[Association between the clustering of adverse childhood experiences and sleep quality in middle-aged and older Chinese adults].

Objective: To examine the association between the clustering of adverse childhood experiences (ACEs) and sleep quality in middle-aged and older Chinese adults. Methods: Data were from the Life History Survey in 2014 and the third wave follow-up survey in 2015 of China Health and Retirement Longitudinal Study (CHARLS). A total of 10 824 participants aged 45 years and above were included in this study. According to the number of ACEs, the participants were divided into four groups: 0, 1, 2-3 and≥4 ACEs. The multivariate logistic regression model was used to analyze the association of ACEs clustering with inappropriate sleep duration and poor sleep quality in middle-aged and older adults. Results: Among the 10 824 participants with an average age of (60.83±9.06) years, 5 211 (48.14%) were males. About 6 111 participants (56.64%) had inappropriate sleep duration, and 3 640 participants (33.63%) had poor sleep quality. After adjusting for covariates including gender, age, residence, marital status, education, household consumption, BMI, smoking, drinking, and depression in adulthood, compared with the 0 ACE group, the risk of inappropriate sleep duration was significantly increased in the 2-3 ACEs group and≥4 ACEs group, while ORs (95%CIs) were 1.26 (1.12-1.41) and 1.43 (1.23-1.66), respectively. The risk of poor sleep quality in the 2-3 ACEs group and≥4 ACEs group was also significantly higher than that in the 0 ACE group, while ORs (95%CIs) were 1.28 (1.12-1.46) and 1.53 (1.29-1.80), respectively. Conclusion: ACEs clustering in childhood could negatively affect sleep duration and quality in middle-aged and older Chinese adults.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with intermediate and advanced/relapsed hepatocellular carcinoma: a TOS-ESMO initiative endorsed by CSCO, ISMPO, JSMO, KSMO, MOS and SSO.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of hepatocellular carcinoma (HCC) was published in 2018, and covered the diagnosis, management, treatment and follow-up of early, intermediate and advanced disease. At the ESMO Asia Meeting in November 2018 it was decided by both the ESMO and the Taiwan Oncology Society (TOS) to convene a special guidelines meeting immediately after the Taiwan Joint Cancer Conference (TJCC) in May 2019 in Taipei. The aim was to adapt the ESMO 2018 guidelines to take into account both the ethnic and the geographic differences in practice associated with the treatment of HCC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with intermediate and advanced/relapsed HCC representing the oncology societies of Taiwan (TOS), China (CSCO), India (ISMPO) Japan (JSMO), Korea (KSMO), Malaysia (MOS) and Singapore (SSO). The voting was based on scientific evidence, and was independent of the current treatment practices, the drug availability and reimbursement situations in the individual participating Asian countries.

Lenalidomide as second-line therapy for advanced hepatocellular carcinoma: exploration of biomarkers for treatment efficacy.

BACKGROUND: Lenalidomide has immunomodulatory and anti-angiogenic effects and showed moderate anti-tumour efficacy in patients with. advanced hepatocellular carcinoma (HCC) AIM: To explore potential biomarkers of lenalidomide efficacy as second-line therapy for HCC. METHODS: Eligible patients were diagnosed with advanced HCC, documented progression on sorafenib, and Child-Pugh class A liver function. Patients received 25 mg/day lenalidomide orally on days 1-21 every 4 weeks. The primary endpoint was 6 month progression-free survival rate. Early α-fetoprotein response was defined as a > 20% decline of α-fetoprotein levels from baseline within the first 4 weeks of treatment. Vascular response, evaluated using dynamic contrast-enhanced magnetic resonance imaging, was defined as a > 40% decline in Ktrans after 2 weeks of treatment. The percentage of peripheral blood lymphocyte subsets were also analysed. RESULTS: Fifty-five patients were enrolled. The response rate was 13%, and the disease-control rate was 53%. The 6 month progression-free survival rate was 9.1%. The median progression-free and overall survival was 1.8 months and 8.9 months respectively. Early α-fetoprotein response was significantly associated with higher disease-control rate (76% vs 22%, P = .001) and longer progression-free survival (P = .020). Vascular response was not associated with any treatment outcomes. Patients with a high pre-treatment B cell percentage were more likely to have disease control (70% vs 36%, P = .010) and exhibited longer progression-free survival (P < .001) and overall survival (P = .042). CONCLUSIONS: Lenalidomide exhibited moderate activity as second-line therapy for advanced HCC. Its immunomodulatory effects should be further explored (www.clinicaltrials.gov NCT01545804).

