Midterm clinical outcome of a case of aortic arch aneurysm treated with a novel arch stentgraft system.

INTRODUCTION: Open surgery is the gold standard treatment for aortic arch disease. However, due to its complexity, open arch replacement is associated with considerable risk of mortality and morbidity. METHOD: We report a case of a 71-year-old gentleman with multiple comorbidities and symptomatic 7 cm aortic arch aneurysm who was treated with a single-stage carotid-carotid and left carotid-axillary bypass followed by zone 0 aortic arch stenting with bimodular Nexus™ stent graft. RESULTS: Post-operatively, the patient suffered from a minor stroke with full neurological recovery. Follow-up computed tomography of the aorta 3 years post-stenting showed excellent stent position with no endoleak and complete resolution of the saccular aneurysm. DISCUSSION: The midterm result of our patient who was successfully treated with an off-the-shelf single branch, bimodular stent graft system is excellent with complete resolution of the arch saccular aneurysm at 3-year after the operation.

A phase II clinical study on the efficacy and predictive biomarker of pegylated recombinant arginase on hepatocellular carcinoma.

BACKGROUND: Pegylated recombinant human arginase (PEG-BCT-100) is an arginine depleting drug. Preclinical studies showed that HCC is reliant on exogenous arginine for growth due to the under-expression of the arginine regenerating enzymes argininosuccinate synthetase (ASS) and ornithine transcarbamylase (OTC). METHODS: This is a single arm open-label Phase II trial to assess the potential clinical efficacy of PEG-BCT-100 in chemo naïve sorafenib-failure HCC patients. Pre-treatment tumour biopsy was mandated for ASS and OTC expression by immunohistochemistry (IHC). Weekly intravenous PEG-BCT-100 at 2.7 mg/kg was given. Primary endpoint was time to progression (TTP); secondary endpoints included radiological response as per RECIST1.1, progression free survival (PFS) and overall survival (OS). Treatment outcomes were correlated with tumour immunohistochemical expressions of ASS and OTC. RESULTS: In total 27 patients were recruited. The median TTP and PFS were both 6 weeks (95% CI, 5.9-6.0 weeks). The disease control rate (DCR) was 21.7% (5 stable disease). The drug was well tolerated. Post hoc analysis showed that duration of arginine depletion correlated with OS. For patients with available IHC results, 10 patients with ASS-negative tumour had OS of 35 weeks (95% CI: 8.3-78.0 weeks) vs. 15.14 weeks (95% CI: 13.4-15.1 weeks) in 3 with ASS-positive tumour; expression of OTC did not correlate with treatment outcomes. CONCLUSIONS: PEG-BCT-100 in chemo naïve post-sorafenib HCC is well tolerated with moderate DCR. ASS-negative confers OS advantage over ASS-positive HCC. ASS-negativity is a potential biomarker for OS in HCC and possibly for other ASS-negative arginine auxotrophic cancers. TRIAL REGISTRATION NUMBER: NCT01092091. Date of registration: March 23, 2010.

Valiant NAVION stent graft system application: First Asian case-series analysis.

BACKGROUND AND AIM: The Valiant NavionTM stent graft system is a third-generation low profile thoracic endograft designed for thoracic endovascular aortic repair. In this population analysis, we report on the first Asian all-comers experience and outcomes who underwent thoracic endovascular aortic repair with the use of this new stent graft system. METHODS: Between May 2019 and October 2020, 21 patients with different aortic pathologies were prospectively recruited and retrospectively analyzed. Important clinical and device-related outcomes were evaluated. The endpoints included short-term survival, technical success, access failures, major vascular and clinical complications, endoleaks, and hospital stay. RESULTS: The commonest indication of stenting was penetrating aortic ulcers (28.6%) and six (28.6%) patients had emergency stenting performed for aortic transection or rupture. 30 days of survival postprocedure was recorded and complete. There were no major vascular complications. Deployment accuracy was 100%, and the technical success rate was 94.7% (18/19) with one patient having a Type 2 endoleak on follow-up imaging. No neurological complications were noted. The mean operative time was 95 ± 73.6 min and the mean fluoroscopy time was 16.2 ± 10.8 min. Mean hospital stay for elective zone 2, 3, and 4 stenting was 5.3 ± 3.8 days, and only one patient postzone 1 thoracic endovascular aortic repair required a brief (0.5 days) ICU stay. All procedures were performed via the percutaneous transfemoral route with 100% success in percutaneous closure. CONCLUSION: This first reported Asian case series demonstrated versatility, safety, and efficacy of the Valiant NavionTM stent in Asian patients with different aortic pathologies.

