Tissue-specific mitochondrial HIGD1C promotes oxygen sensitivity in carotid body chemoreceptors.

Mammalian carotid body arterial chemoreceptors function as an early warning system for hypoxia, triggering acute life-saving arousal and cardiorespiratory reflexes. To serve this role, carotid body glomus cells are highly sensitive to decreases in oxygen availability. While the mitochondria and plasma membrane signaling proteins have been implicated in oxygen sensing by glomus cells, the mechanism underlying their mitochondrial sensitivity to hypoxia compared to other cells is unknown. Here, we identify HIGD1C, a novel hypoxia-inducible gene domain factor isoform, as an electron transport chain complex IV-interacting protein that is almost exclusively expressed in the carotid body and is therefore not generally necessary for mitochondrial function. Importantly, HIGD1C is required for carotid body oxygen sensing and enhances complex IV sensitivity to hypoxia. Thus, we propose that HIGD1C promotes exquisite oxygen sensing by the carotid body, illustrating how specialized mitochondria can be used as sentinels of metabolic stress to elicit essential adaptive behaviors.

A prospective feasibility study evaluating the 5x-multiplier to standardize discharge prescriptions in cancer surgery patients.

Background: We designed a prospective feasibility study to assess the 5x-multiplier (5x) calculation (eg, 3 pills in last 24 hours × 5 = 15) to standardize discharge opioid prescriptions compared to usual care. Methods: Faculty-based surgical teams volunteered for either 5x or usual care arms. Patients undergoing inpatient (≥ 48 hours) surgery and discharged by surgical teams were included. The primary end point was discharge oral morphine equivalents. Secondary end points were opioid-free discharges and 30-day refill rates. Results: Median last 24-hour oral morphine equivalents was similar between arms (7.5 mg 5x vs 10 mg usual care, P = .830). Median discharge oral morphine equivalents were less in the 5x arm (50 mg 5x vs 75 mg usual care, P < .001). Opioid-free discharges included 33.5% 5x vs 18.0% usual care arm patients (P < .001). Thirty-day refill rates were similar (15.3% 5x vs 16.5% usual care, P = .742). Conclusion: The 5x-multiplier was associated with reduced opioid prescriptions without increased refills and can be feasibly implemented across a diverse surgical practice.

A Predictive Model for Nodal Metastases in Patients With Appendiceal Cancers.

BACKGROUND: Histologic subtypes of appendiceal cancer vary in their propensity for metastases to regional lymph nodes (LN). A predictive model would help direct subsequent surgical therapy. METHODS: The National Cancer Database was queried for patients with appendiceal cancer undergoing surgery between 1998 and 2012. Multivariable logistic regression was used to develop a predictive model of LN metastases which was internally validated using Brier score and Area under the Curve (AUC). RESULTS: A total of 21,647 patients were identified, of whom 9079 (41.9%) had node negative disease, 4575 (21.1%) node positive disease, and 7993 (36.9%) unknown LN status. The strongest predictors of LN positivity were histology (carcinoid tumors OR 12.78, 95% CI 9.01-18.12), increasing T Stage (T3 OR 3.36, 95% CI 2.52-4.50, T4 OR 6.30, 95% CI 4.71-8.42), and tumor grade (G3 OR 5.55, 95% CI 4.78-6.45, G4 OR 5.98, 95% CI 4.30-8.31). The coefficients from the regression analysis were used to construct a calculator that generated predicted probabilities of LN metastases given certain inputs. Internal validation of the overall model showed an AUC of 0.75 (95% CI 0.74-0.76) and Brier score of 0.188. Histology-specific predictive models were also constructed with an AUC that varied from 0.669 for signet cell to 0.75 for goblet cell tumors. CONCLUSIONS: The risk for nodal metastases in patients with appendiceal cancers can be quantified with reasonable accuracy using a predictive model incorporating patient age, sex, tumor histology, T-stage, and grade. This can help inform clinical decision making regarding the need for a right hemicolectomy following appendectomy.

Comparative Effectiveness of Pylorus-Preserving Versus Standard Pancreaticoduodenectomy in Clinical Practice.

