Magnetic Resonance Imaging of Macrophage Response to Radiation Therapy.

BACKGROUND: Magnetic resonance imaging (MRI) is a non-invasive imaging modality which, in conjunction with biopsies, provide a qualitative assessment of tumor response to treatment. Intravenous injection of contrast agents such as fluorine (19F) nanoemulsions labels systemic macrophages, which can, then, be tracked in real time with MRI. This method can provide quantifiable insights into the behavior of tumor-associated macrophages (TAMs) in the tumor microenvironment and macrophage recruitment during therapy. METHODS: Female mice received mammary fat pad injections of murine breast or colon cancer cell lines. The mice then received an intravenous 19F nanoemulsion injection, followed by a baseline 19F MRI. For each cancer model, half of the mice then received 8 Gy of localized radiation therapy (RT), while others remained untreated. The mice were monitored for two weeks for tumor growth and 9F signal using MRI. RESULTS: Across both cohorts, the RT-treated groups presented significant tumor growth reduction or arrest, contrary to the untreated groups. Similarly, the fluorine signal in treated groups increased significantly as early as four days post therapy. The fluorine signal change correlated to tumor volumes irrespective of time. CONCLUSION: These results demonstrate the potential of 19F MRI to non-invasively track macrophages during radiation therapy and its prognostic value with regard to tumor growth.

Liver Transplantation for Severe Hepatic Trauma: a multicenter analysis from the UNOS dataset.

BACKGROUND: Orthotopic liver transplantation (OLT) is rarely indicated after hepatic trauma but it can be the only therapeutic option in some patients. There are scarce data analyzing the surgical outcomes of OLT after trauma. METHODS: We used the UNOS dataset to identify patients who underwent OLT for trauma from 1987 to 2022, and compared them to a cohort of patients transplanted for other indications. Cox proportional hazard and multivariable logistic regression analyses were performed to assess predictors of graft and patient survival. RESULTS: 72 patients underwent OLT for trauma during the study period. Patients with trauma were more frequently on mechanical ventilation at the time of transplantation (26.4% vs. 7.6%, p < 0.001) and had a greater incidence of pre-transplant portal vein thrombosis (PVT) (12.5% vs. 4%, p = 0.002). Our 4:1 matched analysis showed that trauma patients had significantly shorter wait times, higher incidence of pre-transplant PVT and prolonged length of stay (LOS). Trauma was associated with decreased overall graft survival (HR = 1.42, 95% CI = 1.01-1.98), and increased LOS (p = 0.048). There were no significant differences in long term patient survival. CONCLUSION: Unique physiological and vascular challenges after severe hepatic trauma might be associated with decreased graft survival in patients requiring liver transplantation. LEVEL OF EVIDENCE: Retrospective cohort study, III.

Metabolic Disruption Induced by mTOR Signaling Pathway Inhibition in Regulatory T-Cell Expansion for Clinical Application.

BACKGROUND: Regulatory T cell (Treg) therapy is considered an alternative approach to induce tolerance in transplantation. If successful, this therapy may have implications on immunosuppression minimization/withdrawal to reduce drug-induced toxicity in patients. The aim of this study was to assess the efficacy of the mTORC1/C2 inhibitor, AZD8055, in the manufacturing of clinically competent Treg cells and compare the effects with those induced by rapamycin (RAPA), another mTOR inhibitor commonly used in Treg expansion protocols. METHODS: Primary human Treg cells were isolated from leukapheresis product. Cell viability, expansion rates, suppressive function, autophagy, mitochondrial unfolded protein response (mitoUPR), and cell metabolic profile were assessed. RESULTS: We observed a stronger inhibition of the mTORC2 signaling pathway and downstream events triggered by Interleukin 2 (IL2)-receptor in AZD8055-treated cells compared with those treated with RAPA. AZD8055 induced progressive metabolic changes in mitochondrial respiration and glycolytic pathways that disrupted the long-term expansion and suppressive function of Tregs. Unlike RAPA, AZD8055 treatment impaired autophagy and enhanced the mitoUPR cell stress response pathway. CONCLUSIONS: A distinct pattern of mTOR inhibition by AZD, compared with RAPA, induced mitochondrial stress response and dysfunction, impaired autophagy, and disrupted cellular bioenergetics, resulting in the loss of proliferative potential and suppressive function of Treg cells.

