Forkhead box M1 (FOXM1) transcription factor is a key oncogenic driver of aggressive human meningioma progression.

AIMS: Aggressive meningioma remains incurable with neither chemo- nor targeted therapies proven effective, largely due to unidentified genetic alterations and/or aberrant oncogenic pathways driving the disease progression. In this study, we examined the expression and function of Forkhead box M1 (FOXM1) transcription factor during meningioma progression. METHODS: Human meningioma samples (n = 101) were collected, followed by Western blotting, quantitative PCR, immunohistochemical and progression-free survival (PFS) analyses. For in vitro assays, FOXM1 was overexpressed or knocked-down in benign (SF4433 and SF4068) or malignant (SF3061 and IOMM-Lee) human meningioma cell lines respectively. For in vivo studies, siomycin A (a FOXM1 inhibitor)-pretreated or control IOMM-Lee cells were implanted subcutaneously in nude mice. RESULTS: FOXM1 expression was increased in higher grades of meningioma and correlated with the mitotic index in the tumour tissue. Moreover, FOXM1 was increased in recurrent meningioma compared with the matched primary lesions. The patients who had higher FOXM1 expression had shorter PFS. In the subsequent in vitro assays, knockdown of FOXM1 in malignant meningioma cell lines resulted in decreased tumour cell proliferation, angiogenesis and invasion, potentially via regulation of ß-catenin, cyclin D1, p21, interleukin-8, vascular endothelial growth factor-A, PLAU, and epithelial-to-mesenchymal transition-related genes, whereas overexpression of FOXM1 in benign meningioma cell lines had the opposite effects. Last, suppression of FOXM1 using a pharmacological inhibitor, siomycin A, decreased tumour growth in an in vivo mouse model. CONCLUSIONS: Our data demonstrate that FOXM1 is a key transcription factor regulating oncogenic signalling pathways in meningioma progression, and a promising therapeutic target for aggressive meningioma.

Analysis of the Beaufort Gyre Freshwater Content in 2003-2018.

Hydrographic data collected from research cruises, bottom-anchored moorings, drifting Ice-Tethered Profilers, and satellite altimetry in the Beaufort Gyre region of the Arctic Ocean document an increase of more than 6,400 km3 of liquid freshwater content from 2003 to 2018: a 40% growth relative to the climatology of the 1970s. This fresh water accumulation is shown to result from persistent anticyclonic atmospheric wind forcing (1997-2018) accompanied by sea ice melt, a wind-forced redirection of Mackenzie River discharge from predominantly eastward to westward flow, and a contribution of low salinity waters of Pacific Ocean origin via Bering Strait. Despite significant uncertainties in the different observations, this study has demonstrated the synergistic value of having multiple diverse datasets to obtain a more comprehensive understanding of Beaufort Gyre freshwater content variability. For example, Beaufort Gyre Observational System (BGOS) surveys clearly show the interannual increase in freshwater content, but without satellite or Ice-Tethered Profiler measurements, it is not possible to resolve the seasonal cycle of freshwater content, which in fact is larger than the year-to-year variability, or the more subtle interannual variations.

Adjuvant concurrent chemoradiation therapy in patients with microscopic residual tumor after curative resection for extrahepatic cholangiocarcinoma

Purpose: We investigated the role of adjuvant concurrent chemoradiation therapy (CCRT) in patients with a microscopically positive resection margin (R1) after curative resection for extrahepatic cholangiocarcinoma (EHCC). Methods/patients: A total of 84 patients treated with curative resection for EHCC were included. Fifty-two patients with negative resection margins did not receive any adjuvant treatments (R0 + S group). The remaining 32 patients with microscopically positive resection margins received either adjuvant CCRT (R1 + CCRT group, n = 19) or adjuvant radiation therapy (RT) alone (R1 + RT group, n = 13). Results: During the median follow-up period of 26 months, the 2-year locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival rates (OS) were: 81.8, 62.6, and 61.5% for R0 + S group; 71.8, 57.8, and 57.9% for R1 + CCRT group; and 16.8, 9.6, and 15.4% for R1 + RT group, respectively. Multivariate analysis revealed that the R1 + CCRT group did not show any significant difference in survival rates compared with the R0 + S group. The R1 + RT group had lower LRRFS [hazard ratio (HR) 3.008; p = 0.044], DFS (HR 2.364; p = 0.022), and OS (HR 2.417; p = 0.011) when compared with the R0 + S and R1 + CCRT group. Conclusions: A lack of significant survival difference between R0 + S group and R1 + CCRT group suggests that adjuvant CCRT ameliorates the negative effect of microscopic positive resection margin. In contrast, adjuvant RT alone is appeared to be inadequate for controlling microscopically residual tumor

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Correlation between risk of hepatitis B virus recurrence and tissue expression of covalently closed circular DNA in living donor liver transplant recipients treated with high-dose hepatitis B immunoglobulin.