Updated results from GEST study: a randomized, three-arm phase III study for advanced pancreatic cancer.

PURPOSE: The GEST study showed non-inferiority of S-1 but not superiority of gemcitabine plus S-1 (GS) to gemcitabine alone for overall survival with the data by the cut-off date of 31st July in 2010 for chemo-naïve patients with advanced pancreatic cancer. We considered it important to determine whether S-1 maintains non-inferiority after a long-term follow-up in the GEST study and to obtain a firm positive conclusion. In addition, it may be an interesting challenge to explore the efficacious profile of GS in the long-term follow-up study. Using the data from the follow-up period, background and efficacy in patients from Taiwan and Japan, as well as the rates of tumor shrinkage in locally advanced and metastatic patients (Waterfall plot) were also analyzed. METHODS: The results of the primary analysis were reconfirmed, and subset analysis of overall survival and progression-free survival was performed based on the overall survival data updated by the cut-off date of 31st July in 2011. RESULTS: The median follow-up period was 29.8 months, and 795 deaths occurred (95.6%). The median overall survival was 8.8 months for gemcitabine, 9.7 months for S-1 (hazard ratio [HR], 0.96; 97.5% confidence interval [CI], 0.79-1.17), and 9.9 months for GS (HR 0.91; 97.5% CI 0.75-1.11). In patients with performance status (PS) 0, the median overall survival was 9.8 months for gemcitabine, 10.9 months for S-1, and 10.5 months for GS. In patients with PS 1, the median overall survival was 6.2 months for gemcitabine, 6.3 months for S-1, and 9.6 months for GS. CONCLUSION: Our survey reconfirmed the non-inferiority of S-1 to gemcitabine and showed S-1 can be used as one of the standard treatment options for advanced pancreatic cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00498225.

Phase I study of nanoliposomal irinotecan (PEP02) in advanced solid tumor patients.

PURPOSE: To define the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and pharmacokinetics (PK) of PEP02, a novel liposome-encapsulated irinotecan, in patients with advanced refractory solid tumors. METHODS: Patients were enrolled in cohorts of one to three to receive escalating dose of PEP02 in a phase I trial. PEP02, from 60 to 180 mg/m(2), was given as a 90-min intravenous infusion, every 3 weeks. RESULTS: A total of 11 patients were enrolled into three dose levels: 60 (one patient), 120 (six patients) and 180 mg/m(2) (four patients). DLT was observed in three patients, one at 120 mg/m(2) (grade 3 catheter-related infection) and two at 180 mg/m(2) (grade 4 neutropenia lasting for >3 days in one, grade 4 hematological toxicities and grade 4 diarrhea in the other). MTD was determined as 120 mg/m(2). Comparing with those after free-form irinotecan in the literature, the dose-normalized PK of SN-38 (the active metabolite) after PEP02 was characterized by lower C max, prolonged terminal half-life and higher AUC but with significant inter-individual variation. One patient who died of treatment-related toxicity had significantly higher C max and AUC levels of SN-38 than those of the other three patients at 180 mg/m(2). Post hoc pharmacogenetic study showed that the patient had a combined heterozygosity genotype of UGT1A1*6/*28. Two patients had objective tumor response. CONCLUSIONS: PEP02 apparently modified the PK parameters of irinotecan and SN-38 by liposome encapsulation. The MTD of PEP02 monotherapy at 3-week interval is 120 mg/m(2), which will be the recommended dose for future studies.