OBJECTIVES: We compared risk-adjusted short- and long-term outcomes between standard pancreaticoduodenectomy (SPD) and a pylorus-preserving pancreaticoduodenectomy (PPPD). METHODS: The National Cancer Database was queried for the years 2004 to 2014 to identify patients with adenocarcinoma of the pancreatic head undergoing SPD and PPD. Margin status, lymph node yield, length of stay (LOS), 30- and 90-day mortality, and overall survival were compared. RESULTS: A total of 11,172 patients were identified, of whom 9332 (83.5%) underwent SPD and 1840 (16.5%) PPPD. There was no difference in patient age, sex, stage, tumor grade, radiation treatment, and chemotherapy treatment between the 2 groups. Total number of regional lymph nodes was examined, and surgical margin status and overall survival were also comparable. However, patients undergoing PPPD had a shorter LOS (11.3 vs 12.3 days, P < 0.001), lower 30-day mortality (2.5% vs 3.7%, P = 0.02), and 90-day mortality (5.5% vs 6.9%, P = 0.03). On multivariate analyses, patients undergoing SPD were at higher risk for 30-day mortality compared with PPPD (odds ratio, 1.51; 95% confidence interval, 1.07-2.13). CONCLUSIONS: Standard pancreaticoduodenectomy and PPPD are oncologically equivalent, yet PPPD is associated with a reduction in postoperative mortality and shorter LOS.

Enhanced recovery in liver surgery decreases postoperative outpatient use of opioids.

BACKGROUND: Pathways of enhanced recovery in liver surgery decrease inpatient opioid use; however, little data exist regarding their effect on discharge prescriptions and post-discharge opioid intake. METHODS: For consecutive patients undergoing liver resection from 2011-2018, clinicopathologic factors were compared between patients exposed to enhanced recovery vs. traditional care pathways. Multivariable analysis was used to determine factors predictive for traditional opioid use at the first postoperative follow-up. The enhanced recovery in liver surgery protocol included opioid-sparing analgesia, goal-directed fluid therapy, early postoperative feeding, and early ambulation. RESULTS: Of 244 cases, 147 enhanced recovery patients were compared with 97 traditional pathway patients. Enhanced recovery patients were older (median 57 years vs 52 years, P = .031) and more frequently had minimally invasive operations (37% vs 16%, P < .001), with fewer major complications (2% vs 9%, P = .011). Enhanced recovery patients were less likely to be discharged with a prescription for traditional opioids (26% vs 79%, P < .001) and less likely to require opioids at their first postoperative visit (19% vs 61%, P < .001) despite similarly low patient-reported pain scores (median 2/10 both groups, P = .500). On multivariable analysis, the traditional recovery pathway was independently associated with traditional opioid use at the first follow-up (odds ratio 6.4, 95% confidence interval 3.5-12.1; P < .001). CONCLUSION: The implementation of an enhanced recovery in liver surgery pathway with opioid-sparing techniques was associated with decreased postoperative discharge prescriptions for opioids and outpatient opioid use after oncologic liver surgery, while achieving the same level of pain control. For this and other populations at risk of persistent opioid use, enhanced recovery strategies can eliminate excess availability of opioids.

Enhanced recovery in liver surgery.

Enhanced recovery in liver surgery has been shown to improve outcomes including patient-reported outcomes, length of stay, return to intended oncology therapy, and cost. The goal of this chapter will be to review the elements of a modern enhanced recovery pathway that is utilized across the entire episode of care in liver surgery.

Implementation of a standardized electronic tool improves compliance, accuracy, and efficiency of trainee-to-trainee patient care handoffs after complex general surgical oncology procedures.

BACKGROUND: Duty-hour regulations have increased the frequency of trainee-trainee patient handoffs. Each handoff creates a potential source for communication errors that can lead to near-miss and patient-harm events. We investigated the utility, efficacy, and trainee experience associated with implementation of a novel, standardized, electronic handoff system. METHODS: We conducted a prospective intervention study of trainee-trainee handoffs of inpatients undergoing complex general surgical oncology procedures at a large tertiary institution. Preimplementation data were measured using trainee surveys and direct observation and by tracking delinquencies in charting. A standardized electronic handoff tool was created in a research electronic data capture (REDCap) database using the previously validated I-PASS methodology (illness severity, patient summary, action list, situational awareness and contingency planning, and synthesis). Electronic handoff was augmented by direct communication via phone or face-to-face interaction for inpatients deemed "watcher" or "unstable." Postimplementation handoff compliance, communication errors, and trainee work flow were measured and compared to preimplementation values using standard statistical analysis. RESULTS: A total of 474 handoffs (203 preintervention and 271 postintervention) were observed over the study period; 86 handoffs involved patients admitted to the surgical intensive care unit, 344 patients admitted to the surgical stepdown unit, and 44 patients on the surgery ward. Implementation of the structured electronic tool resulted in an increase in trainee handoff compliance from 73% to 96% (P < .001) and decreased errors in communication by 50% (P = .044) while improving trainee efficiency and workflow. CONCLUSION: A standardized electronic tool augmented by direct communication for higher acuity patients can improve compliance, accuracy, and efficiency of handoff communication between surgery trainees.

