Brent T. Xia

A multi-institutional comparison of perioperative outcomes of robotic and open pancreaticoduodenectomy

Objectives: Limited data exist comparing robotic and open approaches to pancreaticoduodenectomy (PD). We performed a multicenter comparison of perioperative outcomes of robotic PD (RPD) and open PD (OPD). Methods: Perioperative data for patients who underwent postlearning curve PD at 8 centers (8/2011–1/2015) were assessed. Univariate analyses of clinicopathologic and treatment factors were performed, and multivariable models were constructed to determine associations of operative approach (RPD or OPD) with perioperative outcomes. Results: Of the 1028 patients, 211 (20.5%) underwent RPD (4.7% conversions) and 817 (79.5%) underwent OPD. As compared with OPD, RPD patients had higher body mass index, rates of prior abdominal surgery, and softer pancreatic remnants, whereas OPD patients had a higher percentage of pancreatic ductal adenocarcinoma cases, and greater proportion of nondilated (<3 mm) pancreatic ducts. On multivariable analysis, as compared with OPD, RPD was associated with longer operative times [mean difference = 75.4 minutes, 95% confidence interval (CI) 17.5–133.3, P = 0.01], reduced blood loss (mean difference = −181 mL, 95% CI −355–(−7.7), P = 0.04) and reductions in major complications (odds ratio = 0.64, 95% CI 0.47–0.85, P = 0.003). No associations were demonstrated between operative approach and 90-day mortality, clinically relevant postoperative pancreatic fistula and wound infection, length of stay, or 90-day readmission. In the subset of 522 (51%) pancreatic ductal adenocarcinomas, operative approach was not a significant independent predictor of margin status or suboptimal lymphadenectomy (<12 lymph nodes harvested). Conclusions: Postlearning curve RPD can be performed with similar perioperative outcomes achieved with OPD. Further studies of cost, quality of life, and long-term oncologic outcomes are needed.

Amitriptyline Usage Exacerbates the Immune Suppression Following Burn Injury.

ABSTRACT Currently, over 10% of the US population is taking antidepressants. Numerous antidepressants such as amitriptyline are known to inhibit acid sphingomyelinase (Asm), an enzyme that is known to mediate leukocyte function and homeostasis. Severe burn injury can lead to an immunosuppressive state that is characterized by decreased leukocyte function and numbers as well as increased susceptibility to infection. Based upon the intersection of these facts, we hypothesized that amitriptyline-treated, scald-injured mice would have an altered immune response to injury as compared with untreated scald mice. Prior to burn, mice were pretreated with amitriptyline. Drug- or saline-treated mice were subjected full thickness dorsal scald- or sham-injury. Immune cells from spleen, thymus, and bone marrow were subsequently harvested and characterized. We first observed that amitriptyline prior to burn injury increased body mass loss and spleen contraction. Both amitriptylinetreatment and burn injury resulted in a 40% decrease of leukocyte Asm activity. Following scald injury, we demonstrate increased reduction of lymphocyte precursors in the bone marrow and thymus, as well as mature leukocytes in the spleen in mice that were treated with amitriptyline. We also demonstrate that amitriptyline treatment prior to injury reduced neutrophil accumulation following peptidoglycan stimulus in scald-injured mice. These data show that Asm alterations can play a significant role in mediating alterations to the immune system after injury. The data further suggest that those taking antidepressants may be at a higher risk for complications following burn injury.

Does radiologic response correlate to pathologic response in patients undergoing neoadjuvant therapy for borderline resectable pancreatic malignancy

In patients with borderline resectable pancreas cancers, clinicians frequently consider radiographic response as the primary driver of whether patients should be offered surgical intervention following neoadjuvant therapy (NT). We sought to determine any correlation between radiographic and pathologic response rates following NT.

