The risk of clinically-relevant pancreatic fistula after pancreaticoduodenectomy is better predicted by a postoperative trend in drain fluid amylase compared to day 1 values in isolation.

BACKGROUND: Recent studies support early drain removal after pancreaticoduodenectomy in patients with a drain fluid amylase on postoperative day 1 (DFA1) level of ≤5,000. The use of DFA1 to guide drain management is increasingly common among pancreatic surgeons; however, the benefit of checking additional drain fluid amylases beyond DFA1 is less known. We sought to determine whether a change in drain fluid amylase (ΔDFA) is a more reliable predictor of clinically relevant postoperative fistula than DFA1 alone. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Plan, pancreaticoduodenectomy patients with intraoperative drain placement, known DFA1, highest recorded drain fluid amylase value on postoperative day 2 to 5 (DFA2nd), day of drain removal, and clinically relevant postoperative fistula status were reviewed. Logistic models compared the predictive performance of DFA1 alone versus DFA1 + ΔDFA. RESULTS: A total of 2,417 patients with an overall clinically relevant postoperative fistula rate of 12.6% were analyzed. On multivariable regression, clinical predictors for clinically relevant postoperative fistula included body mass index, steroid use, operative time, and gland texture. These variables were used to develop model 1 (DFA1 alone) and model 2 (DFA1 + ΔDFA). Model 2 outperformed model 1 in predicting the risk of clinically relevant postoperative fistula. According to model 2 predictions, the risk of clinically relevant postoperative fistula increased with any rise in drain fluid amylase, regardless of whether the DFA1 was above or below 5,000 U/L. The risk of clinically relevant postoperative fistula significantly decreased with any drop in drain fluid amylase, with an odds reduction of approximately 50% corresponding with a 70% decrease in drain fluid amylase (P < .001). A risk calculator was developed using DFA1 and a secondary DFA value in conjunction with other clinical predictors for clinically relevant postoperative fistula. CONCLUSION: Clinically relevant postoperative fistula after pancreaticoduodenectomy is more accurately predicted by DFA1 and ΔDFA versus DFA1 in isolation. We developed a novel risk calculator to provide an individualized approach to drain management after pancreaticoduodenectomy.

Robotic Pancreaticoduodenectomy: Increased Adoption and Improved Outcomes: Is Laparoscopy Still Justified?

OBJECTIVE: To compare the rate of postoperative 30-day complications between laparoscopic pancreaticoduodenectomy (LPD) and robotic pancreaticoduodenectomy (RPD). BACKGROUND: Previous studies suggest that minimally invasive pancreaticoduodenectomy (MI-PD)-either LPD or RPD-is noninferior to open pancreaticoduodenectomy in terms of operative outcomes. However, a direct comparison of the two minimally invasive approaches has not been rigorously performed. METHODS: Patients who underwent MI-PD were abstracted from the 2014 to 2019 pancreas-targeted American College of Surgeons National Sample Quality Improvement Program (ACS NSQIP) dataset. Optimal outcome was defined as absence of postoperative mortality, serious complication, percutaneous drainage, reoperation, and prolonged length of stay (75th percentile, 11 days) with no readmission. Multivariable logistic regression models were used to compare optimal outcome of RPD and LPD. RESULTS: A total of 1540 MI-PDs were identified between 2014 and 2019, of which 885 (57%) were RPD and 655 (43%) were LPD. The rate of RPD cases/year significantly increased from 2.4% to 8.4% ( P =0.008) from 2014 to 2019, while LPD remained unchanged. Similarly, the rate of optimal outcome for RPD increased during the study period from 48.2% to 57.8% ( P <0.001) but significantly decreased for LPD (53.5% to 44.9%, P <0.001). During 2018-2019, RPD outcomes surpassed LPD for any complication [odds ratio (OR)=0.58, P =0.004], serious complications (OR=0.61, P =0.011), and optimal outcome (OR=1.78, P =0.001). CONCLUSIONS: RPD adoption increased compared with LPD and was associated with decreased overall complications, serious complications, and increased optimal outcome compared with LPD in 2018-2019.