BACKGROUND AND AIMS: Despite the application of prophylaxis, the risk of hepatitis B virus (HBV) recurrence remains. However, actual mechanism(s) and definite risk factor(s) are obscure. The present study examined the correlation between the HBV load in liver explants and post-liver transplant (OLT) HBV recurrence. METHODS: HBV DNA was extracted from liver tissue taken from 50 living donor OLT (LDLT) patients using the QuickGene DNA Tissue Kit S (Fujifilm, Tokyo, Japan) and subjected to real-time polymerase chain reaction with the following primers: 5'-CACATGGCCTCCAAGGAGTAA-3' (forward primer) and 5'-TGAGGGTCTCTCTCTTCCTCTTGT-3' (reverse primer). To prevent HBV infection, patients were treated daily with high-dose (10,000 IU) hepatitis B immunoglobulin (HBIG) for the first week after LDLT. They then received weekly doses for the next month and then monthly doses for ≤1 year. If the anti-hepatitis surface antigen antibody titer was <1,000 IU/L, an antiviral agent (AVA) was added to the regimen. RESULTS: The mean (±SD) tissue HBV DNA and covalently closed circular DNA (cccDNA) loads were -0.8 ± 1.2 (range, -2.9 to 2.6) and -2.3 ± 1.1 (range, -4.6 to 0.6) log10 copies/cell, respectively. There was a significant correlation between serum and tissue HBV DNA (r = 0.65; P = .00) and cccDNA concentrations (r = 0.55; P = .00). Six patients suffered HBV recurrence and 9 required additional AVA. There was no direct correlation between HBV recurrence and tissue cccDNA concentration. However, the concentration of cccDNA was significantly greater those patients suffering recurrence and receiving AVA treatment (high-risk group). CONCLUSION: High tissue cccDNA concentrations may be a risk factor for HBV recurrence despite high-dose HBIG prophylaxis.

Dental image replacement on cone beam computed tomography with three-dimensional optical scanning of a dental cast, occlusal bite, or bite tray impression.

The goal of the present study was to compare the accuracy of dental image replacement on a cone beam computed tomography (CBCT) image using digital image data from three-dimensional (3D) optical scanning of a dental cast, occlusal bite, and bite tray impression. A Bracket Typodont dental model was used. CBCT of the dental model was performed and the data were converted to stereolithography (STL) format. Three experimental materials, a dental cast, occlusal bite, and bite tray impression, were optically scanned in 3D. STL files converted from the CBCT of the Typodont model and the 3D optical-scanned STL files of the study materials were image-registered. The error range of each methodology was measured and compared with a 3D optical scan of the Typodont. For the three materials, the smallest error observed was 0.099±0.114mm (mean error±standard deviation) for registering the 3D optical scan image of the dental cast onto the CBCT dental image. Although producing a dental cast can be laborious, the study results indicate that it is the preferred method. In addition, an occlusal bite is recommended when bite impression materials are used.

External biliary drainage in living donor liver transplantation using duct-to-duct anastomosis.

PURPOSE: This study compared the incidence of biliary complication (BC) in adult living donor liver transplant recipients who underwent right-lobe duct-to-duct anastomosis (DDA) with or without external biliary drainage (EBD) and intended to optimize EBD tube clamping. METHODS: This study consisted of a retrospective assessment of EBD effect and a prospective trial for EBD tube-clamping optimization. The retrospective study included the EBD group (n = 208) and the non-EBD group (n = 145). The prospective study included 60 patients with EBD. RESULTS: In the retrospective study, single DDA was performed in 83.7% of the EBD group and 80.7% of the non-EBD group (P = .47). One-year overall incidence of BC was 14.4% in the EBD group and 16.8% in the non-EBD group (P = .48). The incidence of early anastomotic bile leakage was 1.0% in the EBD group and 4.8% in the non-EBD group (P = .036). In the prospective study, there was no difference in tube-clamping success rates between low- and high-output EBD groups. There was also no statistical difference between the success and failure groups in terms of graft duct size, liver function tests, and post-transplant days at tube clamping. CONCLUSIONS: The size of our EBD tube was too small for the graft duct size, therefore its main role appeared to be early biliary decompression, which helped prevent bile leakage and also simplified the route of cholangiogram in detecting early BC. Hence, EBD is worthy of performing in selected patients with a high risk of anastomotic bile leak.