Genetic polymorphisms and tissue expression of interleukin-22 associated with risk and therapeutic response of gastric mucosa-associated lymphoid tissue lymphoma.

Chronic Helicobacter pylori-stimulated immune reactions determine the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. We aimed to explore the genetic predisposition to this lymphoma and its clinical implication. A total of 68 patients and 140 unrelated controls were genotyped for 84 single-nucleotide polymorphisms in genes encoding cytokines, chemokines and related receptors that play important roles in T cell-mediated gastrointestinal immunity. Five genotypes in IL-22, namely CC at rs1179246, CC at rs2227485, AA at rs4913428, AA at rs1026788 and TT at rs7314777, were associated with disease susceptibility. The former four genotypes resided in the same linkage disequilibrium block (r(2)=0.99) that conferred an approximately threefold higher risk. In vitro experiments demonstrated that co-culturing peripheral mononuclear cells or CD4(+) T cells with H. pylori stimulated the secretion of interleukin-22 (IL-22), and that IL-22 induced the expression of antimicrobial proteins, RegIIIα and lipocalin-2, in gastric epithelial cells. Furthermore, patients with gastric tissue expressing IL-22 were more likely to respond to H. pylori eradication (14/22 vs 4/19, P<0.006). We conclude that susceptibility of gastric MALT lymphoma is influenced by genetic polymorphisms in IL-22, the product of which is involved in mucosal immunity against H. pylori and associated with tumor response to H. pylori eradication.

Helicobacter pylori-related diffuse large B-cell lymphoma of the stomach: a distinct entity with lower aggressiveness and higher chemosensitivity.

We recently showed that Helicobacter pylori (HP)-positive gastric 'pure' diffuse large B-cell lymphoma (DLBCL) may respond to HP eradication therapy. However, whether these HP-related 'pure' DLBCL of the stomach may differ fundamentally from those unrelated to HP remains unclear. In this study, we compared the clinicopathologic features of these two groups of patients who had been uniformly treated by conventional chemotherapy. Forty-six patients were designated HP-positive and 49 were HP-negative by conventional criteria. HP-positive patients had a lower International Prognostic Index score (0-1, 65% vs 43%, P=0.029), a lower clinical stage (I-IIE1, 70% vs 39%, P=0.003), a better tumor response to chemotherapy (complete pathologic response, 76% vs 47%, P=0.004) and significantly superior 5-year event-free survival (EFS) (71.7% vs 31.8%, P<0.001) and overall survival (OS) (76.1% vs 39.8%, P<0.001). To draw a closer biologic link with HP, HP-positive tumors were further examined for CagA expression in lymphoma cells. Compared with CagA-negative cases (n=16), CagA-positive cases (n=27) were associated with high phosphorylated SHP-2 expression (P=0.016), and even better 5-year EFS (85.2% vs 46.3%, P=0.002) and OS (88.9% vs 52.9%, P=0.003). HP-related gastric 'pure' DLBCL may be a distinct tumor entity, which is less aggressive, and responds better to conventional chemotherapy.

A phase I study of two dosing schedules of volasertib (BI 6727), an intravenous polo-like kinase inhibitor, in patients with advanced solid malignancies.

