Mazen S. Zenati

250 Robotic Pancreatic Resections: Safety and Feasibility

Background and Objectives: Computer-assisted robotic surgery allows complex resections and anastomotic reconstructions to be performed with nearly identical standards to open surgery. We applied this technology to a variety of pancreatic resections to assess the safety, feasibility, versatility, and reliability of this technology. Methods: A retrospective review of a prospective database of robotic pancreatic resections at a single institution between August 2008 and November 2012 was performed. Perioperative outcomes were analyzed. Results: A total of 250 consecutive robotic pancreatic resections were analyzed; pancreaticoduodenectomy (132), distal pancreatectomy (83), central pancreatectomy (13), pancreatic enucleation (10), total pancreatectomy (5), Appleby resection (4), and Frey procedure (3). Thirty-day and 90-day mortality was 0.8% and 2.0%. Rate of Clavien 3 and 4 complications was 14% and 6%. The International Study Group on Pancreatic Fistula grade C fistula rate was 4%. Mean operative time for the 2 most common procedures was 529 ± 103 minutes for pancreaticoduodenectomy and 257 ± 93 minutes for distal pancreatectomy. Continuous improvement in operative times was observed over the course of the experience. Conversion to open procedure was required in 16 patients (6%) (11 with pancreaticoduodenectomy, 2 with distal pancreatectomy, 2 with central pancreatectomy, 1 with total pancreatectomy) for failure to progress (14) and bleeding (2). Conclusions: This represents to our knowledge the largest series of robotic pancreatic resections. Safety and feasibility metrics including the low incidence of conversion support the robustness of this platform and suggest no unanticipated risks inherent to this new technology. By defining these early outcome metrics, this report begins to establish a framework for comparative effectiveness studies of this platform.

Activity of azacitidine in chronic myelomonocytic leukemia

Hypomethylating drugs are useful in the management of myelodysplastic syndrome (MDS). Two of these drugs, azacitidine and decitabine, have received FDA approval for the treatment of MDS and chronic myelomonocytic leukemia (CMML). However, phase 2 and 3 studies that assessed these agents in MDS included only a small number of patients with CMML. The objective of this study was to evaluate the efficacy and safety of azacitidine in the treatment of CMML.

Long-term survival, nutritional autonomy, and quality of life after intestinal and multivisceral transplantation.

Objective:To assess long-term survival, graft function, and health-related quality of life (QOL) after visceral transplantation. Background:Despite continual improvement in early survival, the long-term therapeutic efficacy of visceral transplantation has yet to be defined. Methods:A prospective cross-sectional study was performed on 227 visceral allograft recipients who survived beyond the 5-year milestone. Clinical data were used to assess outcome including graft function and long-term survival predictors. The socioeconomic milestones and QOL measures were assessed by clinical evaluation, professional consultation, and validated QOL inventory. Results:Of 376 recipients, 227 survived beyond 5 years, with conditional survival of 75% at 10 years and 61% at 15 years. With a mean follow-up of 10 ± 4 years, 177 (92 adults, 85 children) are alive, with 118 (67%) recipients 18 years or older. Nonfunctional social support and noninclusion of the liver in the visceral allograft are the most significant survival risk factors. Nutritional autonomy was achievable in 160 (90%) survivors, with current serum albumin level of 3.7 ± 0.5 gm/dL and body mass index of 25 ± 6 kg/m2. Despite coexistence or development of neuropsychiatric disorders, most survivors were reintegrated to society with self-sustained socioeconomic status. In parallel, most of the psychological, emotional, and social QOL measures significantly (P < 0.05) improved after transplantation. Current morbidities with potential impact on global health included dysmotility (59%), hypertension (37%), osteoporosis (22%), and diabetes (11%), with significantly (P < 0.05) higher incidence among adult recipients. Conclusions:With new tactics to further improve long-term survival including social support measures, visceral transplantation has achieved excellent nutritional autonomy and good QOL.