Prospective double-blinded randomized controlled trial of Microwave versus RadioFrequency Ablation for hepatocellular carcinoma (McRFA trial).

BACKGROUND: Microwave (MWA) and radiofrequency ablation are the commonly used local ablation for hepatocellular carcinoma (HCC). Studies comparing both techniques are scarce. The aim of this study was to compare the efficacy of MWA versus RFA as a treatment for HCC. METHODS: Patients with HCC who were suitable for local ablation were randomized into MWA or RFA. All patients were followed up regularly with contrast-enhanced computed tomography (CT) performed at 1, 3, 6 and 12 months after ablation. Both patients and the radiologists who interpreted the post-procedure CT scans were blinded to the treatment allocation. Treatment-related morbidity, overall and disease-free survivals were analyzed. RESULTS: A total of 93 patients were recruited. Among them, 47 and 46 patients were randomized to MWA and RFA respectively. Patients in two groups were comparable in baseline demographics and tumor characteristics. With a median follow-up of around 30 months, there were no significant difference in the treatment-related morbidity, overall and disease-free survivals. MWA had a significantly shorter overall ablation time when compared with RFA (12 min vs 24 min, p < 0.001). CONCLUSIONS: MWA is no different to RFA with respect to completeness of ablation and survivals. It is, however, as safe and effective as RFA in treating small HCC.

Thickness-to-Height Ratio of Intravesical Prostatic Protrusion Predicts the Clinical Outcome and Morbidity of Prostatic Artery Embolization for Benign Prostatic Hyperplasia.

PURPOSE: To evaluate the presence of intravesical prostatic protrusion (IPP) and its thickness-to-height (T/H) ratio as a predictor for the clinical outcome and morbidity of prostatic artery embolization (PAE) for benign prostatic hyperplasia. MATERIALS AND METHODS: This was a prospective, single-center, institutional review board-approved study from June 2015 to December 2018 of 82 consecutive patients (age, 53-79 years; median, 66 years) with International Prostate Symptom Score (IPSS) ≥15 and quality-of-life (QOL) score ≥3. The presence of IPP and its T/H ratio were assessed on baseline magnetic resonance imaging for their correlation with the clinical outcomes of suboptimal IPSS (IPSS ≥10) and suboptimal QOL (QOL ≥3) up to 12 months after PAE and the occurrence of post-procedure complications (≤30 days), which caused a certain degree of urinary outflow obstruction. The chi-squared test was used for analysis. RESULTS: IPP was present in 57 of 82 patients (69.5%). The presence of IPP correlated with the occurrence of post-procedure complications (P = .009) but not with suboptimal IPSS at 12 months (P = .758). IPP with a T/H ratio ≤1.3 correlated with suboptimal IPSS at 12 months (P = .025) and suboptimal QOL at 6 months (P = .025) and 12 months (P = .008), as well as with the occurrence of post-procedure complications (P = .009). CONCLUSIONS: IPP with a T/H ratio ≤1.3 predicted the occurrence of post-procedure complications with urinary obstruction. A T/H ratio ≤1.3 but not the presence of IPP alone predicted the clinical outcome up to 12 months after PAE.

The association of liver function and quality of life of patients with liver cancer.