Long-term outcome of living donor liver transplantation for patients with alcoholic liver disease.

BACKGROUND: Because most liver transplantation (LT) studies for alcoholic liver disease (ALD) were performed on deceased donor LT, little was still known following living donor LT (LDLT). METHODS: The clinical outcomes of 126 ALD patients who underwent LDLT for 11 years in a high-volume LT center were assessed retrospectively. RESULTS: ALD cases were 5.7% of adult LDLT indication (n = 2196). ALD was 1.9% (4 of 207) during 2000 to 2001, whereas the proportion gradually increased up to 11.3% (34 of 301) in 2010. The model for end-stage liver disease score was 22.1 ± 9.9, and 6-month abstinence was observed in 105 (83.3%). There were 123 (97.6%) related donors. Single-graft and dual-graft were implanted into 111 and 15 patients, respectively. Main graft type was single right liver graft (n = 108; 85.7%). Graft-to-recipient weight ratio was 1.02 ± 0.16. Perioperative mortality within 3 months occurred in 5 (4.0%). Overall 1-, 3-, 5-, and 10-year patient survival rates were 92.1%, 88.0%, 85.8%, and 83.7%, respectively. Three patients died of alcohol abuse. De novo hepatitis B virus infection occurred in 2 of 26 patients after implantation of core antibody-positive graft and no further cases happened after strict application of prophylaxis. CONCLUSIONS: The results of this study revealed that the survival outcome of LDLT in ALD patients is comparable with that of deceased donor LT. To achieve favorable long-term survival, a multidisciplinary approach can be an effective strategy, including the interaction between the patient, the physician, and the family members.

Long-term survival analysis of liver transplantation for hepatocellular carcinoma with bile duct tumor thrombus.

BACKGROUND: Long-term prognosis of liver transplantation (LT) for hepatocellular carcinoma (HCC) with macroscopic bile duct tumor thrombus (BDTT) has not been well assessed. This study intended to analyze the post-transplantation outcomes in patients who had HCC with macroscopic BDTT. METHODS: A retrospective study was performed with 14 patients who underwent LT for HCC with BDTT (0.7%) after selection from an institutional database of 2052 adult LT cases. RESULTS: Types of LT were living donor LT in 13 and deceased donor LT in 1. The extents of BDTT were Ueda type 1 in 4, type 2 in 3, and type 3 in 7. Milan criteria were met in 8 (57.1%). Concurrent bile duct resection was performed in 7 (50%). Mean model for end-stage liver disease score was 18.7 ± 4.9. Mean graft-recipient weight ratio was 1.2 ± 0.3. There was one case of perioperative mortality and one case of HCC-unrelated late mortality. Cumulative HCC recurrence rates were 15.4% at 1 year, 46.2% at 3 years, and 46.2% at 5 years. Overall patient survival rates were 92.9% at 1 year, 57.1% at 3 years, and 50% at 5 years. Univariate risk factor analyses revealed that only macrovascular invasion was a significant risk factor for HCC recurrence (P = .019). CONCLUSIONS: The results of this study revealed that LT for HCC with macroscopic BDTT has a high risk of post-transplantation HCC recurrence; therefore, further large-volume studies are necessary to elucidate the risk factors.

Complications analysis of polytetrafluoroethylene grafts used for middle hepatic vein reconstruction in living-donor liver transplantation.

