A case of acute colonic pseudo-obstruction, sigmoid volvulus, and massive pneumoperitoneum in a young female patient.

INTRODUCTION AND IMPORTANCE: Acute colonic pseudo-obstruction (ACPO) is an uncommon phenomenon that is especially rare in young patients and can result in bowl ischemia and perforation if left untreated. Furthermore, pneumoperitoneum is almost always a concerning imaging finding and in the context of recent colonic resection may be a sign of anastomotic leakage. CASE PRESENTATION: We describe a case of a young female patient with postpartum ACPO who subsequently underwent a hemicolectomy with colorectal anastomosis. The patient's hospital course was complicated by massive postoperative pneumoperitoneum that resulted in resection of the anastomosis and creation of an end colostomy. However, despite this measure, there was recurrent pneumoperitoneum on cross-sectional imaging 36 h later. This was treated non-operatively and the remainder of their hospital course was uneventful. CLINICAL DISCUSSION: A potential etiology for ACPO during pregnancy may be due to compression of parasympathetic plexus nerves by the gravid uterus. Idiopathic pneumoperitoneum has been documented on a number of occasions, though this is generally in older patients. It can present with signs of peritonitis or can be asymptomatic. Simultaneous pneumothorax and pneumoperitoneum is rare and may be due to the transmission of air from the peritoneum to the mediastinum and thorax. The pneumoperitoneum itself may be due the air leakage through the significantly distended colon into the peritoneum. CONCLUSION: The combination of ACPO following pregnancy and associated pneumothorax, pneumomediastinum, and recurrent pneumoperitoneum suggest a communicating defect between the thoracic, mediastinal, and peritoneal cavities. Furthermore, the possibility of underlying colonic dysmotility should be considered prior to the restoration of large bowel continuity.

Incidence of attrition among early-career abdominal transplant surgeons.

BACKGROUND: The prevalence of burnout and depression among abdominal transplant surgeons has been well described. However, the incidence of early-career transplant surgeons leaving the field is unknown. The objective of this study was to quantify the incidence of attrition among early-career abdominal transplant surgeons. METHODS: A custom database from the Organ Procurement and Transplantation Network with encrypted surgeon-specific identifiers was queried for transplant surgeons who entered the field between 2008 and 2019. Surgeons who experienced attrition, defined as not completing a subsequent transplant after a minimum of 5, were identified. Surgeon-specific case volumes, case mix, and recipient outcomes were modeled to describe their association with attrition. RESULTS: Between 2008 and 2018, 496 abdominal transplant surgeons entered the field and performed 76,465 transplant procedures. A total of 24.4% (n = 121) experienced attrition, with a median time to attrition of 2.75 years. Attrition surgeons completed fewer kidney (7 vs 21, P < .01), pancreas (0.52 vs 1.43, P < .01), and liver transplants (1 vs 4, P < .01) in their first year of practice. Attrition surgeons completed a smaller proportion of their transplant center's volume (9% vs 18%, P < .01) and were less likely to participate in pediatric transplants (26.5% vs 52.5%, P < .01) and living donor kidney transplants (64.5% vs 84.5%, P < .01). On multivariable analysis, performing fewer kidney (odds ratio: 0.98, 95% confidence interval: 0.98-0.99) and liver transplants (odds ratio: 0.98, 95% confidence interval: 0.97-0.98) by year 5 and completing a smaller proportion of their centers' volume (odds ratio: 0.96, 95% confidence interval: 0.94-0.98) were associated with attrition. Furthermore, attrition surgeons had worse allograft and patient survival for liver transplant recipients (both log-rank P < .01). CONCLUSION: This investigation was the first to quantify the high incidence of attrition experienced by early-career abdominal transplant surgeons and its association with surgeon-specific case volumes, case mix, and worse recipient outcomes. These findings suggested the abdominal transplant workforce is struggling to retain their fellowship-trained surgeons.

Propranolol Reduces p-tau Accumulation and Improves Behavior Outcomes in a Polytrauma Murine Model.