500 Minimally Invasive Robotic Pancreatoduodenectomies: One Decade of Optimizing Performance.

OBJECTIVES: This study aims to present the outcomes of our decade-long experience of robotic pancreatoduodenectomy and provide insights into successful program implementation. BACKGROUND: Despite significant improvement in mortality over the past 30 years, morbidity following open pancreatoduodenectomy remains high. We implemented a minimally invasive pancreatic surgery program based on the robotic platform as one potential method of improving outcomes for this operation. METHODS: A retrospective review of a prospectively maintained institutional database was performed to identify patients who underwent robotic pancreatoduodenectomy (RPD) between 2008 and 2017 at the University of Pittsburgh. RESULTS: In total, 500 consecutive RPDs were included. Operative time, conversion to open, blood loss, and clinically relevant postoperative pancreatic fistula improved early in the experience and have remained low despite increasing complexity of case selection as reflected by increasing number of patients with pancreatic cancer, vascular resections, and higher Charlson Comorbidity scores (all P<0.05). Operating room time plateaued after 240 cases at a median time of 391 minutes (interquartile rang 340-477). Major complications (Clavien >2) occurred in less than 24%, clinically relevant postoperative pancreatic fistula in 7.8%, 30- and 90-day mortality were 1.4% and 3.1% respectively, and median length of stay was 8 days. Outcomes were not impacted by integration of trainees or expansion of selection criteria. CONCLUSIONS: Structured implementation of robotic pancreatoduodenectomy can be associated with excellent outcomes. In the largest series of RPD, we establish benchmarks for the surgical community to consider when adopting this approach.

Optimal Pancreatic Surgery: Are We Making Progress in North America?

OBJECTIVE: Our aims were to assess North American trends in the management of patients undergoing pancreatoduodenectomy (PD) and distal pancreatectomy (DP), and to quantify the delivery of optimal pancreatic surgery. BACKGROUND: Morbidity after pancreatectomy remains unacceptably high. Recent literature suggests that composite measures may more accurately define surgical quality. METHODS: The 2013 to 2017 American College of Surgeons National Surgical Quality Improvement Program Participant Use Files were queried to identify patients undergoing PD (N = 16,222) and DP (N = 7946). Patient, process, procedure, and 30-day postoperative outcome variables were analyzed over time. Optimal pancreatic surgery was defined as the absence of postoperative mortality, serious morbidity, percutaneous drainage, and reoperation while achieving a length of stay equal to or less than the 75th percentile (12 days for PD and 7 days for DP) with no readmissions. Risk-adjusted time-trend analyses were performed using logistic regression, and the threshold for statistical significance was P ≤ 0.05. RESULTS: The use of minimally invasive PD did not change over time, but robotic PD increased (2.5 to 4.2%; P < 0.001) and laparoscopic PD decreased (5.8% to 4.3%; P < 0.02). Operative times decreased (P < 0.05) and fewer transfusions were administered (P < 0.001). The percentage of patients with a drain fluid amylase checked on postoperative day 1 increased (P < 0.001), and a greater percentage of surgical drains were removed by postoperative day 3 (P < 0.001). Overall morbidity (P < 0.02), mortality (P < 0.05), and postoperative length of stay (P = 0.002) decreased. Finally, the rate of optimal pancreatic surgery increased for PD (53.7% to 56.9%; P < 0.01) and DP (53.3% to 58.5%; P < 0.001), and alspo for patients with pancreatic cancer (P < 0.01). CONCLUSIONS: From 2013 to 2017, pre, intra, and perioperative pancreatectomy processes have evolved, and multiple postoperative outcomes have improved. Thus, in 4 years, optimal pancreatic surgery in North America has increased by 3% to 5%.

A Combination of Robotic Approach and ERAS Pathway Optimizes Outcomes and Cost for Pancreatoduodenectomy.

OBJECTIVE: To determine the impact of enhanced recovery after surgery (ERAS) pathway implementation on outcomes, and cost of robotic and open pancreatoduodenectomy. BACKGROUND: ERAS pathways have shown benefit in open pancreatoduodenectomy (OPD). The impact of ERAS on robotic pancreatoduodenectomy (RPD) is unknown. METHODS: Retrospective review of consecutive RPD and OPDs in the pre-ERAS (July, 2014-July, 2015) and ERAS (July, 2015-July, 2016) period. Univariate and multivariate logistic regression was used to determine impact of ERAS and operative approach alone, or in combination (pre-ERAS + OPD, pre-ERAS + RPD, ERAS + OPD, ERAS + RPD) on length of hospital stay (LOS) and overall cost. RESULTS: In all, 254 consecutive pancreatoduodenectomies (RPD 62%, OPD 38%) were analyzed (median age 67, 47% female). ERAS patients had shorter LOS (6 vs 8 days; P = 0.004) and decreased overall cost (USD 20,362 vs 24,277; P = 0.001) compared with non-ERAS patients, whereas RPD was associated with decreased LOS (7 vs 8 days; P = 0.0001) and similar cost compared with OPD. On multivariable analysis (MVA), RPD was predictive of shorter LOS [odds ratio (OR) 0.33, confidence interval (CI) 0.16-0.67, P = 0.002), whereas ERAS was protective against high cost (OR 0.57, CI 0.33-0.97, P = 0.037). On MVA, when combining operative approach with ERAS pathway use, a combined ERAS + RPD approach was associated with reduced LOS and optimal cost compared with other combinations (pre-ERAS + OPD, pre-ERAS + RPD, ERAS + OPD). CONCLUSION: ERAS implementation is independently associated with cost savings for pancreatoduodenectomy. A combination of ERAS and robotic approach synergistically decreases hospital stay and overall cost compared with other strategies.