BACKGROUND: Polo-like kinase 1 (Plk1) has an important role in mitosis. Volasertib (BI 6727), a potent and selective cell cycle kinase inhibitor, induces mitotic arrest and apoptosis by targeting Plk; this phase I study sought to determine its maximum tolerated dose (MTD) in Asian patients with advanced solid tumours. METHODS: Patients were enrolled simultaneously into two 3-week schedules of volasertib: a 2-h infusion on day 1 (schedule A) or days 1 and 8 (schedule B). Dose escalation followed a 3+3 design. The MTD was determined based on dose-limiting toxicities (DLT) in the first treatment course. RESULTS: Among 59 treated patients, the most common first course DLTs were reversible thrombocytopenia, neutropenia and febrile neutropenia; MTDs were 300 mg for schedule A and 150 mg for schedule B. Volasertib exhibited multi-exponential pharmacokinetics (PK), a long terminal half-life of ∼135 h, a large volume of distribution (>3000 l), and a moderate clearance. Partial responses were observed in two pre-treated patients (ureteral cancer; melanoma). Volasertib was generally well tolerated, with an adverse event profile consistent with its antimitotic mode of action and a favourable PK profile. CONCLUSIONS: These data support further development of volasertib and a harmonised dosing for Asian and Caucasian patients.

Helicobacter pylori sensitizes TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in human gastric epithelial cells through regulation of FLIP.

Helicobacter pylori (H. pylori) infection is associated with chronic gastritis, peptic ulcer and gastric cancer. Apoptosis induced by microbial infections is implicated in the pathogenesis of H. pylori infection. Here we show that human gastric epithelial cells sensitized to H. pylori confer susceptibility to TRAIL-mediated apoptosis via modulation of death receptor signaling. Human gastric epithelial cells are intrinsically resistant to TRAIL-mediated apoptosis. The induction of TRAIL sensitivity by H. pylori is dependent on the activation of caspase-8 and its downstream pathway. H. pylori induces caspase-8 activation via enhanced assembly of the TRAIL death-inducing signaling complex (DISC) through downregulation of cellular FLICE-inhibitory protein (FLIP). Overexpression of FLIP abolished the H. pylori-induced TRAIL sensitivity in human gastric epithelial cells. Our study thus demonstrates that H. pylori induces sensitivity to TRAIL apoptosis by regulation of FLIP and assembly of DISC, which initiates caspase activation, resulting in the breakdown of resistance to apoptosis, and provides insight into the pathogenesis of gastric damage in Helicobacter infection. Modulation of host apoptosis signaling by bacterial interaction adds a new dimension to the pathogenesis of Helicobacter.

Detection of the Helicobacter pylori CagA protein in gastric mucosa-associated lymphoid tissue lymphoma cells: clinical and biological significance.

We previously reported that CagA can be translocated into B cells in Helicobacter pylori (HP) coculture media, and the translocation appears biologically significant as activation of the relevant cellular pathways was noticed. In this study, we further explore if CagA can be detected in malignant B cells of HP-positive gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Expression of CagA was evaluated by immunohistochemistry. CagA expression was further confirmed by western blot analysis. The association between CagA expression in malignant B cells and tumor response to HP eradication therapy (HPE) was evaluated in 64 stage IE gastric MALT lymphoma patients. We detected CagA expression in 31 (48.4%) of 64 patients: 26 (68.4%) of the 38 HP-dependent cases and 5 (19.2%) of the 26 HP-independent cases (P<0.001). Patients with CagA expression responded to HPE quicker than those without (median time to complete remission, 3.0 vs 6.5 months, P=0.025). Our results indicated that CagA can be translocated into malignant B cells of MALT lymphoma, and the translocation is clinically and biologically significant.

Mcl-1-dependent activation of Beclin 1 mediates autophagic cell death induced by sorafenib and SC-59 in hepatocellular carcinoma cells.