BACKGROUND: We previously showed that ringed polytetrafluoroethylene (PTFE) grafts combined with small allograft patches showed high patency rates similar to those of iliac vein grafts and therefore that they can be used for middle hepatic vein (MHV) reconstruction. Although such use of PTFE graft showed high patency rates, its long-term safety regarding infection and other types of complications were not presented. In this study, we investigated the actual risk of complications directly associated with PTFE graft interposition for MHV reconstruction. METHODS: During the study period of 30 months, we performed 215 cases of adult living-donor liver transplantation with modified right lobe graft and PTFE grafts. We classified the potential complications directly associated with PTFE graft interposition as infectious and surgical complications. The medical records of study patients were retrospectively reviewed. RESULTS: MHV graft patency rate was 76.3% at 6 months and 36.7% at 12 months. Their 1-year graft and patient survival rates were 92.6% and 93.5%, respectively. The 1-year actual incidences of infectious complication and surgical complication were near zero and 1 case (0.5%), respectively. In 1 recipient, the PTFE graft penetrated into the stomach wall 6 months after transplantation, but the patient did not complain of any specific symptoms. The PTFE graft was removed with the use of laparotomy, and the patient recovered uneventfully. CONCLUSIONS: Although the incidence of PTFE graft-associated complication rate is very low, we suggest that it is necessary to closely monitor the PTFE graft, because unexpected complications can happen during long-term follow-up.

Comparison of the efficacies of oral iron and pramipexole for the treatment of restless legs syndrome patients with low serum ferritin.

BACKGROUND AND PURPOSE: It is not clear which is preferred between iron supplement and a dopamine agonist in the treatment of restless legs syndrome (RLS) with iron deficiency. The efficacies of oral iron supplementation and pramipexole for treatment of RLS with low-normal serum ferritin (15-50 ng/ml) were compared. METHODS: Thirty RLS patients who took either oral iron or pramipexole for 12 weeks and were followed at 2, 4, 8 and 12 weeks after treatment commencement were enrolled. Severities of RLS symptoms were assessed using the international RLS study group rating scale for severity (IRLS) at every visit. Treatment response was defined as a decrease in IRLS score of at least 50% from baseline. RESULTS: The 30 subjects were assigned equally to an iron or pramipexole group. At baseline, IRLS scores and serum ferritin levels were similar between these two groups. After 12 weeks, IRLS scores were lower than those at baseline in both groups (iron -9.1 ± 7.07, P < 0.001; pramipexole -8.7 ± 8.31, P = 0.001) and similar between the two groups. Changes in IRLS scores from baseline were similar between the two groups at each visit. The response rates of the groups were identical at 46.7%. CONCLUSIONS: Pramipexole was not different from oral iron in terms of efficacy and improvement speed in RLS patients with a low-normal serum ferritin, but response rate of either oral iron or pramipexole alone was moderate. Some proportion of RLS patients with iron deficiency might benefit from combined use of oral iron and dopamine agonists.

Survival rates among patients awaiting deceased donor liver transplants at a single high-volume Korean center.

BACKGROUND: Since the establishment of the Korean Network for Organ Sharing (KONOS) in 2000, thousands of patients have been enrolled on the waiting list, but only a small proportion have received a deceased donor liver transplantation. This report on waiting list mortality in Korea based on data from a single institution. METHODS: The 1772 patients enrolled on the waiting list between February 2000 and December 2011 either have not yet received at the time of analysis or have died before receiving an organ. Survival information was obtained in February 2012 by reviewing medical records or by telephone. We excluded patients who died immediately after enrollment or after retransplantation. RESULTS: Primary diagnoses of those awaiting transplantation were hepatitis B virus-associated cirrhosis (63.7%), alcoholic liver disease (14.3%), hepatitis C virus-associated cirrhosis (13.8%), and acute liver failure due to other causes (8.1%). The priority status of patients on the waiting list was KONOS status 1 (highest priority) in 3.8%, status 2A in 3.9%, status 2B in 41.9%, status 3 to 7 (lowest priority) in 50.5%. Their median survival periods were 1, 1, 18, and 59 months, respectively. The mean Child-Pugh score was 8.5 ± 2.5 and Model for End-stage Liver Disease (MELD) score 18.1 ± 9.8. CONCLUSIONS: Patients with high MELD scores or hepatocellular carcinoma succumbed soon after being entered on to the waiting list. By increasing organ donation rates and developing a risk-based allocation system, it should be possible to reduce mortality among patients on organ waiting lists.

Unification venoplasty to cope with recipient portal vein anomaly during living donor liver transplantation.