Defining the Impact of Surgical Approach on Perioperative Outcomes for Patients with Gastric Cardia Malignancy.

BACKGROUND: Gastric cardia cancer is currently treated with several operations. The purpose of the current study was to compare outcomes associated with three common operative approaches. METHODS: The ACS-NSQIP Participant Use File was searched to identify all patients with gastric cardia malignancy who underwent total gastrectomy (TG), transhiatal esophagectomy (THE), or thoraco-abdominal esophagectomy (TAE) between 2005 and 2012. Demographic, perioperative risk factors, and outcomes were analyzed. RESULTS: Overall, there were 982 patients identified in the database who met inclusion criteria. The median age was 65 years (range 20-88) and 807 (82.2%) were male. The number of patients allocated to each approach was 204 TGs (20.8%), 271 THE (27.6%), and 507 TAE (51.6%). All approaches had similar major morbidity, cardiopulmonary morbidity, and 30-day mortality, however, TAE was associated with the highest overall morbidity (TAE 49.9% vs. TG 40.7% and THE 43.5%, p = 0.048). The independent risk factors predicting mortality were age greater than 65 years, history of myocardial infarction, and postoperative cardiopulmonary morbidity. CONCLUSIONS: For patients with proximal gastric cancer, the three most common operative approaches were associated with clinically-significant rates of overall and major morbidity. Approach-associated morbidity should be considered along with tumor location and extent when choosing a technique for resection of gastric cardia malignancy.

Advances in hepatectomy technique: Toward zero transfusions in the modern era of liver surgery.

BACKGROUND: Perioperative blood transfusions suppress immunity and increase hospital costs. Despite multiple improvements in perioperative care, rates of transfusion during/after hepatectomy are reported to range from 25 to 50%. The purpose of this study was to determine the current risk factors for perihepatectomy transfusion by assessing the impact of recent technical advances in liver surgery on transfusion rates. METHODS: Using our prospectively maintained hepatobiliary tumor database from a high-volume center, a modern cohort of 2,249 hepatectomies (2004-2013) were identified. Patient and operative characteristics were compared between 2 time periods, 2004-2008 (n = 1,139) and 2009-2013 (n = 1,110). Throughout the study interval, transfusions were given based on clinical assessment and not triggered by laboratory thresholds. RESULTS: Compared with the early cohort, the recent cohort had more patients with an American Society of Anesthesiologists score of ≥ 3 (79 vs 74%), preoperative chemotherapy (73 vs 68%), and a lesser median preoperative hemoglobin (12.9 vs 13.1 mg/dL) and platelet (215,000 vs 243,000) values (all P < .001). Despite these adverse risk factors, with an increasing use of the 2-surgeon resection technique (63 vs 50%), estimated blood loss (309 vs 394 mL), transfusion rates (6 vs 15%), and duration of stay (7.0 vs 8.4 days) were decreased (all P < .001) with no change in overall morbidity or mortality. Multivariate analysis of the recent cohort determined that the independent risk factors associated with transfusion were preoperative anemia and >350 mL of blood loss. The only independent factor associated with less transfusion was use of the 2-surgeon technique for hepatic parenchymal transection. CONCLUSION: With the exception of patients with moderate to severe preoperative anemia requiring major hepatectomy, recent technical advances have decreased significantly the need for transfusion in liver surgery.

Venous Thromboembolism Prophylaxis in Liver Surgery.

BACKGROUND: At a recently concluded Americas Hepato-Pancreato-Biliary Association Annual Meeting, a Clinical Practice Guidelines Conference Series was convened with the topic focusing on Venous Thromboembolism (VTE) Prophylaxis in Liver Surgery. The symposium brought together hepatobiliary surgeons from three continents as well as medical experts in hematology and coagulation. METHODS: The content of the discussion included literature reviews, evaluation of multi-institutional VTE outcome data, and examination of practice patterns at multiple high-volume centers. RESULTS: Literature review demonstrated that, within gastrointestinal surgery, liver resection patients are at particularly high-risk for VTE. Recent evidence clearly indicates a direct relationship between the magnitude of hepatectomy and postoperative VTE rates, however, the PT/INR does not accurately reflect the coagulation status of the post-hepatectomy patient. Evaluation of available data and practice patterns regarding the utilization and timing of anticoagulant VTE prophylaxis led to recommendations regarding preoperative and postoperative thromboprophylaxis for liver surgery patients. CONCLUSIONS: This conference was effective in consolidating our knowledge of coagulation abnormalities after liver resection. Based on the expert review of the available data and practice patterns, a number of recommendations were developed.