Tumor Recurrence Is Independent of Pancreatic Fistula in Patients after Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma

BACKGROUND Recurrence of pancreatic adenocarcinoma after pancreaticoduodenectomy (PD) can be increased in patients with pancreatic fistula (PF). The purpose of our study was to determine if a relationship exists between PF and tumor recurrence (both peritoneal and local) in patients after PD for pancreatic ductal adenocarcinoma. STUDY DESIGN A single-institution, retrospective analysis of 221 patients who underwent PD from January 2001 to December 2009 was conducted. Electronic charts and medical records were queried for tumor characteristics, recurrence, and complications. Presence and grading of PF was determined using the criteria of the International Study Group on Pancreatic Fistula. Data were analyzed using chi-square and Kaplan-Meier survival statistics. RESULTS There were 114 male and 107 female patients. Mean age was 66 years (range 35 to 91 years). The vast majority (84%) of patients had stage II disease; 143 (65%) had positive lymph nodes (median 2 positive nodes; range 1 to 17 positive nodes). Pancreatic fistula developed in 23 patients (grade A, n = 9; grade B, n = 13; grade C, n = 1; 10.2%). Peritoneal recurrence was noted in 20 patients (9%). Of the 23 patients with PF, peritoneal recurrence developed in 3 (13%). Of the 198 patients without PF, peritoneal recurrence developed in 17 (10%). Local recurrence occurred in 47 patients (21%), 5 (2%) in patients with PF and 42 (21%) in those without PF (p = NS). In Kaplan-Meier survival analysis, there was no significant difference in recurrence-free survival (p = 0.4) and overall survival (p = 0.3) for those with PF vs those without PF. CONCLUSIONS Patients with PF after PD were not found to have a significant increase in local or peritoneal recurrence. Therefore, in this analysis, postoperative PF does not appear to serve as an adverse prognostic marker.

Cell-derived Nanoparticles are Endogenous Modulators of Sepsis with Therapeutic Potential.

ABSTRACT Cell-derived nanoparticles (CDNPs) containing cytosolic proteins and RNAs/DNAs can be isolated from stressed eukaryotic cells. Previously, CDNPs isolated from cultured cells exerted immunomodulatory activities in different infections. Here, we sought to elucidate the role of CDNPs using a murine model of cecal ligation and puncture (CLP). We hypothesized that CDNPs influence the immune response at the site of infection, where severe cellular stress occurs. We observed early CDNP accumulation in the peritoneum after 4 h and continued CDNP presence 24 h after CLP. To determine whether CDNPs influence the host response to sepsis, we isolated CDNPs from a murine fibroblast cell line stressed by nutrient-deprivation, and injected them into septic mice. CDNP-treated mice demonstrated decreased peritoneal interleukin 6 levels and an approximately 2-log lower bacterial load compared with control mice 24 h after CLP. Additionally, a 20% CFU reduction was observed when incubating CDNPs with Pseudomona aeroginosa, indicating that CDNPs are bactericidal. To identify CDNP-responsive cells, CFSE-labeled CDNPs were injected into mice at the time of CLP. We observed that CDNPs were preferentially ingested by F4/80+ macrophages, and to a lesser degree, associated with inflammatory monocytes and neutrophils. Strikingly, CDNP-ingesting cells demonstrated elevated CD11b and MHCII expression compared with control cells. Altogether, our data indicate that CDNPs enhance the immune response at the site of infection and promote bacterial clearance, by direct bacterial killing and increasing phagocyte activation. Thus, CDNPs represent a novel, unexplored endogenous sepsis modulator with therapeutic potential.

Idiopathic granulomatous mastitis: A diagnostic and therapeutic challenge

BACKGROUND Idiopathic granulomatous mastitis is a rare benign breast disease of women of reproductive age. It usually presents as a painful mass. Since the etiology is unclear, directed diagnosis and management is lacking. METHODS This is a retrospective chart review of 14 patients, over twelve years (2004-2016), identified through query of pathology findings. RESULTS Two asymptomatic patients were diagnosed after oncologic breast resection following neoadjuvant chemotherapy. The remaining twelve patients were young (31.7 years, range 23-43 years), predominantly non-white (50% African/African-American, 36% Hispanic, 7% Asian), pregnant within the last five years (86%), with no prior granulomatous disease. Evaluation included breast imaging, microbial cultures and staining, and biopsy. Treatment included antibiotics (57%), corticosteroids (21%), methotrexate (7%), and/or surgery (71%). Imaging suggests segmental masses, possibly abscess. CONCLUSION Granulomatous mastitis is uncommon, and difficult to diagnose and manage. We review our experience, the literature, and propose an algorithm for diagnosis and management.

