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Background: The objective of this study was to evaluate the efficacy and safety of induction chemotherapy (ICT), GOFL (gemcitabine, oxaliplatin plus fluorouracil (5-FU)/leucovorin) versus modified FOLFIRINOX (irinotecan, oxaliplatin plus 5-FU/leucovorin), followed by concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic adenocarcinoma (LAPC). Methods: Chemo-naive patients with measurable LAPC were eligible and randomly assigned to receive biweekly ICT with either mFOLFIRINOX or GOFL for 3 months. Patients without systemic progression would have 5-FU- or gemcitabine-based CCRT (5040 cGy/28 fractions) and were then subjected to surgery or continuation of chemotherapy until treatment failure. The primary endpoint was 9-month progression-free survival (PFS) rate. Results: Between July 2013 and January 2019, 55 patients were enrolled. After ICT, 21 (77.8%) of 27 patients who received mFOLFIRINOX and 17 (60.7%) of 28 patients who received GOFL completed CCRT. Of them, one and five had per-protocol R0/R1 resection. On intent-to-treat analysis, the 9-month PFS rate, median PFS and overall survival in mFOLFIRINOX and GOFL arms were 30.5% versus 35.9%, 6.6 (95% confidence interval: 5.9–12.5) versus 7.6 months (3.9–12.3) and 19.6 (13.4–22.9) versus 17.9 months (13.4–23.9), respectively. Grade 3–4 neutropenia and diarrhoea during induction mFOLFIRINOX and GOFL were 37.0% versus 21.4% and 14.8% versus 3.6%, respectively. Conclusion: Induction GOFL and mFOLFIRINOX followed by CCRT provided similar clinical outcomes in LAPC patients. Clinicaltrial.gov identifier: NCT01867892. [ABSTRACT FROM AUTHOR]

Background: Although the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-PAN26 is widely used to assess health-related quality of life (HRQoL), its group-level minimal important difference (MID) and individual-level responder definition (RD) are not established; we calculated MID and RD using HRQoL data from the APACT trial in patients with surgically resected pancreatic cancer who received adjuvant chemotherapy. Methods: HRQoL was assessed using EORTC QLQ-C30 and QLQ-PAN26 at baseline, during treatment, at end of treatment, and during follow-up. Distribution-based MIDs were estimated using 0.5 × baseline standard deviation (SD) and reliability-based (intraclass correlation) standard error of measurement (SEM). Anchor-based MIDs and RDs (anchor, QLQ-C30 overall health) were estimated using a linear mixed model. Results: Overall, 772 patients completed the baseline assessment. Distribution-based MIDs (0.5 × SD) for QLQ-PAN26 scales ranged from 12 to 13, except hepatic symptoms (≈8), pancreatic pain (≈10), and sexual dysfunction (≈17); those for stand-alone items ranged from 12 to 16. The SEM values were similar. Among scales/items sufficiently correlated (r > 0.30) with the anchor, MIDs ranged from 5 to 9. Within-patient QLQ-PAN26 RD estimates varied by direction (deterioration vs. improvement) and scale/item, but all values were lower than the true possible within-patient change (e.g. 16.7 points for a two-item scale) given a one-category change on the raw scale. Conclusions: Compared with distribution-based MIDs, anchor-based MIDs were twice as sensitive in detecting group-level changes in QLQ-PAN26 scales/items. For interpreting clinically meaningful change, RDs cannot be less than the true minimum of the scale. The group-level MID may help clinicians/researchers interpret HRQoL changes. Trial registration: ClinicalTrials.gov NCT01964430; Eudra CT 2013-003398-91. [ABSTRACT FROM AUTHOR]

