Pulse Oximetry Is Insensitive for Detection of Hepatopulmonary Syndrome in Patients Evaluated for Liver Transplantation.

Screening for hepatopulmonary syndrome (HPS) using pulse oximetry is recommended in liver transplant (LT) candidates because mortality is increased, independently of the severity of the oxygenation defect. LT exception points may be afforded to those with HPS and severe hypoxemia. We assessed the screening characteristics of pulse oximetry for HPS. The Pulmonary Vascular Complications of Liver Disease 2 study is a multicenter, prospective cohort study of adults undergoing their first LT evaluation. Patients underwent protocolized assessment of oxygen saturation by pulse oximetry (SpO2 ), arterial blood gas, spirometry, and contrast-enhanced echocardiography (CE). HPS was defined as an alveolar-arterial gradient ≥15 mm Hg (≥20 mm Hg if age >64 years), intrapulmonary vascular dilatation on CE, and absence of lung disease. The study sample included 363 patients. Of these, 75 (20.7%; 95% confidence interval [CI], 16.6%-25.2%) met the criteria for HPS. The area under the receiver operating characteristic curve (or c-statistic) for SpO2 in discriminating HPS was 0.59 (95% CI, 0.51-0.66). An SpO2 <96%, recommended by practice guidelines as a threshold to require further testing, had low sensitivity (28%; 95% CI, 18%-28%). The c-statistic of SpO2 in discriminating HPS with a partial pressure of oxygen (PaO2 ) <60 mm Hg (eligible for LT exception points) was 0.76 (95% CI, 0.46-1.00). An SpO2 cutoff of <96% had higher sensitivity for detecting HPS with PaO2 <60 mm Hg (71%; 95% CI, 38%-100%) but was still inadequate. Conclusion: Pulse oximetry is not sufficiently sensitive to screen for HPS in LT candidates. Arterial blood gas and CE are required in LT candidates for diagnosis of HPS.

Incorporation of Procedure-specific Risk Into the ACS-NSQIP Surgical Risk Calculator Improves the Prediction of Morbidity and Mortality After Pancreatoduodenectomy.

OBJECTIVE: This multicenter study sought to evaluate the accuracy of the American College of Surgeons National Surgical Quality Improvement Program's (ACS-NSQIP) surgical risk calculator for predicting outcomes after pancreatoduodenectomy (PD) and to determine whether incorporating other factors improves its predictive capacity. BACKGROUND: The ACS-NSQIP surgical risk calculator has been proposed as a decision-support tool to predict complication risk after various operations. Although it considers 21 preoperative factors, it does not include procedure-specific variables, which have demonstrated a strong predictive capacity for the most common and morbid complication after PD - clinically relevant pancreatic fistula (CR-POPF). The validated Fistula Risk Score (FRS) intraoperatively predicts the occurrence of CR-POPF and serious complications after PD. METHODS: This study of 1480 PDs involved 47 surgeons at 17 high-volume institutions. Patient complication risk was calculated using both the universal calculator and a procedure-specific model that incorporated the FRS and surgeon/institutional factors. The performance of each model was compared using the c-statistic and Brier score. RESULTS: The FRS was significantly associated with 30-day mortality, 90-day mortality, serious complications, and reoperation (all P < 0.0001). The procedure-specific model outperformed the universal calculator for 30-day mortality (c-statistic: 0.79 vs 0.68; Brier score: 0.020 vs 0.021), 90-day mortality, serious complications, and reoperation. Neither surgeon experience nor institutional volume significantly predicted mortality; however, surgeons with a career PD volume >450 were less likely to have serious complications (P < 0.001) or perform reoperations (P < 0.001). CONCLUSIONS: Procedure-specific complication risk influences outcomes after pancreatoduodenectomy; therefore, risk adjustment for performance assessment and comparative research should consider these preoperative and intraoperative factors along with conventional ACS-NSQIP preoperative variables.

Pancreatic fistula risk for pancreatoduodenectomy: an international survey of surgeon perception.