Liver transplantation for biliary cysts: perioperative and long-term outcomes.

BACKGROUND: Biliary cysts (BC) is a rare indication for orthotopic liver transplantation (OLT). METHODS: We queried the UNOS dataset to identify patients who underwent OLT for Caroli's disease (CD) and choledochal cysts (CC). All patients with BC (CD + CC) were compared to a cohort of patients transplanted for other indications. Patients with CC were also compared to those with CD. Cox proportional hazard model was performed to assess predictors of graft and patient survival. RESULTS: 261 patients underwent OLT for BC. Patients with BC had better pre-operative liver function compared to those transplanted for other indications. 5-year graft and patient survival were 72% and 81%, respectively, similar to those transplanted for other indications after matching. Patients with CC were younger and had increased preoperative cholestasis compared to those with CD. Donor age, race, and gender were predictors of poor graft and patient survival in patients transplanted for CC. CONCLUSIONS: Patients with BC have similar outcomes to those transplanted for other indications and more frequently require MELD score exception. In patients transplanted for choledochal cysts, female gender, donor age, and African-American race were independent predictors of poor survival. Pediatric patients transplanted for Caroli's disease had better survival compared to adults.

An Examination of the Relationship between Visualization Media and Consumer Product Evaluation.

Virtual product presentations that rely on static images and text are often insufficient to communicate all the information that is necessary to accurately evaluate a product. Technologies such as Virtual Reality (VR) or Augmented Reality (AR) have enabled more sophisticated representation methods, but certain product characteristics are difficult to assess and may result in perceptual differences when a product is evaluated in different visual media. In this paper, we report two case studies in which a group of participants evaluated three designs of two product typologies (i.e., a desktop telephone and a coffee maker) as presented in three different visual media (i.e., photorealistic renderings, AR, and VR for the first case study; and photographs, a non-immersive virtual environment, and AR for the second case study) using eight semantic scales. An inferential statistical method using Aligned Rank Transform (ART) proceedings was applied to determine perceptual differences between groups. Our results show that in both cases product attributes in Jordan's physio-pleasure category are the most affected by the presentation media. The socio-pleasure category was also affected for the case of the coffee makers. The level of immersion afforded by the medium significantly affects product evaluation.

Anti-neoplastic sulfonamides alter the metabolic homeostasis and disrupt the suppressor activity of regulatory T cells.

Regulatory T cells (Tregs) are essential to maintain self-tolerance and immune homeostasis but, as components of the tumor microenvironment (TME), are also a major barrier to effective cancer immunosurveillance and immunotherapy. FH535 and its derivative Y3 are two N-aryl-benzene-sulfonamides (NABs) that inhibit HCC cell proliferation and tumor progression. However, the impact of NABs on the immune cells in the TME is not yet known. Analyses of explanted livers from patients with hepatocellular carcinoma (HCC) showed that high levels of tumor-infiltrating Tregs were associated with poor tumor differentiation. These results lead us to investigate the immunomodulatory effects of NABs in regulatory and effector T cells. Exposure of primary human Tregs to NABs induced a rapid but temporary increase of cell expansion, a gradual disruption of suppressor activity, and concomitant bioenergetics and autophagic flux dysregulations. In contrast to Tregs, no gross effects were observed in effector T cells. Addition of Rapamycin prevented the functional decay of Tregs and restored their metabolic profile, suggesting that NAB effects require the integrity of the mTOR pathway. This study revealed the immunomodulatory properties of NABs with a preferential impact on Treg activity and provided novel insights into the anti-tumor potential of sulfonamides.