Rapid assessment of technical competency: the 8-min suture test.

BACKGROUND: Although simulation training and evaluation have become increasingly popular for teaching minimally invasive surgery, tools to measure open surgical skills remain underdeveloped. As there is increasing demand for objective measures of technical competency at the completion of surgical training (postgraduate year [PGY]-6 and -7), this project was designed to assess the feasibility, reliability, and validity of a novel open surgical skills evaluation tool, the 8-min suture test (8MST). METHODS: During an annual surgical skills laboratory session, fellows and residents were asked to complete a simulated end-to-end vascular anastomosis. They were limited to 8 min to perform the anastomosis between two 12-mm Dacron grafts mounted on a customized platform. Their real-time and video-recorded performance was scored by two blinded evaluators and compared with their faculty-rated technical performance on clinical rotations completed around the time of 8MST administration. RESULTS: PGY-6 and PGY-7 trainees were compared across several domains including 8MST total score (4.6 versus 5.5, P = 0.030), 8MST setup score (2.3 versus 2.4, P = 0.797), 8MST technical score (2.3 versus 3.1, P = 0.026), and clinical performance score (3.1 versus 3.6, P = 0.006). Comparison of 8MST total score to the clinical performance score identified a strong relationship with a Pearson r = 0.55 (P < 0.001) and r(2) = 0.30. Additionally, 8MST displayed high inter-rater reliability and test-retest reliability. CONCLUSIONS: The 8MST is a rapid, feasible, inexpensive, reliable, and valid test for assessment of surgical trainee technical abilities.

After Pancreatectomy, the "90 Days from Surgery" Definition Is Superior to the "30 Days from Discharge" Definition for Capture of Clinically Relevant Readmissions.

BACKGROUND: Previous studies by different authors have reported their readmission rates after pancreatectomy as either "30 days from discharge" or "90 days from surgery." The objective of this study was to determine which of these definitions captures the most surgery-related complications. METHODS: A prospectively maintained database at a high volume center was queried to identify all individuals who underwent pancreatectomy between 2000 and 2012 for any diagnosis. The data was analyzed at 30 days after discharge and 90 days after operation. The optimal timing for complication reporting was defined as the time point that maximized the capture of surgery-related readmissions and direct major surgical complications while minimizing the capture of disease (cancer)-related readmissions. RESULTS: There were 1123 patients included during the study time period. The median age was 63 years old, and 55.6% were male. Operations included 833 (74.2%) pancreaticoduodenectomies, 257 (22.9%) distal pancreatectomies, 18 (1.6%) total pancreatectomies, and 15 (1.3%) central pancreatectomies. Surgery-related readmissions occurred in 248 (22%) individuals, while readmission related to malignant disease progression occurred in 25 (2%) individuals. The 30 days from discharge definition captured 184 surgery-related readmissions and 1 disease-related readmission (sensitivity 0.74, specificity 0.96). The 90 days from surgery definition captured 215 surgery-related readmissions and 1 disease-related readmission (sensitivity 0.87, specificity 0.96). Major surgical complication was the only independent factor associated with readmission not captured by the 30 days from discharge definition (p = 0.002, HR 3.94, 95% CI 1.44­12.22). CONCLUSION: The 90 days from surgery definition was superior to the 30 days from discharge definition, especially with regards to readmission related to major surgical complications.

Patient-Reported Outcomes Accurately Measure the Value of an Enhanced Recovery Program in Liver Surgery.