Robotic pancreatoduodenectomy with vascular resection: Outcomes and learning curve.

INTRODUCTION: The safety, efficacy, and learning curve for robotic pancreatoduodenecomy has been reported; however, the outcomes and learning curve of robotic pancreatoduodenecomy with vascular resections remain unknown. Our aim was to evaluate the outcomes of robotic pancreatoduodenecomy with vascular resections compared with robotic pancreatoduodenecomy without vascular resection and to identify the learning curve and benchmarks for improved performance during robotic pancreatoduodenecomy with vascular resections. METHODS: A retrospective review of consecutive patients who underwent robotic pancreatoduodenecomy with vascular resections and robotic pancreatoduodenecomy between 2011 and 2017. Patients were analyzed consecutively, and a cumulative sum analysis was performed to detect improvements in performance over time. RESULTS: Of 380 consecutive robotic pancreatoduodenecomy patients, 50 (13%) underwent robotic pancreatoduodenecomy with vascular resections. Compared with robotic pancreatoduodenecomy, robotic pancreatoduodenecomy with vascular resections were more likely to have had pancreatic adenocarcinoma (84% vs 42%) and had received neoadjuvant therapy (35% vs 65%, P < .01). Robotic pancreatoduodenecomy with vascular resections operative time revealed a steady, significant decrease (Rho = -0.38, p = .006) with marked initial improvement after the first 8 cases and maturation of the learning curve after 35 cases. A significant decrease in duration of the hospital stay was observed throughout the experience (Rho = -0.528, P < .0001), whereas margin status, pancreatic fistula, major morbidity, and mortality remained constant and comparable to robotic pancreatoduodenecomy alone. CONCLUSION: Robotic pancreatoduodenectomy with vascular resections is safe and feasible. For surgeons who have surpassed the learning curve of robotic pancreatoduodenectomy, it appears that improvements in performance of robotic pancreatoduodenecomy with vascular resections can be observed after 35 cases.

Identification of an Optimal Cut-off for Drain Fluid Amylase on Postoperative Day 1 for Predicting Clinically Relevant Fistula After Distal Pancreatectomy: A Multi-institutional Analysis and External Validation.

OBJECTIVE: The aim of this study was to investigate the relationship between drain fluid amylase value on the first postoperative day (DFA1) and clinically relevant fistula (CR-POPF) after distal pancreatectomy (DP), and to identify the cut-off of DFA1 that optimizes CR-POPF prediction. BACKGROUND: DFA1 is a well-recognized predictor of CR-POPF after pancreatoduodenectomy, but its role in DP is largely unexplored. METHODS: DFA1 levels were correlated with CR-POPF in 2 independent multi-institutional sets of DP patients: developmental (n = 338; years 2012 to 2017) and validation cohort (n = 166; years 2006 to 2016). Cut-off choice was based on Youden index calculation, and its ability to predict CR-POPF occurrence was tested in a multivariable regression model adjusted for clinical, demographic, operative, and pathological variables. RESULTS: In the developmental set, median DFA1 was 1745 U/L and the CR-POPF rate was 21.9%. DFA1 correlated with CR-POPF with an area under the curve of 0.737 (P < 0.001). A DFA1 of 2000 U/L had the highest Youden index, with 74.3% sensitivity and 62.1% specificity. Patients in the validation cohort displayed different demographic and operative characteristics, lower values of DFA1 (784.5 U/L, P < 0.001), and reduced CR-POPF rate (10.2%, P < 0.001). However, a DFA1 of 2000 U/L had the highest Youden index in this cohort as well, with 64.7% sensitivity and 75.8% specificity. At multivariable analysis, DFA1 ≥2000 U/L was the only factor significantly associated with CR-POPF in both cohorts. CONCLUSION: A DFA1 of 2000 U/L optimizes CR-POPF prediction after DP. These results provide the substrate to define best practices and improve outcomes for patients receiving DP.

Risk Factors and Mitigation Strategies for Pancreatic Fistula After Distal Pancreatectomy: Analysis of 2026 Resections From the International, Multi-institutional Distal Pancreatectomy Study Group.