Background: The effects of cigarette smoking and alcohol consumption on the risk of alopecia areata (AA) are unclear. Objective: The aim was to examine the association of cigarette smoking and alcohol consumption with AA. Methods: We collected participants from four rounds (2001, 2005, 2009, and 2013) of the Taiwan National Health Interview Survey. Incident AA cases were identified from the National Health Insurance database. Results: Of the 60,055 participants, 154 developed AA during the 647,902 person-years of follow-up. After controlling for confounders, current smokers had a higher risk of incident AA than never smokers [adjusted hazard ratio (aHR) 1.88; 95% confidence interval (CI) 1.22–2.88]. There was a trend toward an increased risk of AA with increasing numbers of years of smoking and cumulative pack-years of smoking among current smokers. The aHRs (95% CIs) of current smokers of > 5 and ≤ 15 cigarettes per day, > 10 and ≤ 20 years of smoking, ≤ 10, and > 10 and ≤ 20 pack-years of smoking were 2.03 (1.17–3.51), 2.25 (1.21–4.18), 1.86 (1.12–3.09), and 2.04 (1.04–4.01), respectively. Conversely, social and regular drinkers had significantly lower risks of AA than never drinkers [aHRs (95% CIs) 0.65 (0.43–0.98) and 0.49 (0.26–0.93), respectively]. Conclusion: Current smokers had an increased risk of developing AA, while alcohol consumption was associated with a decreased risk of AA. [ABSTRACT FROM AUTHOR]

Studies investigating the risk for dementia in psoriatic patients remain inconclusive. There are a limited number of population-based studies on the association between psoriasis and dementia. This study aims to investigate the risk for dementia in psoriatic patients. This nationwide population-based cohort study was based on data obtained from the Taiwan National Health Insurance Research Database between 2000 and 2012. A total of 111,825 patients with psoriasis and 111,825 age-, sex-, and index date-matched controls were recruited. The hazard ratio (HR) for subsequent dementia in patients with psoriasis was analyzed using a Cox model and a Fine-Gray competing risk model. During 1,358,774 person-years of follow-up, 2688 patients developed dementia in the psoriatic cohort, and 2062 developed dementia in the control cohort. In the multivariate adjusted Cox model, the hazard ratio (HR) of psoriatic patients for dementia was 1.02 [95% confidence interval (CI) 0.96–1.09] relative to the controls. Psoriasis did not increase the risk for dementia (both vascular dementia and degenerative dementia). In the competing risk model, the HR of dementia was 0.96 (95% CI 0.90–1.02) for psoriatic patients. Compared to psoriatic patients who had not received phototherapy or systemic treatment, those psoriatic patients receiving phototherapy or systemic treatment had a lower risk for dementia. However, this phenomenon was not observed in psoriatic patients who were observed for longer than 6 years. Psoriasis was not found to be a risk factor for dementia. Phototherapy and systemic treatment might not have a protective effect against dementia in psoriatic patients. [ABSTRACT FROM AUTHOR]

Background: There is evidence suggesting an association between bullous pemphigoid (BP) and a range of neurological diseases. Whether neurological cancer is a risk factor for BP remains unknown. Objective: The aim of the study was to investigate the risk of subsequent BP among patients with neurological cancer. Methods: This nationwide population-based cohort study was based on data obtained from the Taiwan National Health Insurance Research Database between 2000 and 2012. A total of 8313 patients with neurological cancer and 33,252 age-, sex-, and index-date-matched controls were recruited. The hazard ratio (HR) for subsequent BP in patients with neurological cancer was analyzed using a Cox model and Fine-Gray competing risk model, with mortality as the competing event. Results: The incidence rates of BP per 100,000 person-years were 37.2 for patients with neurological cancer and 6.8 for controls. The crude incidence rate ratio was 5.49 (95% confidence interval [CI] 2.18–13.30). The mean time to occurrence of BP was 4.48 ± 3.40 years for patients with neurological cancer. Neurological cancer (HR 9.65, 95% CI 3.76–24.77 for the Cox model; HR 2.41, 95% CI 1.14–5.14 for the competing risk model), age per year (HR 1.10, 95% CI 1.05–1.15 for the Cox model; HR 1.06, 95% CI 1.02–1.09 for the competing risk model), and dementia (HR 6.31, 95% CI 2.49–15.99 for the Cox model; HR 7.50, 95% CI 2.84–19.85 for the competing risk model) significantly increased the risk of BP. Conclusions: Neurological cancer increased the risk for subsequent BP by 2.4-fold, with a relatively short gap of 4.5 years. [ABSTRACT FROM AUTHOR]