Assessment of Quality Outcomes for Robotic Pancreaticoduodenectomy: Identification of the Learning Curve

IMPORTANCE Quality assessment is an important instrument to ensure optimal surgical outcomes, particularly during the adoption of new surgical technology. The use of the robotic platform for complex pancreatic resections, such as the pancreaticoduodenectomy, requires close monitoring of outcomes during its implementation phase to ensure patient safety is maintained and the learning curve identified. OBJECTIVE To report the results of a quality analysis and learning curve during the implementation of robotic pancreaticoduodenectomy (RPD). DESIGN, SETTING, AND PARTICIPANTS A retrospective review of a prospectively maintained database of 200 consecutive patients who underwent RPD in a large academic center from October 3, 2008, through March 1, 2014, was evaluated for important metrics of quality. Patients were analyzed in groups of 20 to minimize demographic differences and optimize the ability to detect statistically meaningful changes in performance. EXPOSURES Robotic pancreaticoduodenectomy. MAIN OUTCOMES AND MEASURES Optimization of perioperative outcome parameters. RESULTS No statistical differences in mortality rates or major morbidity were noted during the study. Statistical improvements in estimated blood loss and conversions to open surgery occurred after 20 cases (600 mL vs 250 mL [P = .002] and 35.0% vs 3.3% [P < .001], respectively), incidence of pancreatic fistula after 40 cases (27.5% vs 14.4%; P = .04), and operative time after 80 cases (581 minutes vs 417 minutes [P < .001]). Complication rates, lengths of stay, and readmission rates showed continuous improvement that did not reach statistical significance. Outcomes for the last 120 cases (representing optimized metrics beyond the learning curve) included a mean operative time of 417 minutes, median estimated blood loss of 250 mL, a conversion rate of 3.3%, 90-day mortality of 3.3%, a clinically significant (grade B/C) pancreatic fistula rate of 6.9%, and a median length of stay of 9 days. CONCLUSIONS AND RELEVANCE Continuous assessment of quality metrics allows for safe implementation of RPD. We identified several inflexion points corresponding to optimization of performance metrics for RPD that can be used as benchmarks for surgeons who are adopting this technology.

Isolated iliac artery aneurysms: A contemporary comparison of endovascular and open repair

OBJECTIVE Iliac artery aneurysms are rare but associated with significant morbidity and mortality when ruptured. This study compares recent open and endovascular repairs of iliac aneurysms at a single institution. METHODS Patients were identified and charts reviewed using ICD-9 and CPT codes for iliac artery aneurysm and open or endovascular repair performed between January 2000 and January 2006. Baseline characteristics, procedure-related variables, and follow-up data were retrospectively reviewed. RESULTS A total of 71 patients were treated with isolated iliac artery aneurysms. There were 19 open and 52 endovascular repairs. Seven presented with acute ruptures and were treated by open (4) or endovascular (3) repair. Preoperative comorbidities were similar between the two groups. Major perioperative (30 day) complications included three deaths in the open group from cardiovascular complications, all after ruptured aneurysm repair, and one death in the endovascular group (after rupture; one additional perioperative death occurred after 30 days due to colonic infarction) (P = NS). Postoperative complications were less frequent in the endovascular group, although this did not reach statistical significance. The mortality was 50% in the open group and 33% in the endovascular group for patients presenting with a ruptured aneurysm (P = NS). Transfusion requirement was significantly higher in the open group (47%) than in the endovascular group (6%) (P = .03). The mean follow-up was 20 +/- 5 months in the open group and 17 +/- 2 months in the endovascular group (P = NS). Long-term complications included two limb thromboses following repair with a bifurcated stent graft that were treated with thrombolysis plus stenting or a fem-fem bypass. Three endoleaks were identified on postop CT scans, all of which were successfully managed with endovascular techniques. There were no postoperative ruptures or aneurysm-related death. The mean postoperative length of stay was 5.2 +/- 2.3 days (open) and 1.3 +/- 1.0 days (endovascular) (P = .04). CONCLUSIONS This is the first large, case control study comparing open vs endovascular repair of isolated iliac artery aneurysms. Endovascular repair of iliac artery aneurysms is safe and results in decreased length of stay, lower requirement for perioperative blood transfusion, and similar intermediate term outcomes as open repair.