INTRODUCTION: Traumatic brain injury (TBI) can lead to neurocognitive decline, in part due to phosphorylated tau (p-tau). Whether p-tau accumulation worsens in the setting of polytrauma remains unknown. Propranolol has shown clinical benefit in head injuries; however, the underlying mechanism is also unknown. We hypothesize that hemorrhagic shock would worsen p-tau accumulation but that propranolol would improve functional outcomes on behavioral studies. METHODS: A murine polytrauma model was developed to examine the accumulation of p-tau and whether it can be mitigated by early administration of propranolol. TBI was induced using a weight-drop model and hemorrhagic shock was achieved via controlled hemorrhage for 1 h. Mice were given intraperitoneal propranolol 4 mg/kg or saline control. The animals underwent behavioral testing at 30 d postinjury and were sacrificed for cerebral histological analysis. These studies were completed in male and female mice. RESULTS: TBI alone led to increased p-tau generation compared to sham on both immunohistochemistry and immunofluorescence (P < 0.05). The addition of hemorrhage led to greater accumulation of p-tau in the hippocampus (P < 0.007). In male mice, p-tau accumulation decreased with propranolol administration for both polytrauma and TBI alone (P < 0.0001). Male mice treated with propranolol also outperformed saline-control mice on the hippocampal-dependent behavioral assessment (P = 0.0013). These results were not replicated in female mice; the addition of hemorrhage did not increase p-tau accumulation and propranolol did not demonstrate a therapeutic effect. CONCLUSIONS: Polytrauma including TBI generates high levels of hippocampal p-tau, but propranolol may help prevent this accumulation to improve both neuropathological and functional outcomes in males.

Do Lymph Node Metastases Matter in Appendiceal Cancer with Peritoneal Carcinomatosis? A US HIPEC Collaborative Study.

BACKGROUND: Whether formal regional lymph node (LN) evaluation is necessary for patients with appendiceal adenocarcinoma (AA) who have peritoneal metastases is unclear. The aim of this study was to evaluate the prognostic value of LN metastases on survival in patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). METHODS: A retrospective analysis of the US HIPEC collaborative, a multi-institutional consortium comprising 12 high-volume centers, was performed to identify patients with AA who underwent CRS-HIPEC with adequate LN sampling (≥ 12 LNs). RESULTS: Two hundred-fifty patients with AA who underwent CRS-HIPEC were included. Outcomes were compared between LN - and LN + disease. Baseline patient characteristics between groups were similar, with most patients undergoing complete cytoreduction (0/1: 86.0% vs. 76.8%, p = 0.08), respectively. More adverse tumor factors were found in patients with LN + disease, including poor differentiation, signet ring cells, and lymphovascular invasion. Multivariate analysis of overall survival (OS) found LN + disease was independently associated with worse OS (HR: 2.82 95%CI: 1.25-6.34, p = 0.01), even after correction for receipt of systemic therapy. On Kaplan-Meier analysis, median OS was lower in patients with LN + disease (25.9 months vs. 91.4 months, p < 0.01). LN + disease remained associated with poor OS following propensity score matching (HR: 4.98 95%CI: 1.72-14.40, p < 0.01) and in patients with PCI ≥ 20 (HR: 3.68 95%CI: 1.54-8.80, p < 0.01). CONCLUSIONS: In this large multi-institutional study of patients with AA undergoing CRS-HIPEC, LN status remained associated with worse OS even in the setting of advanced peritoneal carcinomatosis. Formal LN evaluation should be performed for most patients with AA undergoing CRS-HIPEC.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases: A Summary of Key Clinical Trials.

The peritoneal cavity is a common site of metastatic spread from colorectal cancer (CRC). Patients with peritoneal metastases (PM) often have aggressive underlying tumor biology and poor survival. While only a minority of patients with CRC have potentially resectable disease, the high overall incidence of CRC makes management of PM a common clinical problem. In this population, cytoreductive surgery (CRS)-hyperthermic intraperitoneal chemotherapy (HIPEC) is the only effective therapy for appropriately selected patients. In this narrative review, we summarize the existing literature on CRS-HIPEC in colorectal PM. Recent prospective clinical trials have shown conflicting evidence regarding the benefit of HIPEC perfusion in addition to CRS. Current strategies to prevent PM in those at high-risk have been shown to be ineffective. Herein we will provide a framework for clinicians to understand and apply these data to treat this complex disease presentation.

Blood product resuscitation mitigates the effects of aeromedical evacuation after polytrauma.