Cell sorting microbeads as novel contrast agent for magnetic resonance imaging.

The success of several cell-based therapies and prevalent use of magnetic resonance imaging (MRI) in the clinic has fueled the development of contrast agents for specific cell tracking applications. Safe and efficient labeling of non-phagocytic cell types such as T cells nonetheless remains challenging. We developed a one-stop shop approach where the T cell sorting agent also labels the cells which can subsequently be depicted using non-invasive MRI. We compared the MR signal effects of magnetic-assisted cell sorting microbeads (CD25) to the current preclinical gold standard, ferumoxytol. We investigated in vitro labeling efficiency of regulatory T cells (Tregs) with MRI and histopathologic confirmation. Thereafter, Tregs and T cells were labeled with CD25 microbeads in vitro and delivered via intravenous injection. Liver MRIs pre- and 24 h post-injection were performed to determine in vivo tracking feasibility. We show that CD25 microbeads exhibit T2 signal decay properties similar to other iron oxide contrast agents. CD25 microbeads are readily internalized by Tregs and can be detected by non-invasive MRI with dose dependent T2 signal suppression. Systemically injected labeled Tregs can be detected in the liver 24 h post-injection, contrary to T cell control. Our CD25 microbead-based labeling method is an effective tool for Treg tagging, yielding detectable MR signal change in cell phantoms and in vivo. This novel cellular tracking method will be key in tracking the fate of Tregs in inflammatory pathologies and solid organ transplantation.

Predictors of Liver Failure in Non-Cirrhotic Patients Undergoing Hepatectomy.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is associated with high mortality following liver resection. There have been limited studies evaluating predictors of PHLF and clinically significant PHLF in non-cirrhotic patients. METHODS: This was a retrospective cohort study using the National Surgical Quality Improvement Program database (NSQIP) to evaluate 8,093 non-cirrhotic patients undergoing hepatectomy from 2014 to 2018. Primary endpoints were PHLF and clinically significant PHLF (PHLF grade B or C). RESULTS: Among all patients, 4.74% (n = 383) developed PHLF and 2.5% clinically significant PHLF (n = 203). The overall 30-day mortality was 1.35% (n = 109), 11.5% (n = 44) in patients with PHLF, and 19.2% in those with clinically significant PHLF. Factors associated with PHLF were: metastatic liver disease (OR = 1.84, CI = 1.14-2.98), trisectionectomy (OR = 3.71, CI = 2.59-5.32), right total lobectomy (OR = 4.17, CI = 3.06-5.68), transfusions (OR = 1.99, CI = 1.52-2.62), organ/space SSI (OR = 2.84, CI = 2.02-3.98), post-operative pneumonia (OR = 2.43, CI = 1.57-3.76), sepsis (OR = 2.27, CI = 1.47-3.51), and septic shock (OR = 5.67, CI = 3.43-9.36). Patients who developed PHLF or clinically significant PHLF had 2-threefold increased risk of perioperative mortality. Post-hepatectomy renal failure (OR = 8.47, CI = 3.96-18.1), older age (OR = 1.04, CI = 1.014-1.063), male sex (OR = 1.83, CI = 1.07-3.14), sepsis (OR = 2.96, CI = 1.22-7.2), and septic shock (OR = 3.92, CI = 1.61-9.58) were independently associated with 30-mortality in patients with clinically significant PHLF. CONCLUSION: PHLF in non-cirrhotic patients increased the risk of perioperative mortality and is associated with the extent of hepatectomy and infectious complications. Careful evaluation of the liver remnant, antibiotic prophylaxis, nutritional assessment, and timely management of post-operative infections could decrease major morbidity and mortality following hepatectomy.

Untangling the Knots of Regulatory T Cell Therapy in Solid Organ Transplantation.