OBJECTIVE: To identify a clinical fistula risk score following distal pancreatectomy. BACKGROUND: Clinically relevant pancreatic fistula (CR-POPF) following distal pancreatectomy (DP) is a dominant contributor to procedural morbidity, yet risk factors attributable to CR-POPF and effective practices to reduce its occurrence remain elusive. METHODS: This multinational, retrospective study of 2026 DPs involved 52 surgeons at 10 institutions (2001-2016). CR-POPFs were defined by 2016 International Study Group criteria, and risk models generated using stepwise logistic regression analysis were evaluated by c-statistic. Mitigation strategies were assessed by regression modeling while controlling for identified risk factors and treating institution. RESULTS: CR-POPF occurred following 306 (15.1%) DPs. Risk factors independently associated with CR-POPF included: age (<60 yrs: OR 1.42, 95% CI 1.05-1.82), obesity (OR 1.54, 95% CI 1.19-2.12), hypoalbuminenia (OR 1.63, 95% CI 1.06-2.51), the absence of epidural anesthesia (OR 1.59, 95% CI 1.17-2.16), neuroendocrine or nonmalignant pathology (OR 1.56, 95% CI 1.18-2.06), concomitant splenectomy (OR 1.99, 95% CI 1.25-3.17), and vascular resection (OR 2.29, 95% CI 1.25-3.17). After adjusting for inherent risk between cases by multivariable regression, the following were not independently associated with CR-POPF: method of transection, suture ligation of the pancreatic duct, staple size, the use of staple line reinforcement, tissue patches, biologic sealants, or prophylactic octreotide. Intraoperative drainage was associated with a greater fistula rate (OR 2.09, 95% CI 1.51-3.78) but reduced fistula severity (P < 0.001). CONCLUSIONS: From this large analysis of pancreatic fistula following DP, CR-POPF occurrence cannot be reliably predicted. Opportunities for developing a risk score model are limited for performing risk-adjusted analyses of mitigation strategies and surgeon performance.

Fitbit step counts during inpatient recovery from cancer surgery as a predictor of readmission.

Background: Postoperative ambulation is encouraged to promote timely recovery but is rarely monitored objectively or examined as a predictor of clinical outcomes, despite growing availability of wearable devices that allow passive quantification and remote real-time monitoring of the number of steps taken during recovery. Purpose: To determine whether the number of steps taken during inpatient recovery predicts 30- and 60-day readmission risk after metastatic cancer surgery. Methods: Patients diagnosed with metastatic peritoneal cancer and scheduled for surgical resection were enrolled in this observational cohort study at their preoperative clinic visit. Fitbits were placed on patients' wrists upon transfer from the ICU following surgery and worn for the duration of their inpatient stay. Information about hospital readmission was extracted from electronic medical records. Results: Seventy-one patients participated in the study (mean age = 57.14, range = 31-80 years; 42% female; 51% diagnosed with appendiceal cancer). Mean steps per day were calculated for each participant over the entire inpatient recovery period (mean stay = 12.12 days, 4-37 days). Readmission within 30 and 60 days was medically indicated for 34% and 39% of patients, respectively. After statistically adjusting for age, body mass index, comorbidity, and length of postoperative stay, higher mean steps per day predicted lower 30-day and 60-day readmission risk. Conclusions: Higher Fitbit step counts during inpatient recovery predicted lower risk of 30- and 60-day readmission after surgery for metastatic peritoneal cancer. Results suggest that passively monitoring perioperative ambulation may identify patients at risk for readmission and highlight opportunities for behavioral intervention.

Characterization and Optimal Management of High-risk Pancreatic Anastomoses During Pancreatoduodenectomy.

OBJECTIVE: The aim of this study was to identify the optimal fistula mitigation strategy following pancreaticoduodenectomy. BACKGROUND: The utility of technical strategies to prevent clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreatoduodenectomy (PD) may vary by the circumstances of the anastomosis. The Fistula Risk Score (FRS) identifies a distinct high-risk cohort (FRS 7 to 10) that demonstrates substantially worse clinical outcomes. The value of various fistula mitigation strategies in these particular high-stakes cases has not been previously explored. METHODS: This multinational study included 5323 PDs performed by 62 surgeons at 17 institutions. Mitigation strategies, including both technique related (ie, pancreatogastrostomy reconstruction; dunking; tissue patches) and the use of adjuvant strategies (ie, intraperitoneal drains; anastomotic stents; prophylactic octreotide; tissue sealants), were evaluated using multivariable regression analysis and propensity score matching. RESULTS: A total of 522 (9.8%) PDs met high-risk FRS criteria, with an observed CR-POPF rate of 29.1%. Pancreatogastrostomy, prophylactic octreotide, and omission of externalized stents were each associated with an increased rate of CR-POPF (all P < 0.001). In a multivariable model accounting for patient, surgeon, and institutional characteristics, the use of external stents [odds ratio (OR) 0.45, 95% confidence interval (95% CI) 0.25-0.81] and the omission of prophylactic octreotide (OR 0.49, 95% CI 0.30-0.78) were independently associated with decreased CR-POPF occurrence. In the propensity score matched cohort, an "optimal" mitigation strategy (ie, externalized stent and no prophylactic octreotide) was associated with a reduced rate of CR-POPF (13.2% vs 33.5%, P < 0.001). CONCLUSIONS: The scenarios identified by the high-risk FRS zone represent challenging anastomoses associated with markedly elevated rates of fistula. Externalized stents and omission of prophylactic octreotide, in the setting of intraperitoneal drainage and pancreaticojejunostomy reconstruction, provides optimal outcomes.