BACKGROUND: The combined injury of traumatic brain injury and hemorrhagic shock has been shown to worsen coagulopathy and systemic inflammation, thereby increasing posttraumatic morbidity and mortality. Aeromedical evacuation to definitive care may exacerbate postinjury morbidity because of the inherent hypobaric hypoxic environment. We hypothesized that blood product resuscitation may mitigate the adverse physiologic effects of postinjury flight. METHODS: An established porcine model of controlled cortical injury was used to induce traumatic brain injury. Intracerebral monitors were placed to record intracranial pressure, brain tissue oxygenation, and cerebral perfusion. Each of the 42 pigs was hemorrhaged to a goal mean arterial pressure of 40 ± 5 mm Hg for 1 hour. Pigs were grouped according to resuscitation strategy used-Lactated Ringer's (LR) or shed whole blood (WB)-then placed in an altitude chamber for 2 hours at ground, 8,000 ft, or 22,000 ft, and then observed for 4 hours. Hourly blood samples were analyzed for proinflammatory cytokines and lactate. Internal jugular vein blood flow was monitored continuously for microbubble formation with altitude changes. RESULTS: Cerebral perfusion, tissue oxygenation, and intracranial pressure were unchanged among the six study groups. Venous microbubbles were not observed even with differing altitude or resuscitation strategy. Serum lactate levels from hour 2 of flight to the end of observation were significantly elevated in 22,000 + LR compared with 8,000 + LR and 22,000 + WB. Serum IL-6 levels were significantly elevated in 22,000 + LR compared with 22,000 + WB, 8,000 + LR and ground+LR at hour 1 of observation. Serum tumor necrosis factor-α was significantly elevated at hour 2 of flight in 8,000 + LR versus ground+LR, and in 22,000 + LR vs. 22,000 + WB at hour 1 of observation. Serum IL-1ß was significantly elevated hour 1 of flight between 8,000 + LR and ground+LR. CONCLUSION: Crystalloid resuscitation during aeromedical transport may cause a prolonged lactic acidosis and proinflammatory response that can predispose multiple-injury patients to secondary cellular injury. This physiologic insult may be prevented by using blood product resuscitation strategies.

Utilization and effectiveness of the organ procurement and transplantation network "safety-net" policy.

BACKGROUND: Liver transplant recipients with persistent renal dysfunction may be prioritized on the kidney transplant waitlist based on the Organ Procurement and Transplantation Network "safety-net" policy implemented in 2017. The aim of this study was to evaluate the utilization of kidney transplant and posttransplant outcomes, of liver transplant recipients with persistent renal dysfunction before and after implementation of the Organ Procurement and Transplantation Network kidney safety-net policy and standardization of simultaneous liver-kidney requirements. METHODS: Using the United Network for Organ Sharing database from January 2015 to March 2019, outcomes of liver transplant recipients listed for kidney transplant and the subset who received kidney after liver transplants were compared before and after policy implementation. RESULTS: Liver transplant recipients listed for kidney transplant increased from 58 to 200, and kidney after liver transplants increased from 29.3% to 42.5% after safety-net policy implementation. Post-policy kidney after liver transplants received more local organs (91.8% vs 70.6%, P = .03) and trended toward shorter waitlist time (47 [17-123] vs 84 [37-226] days, P = .051). The pre- and post-policy cohorts had similar (P > .05) kidney donor profile index (0.43 [0.27-0.69] vs 0.42 [0.28-0.58]) and delayed graft function (11.8% vs 14.1%). Patient, kidney graft, and liver graft survival were similar (P > .05) between pre and post-policy cohorts. Patient and kidney graft survival were similar between kidney after liver transplants and propensity score-matched kidney transplant alone recipients. Patient, kidney, and liver graft survival were similar between kidney after liver transplants and propensity score-matched simultaneous liver-kidney transplant recipients. CONCLUSION: This study demonstrates that after Organ Procurement and Transplantation Network "safety-net" policy implementation, there has been an increase in liver transplant recipients with renal dysfunction who are listed for and undergo kidney transplant with excellent short-term results.

Antimicrobial Coating Prevents Ventilator-Associated Pneumonia in a 72 hour Large Animal Model.