INTRODUCTION: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a morbid complication following pancreatoduodenectomy (PD). It is unclear how pancreatic surgeons perceive risk for this complication, and the implications thereof. METHODS: A web-based survey was distributed to members of 22 international GI surgical societies. CR-POPF risk factors were categorized as follows: (i) patient factors, (ii) pancreatic gland characteristics, (iii) intraoperative variables, (iv) perioperative mitigation techniques, or (v) institutional features. RESULTS: Surveys were completed by 897 surgeons worldwide. The most commonly cited contributors to CR-POPF risk were gland characteristics (90.7%), while patient and intraoperative factors were selected 71.2 and 69.3% of the time, respectively. Conversely, institutional features (31.7%) and perioperative mitigation techniques (21.3%) were rarely recognized. Eighty percent of surgeons use drain amylase concentration to guide drain removal decision-making; however, only 45.2% of surgeon remove drains early based upon drain amylase values. When evaluating clinical scenarios, surgeons were able to identify both negligible and high risk scenarios but struggled to differentiate between low and moderate CR-POPF risk. CONCLUSION: This international study analyzed how surgeons discern CR-POPF risk for PD. There was considerable variability in surgeons' perceptions of risk, which may have an adverse effect on the clinical use of risk adjustment measures.

The influence of fellowship training on the practice of pancreatoduodenectomy.

BACKGROUND: There has been a proliferation of gastrointestinal surgical fellowships; however, little is known regarding their association with surgical volume and management approaches. METHODS: Surveys were distributed to members of GI surgical societies. Responses were evaluated to define relationships between fellowship training and surgical practice with pancreatoduodenectomy (PD). RESULTS: Surveys were completed by 889 surgeons, 84.1% of whom had completed fellowship training. Fellowship completion was associated with a primarily HPB or surgical oncology-focused practice (p < 0.001), and greater median annual PD volume (p = 0.030). Transplant and HPB fellowship-trained respondents were more likely to have high-volume (≥20) annual practice (p = 0.005 and 0.029, respectively). Regarding putative fistula mitigation strategies, HPB-trained surgeons were more likely to use stents, biologic sealants, and autologous tissue patches (p = 0.007, <0.001 and 0.001, respectively). Surgical oncology trainees reported greater autologous patch use (p = 0.003). HPB fellowship-trained surgeons were less likely to routinely use intraperitoneal drainage (p = 0.036) but more likely to utilize early (POD ≤ 3) drain amylase values to guide removal (p < 0.001). Finally, HPB fellowship-trained surgeons were more likely to use the Fistula Risk Score in their practice (29 vs. 21%, p = 0.008). CONCLUSION: Fellowship training correlated with significant differences in surgeon experience, operative approach, and use of available fistula mitigation strategies for PD.

Defining the practice of pancreatoduodenectomy around the world.

BACKGROUND: Pancreatoduodenectomy (PD) is a technically challenging operation characterized by numerous management decisions. OBJECTIVE: This study was designed to test the hypothesis that there is significant variation in the contemporary global practice of PD. METHODS: A survey with native-language translation was distributed to members of 22 international gastrointestinal surgical societies. Practice patterns and surgical decision making for PD were assessed. Regions were categorized as North America, South/Central America, Asia/Australia, and Europe/Africa/Middle East. RESULTS: Surveys were completed by 897 surgeons, representing six continents and eight languages. The median age and length of experience of respondents were 45 years and 13 years, respectively. In 2013, surgeons performed a median of 12 PDs and reported a median career total of 80 PDs; only 53.8% of respondents had surpassed the number of PDs considered necessary to surmount the learning curve (>60). Significant regional differences were observed in annual and career PD volumes (P < 0.001). Only 3.7% of respondents practised pancreas surgery exclusively, but 54.8% performed only hepatopancreatobiliary surgery. Worldwide, the preferred form of anastomotic reconstruction was pancreatojejunostomy (88.7%). Regional variability was evident in terms of anastomotic/suture technique, stent use and drain use (including type and number), as well as in the use of octreotide, sealants and autologous patches (P < 0.02 for all). CONCLUSIONS: Globally, there is significant variability in the practice of PD. Many of these choices contrast with established randomized evidence and may contribute to variance in outcomes.

Clinical Impact of Intrapulmonary Vascular Dilatation in Candidates for Liver Transplant.

