Jonathan Hundley

Predictors of surgical site infection after liver resection: a multicentre analysis using National Surgical Quality Improvement Program data.

BACKGROUND   Postoperative infections are frequent complications after liver resection and have significant impact on length of stay, morbidity and mortality. Surgical site infection (SSI) is the most common nosocomial infection in surgical patients, accounting for 38% of all such infections. OBJECTIVES   This study aimed to identify predictors of SSI and organ space SSI after liver resection. METHODS   Data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database for patients who underwent liver resection in 2005, 2006 or 2007 in any of 173 hospitals throughout the USA were analysed. All patients who underwent a segmental resection, left hepatectomy, right hepatectomy or trisectionectomy were included. RESULTS   The ACS-NSQIP database contained 2332 patients who underwent hepatectomy during 2005-2007. Rates of SSI varied significantly across primary procedures, ranging from 9.7% in segmental resection patients to 18.3% in trisectionectomy patients. A preoperative open wound, hypernatraemia, hypoalbuminaemia, elevated serum bilirubin, dialysis and longer operative time were independent predictors for SSI and for organ space SSI. CONCLUSIONS   These findings may contribute towards the identification of patients at risk for SSI and the development of strategies to reduce the incidence of SSI and subsequent costs after liver resection.

Risk Factors for Venous Thromboembolism in Patients with Chronic Liver Disease

BACKGROUND Pharmacologic prophylaxis for venous thromboembolism (VTE) in patients with chronic liver disease (CLD) presents a unique challenge because of coagulopathies associated with the disease. When evaluating whether these patients require VTE prophylaxis upon hospitalization, it would be advantageous if risk factors for the development of VTE in this population were known. OBJECTIVE To evaluate risk factors associated with the development of VTE in patients with CLD. METHODS A retrospective case-control study was conducted. Patients admitted to the University of Kentucky Chandler Hospital from October 2006 to July 2010 with a diagnosis of CLD and VTE were matched in a 1:3 fashion with CLD patients without VTE. The primary objective was to determine whether there were significant differences in laboratory values between the 2 groups. RESULTS During this time, 27 patients with CLD (1.0%) were diagnosed with VTE. These patients had significantly lower median aspartate aminotransferase (AST) (47 vs 70 U/L, p = 0.04), alanine transaminase (ALT) (24.5 vs 36 U/L, p = 0.02), albumin (2.1 vs 2.4 g/dL, p = 0.02) and hematocrit (Hct) (28.3% vs 32%, p = 0.03) values compared to the control patients. Patients with albumin lower than 1.9 g/dL had a 5.1 times greater risk of VTE compared to patients with albumin of 2.8 g/dL and higher (OR 5.14, 95% CI 1.05–25.2). CONCLUSIONS Patients with CLD who developed VTE had significantly lower AST, ALT, albumin, and Hct compared to those of control patients. Studies are necessary to further examine the significance of this finding.

PKI-587 and sorafenib alone and in combination on inhibition of liver cancer stem cell proliferation

BACKGROUND Deregulated Ras/Raf/mitogen-activated protein kinase and PI3 K/AKT/mTOR signaling pathways are significant in hepatocellular carcinoma proliferation (HCC). In this study we evaluated differences in the antiproliferative effect of dual PI3 K/Akt/mTOR and Ras/Raf/mitogen-activated protein kinase inhibition of non liver cancer stem cell lines (PLC and HuH7) and liver cancer stem cell (LCSC) lines (CD133, CD44, CD24, and aldehyde dehydrogenase 1-positive cells). MATERIALS AND METHODS Flow cytometry was performed on the resulting tumors to identify the LCSC markers CD133, CD44, CD24, and aldehyde dehydrogenase 1. Methylthiazol tetrazolium assay was used to assess cellular proliferation. Finally, a Western blot assay was used to evaluate for inhibition of specific enzymes in these two signaling pathways. RESULTS Using flow cytometry, we found that LCSC contain 64.4% CD133 + cells, 83.2% CD44 + cells, and 96.4% CD24 + cells. PKI-587 and sorafenib caused inhibiton of LCSC and HCC cell proliferation. PLC cells were more sensitive to PKI-587 than LCSC or Huh7 (P < 0.001). Interestingly, HuH7 cells were more sensitive to sorafenib than LCSC or PLC cells. Additionally, combination therapy with PKI-587 and sorafenib caused significantly more inhibition than monotherapy in HuH7, PLC, and LCSC. Using the methylthiazol tetrazolium assay, we found that the LCSC proliferation was inhibited with sorafenib monotherapy 39% at 5 μM (P < 0.001; n = 12) and 67% by PKI-587 at 0.1 μM (P = 0.002, n = 12) compared with control. The combination of PKI-587 and sorafenib, however, synergistically inhibited LCSC proliferation by 86% (P = 0.002; n = 12). CONCLUSIONS LCSC (CD133+, CD44+, CD24+) were able to develop very aggressive tumors with low cell concentrations at 4 to 6 wk. Cells CD133+, CD44+, CD24+, which demonstrated at least moderate resistance to therapy in vitro. The combination of PKI-587 and sorafenib was better than either drug alone at inhibiting of LCSC and on HCC cell proliferation.