Background Ruxolitinib, a Janus kinase 1 (JAK1)/JAK2 inhibitor, plus capecitabine improved overall survival (OS) vs capecitabine in a subgroup analysis of patients with metastatic pancreatic cancer and systemic inflammation (C-reactive protein [CRP] >13 mg/dL) in the randomized phase II RECAP study. We report results from two randomized phase III studies, JANUS 1 (NCT02117479) and JANUS 2 (NCT02119663). Patients and Methods Adults with advanced/metastatic pancreatic cancer, one prior chemotherapy regimen and CRP >10 mg/L were randomized 1:1 (stratified by modified Glasgow Prognostic Score [1 vs 2] and Eastern Cooperative Oncology Group performance status [0/1 vs 2]) to 21-day cycles of ruxolitinib 15 mg twice daily plus capecitabine 2000 mg/m2/day (Days 1-14) or placebo plus capecitabine. The primary endpoint was OS. Results Both studies were terminated following a planned interim futility/efficacy analysis of JANUS 1. Overall, 321 and 86 patients were randomized in JANUS 1 (ruxolitinib: n = 161; placebo: n = 160) and JANUS 2 (ruxolitinib: n = 43; placebo: n = 43). There was no significant difference in OS or progression-free survival (PFS) between treatments in JANUS 1 (OS: hazard ratio [HR], 0.969, 95% confidence interval [CI], 0.747-1.256; PFS: HR, 1.056; 95% CI, 0.827-1.348) or JANUS 2 (OS: HR, 1.584; 95% CI, 0.886-2.830; PFS: HR, 1.166; 95% CI, 0.687-1.978). The most common hematologic adverse event was anemia. No new safety signals with ruxolitinib or capecitabine were identified. Conclusions Ruxolitinib plus capecitabine was well tolerated in refractory pancreatic cancer patients; this combination did not improve survival. [ABSTRACT FROM AUTHOR]

Background: Post-hoc analyses of AFP response and progression and their relationship with objective measures of response and survival were performed in patients from REACH.Methods: Serum AFP was measured at baseline and every 3 cycles (2 weeks/cycle). Associations between AFP and radiographic progression and efficacy end points were analysed.Results: Median percent AFP increase from baseline was smaller in the ramucirumab than in the placebo arm throughout treatment. Time to AFP progression (HR 0.621; P < 0.0001) and to radiographic progression (HR 0.613; P < 0.0001) favoured ramucirumab. Association between AFP and radiographic progression was shown at 6 (OR 6.44, 95% CI 4.03, 10.29; P < 0.0001) and 12 weeks (OR 2.28, 95% CI 1.47, 3.53; P = 0.0002). AFP response was higher with ramucirumab compared with placebo (P < 0.0001). More patients in the ramucirumab arm experienced tumour shrinkage and AFP response compared with placebo. Survival was longer in patients with AFP response (13.6 months) than in patients without (6.2 months), irrespective of treatment (HR 0.457, P < 0.0001).Conclusions: Treatment with ramucirumab prolonged time to AFP progression, slowed AFP increase and was more likely to induce AFP response. Similar benefits in radiographic progression and response correlated with AFP changes. [ABSTRACT FROM AUTHOR]

Background: We investigated the efficacy and safety of 60, 120, or 240 mg of Z-360, which is a highly potent cholecystokinin2-receptor-selective antagonist, combined with gemcitabine in patients with metastatic pancreatic cancer.Methods: Patients were randomly assigned in a 1:1:1:1 ratio to one of four treatment groups. Patients received 1000 mg/m2 gemcitabine for each cycle and Z-360 tablets of 60 mg (GZ 60 mg group), 120, 240 mg or placebo tablets (Gem group) orally twice daily. The primary endpoint was overall survival (OS).Results: The median OS was 1.3 months longer in the GZ 60 mg group compared with the Gem group (8.5 vs. 7.2 months) and the risk of death was reduced by 19% compared with the Gem group, although there were no statistically significant differences. The study treatments were well tolerated.Conclusions: In this Phase II study, no statistically significant differences between the GZ groups and Gem group were detected in any analysis. However, Z-360 in dose of 60 mg tends to improve OS in patients with metastatic pancreatic cancer with low toxic effect. Further exploratory trials with other agents such as gemcitabine plus nab-paclitaxel might be beneficial. [ABSTRACT FROM AUTHOR]