Postoperative narcotic use is associated with development of clinically relevant pancreatic fistulas after distal pancreatectomy.

BACKGROUND: Various strategies to decrease postoperative pancreatic fistula after a distal pancreatectomy have proved unsuccessful. Because narcotics can cause spasm of the sphincter of Oddi and thereby increase pressure within the pancreatic duct stump, we hypothesized that increased narcotic use would be associated with increased occurrence of clinically relevant postoperative pancreatic fistula after distal pancreatectomy. METHODS: Retrospective analysis of consecutive distal pancreatectomies (2011-2016) was performed. Postoperative narcotic use was calculated in morphine equivalents. Postoperative pancreatic fistula was graded according to the International Study Group on Pancreatic Surgery. Perioperative variables were evaluated using multivariate logistic regression with clinically relevant postoperative pancreatic fistula as the dependent outcome. RESULTS: In the study, 310 distal pancreatectomies were analyzed (61% robotic, 20% open, 19% laparoscopic). Average age was 62 (53% female), and median total dose of morphine equivalents was 424 mg (interquartile range 242-768). Clinically relevant postoperative pancreatic fistula occurred in 21.6%. Clinically relevant postoperative pancreatic fistula and not clinically relevant postoperative pancreatic fistula cohorts were similar in most demographics and operative variables, but clinically relevant postoperative pancreatic fistula patients had fewer stapled transections (80 vs 90%, P=.025), less pancreatic cancers (11 vs 35%, P<.001), and greater median total morphine equivalents (577 vs 403 mg, P < .009). On univariate analysis, clinically relevant postoperative pancreatic fistula was associated with body mass index, nonstapled transection, suture ligation of the PD, a nonpancreatic cancer pathology, prophylactic octreotide, and total morphine equivalents >424 (cohort median). On multivariate analysis, only pancreatic cancer pathology was protective against a clinically relevant postoperative pancreatic fistula (odds ratio 0.24, confidence interval, 0.10-0.50, P=.001), while increasing total morphine equivalents were predictive of a clinically relevant postoperative pancreatic fistula (odds ratio 1.13, confidence interval, 1.01-1.27, P=.035) with a 13% increased risk for every approximate ≈100 mg increase in total morphine equivalents. CONCLUSION: In this retrospective analysis, postoperative narcotic use was associated with the development of clinically relevant postoperative pancreatic fistula after distal pancreatectomy. Limiting narcotic use may be one of the few available mitigating strategies against the development of a clinically relevant postoperative pancreatic fistula after distal pancreatectomy.

Isolated Peripancreatic Necrosis in Acute Pancreatitis Is Infrequent and Leads to Severe Clinical Course Only When Extensive: A Prospective Study From a US Tertiary Center.

GOALS: To explore the diagnostic challenges, management, and clinical outcomes of patients with isolated peripancreatic necrosis (PPN), with emphasis on the extent of involvement, and compare them to pancreatic necrosis (PN). BACKGROUND: PPN, a relatively new term, has been included as a separate entity in the Revised Atlanta Classification. STUDY: Clinical data of recruited acute pancreatitis patients were recorded prospectively. Contrast-enhanced computed tomographic scans were reviewed by expert radiologists blinded to clinical outcomes. RESULTS: In total, 271 of the 400 acute pancreatitis patients underwent contrast-enhanced computed tomography, of which 29 (11%) had PPN (14: limited; 15: extensive) and 124 (46%) PN (40: <30%, 16: 30% to 50%, 68: >50% of parenchyma). Patients with PPN were similar to PN in age (56 y), gender (55% male), and body mass index (29 kg/m(2)). Nutritional support was provided in 18 (62%) patients with PPN and 97 (78%) with PN (P=0.12). Drainage/debridement was required in 2 patients (7%) with PPN and 64 (53%) with parenchymal necrosis (P<0.001). Persistent organ failure rates did not differ significantly (34% vs. 51%, P=0.17), but hospital stay was shorter in patients with PPN (15 vs. 20 d, P=0.05). Limited PPN required no intervention and had similar persistent organ failure rates and hospitalization length with interstitial pancreatitis (both P≥0.12). Extensive PPN mainly developed in patients with persistent organ failure (60%) and rarely required drainage (2/15). CONCLUSIONS: PPN prevalence was lower than PN with a ratio of 1:4. PPN rarely required intervention. Utilizing the extent of involvement has the potential to classify PPN and PN with escalating clinical significance and guide management.