A brief episode of hypotension increases mortality in critically ill trauma patients.

OBJECTIVE Hypotension is associated with increased mortality, however previous studies have failed to account for the depth and duration of hypotension. We evaluated the effect of the duration of hypotension on outcome in injured patients. METHODS Trauma patients admitted to the intensive care unit (ICU) from 1999 to 2000 were prospectively evaluated. Patients transferred to a ward </= 48 hours after admission were excluded. The lowest systolic blood pressure and duration of all episodes of systolic blood pressure below 90 mm Hg were recorded along with the total ICU length of stay and discharge status. The Kruskal-Wallis test, Pearson chi2, and test for trend were used for analysis. RESULTS Patients with hypotension during the first 24 hours of ICU care had an increased mortality rate. A brief (</= 10 minutes) episode of hypotension was associated with increased mortality that increased with duration of hypotension (p = 0.0001). ICU length of stay also increased with duration of hypotension (p = 0.0001). CONCLUSION Brief episodes of hypotension are associated with an increased risk of death in patients requiring admission to the ICU after injury and a longer ICU recovery for those who survive.

The learning curve for robotic distal pancreatectomy: an analysis of outcomes of the first 100 consecutive cases at a high‐volume pancreatic centre

BACKGROUND Robotic distal pancreatectomy (RDP) is performed increasingly, but knowledge of the number of cases required to attain procedural proficiency is lacking. The aim of this study was to identify the learning curve associated with RDP at a high-volume pancreatic centre. METHODS Metrics of perioperative safety and efficiency for all consecutive RDPs were evaluated. Outcomes were followed to 90 days. Cumulative sum (CUSUM) analysis was used to identify inflexion points corresponding to the learning curve. RESULTS Between 2008 and 2013, 100 patients underwent RDP. There was no 90-day mortality. In two patients (2.0%), surgery was converted to laparotomy. Thirty procedures were performed for pancreatic adenocarcinoma. Precipitous operative time reductions from an initial operative time of 331 min were observed after the first 20 and 40 cases to 266 min and 210 min, respectively (P < 0.0001). The likelihood of readmission was significantly lower after the first 40 cases (P = 0.04), and non-significant reductions were observed in incidences of major (Clavien-Dindo Grade II or higher) morbidity and Grade B and C leaks, and length of stay. CONCLUSIONS In this experience, RDP outcomes were optimized after 40 cases. Familiarity with the platform and dedicated training are likely to contribute to significantly shorter learning curves in future adopters.

Assessment of platelet transfusion for reversal of aspirin after traumatic brain injury