BACKGROUND: Quality of life (QOL) assessments with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-HCC18, C30 and HCC18 index scores have been shown to be prognostic factors for overall survival (OS) in patients with hepatocellular carcinoma (HCC), independent of disease stage and liver function. Liver function parameters (including bilirubin, albumin, international normalized ratio [INR], Child-Pugh class, ALBI grade, MELD, alkaline phosphatase [ALP]-to-platelet ratio, albumin-to-ALP ratio) have also been found to be independent prognostic factors for OS in HCC patients. There has been scanty data on whether QOL and baseline liver function per se are correlated in HCC patients. This study investigates the correlations between baseline QOL data and liver function variables in HCC patients. METHODS: From 2007 to 2011, 517 patients were enrolled. Baseline QOL was assessed at diagnosis using the EORTC QLQ-C30 and QLQ-HCC18; thereafter C30 and HCC18 index scores were derived. Clinical and laboratory data were collected. For liver function assessment, Child-Pugh class, ALBI grade, MELD, ALP-to-platelet ratio and albumin-to-ALP ratio were derived. Correlation analyses were performed between QOL and liver function data. RESULTS: Complete QOL data were available in 472 HCC patients. After adjusting for clinical variables, significant correlations were found between QOL (QLQ-C30 and QLQ-HCC18) and dichotomized liver function variables (including Child-Pugh class, ALBI grade and the presence of ascites). It was demonstrated that QOL had significant and potentially clinically important correlations with continuous liver function variables (albumin, bilirubin, ALP and albumin-to-ALP ratio), with the highest Spearman's rank correlation coefficient (rho) exceeding 0.4. HCC18 and C30 index scores were also significantly correlated with these liver function variables. HCC18 index score, which had rho up to 0.37, generally performed better than C30 index score, which had rho up to 0.33. CONCLUSIONS: In HCC patients, baseline QOL assessment (using EORTC QLQ-C30, QLQ-HCC18, C30 index-score or HCC18 index-score) is significantly correlated with liver function. Based on the findings of this study, future trials are warranted to assess whether treatment to enhance liver function could improve HCC patients' QOL.

Correlations of health-related quality of life with serum inflammatory indicators IL-8 and mIBI in patients with hepatocellular carcinoma.

PURPOSE: Health-related quality of life (HRQoL) is a significant prognostic factor for overall survival in hepatocellular carcinoma (HCC) patients, and this is independent of stage and liver function. Inflammation plays a significant role in HCC development and progression. It was hypothesized that the inflammatory status of HCC patients may affect their HRQoL. The relationship between HRQoL and inflammatory status was explored using indicators IL-8 level and modified inflammation-based index (mIBI, based on IL-8, C-reactive protein, and albumin). METHODS: From 2007-2011, HCC patients were enrolled prospectively. Baseline HRQoL assessment utilized the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-HCC18; clinical and laboratory data were collected at diagnosis. Two summary indices, C30 and HCC18 index-scores, were calculated. Correlation analyses were performed between HRQoL and inflammatory markers. RESULTS: In the 445 patients studied, significant correlations were found between IL-8 levels and EORTC QLQ-C30, QLQ-HCC18, C30, and HCC18 index-scores. The strongest correlated factors were those reflective of constitutional symptoms, namely QLQ-C30 "appetite loss" (with Pearson's correlation coefficient, r=0.322, P<0.0001); QLQ-C30 "fatigue" (r=0.311, P<0.0001); QLQ-C30 "role functioning" (r=-0.305, P<0.0001); QLQ-HCC18 "nutrition" (r=0.317, P<0.0001); and QLQ-HCC18 "fatigue" (r=0.306, P<0.0001). In addition, moderate but significant correlations were also observed with HCC18 index score (r=0.321, P<0.0001), and C30 index score (r=0.306, P<0.0001). HRQoL factors were also significantly correlated with mIBI. CONCLUSION: Baseline HRQoL using the conventional assessments of EORTC QLQ-C30 and QLQ-HCC18, as well as C30 and HCC18 index-scores, significantly correlated with inflammatory indicators (IL-8 level and mIBI) in HCC patients. Among the strongest correlations were those between IL-8 level and the two index-scores, as well as HRQoL aspects that represent constitutional symptoms. When paralleled with molecular findings, traditional HRQoL assessment in HCC has gained a new level of understanding: pattern recognition within an HRQoL instrument could potentially identify patients with more severe inflammatory state.