Depressive Symptoms in Patients Scheduled for Hyperthermic Intraperitoneal Chemotherapy With Cytoreductive Surgery: Prospective Associations With Morbidity and Mortality.

PURPOSE: The current study examined prospective relationships between preoperative depressive symptoms and short-term (30-day morbidity and readmission) and long-term (overall survival) outcomes after hyperthermic intraperitoneal chemotherapy with cytoreductive surgery (HIPEC + CS). METHODS: Ninety-eight patients scheduled for HIPEC + CS completed the Center for Epidemiologic Studies-Depression (CES-D) scale before surgery. Demographic and disease-specific factors and information about morbidity and readmission within 30 days after discharge were gathered from medical records. Survival was measured from date of surgery to death. RESULTS: Twenty-eight percent of patients had CES-D scores indicative of clinically significant depressive symptoms. Thirty-day morbidity occurred in 31.9% of patients and readmission in 22.2%. At the time of analysis (median follow-up of 49 months), 71.6% of patients were deceased, with median survival time of 11 months for those who died. After adjusting for relevant preoperative demographic and disease-specific factors, depressive symptoms were associated with greater odds of 30-day morbidity (n = 68; odds ratio, 5.50; 95% CI, 1.23 to 24.73; P = .03) and greater likelihood of 30-day readmission (n = 72; odds ratio, 5.92; 95% CI, 1.27 to 27.64; P = .02). Depressive symptoms were associated with shorter survival after adjustment for preoperative demographic and disease-specific factors (n = 87; hazard ratio, 1.88; 95% CI, 1.07 to 3.31; P = .03). This association was no longer significant when intraoperative/postoperative prognostic variables were added to the statistical model (n = 87; hazard ratio, 1.31; 95% CI, 0.72 to 2.37; P = .37). CONCLUSION: Patients with clinically significant levels of preoperative depressive symptoms are at risk for poor clinical outcomes after HIPEC + CS, including greater risk of 30-day morbidity and readmission. Further research is warranted to determine biobehavioral mechanisms and examine whether effective interventions targeting preoperative depressive symptoms can reduce postoperative risk in this patient population.

GNAS is frequently mutated in both low-grade and high-grade disseminated appendiceal mucinous neoplasms but does not affect survival.

We analyzed a series of 55 disseminated appendiceal mucinous neoplasms treated at our institution for GNAS and KRAS mutations in an attempt to correlate mutation status with clinicopathological findings and patient survival. GNAS mutations (p.R201H, c.602G>A and p.R201C, and c.602C>T) were identified in 17 (31%) of 55 of disseminated mucinous neoplasms and were found in 8 (35%) of 23 low-grade mucinous neoplasms, 7 (37%) of 19 high-grade mucinous adenocarcinomas lacking a signet ring cell component, and 2 (15%) of 13 high-grade mucinous adenocarcinomas with a signet ring cell component. All 7 mucinous adenocarcinomas composed of pure (>95%) signet ring cells harbored wild-type GNAS. There was no significant association between GNAS mutations and sex and age (both with P > .05) or between GNAS mutations and individual adverse histologic features including cytologic grade, destructive invasion, tumor cellularity, angiolymphatic invasion, perineural invasion, and signet ring cells (all with P > .05). KRAS mutations were identified in 22 (40%) of 55 disseminated mucinous neoplasms. GNAS-mutated disseminated appendiceal mucinous neoplasms more frequently harbored concurrent KRAS mutations compared with GNAS wild-type tumors (65% versus 29%, P = .018). GNAS mutations were not significantly associated with overall survival (both with P > .05). Only overall tumor grade was an independent predictor of overall survival in the multivariate analysis (P = .01). Our results indicate that GNAS mutations are frequently identified in both low-grade and high-grade disseminated appendiceal mucinous neoplasms indicating that GNAS mutation status cannot be used to distinguish between low-grade from high-grade appendiceal mucinous neoplasms.