Background and Aims: Self-expandable metallic stent insertion has been a mainstream treatment for relieving the obstructive symptoms of malignant gastric outlet obstruction (MGOO), a late-stage complication of gastrointestinal malignancies. This study aims to investigate the predictive value of stent expansion rates in clinical outcomes in patients with MGOO.Methods: Eighty-seven patients with inoperable MGOO receiving metallic stents were reviewed retrospectively from April 2010 to December 2014. Clinical outcomes, predictors of stent patency, and survival were analyzed.Results: The technical and clinical success rates were 100 and 94.3%, respectively. The median stent patency time was 114 days (range 13-570 days). The median survival time was 133 days (range 13-1145 days). Stent dysfunctions occurred in 28 patients (32.2%), with restenosis accounting for the majority (82%). The stent expansion rate ≥75% at Day 1 predicted the stent patency [hazard ratio (HR) 0.12, P = 0.04]. However, it did not correlate with survival. Non-gastric cancer origins (HR 2.41, P = 0.002) and peritoneal carcinomatosis (HR 2.54, P = 0.001) correlated with poor survival. However, post-stent chemotherapy (HR 0.55, P = 0.03) was related to better outcome. The comparison of clinical outcomes of first and second stent insertions showed no significant difference in the stent expansion rate either at Day 0 and Day 1 (P = 0.97 and P = 0.57).Conclusions: Self-expandable metallic stent insertion is a safe and effective treatment for relieving the obstructive symptoms. The stent expansion rate ≥75% at Day 1 is a novel stent-related predictor of stent patency. [ABSTRACT FROM AUTHOR]

Purpose: Studies have suggested that endometriosis may coexist with irritable bowel syndrome (IBS). Using a population-based cohort study, we followed subjects for a 5-year period to identify the risk of IBS after a diagnosis of endometriosis. Methods: This cohort study used the Taiwan National Health Insurance Database as a source of subjects. A total of 6076 patients with endometriosis from 2000 to 2005 were identified. Their data were compared with those of 30,380 age-matched controls without endometriosis who were randomly selected from the same database. All subjects were tracked for 5 years from the date of cohort entry to identify the risk of IBS. The Cox model was used to evaluate the 5-year event occurrence of IBS. Results: Nine hundred twenty-six patients were diagnosed with IBS, including 256 in the case cohort (4.2 %) and 670 in the control cohort (2.2 %). The Kaplan-Meier survival curves demonstrated significantly lower event-free rates in the case cohort than in the control cohort ( P = 0.001). After adjusting for urbanization level, monthly income, residential region and comorbidities, the hazard ratio (HR) within 5 years revealed a 1.79-fold (95 % confidence interval [CI] 1.55-2.07) greater risk among the cases than the controls. The HR was higher within the first year of follow-up (HR 1.90, 95 % CI 1.42-2.55) and in those women aged 25-34 years (HR 2.17, 95 % CI 1.61-2.92). Conclusions: The risk of IBS among endometriosis patients persisted over 5 years of follow-up. The association detected in this study might have proceeded through shared risk and pathogenic factors. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the safety and efficacy of biweekly capecitabine in combination with oxaliplatin in previously untreated patients with locally advanced or metastatic gastric cancer. Methods: Patients received oral capecitabine 1,000 mg/m twice daily on days 1-10 plus oxaliplatin 85 mg/m as a 2-h intravenous infusion on day 1, every 2 weeks (XELOX). The primary endpoint was overall response rate. Secondary endpoints included progression-free survival, overall survival, and toxicity. Results: From March 2007 to October 2010, 46 patients were enrolled in this phase II study. The median age was 64 years (range 32-85). A total of 391 (median 7.5, range 1-29) cycles were delivered. Among the 41 patients evaluable for tumor response, 9 showed partial response and 25 had stable disease. The overall response rates of the evaluable and intent-to-treat (ITT) populations were 22 % (95 % CI 10-42 %) and 20 % (95 % CI 9-34 %), respectively. In the ITT analysis, the progression-free survival and overall survival were 5.6 months (95 % CI 4.1-6.3 months) and 8.0 months (95 % CI 6.3-10.1 months), respectively. The most common hematological toxicities were thrombocytopenia (35 %) and leucopenia (34 %), whereas the most common non-hematological toxicities were neuropathy (35 %), fatigue (33 %), diarrhea (27 %), vomiting (26 %), and hand-foot syndrome (25 %). Major grade 3-4 toxicities were anemia (11 %), diarrhea (9 %), and hand-foot syndrome (7 %). No patient died of treatment-related toxicities. Conclusions: Although the biweekly XELOX regimen failed its primary response rate endpoint, it showed modest efficacy and an acceptable safety profile in the treatment of advanced gastric cancer. [ABSTRACT FROM AUTHOR]