BACKGROUND: The primary goal of this study was to demonstrate that endotracheal tubes coated with antimicrobial lipids plus mucolytic or antimicrobial lipids with antibiotics plus mucolytic would significantly reduce pneumonia in the lungs of pigs after 72 hours of continuous mechanical ventilation compared to uncoated controls. MATERIALS AND METHODS: Eighteen female pigs were mechanically ventilated for up to 72 hours through uncoated endotracheal tubes, endotracheal tubes coated with the antimicrobial lipid, octadecylamine, and the mucolytic, N-acetylcysteine, or tubes coated with octadecylamine, N-acetylcysteine, doxycycline, and levofloxacin (6 pigs per group). No exogenous bacteria were inoculated into the pigs, pneumonia resulted from the pigs' endogenous oral flora. Vital signs were recorded every 15 minutes and arterial blood gas measurements were obtained for the duration of the experiment. Pigs were sacrificed either after completion of 72 hours of mechanical ventilation or just prior to hypoxic arrest. Lungs, trachea, and endotracheal tubes were harvested for analysis to include bacterial counts of lung, trachea, and endotracheal tubes, lung wet and dry weights, and lung tissue for histology. RESULTS: Pigs ventilated with coated endotracheal tubes were less hypoxic, had less bacterial colonization of the lungs, and survived significantly longer than pigs ventilated with uncoated tubes. Octadecylamine-N-acetylcysteine-doxycycline-levofloxacin coated endotracheal tubes had less bacterial colonization than uncoated or octadecylamine-N-acetylcysteine coated tubes. CONCLUSION: Endotracheal tubes coated with antimicrobial lipids plus mucolytic and antimicrobial lipids with antibiotics plus mucolytic reduced bacterial colonization of pig lungs after prolonged mechanical ventilation and may be an effective strategy to reduce ventilator-associated pneumonia.

National trends for axillary lymph node dissection and survival outcomes for clinical T3/T4 node-negative breast cancer patients undergoing mastectomy with positive lymph nodes.

PURPOSE: Previous studies have suggested axillary lymph node dissection (ALND) can be omitted in early breast cancer patients undergoing mastectomy with positive lymph nodes (LNs). We assessed the national utilization of ALND and overall survival (OS) for larger, locally advanced tumors in patients undergoing mastectomy with positive LNs. METHODS: The National Cancer Database from 2006 to 2016 was queried for mastectomy patients with clinical T3/T4, N0 tumors, and 1-2 positive LNs. Trends and outcomes for ALND were compared to sentinel lymph node biopsy (SLNB) alone. RESULTS: Thousand nine hundred and seventeen women were included. The proportion of ALND decreased from 70% pre-Z0011 to 52% post-Z0011. On Kaplan-Meier analysis, ALND had better OS compared to SLNB alone (p < 0.01). On multivariate analysis, age (p < 0.01), chemotherapy (p < 0.01), and hormonal therapy (p < 0.01) were associated with better OS. In patients who received adjuvant radiation therapy (ART) ALND improved OS on multivariate analysis (p < 0.01). CONCLUSION: This is the first large database study to demonstrate a national trend to forego ALND in mastectomy patients with large or locally advanced tumors (T3/T4abc) and 1-2 positive lymph nodes. This study suggests a survival benefit for ALND, particularly in patients receiving ART. Careful consideration and further investigations should be performed prior to omitting ALND this patient population.

Acute and Chronic Hematologic Implications of Emergency and Elective Splenectomy.

INTRODUCTION: Thrombocytosis and leukocytosis are common after splenectomy. The potential effect of emergency surgery on these postoperative findings is unknown. We hypothesized that emergency splenectomy leads to a more profound and persistent hematologic change as compared to elective splenectomy. METHODS: A retrospective review was conducted of patients who underwent elective or trauma splenectomy. Records were queried for platelet (PLT) and white blood cell (WBC) count prior to splenectomy, on postoperative days 1-5, and at day 14, 1 month, 3 months, 6 months, and 1 year. Complications, including thromboembolic events, infection, need for repeat operation, and readmission within 30 days of discharge, were recorded. RESULTS: 463 patients were identified as being eligible for the study, with 173 patients in the elective cohort and 145 patients in each of the isolated trauma splenectomy and polytrauma cohorts. Both cohorts had peak thrombocytosis at week 2 postoperatively. However, polytrauma patients had a significantly higher peak platelet count (P < 0.01). The PLT:WBC ratio was lower in both trauma cohorts pre-operatively and postoperative day 1. Trauma splenectomy had a higher PLT:WBC ratio on days 2 and 3 whereas polytrauma had a lower ratio on days 4 and 5. Emergency cases had greater reoperation and infection rates, whereas elective cases were more likely to require readmission. Postoperative thromboembolic events were only higher in the polytrauma cohort. CONCLUSIONS: While trauma splenectomy resulted in more profound postoperative leukocytosis and thrombocytosis, there was no correlation with timing of infection or risk of thromboembolic events. These findings suggest that thrombocytosis and leukocytosis may be associated with thrombotic and infectious events but their presence alone does not indicate direct risks of concomitant infection or thrombosis.

Postinjury treatments to make early tactical aeromedical evacuation practical for the brain after TBI.