Peri-operative challenges and long-term outcomes in liver transplantation for polycystic liver disease.

BACKGROUND The purpose of this study was to determine peri-operative mortality and long-term outcomes in patients undergoing liver transplantation in the US using the United Network for Organ Sharing (UNOS) database. METHODS This study is a retrospective review of liver transplantations (LT) recorded in the UNOS database performed between 1988 and 2010. In total, 107 411 LT were performed in the US, 357 (0.3%) were for adult polycystic liver disease (PLD). A random group of 9416 adult patients transplanted for other diagnoses was created for comparison (10% of the adult non-PLD database). RESULTS Two hundred and seventy-one patients in the adult PLD group were females (75.9%), the mean age was 52.3 ± 8.2 [standard deviation (SD)] years. The median length of transplantation hospital stay was 11 days (interquartile range 8-21). Patients from the PLD group versus the comparison group (9416 patients) consisted of more females, lower Model for End-Stage Liver Disease (MELD) scores (17 versus 21 points), more multi-organ transplants (41% versus 4 %), chronic renal failure (creatinine 2.7 versus 1.5) and fewer patients with chronic hepatitis C (1.4% versus 32%). Peri-operative mortality (≤30 days) was 9% in the PLD versus 6% in the comparison group; however, at 1 year PLD survival was similar (85% versus 85%) to other diagnoses and better at 3 (81% versus 77%) and 5 years (77% versus 71%, overall Log Rank P = 0.006). A similar PLD survival advantage was observed in isolated initial transplants (P = 0.019). CONCLUSION In spite of early technical challenges and mortality, transplantation should be considered an option for selected patients with PLD as excellent long-term outcomes can be achieved.

QT prolongation is associated with increased mortality in end stage liver disease

AIM To determine the prevalence of QT prolongation in a large series of end stage liver disease (ESLD) patients and its association to clinical variables and mortality. METHODS The QT interval was measured and corrected for heart rate for each patient, with a prolonged QT cutoff defined as QT > 450 ms for males and QT > 470 ms for females. Multiple clinical variables were evaluated including sex, age, serum sodium, international normalized ratio, creatinine, total bilirubin, beta-blocker use, Model for End-Stage Liver Disease (MELD), MELD-Na, and etiology of liver disease. RESULTS Among 406 ESLD patients analyzed, 207 (51.0%) had QT prolongation. The only clinical variable associated with QT prolongation was male gender (OR = 3.04, 95%CI: 2.01-4.60, P < 0.001). During the study period, 187 patients (46.1%) died. QT prolongation was a significant independent predictor of mortality (OR = 1.69, 95%CI: 1.03-2.77, P = 0.039). In addition, mortality was also associated with viral etiology of ESLD, elevated MELD score and its components (P < 0.05 for all). No significant reversibility in the QT interval was seen after liver transplantation. CONCLUSION QT prolongation was commonly encountered in an ESLD population, especially in males, and served as a strong independent marker for increased mortality in ESLD patients.

Thrombectomy and cavocavostomy for inferior vena cava thrombosis and torsion after piggyback liver transplantation

Although numerous surgical and percu-taneous techniques have been suggested for the man-agement of different IVC complications, there is noconsensus about a standard method of treatment.Here we describe a unique case in which a liverallograft caused kinking of the recipient’s IVC andsubsequent thrombosis after piggyback livertransplantation.Our case involves a 48-year-old male with end-stageliver disease secondary to hepatitis C. He underwentpiggyback liver transplantation in which the suprahe-patic allograft IVC was anastomosed with 3 recipienthepatic veins.On postoperative day 3, the patient developed sig-nificant hemodynamic instability and was re-exploredthrough the same bilateral subcostal incision. Anintraoperative Doppler examination revealed patenthepatic veins with pulsatile flow but also a nearlyocclusive thrombus in the recipient’s IVC extendingfrom the suprarenal IVC to the retrohepatic IVC infe-rior to the piggyback anastomosis. The absence of anoutflow obstruction was confirmed by the lack of apressure gradient across the piggyback anastomosis,which was demonstrated by the direct measurementof the pressures of the recipient’s suprahepatic IVCand the donor’s IVC. Graft rotation and IVC kinkinginferior to the piggyback anastomosis were alsoobserved to be causing IVC stenosis.The decision was made to perform a thrombectomythrough a venotomy on the suprarenal IVC withFogarty balloons. Once an adequate caval flow wasobtained, vascular clamps were applied inferior to thepiggyback anastomosis and slightly superior to therenal veins. The lower aspect of the donor’s IVC wasuntied and anastomosed to the opening on the recipi-ent’s IVC (the site of the thrombectomy) in an end-to-side fashion (Fig. 1). By anchoring the donor’s IVC in2 separate locations, we were able to relieve the kink-ing of the IVC.Three days after the re-exploration, a Doppler ultra-sound examination revealed normal directional flowand patency of the hepatic vasculature. A retrievableGunther Tulip IVC filter was inserted to prevent anyfurther risk of a pulmonary embolism. The patient’sremaining postoperative course was unremarkable.The laboratory values on April 2011 were as follows:total bilirubin, 1.4 mg/dL; aspartate aminotransferase,