Numerous preclinical studies have provided solid evidence supporting adoptive transfer of regulatory T cells (Tregs) to induce organ tolerance. As a result, there are 7 currently active Treg cell-based clinical trials in solid organ transplantation worldwide, all of which are early phase I or phase I/II trials. Although the results of these trials are optimistic and support both safety and feasibility, many experimental and clinical unanswered questions are slowing the progression of this new therapeutic alternative. In this review, we bring to the forefront the major challenges that Treg cell transplant investigators are currently facing, including the phenotypic and functional diversity of Treg cells, lineage stability, non-standardized ex vivo Treg cell manufacturing process, adequacy of administration route, inability of monitoring and tracking infused cells, and lack of biomarkers or validated surrogate endpoints of efficacy in clinical trials. With this plethora of interrogation marks, we are at a challenging and exciting crossroad where properly addressing these questions will determine the successful implementation of Treg cell-based immunotherapy in clinical transplantation.

Hepatic Steatosis is Associated with an Increased Risk of Postoperative Infections and Perioperative Transfusion Requirements in Patients Undergoing Hepatectomy.

BACKGROUND: To determine the impact of hepatic steatosis on perioperative outcomes of patients undergoing hepatectomy. METHODS: We analyzed all hepatectomy patients with normal and fatty liver texture, between 2014 and 2018 using NSQIP. Main endpoints included perioperative transfusions (within 72 h) and infectious complications. RESULTS: A total of 8,237 patients underwent hepatectomy during the study period. The overall rate of fatty liver texture (FLG) was 31% (2,557). Operative duration was significantly longer; inflow occlusion was more common (Pringle maneuver), and the need of transfusions was significantly higher in the FLG compared to the normal liver group (NLG) (p = < 0.001). On multivariate analysis, patients in the FLG had increased risk of developing infectious complications (OR 1.22 [95%IC 1.05-1.41]) and transfusion requirements within 72 h after hepatectomy (OR 1.43 [95% CI 1.24-1.63]). CONCLUSIONS: Hepatic steatosis is an independent risk factor for the development of infectious complications and increased perioperative transfusion requirements in patients undergoing hepatectomy. Those requiring transfusions within 72 h had also an increased risk of infections after hepatectomy.

Perioperative Challenges in Patients Transplanted with Livers from Extreme Obese Donors.

The combination of rising rates of obesity and the shortage of deceased donor livers have forced the consideration of marginal liver donors in terms of body mass index (BMI) for liver transplantation (LT). To date, there are still conflicting data on the impact of donor obesity on post-LT outcomes. We analyzed all patients undergoing LT alone in the United States (US) from October 2005 through December 2019 using the United Network of Organ Sharing (UNOS) data set. We categorized donor BMI >40 kg/m2 as extremely obese (EO). Primary endpoints included 30-day perioperative mortality and early graft loss (EGL) within 7 days. A subgroup analysis was performed for the EO donor group to assess how macrovesicular steatosis (MaS) >30% affects 30-day mortality and EGL within 7 days. A total of 72,616 patients underwent LT during the study period. The 30-day perioperative mortality was significantly higher in the EO donor group (P = 0.02). On multivariate analysis, recipients undergoing LT with EO donors had a 38% higher 30-day mortality risk (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.21-1.69) and 53% increased risk of EGL (OR, 1.53; 95% CI, 1.22-1.90). MaS >30% was independently associated with a 2-fold increased risk of 30-day mortality (P = 0.003) and 3.5-fold increased risk of EGL within 7 days (P < 0.001). The impact of MaS >30% in EGL was 2-fold for all patients transplanted during the study period compared with 3.5-fold in the EO donor group. There is an increased risk of EGL and 30-day perioperative mortality in recipients transplanted with EO donors. Future studies are warranted in morbid and super obese donors to assess the possible effect of obesity-related proinflammatory factors in EGL.