Loss of SMAD4 protein expression is associated with high tumor grade and poor prognosis in disseminated appendiceal mucinous neoplasms.

The distinction between low-grade and high-grade disseminated appendiceal mucinous neoplasms is of critical importance in assessing prognosis and guiding patient therapy. SMAD4 encodes a protein that is a central component of the TGFß signal transduction pathway, and loss of SMAD4 expression has been associated with poor prognosis in carcinomas of the gastrointestinal tract. We reviewed the clinicopathologic and molecular features of 109 disseminated appendiceal mucinous neoplasms identified over an 8-year period at our institution in an attempt to: (1) correlate SMAD4 immunohistochemical expression with tumor grade; and (2) assess the prognostic significance of SMAD4 expression in predicting overall survival. Compared with tumors demonstrating preserved SMAD4 expression, tumors with loss of SMAD4 expression more frequently exhibited high cytologic grade (85% vs. 50%, P=0.035), high cellularity (100% vs. 45%, P<0.001), and destructive invasion (100% vs. 55%, P=0.001). SMAD4 expression significantly correlated with overall tumor grade (P=0.003): all 13 tumors with loss of SMAD4 expression were high grade, whereas all 42 low-grade tumors displayed preserved SMAD4 expression. A significantly higher proportion of tumors with loss of SMAD4 immunohistochemical expression demonstrated loss of heterozygosity at chromosome 18q (38%) compared with tumors with preserved SMAD4 expression (11%) (P=0.049), suggesting that loss of SMAD4 expression is due to genomic deletion in a high proportion of cases. Patients with SMAD4-negative tumors had significantly worse overall survival in comparison with patients with preserved SMAD4 expression (log rank P=0.023). However, our multivariable analysis found that SMAD4 expression was not independent of overall tumor grade in predicting overall survival. Our results indicate that loss of SMAD4 immunohistochemical expression is associated with loss of heterozygosity at chromosome 18q and is always associated with aggressive histologic features in disseminated appendiceal mucinous neoplasms. SMAD4 immunohistochemistry may be a useful ancillary study in select cases of disseminated appendiceal neoplasia, in which the distinction between low-grade and high-grade tumors is difficult.

Outcome analysis of a decade-long experience of isolated hepatic perfusion for unresectable liver metastases at a single institution.

OBJECTIVE: To evaluate outcomes of isolated hepatic perfusion (IHP) on isolated liver metastases (LMs). BACKGROUND: Isolated unresectable LMs are often the main determinant of overall survival (OS) for colorectal cancer (CRC) and other solid malignancies. We hypothesized that IHP can be performed safely and yield impressive responses for a variety of solid tumor pathology, using different perfusion agents. METHODS: Retrospective review of a prospectively collected database of patients undergoing IHP for unresectable solid tumor LM. RESULTS: Between 2003 and 2012, IHP was completed in 91 patients. Primary tumor pathology was CRC = 54, non-CRC = 37 (ocular/cutaneous melanoma = 32, cholangiocarcinoma = 3, appendiceal = 1, and breast = 1). IHP employed Melphalan (n = 69) (CRC = 32, non-CRC = 37), Oxaliplatin (n = 10) (CRC), or Oxaliplatin + 5FU (n = 12) (CRC). Hepatic arterial infusion (HAI) pumps were placed in all CRC patients. There were 3(3.3%) perioperative deaths. Response rates for CRC, melanoma, and cholangiocarcinoma were 68.2%, 57.1%, and 100% respectively. Response rates for CRC patients using 5FU + Oxaliplatin, Oxaliplatin, or Melphalan were 83.3%, 66.7%, and 60.9%, respectively. Median OS for the CRC patients (from IHP date) was 23 months (95% confidence interval: 15-28 months). On univariate analysis, receipt of HAI-FUDR (floxuridine) within 1 year of IHP was the only factor associated with improved OS (P = 0.043) in CRC patients. CONCLUSIONS: IHP results in excellent response rates for patients with unresectable liver metastasis from solid tumors. Improved local control for CRC patients undergoing IHP-HAI may improve survival.