PURPOSE: To cope with recipient portal vein (PV) anomalies, such as early branching of the right posterior section (RPS), during living donor liver transplantation (LDLT) surgery, we performed a simulation study to standardize the surgical technique for unification portal venoplasty. METHODS: This study included an observational analysis of conventional methods utilizing RPS PV, simulation-based design of a new surgical technique, and clinical application of this new technique. RESULTS: In a case encountering RPS PV, a mild anastomotic PV stenosis was persistent over 6 months postsurgery, indicating the need for technical refinement. After computational simulation analysis, we found that simple suturing of the PV branch patch automatically resulted in a funnel-shaped elongation. A prospective recipient study (n = 30) indicated that usual PV reconstruction via the PV bifurcation method is feasible in the absence of unusual donor or recipient PV anomaly. Retrospective living donor PV anatomy analysis (n = 20) revealed that 20-mm-long limbs of the first-order PV branches are necessary to make a 10- to l5-mm-long funneled PV stump. This technique of unification venoplasty for an anomalous recipient PV was applied to an adult patient undergoing LDLT with a right liver graft, for which it was shown to be technically feasible and effective. CONCLUSIONS: A simplified unification venoplasty technique was developed to cope with a recipient PV anomaly in adult LDLT.

Long-term survival outcomes for living donor liver transplant recipients with pathologically nonviable hepatocellular carcinoma.

PURPOSE: Complete necrosis of hepatocellular carcinoma (HCC) lesions has occasionally been found by explant pathology after pretransplant neoadjuvant treatment. This study sought to investigate the long-term prognostic effect of loss of tumor viability after HCC treatment in living donor liver transplant (LDLT) recipients. METHODS: We reviewed retrospectively the 5-year records of 37 patients who demonstrated nonviable HCC on explant pathology. RESULTS: The most common primary disease was hepatitis-B-virus-associated liver cirrhosis (n = 34). Single explant tumors were found in 29 patients; the mean maximal tumor size was 2.1 ± 0.9 cm (range: 0.8-4.0). No patients showed microvascular invasion. The median level of alpha-fetoprotein was 12 ng/mL (range: 1-1160). The 1 patient who showed a recurrence at 20 months remains alive more than 6 years after adrenalectomy and repeated pulmonary metastasectomy. The 5-year HCC recurrence rate was thus 2.1%. There were 2 late mortalities, each due to graft failure and recurrent gastric cancer. The overall patient survival rate was 97.3% at 5 and 92.7% at 10 years. CONCLUSIONS: The results of this study revealed that the loss of tumor viability induced by pretransplant neoadjuvant treatment definitely decreased the risk of post-transplant HCC recurrence. Therefore, patients with nonviable HCC can be regarded as members of a superselect group with minimal risk for HCC recurrence, and may be exempted from routine HCC screening.

Long-term outcome of liver transplantation for combined hepatocellular carcinoma and cholangiocarcinoma.

PURPOSE: Combined hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC) is a rare pair of intrahepatic malignancies. Differential diagnosis among combined HCC-CCC, HCC, or CCC can be difficult; thus malignancies other than ordinary HCC are occasionally encountered unexpectedly in explanted liver specimens. The present study analyzed the long-term outcomes of liver transplantation (OLT) among patients with HCC-CCC. METHODS: Between January 1999 and December 2009, we performed 2137 adult OLT at our institution including 15 cases of pathologically confirmed HCC-CCC, who all underwent OLT with a pretransplant diagnosis of HCC. We reviewed retrospectively the medical records of these 15 patients. RESULTS: Their mean age was 58.9 ± 7.2 years. The median preoperative alpha-fetoprotein level was 32.6 ng/mL. Fourteen patients underwent living donor and one deceased donor OLT. The Milan criteria were met in 12 cases. A single tumor was identified in 8 and multiple lesions in 7 patients. The maximal tumor diameter was 2.9 ± 1.7 cm. Seven patients experienced tumor recurrences: including 6 within the first 12 months. All of the patients who experienced recurrences died at a median 4 months after that diagnosis. The overall patient survival rates were 66.7% at 1 year and 60.0% at 3 and 5 years. Disease-free patient survival rates were 60.0% at 1 year and 53.3% at 3 and 5 years. CONCLUSIONS: Patients with combined HCC-CCC showed a high rate of early recurrences, particularly within the first year.

Analysis of S gene mutation of the hepatitis B virus in adult liver transplant recipients showing resistance to hepatitis B immunoglobulin therapy.