BACKGROUND Platelet transfusion is utilized increasingly for traumatic brain injury (TBI) for the reversal of aspirin (ASA) therapy. Assessment of platelet inhibition and reversal by platelet transfusion after TBI has not been adequately characterized. METHODS A retrospective cohort analysis of TBI patients at a level I trauma center (January 2008-December 2009) was performed. The Aspirin Response Test (ART; VerifyNow) was used to assess platelet inhibition in TBI patients and guide platelet transfusion in patients with ASA-induced suppression. A follow-up ART was obtained after platelet administration. Primary endpoints were progression of intracranial hemorrhage on computed tomography, need for craniotomy, and mortality. RESULTS We analyzed 84 patients (median age, 78 [interquartile range, 64-86)]; 54% male). ASA use was documented in 36 (42%) patients. Initial ART indicated platelet dysfunction in 54 (64%) patients, including 42% of patients without a documented history of ASA use. Of the patients with a documented history of ASA, 2.4% had a normal ART. Of those with an initial ART of <550 ASA response units, 45 received platelets. Repeat ART demonstrated reversal of inhibition in 29 patients (64.4%). Initial responders to transfusion received a greater volume of platelets, suggesting a dose-response relationship. Logistic regression revealed a trend toward higher mortality in nonresponders to transfusion (P = .09). Receiver operating characteristic curve analysis revealed that ART results increased prediction of poor outcome compared with ASA history alone (area under the curve = 0.760 and 0.775, respectively). CONCLUSION The ART should be used to better target and guide platelet transfusions in TBI patients with known or suspected ASA use history. Patients with occult platelet dysfunction can be identified, unnecessary platelet transfusions avoided, and the adequate volume of platelets administered to correct drug-induced dysfunction. A dose-response relationship between quantity of platelets transfused and reversal of ASA inhibition was observed.

Stat 6-Dependent Induction of Myeloid Derived Suppressor Cells After Physical Injury Regulates Nitric Oxide Response to Endotoxin

Objective:To delineate the role of T-helper 2 (Th2) cytokines in the induction of trauma induced myeloid suppressor cells (TIMSC) and the regulation of nitric oxide production. Background:Trauma induces myeloid cells that express CD11b+/Gr1+ and arginase 1 and exhibit an immune suppressing activity. This article explores the mechanisms that induce TIMSC and the effects on nitric oxide production in response to endotoxin. Methods:TIMSC were studied in response to Th2 cytokines and a subsequent challenge to endotoxin. The role of Th2 cytokines was studied in STAT6−/− mice. Accumulation of TIMSC in spleens was studied using flow cytometry and immunhistochemistry. Plasma was recovered to measure accumulation of nitric oxide metabolites. Results:TIMSC accumulated in the spleen of injured mice and were particularly sensitive to IL-4 and IL-13 with large inductions of arginase activity. Significant blunting in both the accumulation of TIMSC in the spleen and induction of arginase 1 was observed in STAT6−/− mice after physical injury. Accumulation of nitric oxide metabolites to endotoxin was observed in STAT6−/− mice. Conclusion:This study shows that induction of CD11b+/Gr1+ cells after physical injury play an essential role in the regulation of nitric oxide production after a septic challenge. The accumulation and induction of arginase 1 in TIMSC is Th2 cytokine dependent. To our knowledge, the role of TIMSC in the regulation of nitric oxide is a novel finding. This observation adds to the possibility that TIMSC could play an important role in immunosuppression observed after physical injury.

Institutional protocol improves retrievable inferior vena cava filter recovery rate

BACKGROUND In the trauma population, the use of retrievable inferior vena cava filters (RIVCF) is rapidly gaining acceptance in patients at high risk for venous thromboembolism. This study reports the impact of an institutional protocol on retrieval rates of RIVCF at a level I trauma center. METHODS A review of an institutional Trauma Registry identified 94 consecutive patients who received RIVCF between January 2004 and February 2007 (group I) before the protocol was instituted. Under the protocol, 61 consecutive trauma patients received RIVCF between August 2007 and July 2008 (group II) and were prospectively followed. RESULTS Filter retrieval eligibility criteria were met in 81% (76/94) of patients in group I and in 61% (37/61) of patients in group II. Of those eligible, retrieval-attempt rates were 42% (32/76) in group I versus 95% (35/37) in group II (P < .001). Clinician oversight of the filter accounted for 89% (39/44) of failure of retrieval attempts; patient noncompliance accounted for the rest in group I. In group II, the latter accounted for all such failures. Retrieval was successful in 37% (28/76) and in 84% (31/37) of the eligible patients in groups I and II, respectively (P < .001). No retrieval procedure-related complications occurred. CONCLUSION An institutional protocol for prospective monitoring of RIVCF significantly increases filter retrieval rate.