Video-assisted thoracic surgery for tiny pulmonary nodules with real-time image guidance in the hybrid theatre: the initial experience.

BACKGROUND: Localization of tiny lung nodules during video-assisted thoracic surgery (VATS) resection can be challenging. Real-time image-guided hookwire localization of the target lesions immediately followed by VATS lung resection in the hybrid operating theatre setting is an emerging approach. METHODS: We retrospectively reviewed our experience with this form of hybrid operating theatre image-guided VATS (iVATS) for lung nodules 1.5 cm or less, or soft in consistency. These patients were compared with matched cohort who received standard hookwire localization in the radiology department. RESULTS: From February 2014 to September 2017, lung nodules of indeterminate nature in 32 consecutive patients with mean size 9.1±4.6 mm underwent iVATS. All were accurately localized by hookwire and successfully resected. There was no postoperative mortality. There were 21 (66%) malignant lesions, all with adequate resection margins. Major outcomes were compared with a comparable cohort of 8 patients who received standard hookwire localization and VATS (sVATS) performed at separate departments operation suites. sVATS groups has significantly longer 'at-risk' period for pneumothorax progression and hookwire dislodgement (109.5±57.1 minutes for sVATS vs. 41.1±15.0 minutes for iVATS, P=0.011), and a higher risk of hookwire dislodgement (25% for sVATS vs. 0 for iVATS, P=0.036). CONCLUSIONS: Real-time image-guided hookwire localization in the hybrid theatre setting is an effective facilitator of VATS resection of tiny lung nodules in selected patients, and may have added advantages in terms of safety and localization accuracy over the conventional sVATS method.

Rationale and design for the detection and neurological impact of cerebrovascular events in non-cardiac surgery patients cohort evaluation (NeuroVISION) study: a prospective international cohort study.

OBJECTIVES: Covert stroke after non-cardiac surgery may have substantial impact on duration and quality of life. In non-surgical patients, covert stroke is more common than overt stroke and is associated with an increased risk of cognitive decline and dementia. Little is known about covert stroke after non-cardiac surgery.NeuroVISION is a multicentre, international, prospective cohort study that will characterise the association between perioperative acute covert stroke and postoperative cognitive function. SETTING AND PARTICIPANTS: We are recruiting study participants from 12 tertiary care hospitals in 10 countries on 5 continents. PARTICIPANTS: We are enrolling patients ≥65 years of age, requiring hospital admission after non-cardiac surgery, who have an anticipated length of hospital stay of at least 2 days after elective non-cardiac surgery that occurs under general or neuraxial anaesthesia. PRIMARY AND SECONDARY OUTCOME MEASURES: Patients are recruited before elective non-cardiac surgery, and their cognitive function is measured using the Montreal Cognitive Assessment (MoCA) instrument. After surgery, a brain MRI study is performed between postoperative days 2 and 9 to determine the presence of acute brain infarction. One year after surgery, the MoCA is used to assess postoperative cognitive function. Physicians and patients are blinded to the MRI study results until after the last patient follow-up visit to reduce outcome ascertainment bias.We will undertake a multivariable logistic regression analysis in which the dependent variable is the change in cognitive function 1 year after surgery, and the independent variables are acute perioperative covert stroke as well as other clinical variables that are associated with cognitive dysfunction. CONCLUSIONS: The NeuroVISION study will characterise the epidemiology of covert stroke and its clinical consequences. This will be the largest and the most comprehensive study of perioperative stroke after non-cardiac surgery. TRIAL REGISTRATION NUMBER: NCT01980511; Pre-results.