BACKGROUND: Traumatic brain injury (TBI) is common in civilians and military personnel. No potential therapeutics have been evaluated to prevent secondary injury induced by the hypobaric hypoxia (HH) environment integral to postinjury aeromedical evacuation (AE). We examined the role of allopurinol, propranolol, adenosine/lidocaine/magnesium (ALM), or amitriptyline administration prior to simulated flight following murine TBI. METHODS: Mice underwent TBI and were given allopurinol, propranolol, amitriptyline, or ALM prior to simulated AE or normobaric normoxia (NN) control. Heart rate (HR), respiratory rate, and oxygen saturation (Spo2) were recorded throughout simulated AE. Mice were sacrificed at 24 hours, 7 days, or 30 days. Serum and cerebral cytokines were assessed by enzyme-linked immunosorbent assay. Motor function testing was performed with Rotarod ambulation. Immunohistochemistry was conducted to examine phosphorylated tau (p-tau) accumulation in the hippocampus at 30 days. RESULTS: While all treatments improved oxygen saturation, propranolol, amitriptyline, and allopurinol improved AE-induced tachycardia. At 24 hours, both propranolol and amitriptyline reduced tumor necrosis factor alpha levels while allopurinol and ALM reduced tumor necrosis factor alpha levels only in NN mice. Propranolol, amitriptyline, and ALM demonstrated lower serum monocyte chemoattractant protein-1 7 days after AE. Both amitriptyline and allopurinol improved Rotarod times for AE mice while only allopurinol improved Rotarod times for NN mice. Propranolol was able to reduce p-tau accumulation under both HH and NN conditions while ALM only reduced p-tau in hypobaric hypoxic conditions. CONCLUSION: Propranolol lowered post-TBI HR with reduced proinflammatory effects, including p-tau reduction. Amitriptyline-induced lower post-TBI HR and improved functional outcomes without affecting inflammatory response. Allopurinol did not affect vital signs but improved late post-TBI systemic inflammation and functional outcomes. Adenosine/lidocaine/magnesium provided no short-term improvements but reduced p-tau accumulation at 30 days in the HH cohort. Allopurinol may be the best of the four treatments to help prevent short-term functional deficits while propranolol may address long-term effects. LEVEL OF EVIDENCE: Basic science article.

Lack of National Adoption of Evidence-Based Treatment for Resectable Gastric Adenocarcinoma.

BACKGROUND: Level 1 evidence for multimodal treatment of resectable gastric adenocarcinoma from the Intergroup 0116 (2001) and MAGIC (2006) trials demonstrated survival benefit of adjuvant chemoradiation (CRT) and perioperative chemotherapy, respectively. We evaluated the adoption of evidence-based treatment in the post-MAGIC era and its impact on survival. METHODS: A total of 7058 patients with resectable gastric adenocarcinoma undergoing definitive surgical resection between 2004 and 2015 were analyzed using the National Cancer Database. RESULTS: Over the study period, the proportion of patients receiving adjuvant CRT decreased from 19.1% to 9.1%, while perioperative chemotherapy increased from 1.9% to 28.6%. Utilization of perioperative chemotherapy surpassed adjuvant CRT in 2011. Evidence-based treatment (either perioperative chemotherapy or adjuvant CRT) had better overall survival (OS) than other treatments for clinical stage II-III patients (p < 0.05). On multivariate analysis of the whole study period, evidence-based treatments were associated with better OS (HR 0.67 [0.60-0.74], p < 0.05). Only 360/1262 (28.5%) patients in the perioperative chemotherapy group completed postoperative therapy, which was associated with improved OS (p < 0.05). For clinical stage III patients (n = 2402), only 806 (33.6%) received evidence-based treatment, while 487 (22.2%) underwent surgery alone. On multivariate analysis of these patients between 2010 and 2015, both perioperative chemotherapy (HR 0.49 [0.35-0.68]) and adjuvant CRT (HR 0.31 [0.21-0.44]) were associated with better OS than surgery alone (p < 0.05). CONCLUSIONS: Since the INT-0116 and MAGIC trials, utilization of evidence-based treatments for resectable gastric adenocarcinoma has increased, with perioperative chemotherapy surpassing adjuvant CRT as the preferred practice. However, overall utilization of these regimens remains quite low nationally despite association with improved OS.

The Role of Hyperthermic Intraperitoneal Chemotherapy for Non-colorectal Peritoneal Surface Malignancies.