Younger Age Is Associated with Improved Survival in Patients Undergoing Liver Transplantation Alone for Metastatic Neuroendocrine Tumors.

BACKGROUND: Neuroendocrine tumor (NET) metastases are a major cause of morbidity and mortality. The role of liver transplantation to treat unresectable metastases from NET is controversial. METHODS: We evaluated outcomes of all patients undergoing "isolated" liver transplantation (LT) for metastatic NETs in the USA, from October 1988 through June 2018 using the UNOS dataset. RESULTS: During the study period, 160,360 LTs were performed. Two hundred six adult patients underwent "isolated" LT for metastatic NETs. The mean (SD) age was 48.2 (11.7) years, ranging from 19 to 75 years; 117 (56.8%) patients were male. Overall 1-, 3-, 5-, and 10-year patient survival rates were 89.1%, 75.3%, 64.9%, and 46.1%, respectively. Tumor recurrence was seen in 70 of 206 patients who underwent LT (34%). The median time to recurrence was 28 months (range, 1 to 192 months) and median wait time for LT was 112 days. Tumor recurrence was significantly higher in transplanted patients waiting less than 6 months compared with those waiting more than 6 months (74.3% vs. 25.7%). Patients' age ≤ 45 years had significantly better survival compared with those > 45 years (p = 0.03). Younger patients with carcinoid tumors had better survival but this trend was not observed in the non-carcinoid group. On multivariable analysis, recipient age, donor age, cold ischemic time MELD score, and tumor recurrence were significant predictors of poor patient survival. CONCLUSIONS: Waiting time longer than 6 months is associated to lower rates of tumor recurrence. Younger patients ≤ 45 years had significantly improved survival after LT for NET metastases.

Mitochondrial uncoupling and the disruption of the metabolic network in hepatocellular carcinoma.

BACKGROUND: Hepatocellular Carcinoma (HCC) is the third most common cause of cancer related death worldwide. Adequate treatment options for patients with advanced HCC are currently limited. MATERIALS AND METHODS: We studied the anti-HCC effect of FH535 and a novel derivative Y3, on proliferation, mitochondrial function and cellular metabolism focusing on the three key substrates, glutamine, glucose, and fatty acids. RESULTS: FH535 and Y3 disrupted mitochondrial redox control in HCC cells that resulted from uncoupling mechanisms that increased proton leakage and decreased ATP production leading to apoptosis. The uncoupling effects of the sulfonamides in HCC cells were supported by the loss of activity of the methylated analogs. The accumulation of ROS significantly contributed to cell damage after the impaired autophagic machinery. These sulfonamides, FH535 and Y3, targeted glutamine and fatty acid metabolism and caused HCC cell reprograming towards the preferential use of glucose and the glycolytic pathway. CONCLUSIONS: FH535, and Y3, demonstrated potent anti-HCC activity by targeting OXPHOS, increasing dangerous levels of ROS and reducing ATP production. These sulfonamides target glutamine and FA metabolic pathways significantly increasing the cellular dependency on glycolysis.

Detailed perioperative risk among patients with extreme obesity undergoing nonbariatric general surgery.