Does Intermittent Pringle Maneuver Increase Postoperative Complications After Hepatectomy for Hepatocellular Carcinoma? A Randomized Controlled Trial.

BACKGROUND: In a previous study, we have shown that intermittent Pringle maneuver (IPM) might increase postoperative complications after hepatectomy for various indications. Complications which thought to be related to IPM were ascites, pleural effusion, wound infection and intra-abdominal collection. The aim of this study was to test the hypothesis that applying IPM during hepatectomy for hepatocellular carcinoma (HCC) could increase postoperative complications. METHODS: Between January 2013 and October 2016, eligible patients who received elective open hepatectomy for HCC were randomized to have IPM or no Pringle maneuver (NPM). Occurrence of various types of postoperative complications was specifically looked for. A routine postoperative day 5 abdominal ultrasound examination and chest X-ray were done to detect and grade any radiological ascites, pleural effusion and intra-abdominal collection. RESULTS: Fifty IPM and 50 NPM patients with histological proven HCC were recruited for final analysis. Demographics and operative parameters were comparable between the two groups. The postoperative complication rates were similar (IPM 36.0 vs. NPM 28.0%, P = 0.391). However, in the IPM group, more patients developed radiological posthepatectomy ascites (42.0 vs. 22.0%, P = 0.032) and pleural effusion (66.0 vs. 38.0%, P = 0.005). In patients with histologically proven cirrhosis, there were 28 IPM and 25 NPM patients. Again, there was no difference in postoperative complication rate but more radiological posthepatectomy ascites and pleural effusion in the IPM group. CONCLUSION: This trial was not able to detect a difference in postoperative complications whether IPM was applied or not, but use of IPM was associated with more subclinical ascites and pleural effusion. (ClinicalTrials.gov NCT01759901). TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01759901.

Microwave ablation provides better survival than liver resection for hepatocellular carcinoma in patients with borderline liver function: application of ALBI score to patient selection.

BACKGROUND: Studies comparing microwave ablation (MWA) and liver resection are lacking. This study evaluates the survival of patients with hepatocellular carcinoma (HCC) treated with liver resection or MWA and the role of Albumin-Bilirubin (ALBI) score in patient selection for treatments. METHODS: This is a retrospective analysis of patients who received curative liver resection or MWA for HCC. Propensity score matching was used at a 1:1 ratio. The value of ALBI grade for patient selection was evaluated. Overall and disease-free survival were compared between two groups. RESULTS: Of the 442 patients underwent MWA or liver resection for HCC during the study period, 63 patients received MWA and 379 patients received liver resection. Propensity scoring matching analysis resulted in 63 matched pairs for further analysis. Subgroup analysis according to the ALBI grade was performed. Liver resection offered better overall and disease-free survivals in patients with ALBI grade 1. MWA provided a significantly better overall survival (p = 0.025) and a trend towards better disease-free survival (p = 0.39) in patients with ALBI grade 2 or 3. CONCLUSIONS: Liver resection offered superior disease-free survival to MWA in patients with HCC. The ALBI grade could identify patients with worse liver function who might gain survival advantage from MWA.

A phase 2 study of the efficacy and biomarker on the combination of transarterial chemoembolization and axitinib in the treatment of inoperable hepatocellular carcinoma.