We investigated the molecular mechanisms underlying the effect of sorafenib and SC-59, a novel sorafenib derivative, on hepatocellular carcinoma (HCC). Sorafenib activated autophagy in a dose- and time-dependent manner in the HCC cell lines PLC5, Sk-Hep1, HepG2 and Hep3B. Sorafenib downregulated phospho-STAT3 (P-STAT3) and subsequently reduced the expression of myeloid cell leukemia-1 (Mcl-1). Inhibition of Mcl-1 by sorafenib resulted in disruption of the Beclin 1-Mcl-1 complex; however, sorafenib did not affect the amount of Beclin 1, suggesting that sorafenib treatment released Beclin 1 from binding with Mcl-1. Silencing of SHP-1 by small interference RNA (siRNA) reduced the effect of sorafenib on P-STAT3 and autophagy. Ectopic expression of Mcl-1 abolished the effect of sorafenib on autophagy. Knockdown of Beclin 1 by siRNA protected the cells from sorafenib-induced autophagy. Moreover, SC-59, a sorafenib derivative, had a more potent effect on cancer cell viability than sorafenib. SC-59 downregulated P-STAT3 and induced autophagy in all tested HCC cell lines. Furthermore, our in vivo data showed that both sorafenib and SC-59 inhibited tumor growth, downregulated P-STAT3, enhanced the activity of SHP-1 and induced autophagy in PLC5 tumors, suggesting that sorafenib and SC-59 activate autophagy in HCC. In conclusion, sorafenib and SC-59 induce autophagy in HCC through a SHP-1-STAT3-Mcl-1-Beclin 1 pathway.

Activating oxidative phosphorylation by a pyruvate dehydrogenase kinase inhibitor overcomes sorafenib resistance of hepatocellular carcinoma.

BACKGROUND: Sorafenib is the only drug approved for the treatment of hepatocellular carcinoma (HCC). The bioenergetic propensity of cancer cells has been correlated to anticancer drug resistance, but such correlation is unclear in sorafenib resistance of HCC. METHODS: Six sorafenib-naive HCC cell lines and one sorafenib-resistant HCC cell line (Huh-7R; derived from sorafenib-sensitive Huh-7) were used. The bioenergetic propensity was calculated by measurement of lactate in the presence or absence of oligomycin. Dichloroacetate (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor, and siRNA of hexokinase 2 (HK2) were used to target relevant pathways of cancer metabolism. Cell viability, mitochondrial membrane potential, and sub-G1 fraction were measured for in vitro efficacy. Reactive oxygen species (ROS), adenosine triphosphate (ATP) and glucose uptake were also measured. A subcutaneous xenograft mouse model was used for in vivo efficacy. RESULTS: The bioenergetic propensity for using glycolysis correlated with decreased sorafenib sensitivity (R(2)=0.9067, among sorafenib-naive cell lines; P=0.003, compared between Huh-7 and Huh-7 R). DCA reduced lactate production and increased ROS and ATP, indicating activation of oxidative phosphorylation (OXPHOS). DCA markedly sensitised sorafenib-resistant HCC cells to sorafenib-induced apoptosis (sub-G1 (combination vs sorafenib): Hep3B, 65.4±8.4% vs 13±2.9%; Huh-7 R, 25.3± 5.7% vs 4.3±1.5%; each P<0.0001), whereas siRNA of HK2 did not. Sorafenib (10 mg kg(-1) per day) plus DCA (100 mg kg(-1) per day) also resulted in superior tumour regression than sorafenib alone in mice (tumour size: -87% vs -36%, P<0.001). CONCLUSION: The bioenergetic propensity is a potentially useful predictive biomarker of sorafenib sensitivity, and activation of OXPHOS by PDK inhibitors may overcome sorafenib resistance of HCC.

Prognosis of advanced hepatocellular carcinoma patients enrolled in clinical trials can be classified by current staging systems.