The Management of Locally Advanced Nonmetastatic Pancreas Cancer

At the time of diagnosis of pancreatic cancer, greater than half of patients have metastatic disease, and less than 20% of patients are resectable. The remaining 30–40% of patients present with borderline resectable (BR) or locally advanced unresectable pancreatic cancer (LAPC). Recently endorsed by the NCCN, the Intergroup definition of BR and LAPC has been developed to promote multicenter collaboration and to standardize future clinical trials.

Microparticles from stored red blood cells promote a hypercoagulable state in a murine model of transfusion

Background Red blood cell‐derived microparticles are biologically active, submicron vesicles shed by erythrocytes during storage. Recent clinical studies have linked the duration of red blood cell storage with thromboembolic events in critically ill transfusion recipients. In the present study, we hypothesized that microparticles from aged packed red blood cell units promote a hypercoagulable state in a murine model of transfusion. Methods Microparticles were isolated from aged, murine packed red blood cell units via serial centrifugation. Healthy male C57BL/6 mice were transfused with microparticles or an equivalent volume of vehicle, and whole blood was harvested for analysis via rotational thromboelastometry. Serum was harvested from a separate set of mice after microparticles or saline injection, and analyzed for fibrinogen levels. Red blood cell‐derived microparticles were analyzed for their ability to convert prothrombin to thrombin. Finally, mice were transfused with either red blood cell microparticles or saline vehicle, and a tail bleeding time assay was performed after an equilibration period of 2, 6, 12, or 24 hours. Results Mice injected with red blood cell‐derived microparticles demonstrated an accelerated clot formation time (109.3 ± 26.9 vs 141.6 ± 28.2 sec) and increased &agr; angle (68.8 ± 5.0 degrees vs 62.8 ± 4.7 degrees) compared with control (each P < .05). Clotting time and maximum clot firmness were not significantly different between the 2 groups. Red blood cell‐derived microparticles exhibited a hundredfold greater conversion of prothrombin substrate to its active thrombin form (66.60 ± 0.03 vs 0.70 ± 0.01 peak OD; P < .0001). Additionally, serum fibrinogen levels were lower in microparticles‐injected mice compared with saline vehicle, suggesting thrombin‐mediated conversion to insoluble fibrin (14.0 vs 16.5 &mgr;g/mL, P < .05). In the tail bleeding time model, there was a more rapid cessation of bleeding at 2 hours posttransfusion (90.6 vs 123.7 sec) and 6 hours posttransfusion (87.1 vs 141.4 sec) in microparticles‐injected mice as compared with saline vehicle (each P < .05). There was no difference in tail bleeding time at 12 or 24 hours. Conclusion Red blood cell‐derived microparticles induce a transient hypercoagulable state through accelerated activation of clotting factors.

The Surgeon’s Role in Treating Chronic Pancreatitis and Incidentally Discovered Pancreatic Lesions

Chronic pancreatitis and incidentally discovered pancreatic lesions present significant diagnostic and therapeutic challenges for surgeons. While both decompressive and resection procedures have been described for treatment of chronic pancreatitis, optimal management must be tailored to each patient’s individual disease characteristics, parenchymal morphology, and ductal anatomy. Surgeons should strive to achieve long-lasting pain relief while preserving native pancreatic function. For patients with incidentally discovered pancreatic lesions, differentiating benign, pre-malignant, and malignant lesions is critical as earlier treatment is thought to result in improved survival. The purpose of this evidence-based manuscript is to review the presentation, workup, surgical management, and associated outcomes for patients with chronic pancreatitis or incidentally discovered solid and cystic lesions of the pancreas.

Role of Leukoreduction of Packed Red Blood Cell Units in Trauma Patients: A Review: Kim Y et al. Leukoreduction in the Trauma Population

Hemorrhagic shock is a leading cause of mortality within the trauma population, and blood transfusion is the standard of care. Leukoreduction filters remove donor leukocytes prior to transfusion of blood products. While the benefits of leukocyte depletion are well documented in scientific literature, these benefits do not translate directly to the clinical setting. This review summarizes current research regarding leukoreduction in the clinical arena, as well as studies performed exclusively in the trauma population.