BACKGROUND: A surge of vascular endothelial growth factor (VEGF) after transarterial chemoembolization (TACE) may contribute to tumor progression. Axitinib is a potent antiangiogenic agent with main activity against VEGF receptors 1 to 3. To the authors' knowledge, its role in combination with TACE for the treatment of patients with inoperable hepatocellular carcinoma (HCC) is unclear. METHODS: A phase 2 clinical trial (ClinicalTrials.gov identifier NCT01352728) was conducted to evaluate the combination treatment. Patients with inoperable HCC who were potential candidates for TACE initiated treatment with axitinib at a dose of 5 mg twice daily and were evaluated for the need for TACE every 8 weeks. Axitinib was withheld 24 hours before TACE, and resumed 24 hours afterward when fulfilling predefined criteria. Radiologic assessment was conducted every 8 weeks. The primary endpoint was the 2-year overall survival (OS) rate. RESULTS: A total of 50 patients were recruited from March 2011 to April 2014. The mean age of the patients was 61.8 years, and 46 patients (92%) had hepatitis B infection. The Barcelona Clinic Liver Cancer stage B/C percentage was 76% (38 cases)/24% (12 cases). The 2-year OS rate was 43.7%, and the median OS was 18.8 months in the intention-to-treat population. Among the evaluable population (44 patients), 40.9% (18 patients) and 27.3% (12 patients) achieved complete and partial responses, respectively. Common grade 3 or above axitinib-related complications included hand-foot skin reaction (14%) and hypertension (24%). The presence of hypertension during treatment was found to be an independent prognosticator (hazard ratio, 0.563; P = .0073) suggestive of a contributory role of axitinib to efficacy. CONCLUSIONS: The combination of axitinib and TACE was potentially efficacious for patients with inoperable HCC with a high radiologic response rate. Cancer 2017;123:3977-85. © 2017 American Cancer Society.

Endovascular Fenestration for Distal Aortic Sealing After Frozen Elephant Trunk With Thoraflex.

We describe a case of total arch replacement with frozen elephant trunk for chronic type B aortic dissecting aneurysm, which resulted in inadvertent landing of the frozen elephant trunk into the false lumen. A radiofrequency puncture system-assisted controlled endovascular fenestration of the dissection flap was performed at the upper abdominal aorta and subsequent thoracic endovascular stenting, successfully redirecting the blood flow from the false to the true lumen. Our case illustrated a possible way to seal distal reentry in chronic type B aortic dissection.

Preemptive Aneurysm Sac Embolization for Thoracic Endovascular Aortic Repair With Inadequate Proximal Landing Zone.

Thoracic endovascular aortic repair (TEVAR) offers a less invasive treatment for aortic arch aneurysms. Clinical challenges arise when there is inadequate proximal landing for zone 1 TEVAR, such that a median sternotomy with total aortic debranching is required before stent deployment. The chimney technique was reported as an alternative approach to stent the arch branches and avoid sternotomy, but it was still associated with considerable chance of a type IA endoleak. We report a case of aortic arch aneurysm with an inadequate proximal landing for zone 1 TEVAR that was treated with debranching of head and neck vessels followed by TEVAR and preemptive and targeted coil embolization of the arch aneurysmal sac. Postoperative computed tomography showed no significant endoleak, and the patient had an unremarkable recovery.

Mycotic aortic arch aneurysm coexistent with constrictive pericarditis: is surgery a dangerous resort?

An elderly man presented with fever and evidence of Salmonella infection, and was diagnosed to have coexisting constrictive pericarditis and mycotic aneurysm of the aortic arch. Pericardiectomy was performed under cardiopulmonary bypass with good result. To avoid deep hypothermic circulatory arrest, an aorto-brachiocephalic bypass, instead of total arch replacement, was performed. This was followed by a staged carotid-carotid bypass, thoracic endovascular stent graft placement. He was subsequently treated with prolonged antibiotics, and inflammatory marker normalized afterwards. He was last seen well 2 years after the operation. Follow-up computer tomography (CT) scan at 18 months post-op showed no evidence of endoleak or fistulation. Our case demonstrated that a hybrid treatment of open pericardiectomy and aortic debranching followed by thoracic endovascular stent graft placement is feasible and associated with satisfactory mid-term outcome.

Coil Embolization of Diverticulum of Kommerell: A Targeted Hybrid Endovascular Technique.