BACKGROUND: Patients enrolled in clinical trials of advanced hepatocellular carcinoma (HCC) are usually required to have good liver reserve and organ function. However, their outcomes are still highly variable. We aimed to examine whether current staging systems can predict the survival of these highly selected patients. METHODS: Patients from clinical trials involving first-line anti-angiogenic therapy were assigned to different stage groups using the American Joint Committee on Cancer (AJCC), Barcelona Clinic Liver Cancer (BCLC), China integrated score, Cancer of the Liver Italian Program (CLIP) score, Chinese University Prognostic Index (CUPI), Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire (GETCH), Japan Integrated Staging (JIS) score, Okuda, Tokyo score, and a new staging system recently proposed. Survival prediction by the 10 systems was then compared by both univariate and multivariate analyses. RESULTS: A total of 157 patients were selected for this study. In univariate analysis, all staging systems can predict patient survival except AJCC, BCLC, and JIS score. Concordance indexes for CLIP score, CUPI, and GETCH (0.752, 0.775, and 0.791, respectively) were significantly higher than those obtained for other staging systems. In multivariate analysis, the CLIP score and CUPI (P<0.001 and 0.009, respectively) predicted survival more accurately than did the other tested staging systems. Hepatitis B infection and poor performance status were also associated with poor survival. CONCLUSION: Several HCC staging systems, especially the CLIP score and CUPI, can predict prognosis of patients who are enrolled in clinical trials of advanced HCC.

Medulloblastoma in adults. Treatment outcome, relapse patterns, and prognostic factors.

BACKGROUND AND PURPOSE: In this study, the clinical outcome and prognostic factors of adult medulloblastoma patients receiving multimodal treatment were investigated. PATIENTS AND METHODS: The clinical manifestations, treatment variables, and outcome of adult patients with medulloblastoma at our institution between 1983 and 2009 were retrospectively reviewed. RESULTS: A total of 20 adult patients were included (median age 22 years). Craniospinal irradiation (CSI) was given postoperatively. The craniospinal axis received a median of 30 Gy (range 23.4-39.6 Gy) in fractions of 1.6-2 Gy/day, and the tumor was boosted to a total median dose of 50 Gy (range 50-55.25 Gy). The 3-year disease-free survival (DFS) and overall survival (OS) rates for all patients were 45% and 50%, respectively. In univariate analysis, Karnofsky Performance Scale (KPS) > 70, neurologic symptoms duration > 30 days, lateral tumor location, standard risk patients, no hydrocephalus, radiotherapy (RT) treatment field (CSI + brain boost), and CSI dose ≥ 30 Gy were associated with better DFS. Standard-risk patients, RT treatment field (CSI + brain boost), and CSI dose ≥ 30 Gy were also significantly associated with better OS. CONCLUSION: The combined modality treatment results in a favorable outcome for adult medulloblastoma patients. Further investigation of the prognostic factors, radiation-related factors, and systemic chemotherapy is needed.

Lack of efficacy to systemic chemotherapy for treatment of metaplastic carcinoma of the breast in the modern era.

Metaplastic carcinoma of the breast (MCB) is a rare subtype of breast cancer. Anecdotal reports are available regarding its response to systemic chemotherapy. We reviewed the records of patients diagnosed with MCB at National Taiwan University Hospital between 1988 and 2009. A total of 46 MCB cases were identified from 8,695 breast tumor patients who underwent biopsy or resection. About 11 of 25 patients with initial bulky disease (T3-4) received neoadjuvant chemotherapy before surgery, and 2 (18.2%) exhibited a partial response. About 12 of 18 patients who developed distant metastasis received palliative systemic chemotherapy. Of them, only 1 (8.3%), 1 (10%), and none (0%) responded to first-, second-, or third- and beyond line chemotherapy, respectively. None of the patients who received anthracyline- (n = 13), vinorelbine- (n = 7), or cyclophosphamide-based (n = 18) chemotherapy responded, whereas 3 (17.6%) of 17 patients who received taxane-based chemotherapy exhibited a partial response. Tumor response to systemic chemotherapy remains generally poor for MCB patients. Taxanes may have modest activity, but need to be validated in further studies.

CIP2A mediates effects of bortezomib on phospho-Akt and apoptosis in hepatocellular carcinoma cells.