BACKGROUND: The obesity epidemic has spread rapidly across the United States. Although overweight and obese patients have a paradoxically lower risk for postoperative morbidity and mortality, the risks associated with extreme classes of obesity (morbid obesity, super obesity, and super-super obesity) have not been described. METHODS: We queried the National Surgical Quality Improvement Program database from 2012 to 2016. Of 1,815,251 surgical cases, there were 3,946 vascular cases, 237,777 emergency procedures, and 75,177 cases with missing data that were removed. The remaining 1,378,711 cases were included in this analysis. Multivariable linear and logistic regression was performed to assess the impact of body mass index on postoperative outcomes. RESULTS: Patients within the super obesity and super-super obesity groups had the highest procedure-adjusted mortality risk among all body mass index classes (odds ratio = 2.31 and 2.63, respectively). Morbid obesity and underweight groups had moderate risk (odds ratio = 1.37 and 1.88, respectively), while those in the overweight and obesity class I and II cohorts had improved or equivocal mortality risk compared to normal body mass index class patients. Risk-adjusted and unadjusted multivariable models demonstrated that extreme obesity classes (morbid obesity, super obesity, and super-super obesity) have a graduated escalation of perioperative morbidity, infectious, and critical care complications. CONCLUSION: Further detailing extreme obesity-related risk beyond the obesity class III umbrella is necessary for accurate risk prediction, especially with the rising prevalence of elective nonbariatric surgery in this population. Preoperative risk assessment tools should consider subgroup risk adjustment to delineate true postoperative complication risk, facilitate patient education, and address modifiable risk factors before surgery.

Effect of operative duration on infectious complications and mortality following hepatectomy.

BACKGROUND: To study mortality and infectious complications (IC) risk relative to operative duration in a large and contemporary cohort of patients undergoing hepatectomy. METHODS: A retrospective cohort study of 21,443 patients from the National Surgical Quality Improvement Program dataset of patients who underwent liver resection from 2012 to 2016. RESULTS: Patients undergoing hepatectomy during the study period (N = 21,443) had a mean operative duration of 243.5 min of which 16.6% (3533) developed at least one IC. The overall 30-day mortality was 1.6%. A significant increase in mortality and IC was demonstrated from 3 h of operating time (OR: 1.99 and OR: 1.94, respectively), peaking at 8 h (OR: 7.15 and OR: 6.37, respectively). Pneumonia, sepsis/septic shock, and SSI presented high prevalence and were linked to significant mortality. After case-matching, elective hepatectomy was associated with a 4-fold increased risk of infectious complications. CONCLUSIONS: Operative duration was associated with a linear increased risk of mortality and IC after hepatectomy. The most critical determinants of IC were ASA class, COPD, CHF, and type of hepatectomy.

Autophagic flux modulation by Wnt/ß-catenin pathway inhibition in hepatocellular carcinoma.

Autophagy targets cellular components for lysosomal-dependent degradation in which the products of degradation may be recycled for protein synthesis and utilized for energy production. Autophagy also plays a critical role in cell homeostasis and the regulation of many physiological and pathological processes and prompts this investigation of new agents to effect abnormal autophagy in hepatocellular carcinoma (HCC). 2,5-Dichloro-N-(2-methyl-4-nitrophenyl) benzenesulfonamide (FH535) is a synthetic inhibitor of the Wnt/ß-catenin pathway that exhibits anti-proliferative and anti-angiogenic effects on different types of cancer cells. The combination of FH535 with sorafenib promotes a synergistic inhibition of HCC and liver cancer stem cell proliferation, mediated in part by the simultaneous disruption of mitochondrial respiration and glycolysis. We demonstrated that FH535 decreased HCC tumor progression in a mouse xenograft model. For the first time, we showed the inhibitory effect of an FH535 derivative, FH535-N, alone and in combination with sorafenib on HCC cell proliferation. Our study revealed the contributing effect of Wnt/ß-catenin pathway inhibition by FH535 and its derivative (FH535-N) through disruption of the autophagic flux in HCC cells.

mTOR Inhibitor Everolimus in Regulatory T Cell Expansion for Clinical Application in Transplantation.