A 57-year-old man was incidentally found to have a dissected diverticulum of Kommerell originating from aberrant origin of right subclavian artery during follow-up for treated colon cancer. A right carotid-axillary bypass was followed by embolization of aberrant artery and the diverticulum by deployment of multiple detachable coils using the Penumbra Ruby System (Penumbra, Alameda, CA). Angiography after embolization showed exclusion of flow to the aberrant artery and a patent right carotid-axillary bypass. The patient recovered uneventfully and remained well for 12 weeks after the operation, without any complications. We believe this targeted endovascular approach can avoid complications related to the coverage of thoracic aorta and reduce the risk of access vessel trauma.

Hybrid DynaCT-guided electromagnetic navigational bronchoscopic biopsy†.

Electromagnetic navigational bronchoscopy-guided biopsy of small pulmonary nodules can be challenging. Navigational error of the system and movement of the biopsy tool during its deployment adversely affect biopsy success. Furthermore, conventional methods to confirm navigational success such as fluoroscopy and radial endobronchial ultrasound become less useful for the biopsy of small lesions. A hybrid operating theatre can provide unparalleled real-time imaging through DynaCT scan to guide and confirm successful navigation and biopsy of difficult-to-reach or small lesions. We describe our technique for DynaCT image-guided electromagnetic navigational bronchoscopic biopsy of a small pulmonary nodule in the hybrid operating theatre. The advantages, disadvantages and special considerations in adopting this approach are discussed.

Phase I/II study of temsirolimus for patients with unresectable Hepatocellular Carcinoma (HCC)- a correlative study to explore potential biomarkers for response.

BACKGROUND: The oncogenic PI3K/Akt/mTOR pathway is frequently activated in HCC. Data on the mTOR inhibitor, temsirolimus, is limited in HCC patients with concomitant chronic liver disease. The objectives of this study were: (1) In phase I, to determine DLTs and MTD of temsirolimus in HCC patients with chronic liver disease; (2) In phase II, to assess activity of temsirolimus in HCC, and (3) to explore potential biomarkers for response. METHODS: Major eligibility criteria included histologically confirmed advanced HCC and adequate organ function. In Phase I part of the study, temsirolimus was given weekly in 3-weekly cycle; dose levels were 20 mg (level 1), 25 mg (level 2) and 30 mg (level 3). The MTD was used in the subsequent phase II part; the primary endpoint was PFS and secondary endpoints were response and OS. In addition, exploratory analysis was conducted on pre-treatment tumour tissues to determine stathmin, pS6, pMTOR or p-AKT expressions as potential biomarkers for response. Overall survival and PFS were calculated using the Kaplan-Meier method. Reassessment CT scans were done every 6 weeks. All adverse events were reported using CTCAE v3. RESULTS: The Phase I part consisted of 19 patients, 2 of 6 patients at level 3 experienced DLT; dose level 2 was determined to be the MTD. The phase II part consisted of 36 patients. Amongst 35 assessable patients, there were 1 PR, 20 SD and 14 PD. Overall, the median PFS was 2.83 months (95% C.I. 1.63-5.24). The median OS was 8.89 months (95% C.I. 5.89-13.30). Grade ≥ 3 that occurred in > 10% of patients included thrombocytopenia (4) and hyponatraemia (4). Exploratory analysis revealed that disease stabilization (defined as CR + PR + SD > 12 weeks) in tumours having high and low pMTOR H-scores to be 70% and 29% respectively (OR 5.667, 95% CI 1.129-28.454, p = 0.035). CONCLUSIONS: In HCC patients with chronic liver disease, the MTD of temsirolimus was 25 mg weekly in a 3-week cycle. The targeted PFS endpoint was not reached. However, further studies to identify appropriate patient subgroup are warranted. TRIAL REGISTRATION: This study has been registered in ClinicalTrials.gov (Id: NCT00321594) on 1 December 2010.