Effects of ovarian morphology on oocyte quantity and quality, granulosa cells, in vitro maturation, and steroid hormone production in buffaloes

The present study was conducted to investigate the effects of ovarian morphology on oocyte quantity and quality, as well as the effect of preincubated granulosa cells (PGCs) on in vitro maturation of buffalo oocytes and steroid hormone production. A total of 52 ovarian pairs were grouped into 3 types: Type I (with functional corpus luteum), Type II (with regressed corpus luteum), or Type III (without corpus luteum). The number of follicles and oocytes per ovary were documented. The follicles were classified into 3 groups: 6 mm. Oocytes were classified according to their morphology into one of 4 grades (A, B, C, or D) and according to their cumulus compactness into 4 groups (>3 layers of cumulus cells, 1 to 3 layers, partial remnants of cumulus cells, or no cumulus cells). Preincubated granulosa cells were used to investigate their steroidogenic potential with in vitro maturation. A greater number of vesicular follicles and aspirated oocytes were found in Type III than in Type II or Type I. The number of Grade A and Grade B oocytes was significantly higher (P 3 layers of cumulus cells had a higher maturation rate than oocytes with partial remnants or no cumulus cells, but had low maturation rate compared to oocytes with 1 to 3 layers of cumulus cells. Besides to the higher maturation rate in compact than denuded oocytes, there was a higher (P < 0.01) rate in compact or denuded oocytes when cultured in vitro with PGCs than the corresponding oocytes with no PGCs. These maturation rates coincided with a higher (P < 0.05) concentration of estradiol-17β when compact oocytes were cultured with or without PGCs compared to denuded oocytes and a higher (P < 0.05) concentration of progesterone after culture with PGCs for both compact and denuded oocytes compared to oocytes with no PGCs. In summary, buffalo ovaries with no corpus luteum may result in a higher number of follicles and good oocytes than those with a corpus luteum. Oocytes with an intact cumulus had better maturation than those with partial or denuded cumulus although the denuded oocytes improved their meiotic competence when cultured in vitro with PGCs.

Effects of ovarian morphology on oocyte quantity and quality, granulosa cells, in vitro maturation, and steroid hormone production in buffaloes

The present study was conducted to investigate the effects of ovarian morphology on oocyte quantity and quality, as well as the effect of preincubated granulosa cells (PGCs) on in vitro maturation of buffalo oocytes and steroid hormone production. A total of 52 ovarian pairs were grouped into 3 types: Type I (with functional corpus luteum), Type II (with regressed corpus luteum), or Type III (without corpus luteum). The number of follicles and oocytes per ovary were documented. The follicles were classified into 3 groups: <2 mm, 2 to 6 mm, and >6 mm. Oocytes were classified according to their morphology into one of 4 grades (A, B, C, or D) and according to their cumulus compactness into 4 groups (>3 layers of cumulus cells, 1 to 3 layers, partial remnants of cumulus cells, or no cumulus cells). Preincubated granulosa cells were used to investigate their steroidogenic potential with in vitro maturation. A greater number of vesicular follicles and aspirated oocytes were found in Type III than in Type II or Type I. The number of Grade A and Grade B oocytes was significantly higher (P < 0.01) in number in Type III ovaries compared to other types. Oocytes with >3 layers of cumulus cells had a higher maturation rate than oocytes with partial remnants or no cumulus cells, but had low maturation rate compared to oocytes with 1 to 3 layers of cumulus cells. Besides to the higher maturation rate in compact than denuded oocytes, there was a higher (P < 0.01) rate in compact or denuded oocytes when cultured in vitro with PGCs than the corresponding oocytes with no PGCs. These maturation rates coincided with a higher (P < 0.05) concentration of estradiol-17β when compact oocytes were cultured with or without PGCs compared to denuded oocytes and a higher (P < 0.05) concentration of progesterone after culture with PGCs for both compact and denuded oocytes compared to oocytes with no PGCs. In summary, buffalo ovaries with no corpus luteum may result in a higher number of follicles and good oocytes than those with a corpus luteum. Oocytes with an intact cumulus had better maturation than those with partial or denuded cumulus although the denuded oocytes improved their meiotic competence when cultured in vitro with PGCs.(AU)

Dexamethasone in the prevention of postextubation stridor in children.

To assess whether there is any advantage in the use of corticosteroid to prevent postextubation stridor in children, we conducted a prospective, randomized, double-blind trial of dexamethasone versus saline solution. The patients were evaluated and then randomly selected to receive either dexamethasone or saline solution according to a stratification based on risk factors for postextubation stridor: age, duration of intubation, upper airway trauma, circulatory compromise, and tracheitis. Dexamethasone, 0.5 mg/kg, was given every 6 hours for a total of six doses beginning 6 to 12 hours before and continuing after endotracheal extubation in a pediatric intensive care setting. There was no statistical difference in incidence of postextubation stridor in the two groups; 23 of 77 children in the placebo group and 16 of 76 in the dexamethasone group had stridor requiring therapy (p = 0.21). We conclude that the routine use of corticosteroids for the prevention of postextubation stridor during uncomplicated pediatric intensive care airway management is unwarranted.