BACKGROUND: Peritoneal carcinomatosis, from a variety of gastrointestinal and gynecological malignancies, has been historically challenging to treat and there remains a wide range of biologic aggressiveness in these patients. Malignancies commonly associated with PC include those of colorectal, appendiceal, gastric, ovarian, sarcoma, small intestinal, and primary peritoneal origin among others. Advances in our understanding of this unique disease process have led to significant interest in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) as an emerging treatment option. The goal of CRS-HIPEC is to remove all visible macroscopic disease while preserving organ function, and then treat microscopic disease through perfusion of the peritoneal cavity with heated chemotherapy. PURPOSE: Although recent reviews have focused on the management of peritoneal carcinomatosis secondary to colorectal cancer given the publication of several recent randomized controlled trials, the purpose of the current review is to summarize the evidence on CRS-HIPEC for non-colorectal peritoneal surface malignancies, including appendiceal neoplasms, malignant peritoneal mesothelioma, gastric cancer, and ovarian cancer. RESULTS: While retrospective studies have clarified the importance of prognostic factors such as the peritoneal carcinomatosis index, completeness of cytoreduction, histopathological characteristics, and lymph node positivity, the lack of convincing level 1 evidence for the use of CRS-HIPEC has led to it remaining a highly controversial topic. CONCLUSION: The decision to utilize CRS-HIPEC should involve a multidisciplinary team approach and evaluation of prognostic factors to balance the short-term morbidity of the operation with maximum long-term benefits. Large, multi-institutional groups and ongoing trials hold promise for clarifying the role of CRS-HIPEC in peritoneal surface malignancies.

Omission of Adjuvant Chemotherapy in Rectal Cancer Patients with Pathologic Complete Response: a National Analysis.

BACKGROUND: An increasing number of patients achieve a pathologic complete response (pCR) after neoadjuvant chemoradiation for locally advanced rectal cancer. Consensus guidelines continue to recommend oncologic resection followed by adjuvant chemotherapy in these patients. We hypothesize that there is significant variability in compliance with this recommendation. METHODS: The National Cancer Database was queried from 2006 to 2015 for patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiation followed by oncologic resection with a pCR (ypT0N0). Hierarchical logistic regression models were used to generate risk and reliability-adjusted rates of adjuvant chemotherapy utilization in patients with pCR at each hospital. RESULTS: In total, 2421 pCR patients were identified. Five-year overall survival was improved in pCR patients who received adjuvant chemotherapy compared with those who did not (92 vs. 85%, p < 0.01). Multivariate analysis indicated that improvement in overall survival remained associated with adjuvant chemotherapy (HR 0.60, 95% CI 0.44-0.82, p < 0.01). The mean adjuvant chemotherapy utilization rate among hospitals was 32%. There was an upward trend in use over the past decade, but two-thirds still do not receive the recommended therapy. High chemotherapy utilizer hospitals were more likely to be academic centers (54.9 vs. 45.9%, p < 0.01) when compared with low chemotherapy utilizers. CONCLUSION: Adjuvant chemotherapy is associated with improved survival in rectal cancer patients with pCR following neoadjuvant chemoradiation and oncologic resection. However, utilization among centers in the USA was only 32% with significant variability across centers. National efforts are needed to standardize treatment patterns according to national guidelines.

The impact of HIPEC vs. EPIC for the treatment of mucinous appendiceal carcinoma: a study from the US HIPEC collaborative.

INTRODUCTION: Mucinous appendiceal carcinoma is a rare malignancy that commonly spreads to the peritoneum leading to peritoneal metastases. Complete cytoreduction with perioperative intraperitoneal chemotherapy (PIC) is the mainstay of treatment, administered as either hyperthermic intra peritoneal chemotherapy (HIPEC) or early post-operative intraperitoneal chemotherapy (EPIC). Our goal was to assess the perioperative and long term survival outcomes associated with these two PIC methods. MATERIALS AND METHODS: Patients with mucinous appendiceal carcinoma were identified in the US HIPEC Collaborative database from 12 academic institutions. Patient demographics, clinical characteristics, and survival outcomes were compared among patients who underwent HIPEC vs. EPIC with inverse probability weighting (IPW) used for adjustment. RESULTS: Among 921 patients with mucinous appendiceal carcinoma, 9% underwent EPIC while 91% underwent HIPEC. There was no difference in Grade III-V complications between the two groups (18.5% for HIPEC vs. 15.0% for EPIC, p=.43) though patients who underwent HIPEC had higher rates of readmissions (21.2% vs. 8.8%, p<.01). Additionally, PIC method was not an independent predictor for overall survival (OS) or recurrence-free survival (RFS) after adjustment on multivariable analysis. CONCLUSIONS: Among patients with mucinous appendiceal carcinoma, both EPIC and HIPEC appear to be associated with similar perioperative and long-term outcomes.