Previously, we reported that Akt inactivation determines the sensitivity of hepatocellular carcinoma (HCC) cells to bortezomib. In this study, we report that cancerous inhibitor of protein phosphatase 2A (CIP2A), a cellular inhibitor of protein phosphatase 2A (PP2A), mediates the apoptotic effect of bortezomib in HCC. Silencing PP2A by small interference RNA (siRNA) abolishes bortezomib-induced down-regulation of phospho-Akt and apoptosis. Bortezomib increases PP2A activity in sensitive HCC cells, including Sk-Hep1, Hep3B and Huh-7, but not in resistant PLC5 cells. Bortezomib down-regulates CIP2A in a dose- and time-dependent manner in all sensitive HCC cells, whereas no alterations in CIP2A were found in resistant PLC5 cells. Knockdown of CIP2A by siRNA restored bortezomib's effects on apoptosis and PP2A activity in PLC5 cells. Moreover, over-expression of CIP2A up-regulated phospho-Akt and protected Sk-Hep1 cells from bortezomib-induced apoptosis. It is significant that, ectopic expression of CIP2A decreased Akt-related PP2A activity, whereas silencing CIP2A increased this activity, indicating that CIP2A negatively regulates Akt-related PP2A activity in HCC cells, furthermore, our in vivo data showed that bortezomib down-regulates CIP2A and up-regulates PP2A activity in Huh-7 tumors, but not in PLC5 tumors. In conclusion, inhibition of CIP2A determines the effects of bortezomib on apoptosis and PP2A-dependent Akt inactivation in HCC.

Efficacy and tolerability of bevacizumab plus capecitabine as first-line therapy in patients with advanced hepatocellular carcinoma.

BACKGROUND: Molecularly targeted agents with anti-angiogenic activity, including bevacizumab, have demonstrated clinical activity in patients with advanced/metastatic hepatocellular carcinoma (HCC). This multicentre phase II study involving patients from several Asian countries sought to evaluate the safety and efficacy of bevacizumab plus capecitabine in this population. METHODS: Histologically proven/clinically diagnosed advanced HCC patients received bevacizumab 7.5 mg kg(-1) on day 1 and capecitabine 800 mg m(-2) twice daily on days 1-14 every 3 weeks as first-line therapy. RESULTS: A total of 45 patients were enrolled; 44 (96%) had extrahepatic metastasis and/or major vessel invasion and 30 (67%) had hepatitis B. No grade 3/4 haematological toxicity occurred. Treatment-related grade 3/4 non-haematological toxicities included diarrhoea (n=2, 4%), nausea/vomiting (n=1, 2%), gastrointestinal bleeding (n=4, 9%) and hand-foot syndrome (n=4, 9%). The overall response rate (RECIST) was 9% and the disease control rate was 52%. Overall, median progression-free survival (PFS) and overall survival (OS) were 2.7 and 5.9 months, respectively. Median PFS and OS were 3.6 and 8.2 months, respectively, for Cancer of the Liver Italian Programme (CLIP) score < or =3 patients, and 1.4 and 3.3 months, respectively, for CLIP score 4 patients. CONCLUSION: The bevacizumab-capecitabine combination shows good tolerability and modest anti-tumour activity in patients with advanced HCC.

Disseminated peritoneal leiomyomatosis responds to systemic chemotherapy.

Leiomyomatosis peritonealis disseminata (LPD) is a rare disease entity characterized by multiple peritoneal tumors composed of benign but proliferative smooth muscle cells. Surgery is the mainstay treatment for LPD. We present a 50-year-old woman who had previously undergone several surgical resections including bilateral oophorectomy for recurrent LPD. Because of progressive tumors in the peritoneum and metastatic tumors in the liver and lungs, systemic chemotherapy with doxorubicin and dacarbazine was prescribed. Objective tumor response was achieved and sustained for 1 year. This case presentation suggests that systemic chemotherapy may be considered as a treatment option for LPD patients developing unresectable or metastatic disease.