BACKGROUND: Enhanced recovery (ER) pathways have become increasingly integrated into surgical practice. Studies that compare ER and traditional pathways often focus on outcomes confined to inpatient hospitalization and rarely assess a patient's functional recovery. The aim of this study was to compare functional outcomes for patients treated on an Enhanced Recovery in Liver Surgery (ERLS) pathway vs a traditional pathway. STUDY DESIGN: One hundred and eighteen hepatectomy patients rated symptom severity and life interference using the validated MD Anderson Symptom Inventory preoperatively and postoperatively at every outpatient visit until 31 days after surgery. The ERLS protocol included patient education, narcotic-sparing anesthesia and analgesia, diet advancement, restrictive fluid administration, early ambulation, and avoidance of drains and tubes. RESULTS: Seventy-five ERLS pathway patients were clinically comparable with 43 patients simultaneously treated on a traditional pathway. The ERLS patients reported lower immediate postoperative pain scores and experienced fewer complications and decreased length of stay. As measured by symptom burden on life interference, ERLS patients were more likely to return to baseline functional status in a shorter time interval. The only independent predictor of faster return to baseline interference levels was treatment on an ERLS pathway (p = 0.021; odds ratio = 2.62). In addition, ERLS pathway patients were more likely to return to intended oncologic therapy (95% vs 87%) at a shorter time interval compared to patients on the traditional pathway (44.7 vs 60.2 days). CONCLUSIONS: In oncologic liver surgery, enhanced recovery's primary mechanism of action is reduction in life interference by postoperative surgical symptoms, allowing patients to return sooner to normal function and adjuvant cancer therapies.

Incomplete reporting of enhanced recovery elements and its impact on achieving quality improvement.

BACKGROUND: Enhanced recovery (ER) protocols are used widely in surgical practice. As protocols are multidisciplinary with multiple components, it is difficult to compare and contrast reports. The present study examined compliance and transferability to clinical practice among ER publications related to colorectal surgery. METHODS: PubMed, Embase and Cochrane Central Register databases were searched for current colorectal ER manuscripts. Each publication was assessed for the number of ER elements, whether the element was explained sufficiently so that it could be transferred to clinical practice, and compliance with the ER element. RESULTS: Some 50 publications met the reporting criteria for inclusion. A total of 22 ER elements were described. The median number of elements included in each publication was 9, and the median number of included patients was 130. The elements most commonly included in ER pathways were early postoperative diet advancement (49, 98 per cent) and early mobilization (47, 94 per cent). Early diet advancement was sufficiently explained in 43 (86 per cent) of the 50 publications, but only 22 (45 per cent) of 49 listing the variable reported compliance. The explanation for early mobilization was satisfactory in 41 (82 per cent) of the 50 publications, although only 14 (30 per cent) of 47 listing the variable reported compliance. Other ER elements had similar rates of explanation and compliance. The most frequently analysed outcome measures were morbidity (49, 98 per cent), length of stay (47, 94 per cent) and mortality (45, 90 per cent). CONCLUSION: The current standard of reporting is frequently incomplete. To transfer knowledge and facilitate implementation of pathways that demonstrate improvements in perioperative care and recovery, a consistent structured reporting platform is needed.

Evaluating surgeon attitudes towards the safety and efficacy of portal vein occlusion and associating liver partition and portal vein ligation: a report of the MALINSA survey.

BACKGROUND: Various techniques, including portal vein embolization (PVE), contralateral portal vein ligation (PVL) and associating liver partition and portal vein ligation (ALPPS), are being used to augment the future liver remnant (FLR) volume in preparation for a major hepatectomy. The present study aims to survey and document the availability, variation, utilization and attitudes toward these techniques across centres in North and South America. METHODS: A descriptive, 20-question survey was developed and internally validated with expert review. The survey was distributed to 115 centres in North and South America. RESULTS: Of the 115 centres, 54 institutions (47%) returned the surveys. Regarding the question of which modality was most likely to produce adequate hypertrophy, the respondents were equally distributed (ALPPS, 37%; PVE, 35%; equal, 22%). The procedure that respondents judged the safest to achieve liver hypertrophy was PVE (82%). Institutions with capability to extended PVE to segment IV rated the likelihood of PVE technical success (6.2 versus 8.5, P = 0.012) and likelihood of subsequent hypertrophy (5.6 versus 7.8, P = 0.011) higher than institutions without this capability. Although the use of modern embolic materials was associated with a likelihood of successful PVE (P = 0.032), only 49% of respondents who performed PVE used embolic microspheres. CONCLUSIONS: There exists significant variability in utilization of and attitudes towards the available techniques for FLR volume augmentation. Penetration of best practice techniques for PVE is lacking, and may be contributing towards disappointment with PVE efficacy, potentially motivating the utilization of the riskier ALPPS procedure.

Successful coil embolization of circumflex iliac artery pseudoaneurysms following paracentesis.

Abdominal paracentesis complicated by perforation of a penetrating arterial branch is an extremely rare complication. We report 2 patients who presented with abdominal wall pseudoaneurysms following abdominal paracentesis for the evaluation and treatment of their hepatic dysfunction. We subsequently review the treatment modalities and interventions performed in each case.