Impact of side-to-side cavocavostomy versus traditional piggyback implantation in liver transplantation.

BACKGROUND: Traditional piggyback implantation has often been used in liver transplant; however, this technique may be hindered by difficult visualization and postoperative incidences of outflow obstruction. Side-to-side cavocavostomy is an alternative approach, but perioperative outcomes associated with this technique remain largely unknown. METHODS: In July 2017, side-to-side cavocavostomy was adopted as the standard implantation technique at our institution by all surgeons (n = 4). A prospective cohort of patients undergoing liver transplant with side-to-side cavocavostomy after July 2017 until October 2018 was compared with a historical cohort of patients who underwent liver transplant with traditional piggyback previously from January 2016 to October 2018. RESULTS: Of 290 liver transplant patients, 50% (n = 145) underwent side-to-side cavocavostomy, while the remainder underwent traditional piggyback. There were no differences in recipient age, sex, race, Model for End-Stage Liver Disease score, or donor characteristics between groups. Side-to-side cavocavostomy was associated with decreased mean number intraoperative, red blood cell transfusions (2 vs 5 units), fresh frozen plasma (5 vs 10 units), cell saver (1.0 vs 2.0 L), and rates of temporary abdominal closure (8.3% vs 24.1%) compared with traditional piggyback (all P < .05). The side-to-side cavocavostomy group had lesser Rt3s of postoperative transfusion rates of red blood cells (21.4% vs 35.9%; P = .01). CONCLUSION: Side-to-side cavocavostomy may be superior to traditional piggyback implantation with regard to technical ease and perioperative transfusion requirements. To determine the optimal implantation technique, futures studies should evaluate side-to-side cavocavostomy versus traditional piggyback in a prospective, multicenter, randomized approach.

Post-TBI splenectomy may exacerbate coagulopathy and platelet activation in a murine model.

INTRODUCTION: Traumatic brain injury (TBI) induces acute hypocoagulability, subacute hypercoagulability, and persistently elevated risk for thromboembolic events. Splenectomy is associated with increased mortality in patients with moderate or severe TBI. We hypothesized that the adverse effects of splenectomy in TBI patients may be secondary to the exacerbation of pathologic coagulation and platelet activation changes. METHODS: An established murine weight-drop TBI model was utilized and a splenectomy was performed immediately following TBI. Sham as well as TBI and splenectomy alone mice were used as injury controls. Mice were sacrificed for blood draws at 1, 6, and 24 h, as well as 7 days post-TBI. Viscoelastic coagulation parameters were assessed by rotational thromboelastometry (ROTEM) and platelet activation was measured by expression of P-selectin via flow cytometry analysis of platelet rich plasma samples. RESULTS: At 6 h following injury, TBI/splenectomy demonstrated hypocoagulability with prolonged clot formation time (CFT) compared to TBI alone. By 24 h following injury, TBI/splenectomy and splenectomy mice were hypercoagulable with a shorter CFT, a higher alpha angle, and increased MCF, despite a lower percentage of platelet contribution to clot compared to TBI alone. However, only the TBI/splenectomy continued to display this hypercoagulable state at 7 days. While TBI/splenectomy had greater P-selectin expression at 1-h post-injury, TBI alone had significantly greater P-selectin expression at 24 h post-injury compared to TBI/splenectomy. Interestingly, P-selectin expression remained elevated only in TBI/splenectomy at 7 days post-injury. CONCLUSION: Splenectomy following TBI exacerbates changes in the post-injury coagulation state. The combination of TBI and splenectomy induces an acute hypocoagulable state that could contribute to an increase in intracranial bleeding. Subacutely, the addition of splenectomy to TBI exacerbates post-injury hypercoagulability and induces persistent platelet activation. These polytrauma effects on coagulation may contribute to the increased mortality observed in patients with combined brain and splenic injuries.

Innate coagulability changes with age in stored packed red blood cells.