BACKGROUND: Intrapulmonary vascular dilatations (IPVD) frequently are detected in patients with liver disease by the delayed appearance of microbubbles at contrast-enhanced echocardiography. IPVD with an elevated alveolar-arterial (A-a) gradient define hepatopulmonary syndrome (HPS); however, the importance of IPVD in the absence of abnormal gas exchange is unknown. We aimed to determine the clinical impact of IPVD in patients with liver disease. METHODS: We performed a cross-sectional study within the Pulmonary Vascular Complications of Liver Disease 2 Study, a multicenter, prospective cohort study of patients being evaluated for liver transplant. We excluded patients with obstructive or restrictive lung disease, HPS, or intracardiac shunting. We compared patients with and those without IPVD. RESULTS: Forty-six patients with IPVD and 81 patients without IPVD were included. Patients with IPVD were more likely to have autoimmune hepatitis and less likely to have cryptogenic cirrhosis and hepatocellular carcinoma. Patients with IPVD had higher Child-Pugh scores (6 [interquartile range (IQR), 5-7] vs 5 [IQR, 4-7]; P = .04), possibly higher Model for End-Stage Liver Disease scores (14.5 [IQR, 11.6-15.8] vs 12.2 [IQR, 9.4-15.5]; P = .06), higher PaO2 levels (97.9 [IQR, 92.0-103.0] vs 89.0 [IQR, 82.0-96.9] mm Hg; P < .001), and lower A-a gradients (9.9 [IQR, 6.2-13.5] vs 14.9 [IQR, 9.0-21.8] mm Hg; P < .001). Symptoms and quality of life were similar between the groups. CONCLUSIONS: Autoimmune hepatitis and increased liver disease severity were associated with the presence of IPVD, which was characterized by higher PaO2 levels. Future studies to better characterize IPVD pathogenesis and the relationship of IPVD to HPS are warranted.

Surgical experience and the practice of pancreatoduodenectomy.

BACKGROUND: Experienced surgeons demonstrate improved pancreatoduodenectomy outcomes, but little is known about what distinguishes their practice. Furthermore, the concept of experience has been variably interpreted in the surgical literature. We investigated how 4 interpretations of experience influence pancreatoduodenectomy management decisions. METHODS: A survey assessing pancreatoduodenectomy practice patterns was distributed by 6 surgical societies. Regression analysis identified behaviors associated with 4 forms of experience: years in practice, surpassing the learning curve (≥50 pancreatoduodenectomies), high annual volume (≥25 pancreatoduodenectomy/year), and high career volume (>200 pancreatoduodenectomy). RESULTS: In the study, 861 surgeons responded, representing 6 continents. Senior surgeons were more likely to use pancreatogastrostomy, dunking/invagination, and external stents (all P < .05). Sixty-five percent of respondents surpassed the learning curve, and these surgeons were more likely to use a 2-layer pancreatic enteric anastomosis, stents, and the Fistula Risk Score (all P < .05). High annual volume surgeons were more likely to use the same reconstruction on every case and autologous tissue patches but less likely to use the Roux limb technique and multiple drains (all P < .05). High career volume surgeons mirrored the behaviors of those surpassing the learning curve except for using the Fistula Risk Score. CONCLUSION: Experience encompasses several components, each of which seems to influence decision making in different ways.

Low ejection fraction in donor hearts is not directly associated with increased recipient mortality.

BACKGROUND: Reduced left ventricular ejection fraction (EF) in the donor heart is often a contraindication for transplant. However, small studies have validated the use of hearts with evidence of myocardial dysfunction to boost the number of organs available for transplant. We hypothesize that donor hearts with reduced EF undergo myocardial recovery after transplant and result in equivalent recipient survival compared with grafts with normal function. METHODS: We examined post-operative outcomes of heart recipients in the database of the United Network for Organ Sharing. Patients were grouped by donor EF as follows: <40% (reduced EF); between 40% and 50% (borderline EF); and ≥50% (normal EF). Propensity score matching was performed to compare separately reduced and borderline EF patients with normal EF patients. RESULTS: Of 30,993 donors from 1996 to 2015, 127 (0.4%) had reduced EF, 613 (2.0%) had borderline EF and 30,253 (97.6%) had normal EF. In each of the 2 propensity score comparisons, the odds of post-operative stroke (p = 0.139, p = 0.551), pacemaker requirement (p = 0.238, p = 0.739), primary graft failure (p = 0.569, p = 0.817), rejection (p = 0.376, p = 0.533) and death at 1 year (p = 0.124, p = 0.247) were equivalent. At roughly 1-year follow-up after transplant, the mean EF of the reduced EF group was 58.0 ± 10.3% compared with 59.5 ± 7.5% in the matched normal EF group (p = 0.289). The mean follow-up EF of the borderline EF group was 58.3 ± 9.1% compared with 59.3 ± 7.7% in the matched normal EF group (p = 0.106). CONCLUSIONS: Recipients of hearts with reduced EF have equivalent 1-year survival compared with recipients of hearts with normal EF. Donor hearts with reduced EF show significant functional recovery after transplant.

A Propensity Score-Matched Analysis of Robotic vs Open Pancreatoduodenectomy on Incidence of Pancreatic Fistula.