BACKGROUND: Experimental and preclinical evidence suggest that adoptive transfer of regulatory T (Treg) cells could be an appropriate therapeutic strategy to induce tolerance and improve graft survival in transplanted patients. The University of Kentucky Transplant Service Line is developing a novel phase I/II clinical trial with ex vivo expanded autologous Treg cells as an adoptive cellular therapy in renal transplant recipients who are using everolimus (EVR)-based immunosuppressive regimen. METHODS: The aim of this study was to determine the mechanisms of action and efficacy of EVR for the development of functionally competent Treg cell-based adoptive immunotherapy in transplantation to integrate a common EVR-based regimen in vivo (in the patient) and ex vivo (in the expansion of autologous Treg cells). CD25 Treg cells were selected from leukapheresis product with a GMP-compliant cell separation system and placed in 5-day (short) or 21-day (long) culture with EVR or rapamycin (RAPA). Multi-parametric flow cytometry analyses were used to monitor the expansion rates, phenotype, autophagic flux, and suppressor function of the cells. phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway profiles of treated cells were analyzed by Western blot and cell bioenergetic parameters by extracellular flux analysis. RESULTS: EVR-treated cells showed temporary slower growth, lower metabolic rates, and reduced phosphorylation of protein kinase B compared with RAPA-treated cells. In spite of these differences, the expansion rates, phenotype, and suppressor function of long-term Treg cells in culture with EVR were similar to those with RAPA. CONCLUSIONS: Our results support the feasibility of EVR to expand functionally competent Treg cells for their clinical use.

Effect of critical care complications on perioperative mortality and hospital length of stay after hepatectomy: A multicenter analysis of 21,443 patients.

OBJECTIVE: To determine predictors of critical care complications (CCC) in patients undergoing hepatectomy. METHODS: All hepatectomy patients in NSQIP from 2012 to 2016 were analyzed. CCC included prolonged ventilation (>48 h), sepsis/septic shock, renal failure/insufficiency, cardiac arrest/AMI and pulmonary embolism. RESULTS: A total of 21,443 patients underwent hepatectomy during the study period. Overall rate of CCC was 11%, with the most common being sepsis/septic shock (6.1%) and respiratory failure (4.9%). On multivariate analysis the preoperative risk factors associated with CCC included ASA Class IV-V (OR:2.04, p < 0.0001), diabetes (OR = 1.28, p = 0.0001), pre-operative ventilator use (OR: 17.75, p = 0.0003); COPD (OR: 1.65, p < 0.0001); pre-operative weight loss >10% (OR: 1.35, p = 0.0026); pre-operative sepsis (OR: 2.14, p < 0.0001). Propensity score matched analysis demonstrated a significant increased risk of mortality in patients with CCC (OR: 26.75, p < 0.0001) and a prolonged LOS of 10.5 days above the mean (ß Estimate: 10.51, p < 0.0001). CONCLUSIONS: ASA class, diabetes, COPD, pre-operative weight loss >10% and pre-operative sepsis are the strongest predictors of CCC after hepatectomy. The presence of CCC significantly increased the risk of peri-operative mortality 26-fold.

Outcomes in patients with portal hypertension undergoing gastrointestinal surgery: A propensity score matched analysis from the NSQIP dataset.

BACKGROUND/AIM: We aim to study the impact of PH in patients undergoing gastrointestinal surgery (GI). METHODS: We queried the ACS-NSQIP database from 2005 through 2010 for patients undergoing GI surgery with PH. Esophageal varices (EV) diagnosis was used as a surrogate of PH. RESULTS: A total of 192,296 patients underwent GI surgery, of which 379 had PH. Regression analyses revealed that patients with PH had a 6-fold (95% CI 4.6-7.9) increase in 30-day mortality, a 3-fold (95% CI 2.5-3.7) increase in morbidity, a 3.2-fold (95% CI 2.6-3.9) increase in critical care complications (CCC), and a 6.5-day (95% CI 5.1-7.8) increase in hospital LOS. After PSM, the impact of PH on the outcomes remained. These differences were significant regardless of the emergent or elective status of the procedure. AUC analysis demonstrated that MELD and MELDNa + score greater than 10.5 was the most predictive of peri-operative mortality in elective PH cases. CONCLUSIONS: PH is associated with an increased risk of poor surgical outcomes in patients undergoing elective and emergent gastrointestinal surgery.