BACKGROUND: Packed red blood cell (pRBC) units administered during resuscitation from hemorrhagic shock are of varied storage ages. We have previously shown that RBC-derived microparticles' impact on thrombogenesis. However, the impact of storage age on pRBC coagulability is unknown. Therefore, we sought to investigate the effect of storage age on innate coagulability and aggregability of stored pRBCs. METHODS: pRBCs prepared from male C57BL/6J mice were stored in Additive Solution-3 according to our standardized murine blood banking protocols for 14 days. Rotational thromboelastometry (ROTEM) was used to assess the innate coagulation status of fresh and 14-day old pRBCs. Viscoelastic coagulation parameters of clotting time (CT), clot formation time (CFT), alpha angle, and maximum clot firmness (MCF) were analyzed to determine coagulability. Plasma was added to the fresh pRBCs and 15-day old pRBCs to determine if the storage-associated coagulopathy was reversible with plasma. Statistical analyses were conducted with a Student's t-test. RESULTS: Fifteen-day old pRBCs demonstrated a significant reduction in MCF (10.3 vs. 24.4 mm, P-value <0.001) and alpha angle (6.0 vs. 27.2 degrees, P-value <0.001) as well as significant prolongation of CFT and CT (1126.5 vs. 571.4 s, P-value <0.001) compared to fresh pRBCs. FFP addition to 15-day old and fresh pRBCs, demonstrated a significant reduction in MCF and persistent prolongation of CFT. This suggests that pRBCs lost coagulability as they aged and this deficit was not completely corrected by plasma administration. CONCLUSIONS: Storage duration may be an important factor in coagulation potential of pRBCs. Transfusion with older pRBCs may contribute to coagulopathy in massively transfused patients.

Can Resuscitative Endovascular Balloon Occlusion of the Aorta Fly? Assessing Aortic Balloon Performance for Aeromedical Evacuation.

BACKGROUND: Noncompressible torso hemorrhage remains a leading cause of death. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) placement may occur before transport; however, its efficacy has not been demonstrated at altitude. We hypothesized that changes in altitude would not result in blood pressure changes proximal to a deployed REBOA. METHODS: A simulation model for 7Fr guidewireless REBOA was used at altitudes up to 22,000 feet. Female pigs then underwent hemorrhagic shock to a mean arterial pressure (MAP) of 40 mm Hg. After hemorrhage, a REBOA catheter was deployed in the REBOA group and positioned but not inflated in the no-REBOA group. Animals underwent simulated aeromedical evacuation at 8000 ft or were left at ground level. After altitude exposure, the balloon was deflated, and the animals were observed. RESULTS: Taking the REBOA catheter to 22,000 ft in the simulation model resulted in a lower systolic blood pressure but a preserved MAP. In the porcine model, REBOA increased both systolic blood pressure and MAP compared with no-REBOA (P < 0.05) and was unaffected by altitude. No differences in postflight blood pressure, acidosis, or systemic inflammatory response were observed between ground and altitude REBOA groups. CONCLUSIONS: REBOA maintained MAP up to 22,000 feet in an inanimate model. In the porcine model, REBOA deployment improved MAP, and the balloon remained effective at altitude.

National Trend of Axillary Management in Clinical T3/T4 N0 Patients Having Breast Conserving Therapy.

BACKGROUND: The ACOSOG Z0011 trial has essentially eliminated axillary lymph node dissection (ALND) in breast conserving therapy (BCT) patients with clinical T1/T2 and 1-2 positive sentinel lymph nodes (SLNs). Currently, ALND is recommended for positive SLNs unless ACOSOG Z0011 criteria are applicable. We aimed to assess the national trends and axillary management before and after the publication of ACOSOG Z0011 for larger tumors. METHODS: An IRB-approved study evaluated the National Cancer Database from 2006 to 2016. Women with clinical T3/T4, N0 who otherwise fit ACOSOG Z0011 criteria were included. Neoadjuvant systemic therapy or known nodal disease was excluded. Clinicopathologic data were compared between two timeframes based on ACOSOZ Z0011 publication and by axillary management. Patients were categorized into SLNB alone (1-5 lymph nodes examined) and ALND (≥10 lymph nodes examined) groups. RESULTS: A total of 230 women fit inclusion criteria, of whom 36% underwent ALND. ALND use decreased from 54% in 2006 to 14% in 2016 (P < 0.01). Comparing ALND to SLNB alone within the pre-Z0011 era, comprehensive community cancer programs had higher proportions of ALND, whereas academic centers had higher rates of SLND alone (P = 0.03). Comparing similar axillary management between eras, SLNB-alone patients in the post-Z0011 era had higher pT and pN stages, were less likely to be Her2 positive, and were more likely to receive systemic treatment. CONCLUSIONS: There is a national trend to forgo ALND in women who have tumors larger than those included in the Z0011 criteria without any clear clinicopathologic indications.