Importance: The adoption of robotic pancreatoduodenectomy (RPD) is gaining momentum; however, its impact on major outcomes, including pancreatic fistula, has yet to be adequately compared with open pancreatoduodenectomy (OPD). Objective: To demonstrate that use of RPD does not increase the incidence of clinically relevant pancreatic fistula (CR-POPF) compared with OPD. Design, Setting, and Participants: Data were accrued from 2846 patients who underwent pancreatoduodenectomies (OPDs, n = 2661; RPDs, n = 185), performed by 51 surgeons at 17 institutions worldwide (2003-2015). All RPDs were conducted at a high-volume, academic, pancreatic surgery specialty center-in a standardized fashion-by surgeons who had surpassed the RPD learning curve. Propensity score matching was used to minimize bias from nonrandomized treatment assignment. The RPD and OPD cohorts were matched by propensity scores accounting for factors significantly associated with either undergoing robotic surgery or CR-POPF occurrence on logistic regression analysis. These variables included pancreatic gland texture, pancreatic duct diameter, intraoperative blood loss, pathologic findings of disease, and intraoperative drain placement. Interventions: Use of RPD or OPD. Main Outcomes and Measures: The major outcome of interest was CR-POPF occurrence, which is the most common and morbid complication following pancreatoduodenectomy. Results: The overall cohort was 51.5% male, with a median age of 64 years (interquartile range, 56-72 years). The propensity score-matched cohort comprised 152 RPDs and 152 OPDs; all covariate imbalances were alleviated. After adjusting for potential confounders, undergoing RPD was associated with a reduced risk for CR-POPF incidence (OR, 0.4 [95% CI, 0.2-0.7]; P = .002) relative to OPD. Other predictors of risk-adjusted CR-POPF occurrence included soft pancreatic parenchyma (OR, 4.7 [95% CI, 3.4-6.6]; P < .001), pathologic findings of high-risk disease (OR, 1.4 [95% CI, 1.1-1.9]; P = .01), small pancreatic duct diameter (vs ≥5 mm: 2 mm, OR, 2.1 [95% CI, 1.4-3.1]; P < .001; ≤1 mm, OR, 1.8 [95% CI, 1.0-3.0]; P = .03), elevated intraoperative blood loss (vs ≤400 mL: 401-700 mL, OR, 1.5 [95% CI, 1.1-2.0]; P = .01; >1000 mL, OR, 2.1 [95% CI, 1.4-2.9]; P < .001), omission of intraoperative drain(s) (OR, 0.5 [95% CI, 0.3-0.8]; P = .005), and octreotide prophylaxis (OR, 3.1 [95% CI, 2.3-4.0]; P < .001). Patients undergoing RPD demonstrated similar CR-POPF rates compared with patients in the OPD cohort (6.6% vs 11.2%; P = .23). This relationship held for both grade B (6.6% vs 9.2%; P = .52) and grade C (0% vs 2.0%; P = .25) POPFs. Robotic pancreatoduodenectomy was also noninferior to OPD in terms of the occurrence of any complication (73.7% vs 66.4%; P = .21), severe complications (Accordion grade ≥3, 23.05% vs 23.7%; P > .99), hospital stay (median: 8 vs 8.5 days; P = .31), 30-day readmission (22.4% vs 21.7%; P > .99), and 90-day mortality (3.3% vs 1.3%; P = .38). Conclusions and Relevance: To our knowledge, this is the first propensity score-matched analysis of robotic vs open pancreatoduodenectomy to date, and it demonstrates that RPD is noninferior to OPD in terms of pancreatic fistula development and other major postoperative outcomes.

Comparing the burden of pancreatic fistulas after pancreatoduodenectomy and distal pancreatectomy.

BACKGROUND: Differences in the behavior of postoperative pancreatic fistulas (POPF) have been described after various pancreatic resections. Here, we compare POPFs after pancreatoduodenectomy (PD) and distal pancreatectomy (DP) using the average complication burden (ACB), a quantitative measure of complication burden. METHODS: From 2001 to 2014, 837 DPs and 1,533 PDs were performed by 14 surgeons at 4 institutions. POPFs were categorized by International Study Group on Pancreatic Fistula standards as biochemical (grade A) or clinically relevant (CR-POPF; grades B and C). ACB values were derived from fistula severity scores based on the Modified Accordion Severity Grading. The ACB of POPFs was compared between PD and DP. RESULTS: POPFs were more common after DP compared with PD (34.5 vs 27.2%; P < .001); however, the incidence of any complication was greater after PD (64.9 vs 53.2%; P < .001). When POPFs occurred, they were more likely to be the highest-graded complication after DP compared with PD (65.1 vs 51.6%; P < .001). ACB significantly varied between PDs and DPs for grade C POPFs (0.804 vs 0.611; P < .001). POPFs accounted for 31.2% of the overall complication burden after DP compared with 17.5% of the burden after PD. ACB differed significantly across both institutions and surgeons in terms of POPFs, nonfistulous complications, and overall complications (all P < .05). CONCLUSION: Although POPFs occur less frequently after PD, they are associated with a greater complication burden compared with DP. ACB varies significantly between health care providers, suggesting the need for risk-adjusted comparisons of complication severity. Using ACB to evaluate a distinct morbidity has the potential to aid in assessing the impact of procedure-specific complications.

