad Distribution of Hepatocyte Proliferation in Liver Homeostasis and Regeneration.

Hepatocyte proliferation is the principal mechanism for generating new hepatocytes in liver homeostasis and regeneration. Recent studies have suggested that this ability is not equally distributed among hepatocytes but concentrated in a small subset of hepatocytes acting like stem cells, located around the central vein or distributed throughout the liver lobule and exhibiting active WNT signaling or high telomerase activity, respectively. These findings were obtained by utilizing components of these growth regulators as markers for genetic lineage tracing. Here, we used random lineage tracing to localize and quantify clonal expansion of hepatocytes in normal and injured liver. We found that modest proliferation of hepatocytes distributed throughout the lobule maintains the hepatocyte mass and that most hepatocytes proliferate to regenerate it, with diploidy providing a growth advantage over polyploidy. These results show that the ability to proliferate is broadly distributed among hepatocytes rather than limited to a rare stem cell-like population.

Outcomes of arterial bypass preceding resection of retroperitoneal masses involving major vessels.

BACKGROUND: Current surgical management of retroperitoneal masses involving major vessels now includes complete en bloc resection with in situ venous, arterial, or combined reconstruction. No studies have investigated preresection arterial bypass for continuous lower extremity perfusion during definitive resection. Here, we characterize and compare the outcomes of surgery for retroperitoneal masses with major vascular involvement by a two-stage approach (femoral-femoral bypass preceding resection) and the traditional one-stage approach (consecutive resection and in situ vascular reconstruction). MATERIALS AND METHODS: We retrospectively reviewed patients who underwent resection of retroperitoneal masses and reconstruction of major arterial or venous structures from 2004 to 2016. Outcomes were compared with unpaired t-tests, chi-squared tests, and Kaplan-Meier analysis. RESULTS: Eight patients underwent a two-stage procedure, and seven underwent a one-stage procedure for retroperitoneal masses with vascular involvement. Mean (±SD) oncologic resection time (443 ± 215 versus 648 ± 128 min, P = 0.047) and postoperative ICU stay (0.9 ± 1.3 versus 4.4 ± 2.9 d, P = 0.018) were significantly shorter for the two-stage approach. CONCLUSIONS: To our knowledge, this is the first report of a two-stage approach for resection of retroperitoneal masses with major vessel involvement. Femoral-femoral arterial bypass before definitive resection could be a viable option for improving intraoperative vascular control and decreasing perioperative complications in these complex procedures.

De novo formation of the biliary system by TGFß-mediated hepatocyte transdifferentiation.

Transdifferentiation is a complete and stable change in cell identity that serves as an alternative to stem-cell-mediated organ regeneration. In adult mammals, findings of transdifferentiation have been limited to the replenishment of cells lost from preexisting structures, in the presence of a fully developed scaffold and niche1. Here we show that transdifferentiation of hepatocytes in the mouse liver can build a structure that failed to form in development-the biliary system in a mouse model that mimics the hepatic phenotype of human Alagille syndrome (ALGS)2. In these mice, hepatocytes convert into mature cholangiocytes and form bile ducts that are effective in draining bile and persist after the cholestatic liver injury is reversed, consistent with transdifferentiation. These findings redefine hepatocyte plasticity, which appeared to be limited to metaplasia, that is, incomplete and transient biliary differentiation as an adaptation to cell injury, based on previous studies in mice with a fully developed biliary system3-6. In contrast to bile duct development7-9, we show that de novo bile duct formation by hepatocyte transdifferentiation is independent of NOTCH signalling. We identify TGFß signalling as the driver of this compensatory mechanism and show that it is active in some patients with ALGS. Furthermore, we show that TGFß signalling can be targeted to enhance the formation of the biliary system from hepatocytes, and that the transdifferentiation-inducing signals and remodelling capacity of the bile-duct-deficient liver can be harnessed with transplanted hepatocytes. Our results define the regenerative potential of mammalian transdifferentiation and reveal opportunities for the treatment of ALGS and other cholestatic liver diseases.

Low ATM expression and progression-free and overall survival in advanced gastric cancer patients treated with first-line XELOX chemotherapy.

BACKGROUND: Gastric cancer (GC) is a leading cause of cancer-specific mortality with limited biologically informed treatments. The ataxia telangiectasia mutated (ATM) gene is critically involved in the repair of double-stranded DNA breaks and a component of DNA damage repair (DDR) pathways. Platinum salts are hypothesized to have increased efficacy in tumors deficient in DDR pathways. We sought to investigate an association between ATM status and response to XELOX in a homogenous first line GC patient cohort. METHODS: A clinically annotated cohort of 137 Korean patients with advanced GC treated with first-line XELOX was retrospectively examined for ATM status by immunohistochemistry. Correlation between ATM expression and clinicopathologic variables was performed by two-tailed, unpaired t-tests and Fisher's exact tests. Kaplan-Meier survival analysis curves and Cox proportional hazards models were used to evaluate for independent predictors of disease-free survival (DFS) and overall survival (OS). RESULTS: Low ATM expression was observed in 19.0% (26/137) of patients and was not associated with clinicopathologic features or response rate to XELOX. Univariate, but not multivariable, logistic regression and Cox analysis identified ATM as an independent risk factor influencing OS and DFS. A higher ECOG score independently predicted worse survival [hazard ratio (HR) 2.96, P=0.016] and complete surgical resection independently protected against progression of disease (HR 0.69, P=0.007). CONCLUSIONS: Low ATM expression was not associated with increased response rates to XELOX in a single-institution cohort of advanced GC patients. Similarly, ATM status did not predict DFS or OS after platinum-based chemotherapy.