BACKGROUND: A considerable proportion of recipients of liver transplantations who are presented hepatitis B immunoglobulin (HBIG) monotherapy for hepatitis B virus (HBV) prophylaxis develop HBIG resistance. In this study, we investigated the mutation patterns in the major hydrophilic region (MHR) of amino acid sequences 100 to 160. METHODS: Using the gene sequence analyzer for amino acid sequences 0 to 226 in the S/pre-S region we analyzed blood samples of 15 patients showing HBIG resistance after high-dose HBIG prophylaxis. RESULTS: Various mutations in the MHR were observed in 14/15 samples: Gly145Arg mutation in 8/13 Adr subtype and 1/2 Ayw subtype samples (60%). The next most common mutation was Gly165Trp in 8/13 Adr subtype but neither of 2 Ayw subtype samples (53.3%). Concurrent antiviral resistance was noted in 5 patients: lamivudine (n = 5), or entecavir (n = 3), but not adefovir, suggesting the occurrence of simultaneous, antiviral cross-resistances. Two patients underwent retransplantation due to the progression of HBV infection despite vigorous antiviral therapy. At diagnosis of HBV recurrence, the mean HBV DNA load was 6.5 × 10(6) copies/mL; 4 patients showed paradoxical coexistence of anti-HBs and HBsAg. Currently, 2 subjects show low-level HBV DNA replication in peripheral blood, although the other 12 had no DNA replication after prolonged antiviral therapy. CONCLUSIONS: This study suggested that various mutations in the "a" determinant were associated with HBIG resistance. Since treatment failure to rescue antiviral therapy was often associated with delayed detection of HBV recurrence rather than concurrent antiviral resistance, frequent HBV surveillance using more sensitive screening tests, such as HBeAg and HBV DNA polymerase chain reaction assay, seems to be mandatory.

Post-transplant assessment of consciousness in acute-on-chronic liver failure patients undergoing liver transplantation using bispectral index monitoring.

PURPOSE: Deterioration of consciousness is a critical situation for liver transplantation (OLT) recipients. The bispectral (BIS) index based on electroencephalographic parameters, is primarily used to monitor the depth of unconsciousness. The present study sought to assess the usefulness of posttransplant BIS index to monitor acute-on-chronic liver failure patients. METHODS: This 1-year retrospective study of 28 adult patients with acute-on-chronic liver failure was performed from July 2011 to June 2012, using post-transplant BIS monitoring. RESULTS: The mean patient age was 51 ± 8 years. Their mean pretransplant Child-Turcotte-Pugh score was 12.3 ± 1.4, and the mean Model for End-stage Liver Disease score, 36.4 ± 5.9. After OLT, the mean initial Glasgow Coma Scale (GCS) score and BIS index were 3.4 ± 1.7 and 43.5 ± 9.1, respectively. After 6 hours the mean GCS and BIS values rose to 8.6 ± 4.0 and 52.4 ± 10.3 and after 12 hours to 9.7 ± 3.4 and 61.3 ± 15.7 respectively. Eye opening in response to a voice occurred at a mean of 8.9 ± 6.7 hours after arrival in the intensive care unit regardless of graft function. The mean GCS and BIS values were 10.6 ± 2.8 and 69.1 ± 13.5, respectively. The endotracheal tube was removed after a median of 140 hours; 9 patients required a tracheostomy. Among them 2 died within the first 3 months after OLT. CONCLUSIONS: BIS monitoring is a noninvasive, simple, easy-to-interpret method to measure consciousness among patients intubated with an endotracheal tube.

The immunomodulatory role of esmolol in patients undergoing laparoscopic gastrectomy due to gastric cancer.

Esmolol has a beneficial effect on the T helper 1/T helper 2 balance in patients with heart failure. The aim of this study was to investigate the immunomodulatory role of esmolol during and after surgery. Patients undergoing laparoscopic gastrectomy due to gastric cancer were enrolled. Patients in the esmolol group (n = 15) received esmolol during surgery, and a saline-treated group (n = 14) served as a control. Cytokines were quantified by sandwich enzyme-linked immunoassays before, during and after surgery. The esmolol group was associated with higher ratios of interferon-γ/interleukin-4 (T helper 1/T helper 2 signature cytokines) than the saline group during (2.36 vs 0.57, respectively, p = 0.041) and after (5.79 vs 0.69, respectively, p = 0.033) surgery. The postoperative increase in interleukin-6 was attenuated in the esmolol group, and the C-reactive protein level on postoperative day 1 was significantly lower in the esmolol group than in the saline group (mean (SD) 26.2 (18.3) mmol.l(-1) vs 56.8 (44.3) mmol.l(-1), p = 0.021). Our findings suggest that esmolol played an immunomodulatory role and mitigated the postoperative inflammatory response in patients under surgical and anaesthetic stress.