Externalized Stents for Pancreatoduodenectomy Provide Value Only in High-Risk Scenarios.

BACKGROUND: Evidence suggests externalized trans-anastomotic stents may be beneficial as a fistula mitigation strategy for pancreatoduodenectomy (PD); however, previous studies have not been rigorously risk-adjusted. METHODS: From 2001 to 2015, PDs were performed at three institutions, with externalized stents placed at the surgeon's discretion. The Fistula Risk Score (FRS) and the Modified Accordion Severity Grading System were used to analyze occurrence and severity of clinically relevant postoperative pancreatic fistula (CR-POPF) across various risk scenarios. RESULTS: Of 729 PDs, externalized stents were placed during 129 (17.7 %). Overall, CR-POPFs occurred in 77 (10.6 %) patients. The median FRS of patients who received externalized stents was significantly higher compared with patients who did not (6 vs. 3, p < 0.0001). Patients with negligible, low, or moderate CR-POPF risk (FRS 0-6) did not demonstrate improved outcomes with externalized stents; however, among high-risk patients (FRS 7-10), stents were associated with significantly reduced rates of CR-POPF (14.0 vs. 36.4 %, p = 0.031), severe complications (p = 0.039), and hospital stay (p = 0.014) compared with no stents. The average complication burden of CR-POPF was significantly lower for patients with externalized stents (p = 0.035). CONCLUSION: This multicenter study, the largest comparative analysis of externalized trans-anastomotic stents versus no stent for PD, demonstrates a risk-stratified benefit to externalized stents.

The Characterization and Prediction of ISGPF Grade C Fistulas Following Pancreatoduodenectomy.

INTRODUCTION: International Study Group of Pancreatic Fistula (ISGPF) grade C postoperative pancreatic fistulas (POPF) are the greatest contributor to major morbidity and mortality following pancreatoduodenectomy (PD); however, their infrequent occurrence has hindered deeper analysis. This study sought to develop a predictive algorithm, which could facilitate effective management of this challenging complication. METHODS: Data were accrued from 4301 PDs worldwide. Demographics, postoperative management, and microbiological characteristics of grade C POPFs were evaluated. American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) preoperative and intraoperative variables were compared between grade C POPFs and a 639-case sample of non-grade C POPFs. Risk factors for grade C POPF formation were identified using regression analysis. RESULTS: Grade C POPFs developed in 79 patients (1.8 %). Deaths (90 days) occurred in 2.0 % (N = 88) of the overall series, with 35 % (N = 25) occurring in the presence of a grade C POPF. Reoperations occurred 72.2 % of the time. The rates of single- and multi-system organ failure were 28.2 and 39.7 %, respectively. Mortality rates escalated with pulmonary, renal, and neurologic organ failure, but they were unaffected by reoperation(s). The median number of complications incurred was four (IQR: 2-5), and the median duration of hospital stay was 32 (IQR: 21-54) days. Warning signs for impending grade C POPFs most often presented on postoperative day (POD) 6. Adjuvant chemotherapy might have benefited 55.7 % of grade C POPF patients, yet it was delayed in 25.6 % and never delivered in 67.4 % of these patients. Predictive models for grade C POPF occurrence based on preoperative factors alone and preoperative and intraoperative factors yielded areas under the receiver operating characteristic curve of 0.73 and 0.84 (both P < 0.000001), respectively. CONCLUSION: This global study represents the largest analysis of grade C POPFs following PD. It describes the severe burden that grade C POPFs incur on patients, with high rates of reoperation and infection, while also potentially worsening overall survival by causing death and delay/omission of adjuvant therapy. Additionally, aggressive clinical management for these POPFs did not improve or worsen 90-day mortality. Predictive tools developed through these data may provide value in managing this difficult complication.