Purpose: To compare the efficacy and toxicity of single-agent gemcitabine with gemcitabine plus cisplatin (G + C) in patients with metastatic pancreatic cancer Methods: Forty-six patients with metastatic pancreatic cancer were randomized to receive gemcitabine alone ( n = 25; 1,000 mg m) or G + C ( n = 21; 1,000 mg m gemcitabine and 25 mg m cisplatin). Treatments were administered once a week for 3 weeks and repeated every 4 weeks. Results: Patient characteristics were comparable between the gemcitabine alone and G + C groups. The gemcitabine dose intensity was similar between the gemcitabine alone and G + C groups (684 ± 32 vs. 617 ± 31 mg m week). The cisplatin dose intensity was 15.1 ± 0.9 mg m week × 9.9 ± 1.8 weeks. Partial response rates were 8 % (2/25) for gemcitabine alone and 4.8 % (1/21) for G + C ( p = 1). The median survival and median time to progression were 7.7 and 4.6 months for gemcitabine alone and 7.9 and 3.6 months for G + C, respectively ( p = 0.752 and p = 0.857, respectively). Clinical benefit was 36 % for gemcitabine alone and 29 % for G + C ( p = 0.592). Quality-adjusted life months were 5.6 ± 0.3 for the gemcitabine alone group and 3.8 ± 0.2 for the G + C group ( p < 0.001). The frequency of grade 3/4 neutropenia (8 vs. 19 %) and anemia (8 vs. 10 %) and the number of hospitalization days per month of survival (4.7 ± 1.3 vs. 6.3 ± 1.6 days; p = 0.431) were not significantly different between patients who received gemcitabine alone and those who received G + C. However, patients in the G + C group had a higher rate of thrombocytopenia than did patients in the gemcitabine alone group (62 vs. 24 %; p = 0.009). Conclusions: Gemcitabine alone and G + C had comparable and modest response rates in metastatic pancreatic cancer, but gemcitabine alone produced less toxicities than did G + C. [ABSTRACT FROM AUTHOR]

Objective: Cytokines play important roles in angiogenesis, inflammation, and cell growth. The present study aimed to investigate the correlation between cytokine changes and clinical characteristics in hepatocellular carcinoma (HCC) patients receiving transcatheter arterial chemoembolization (TACE). Methods: Forty-one TACE-näive HCC patients receiving 73 sessions of TACE and 30 healthy controls were studied. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiogenin, epidermal growth factor (EGF), epidermal growth factor receptor, and transforming growth factor β1 (TGF-β1) before and at 1, 3, 5, 7, and 14 days after TACE as well as clinical parameters were analyzed. Results: Baseline serum levels of VEGF, bFGF, IL-6, IL-8, and TNF-α in HCC patients were significantly elevated, whereas EGF and TGF-β1 levels were lower compared to those in healthy controls ( p < 0.05 for all). Serum IL-6 increased rapidly and peaked on day 1 after TACE administration, whereas VEGF increased more slowly and peaked on day 14 after TACE administration. Patients with post-TACE fever had higher serum IL-6 levels on days 1, 3, and 5 ( p < 0.005 for all). Patients with pre-TACE serum VEGF < 200 pg/ml had a longer survival than those with pre-TACE serum VEGF levels ≥ 200 pg/ml (22.2 months vs. 11.6 months, p = 0.014). Cox multivariate analysis showed that baseline serum VEGF significantly predicted survival for HCC patients receiving TACE. Conclusions: TACE is associated with the modulation of serum angiogenic, inflammatory, and cell growth cytokines in HCC patients. Serum IL-6 correlates with post-TACE fever, and baseline serum VEGF independently predicts patient survival. [ABSTRACT FROM AUTHOR]

Background: Gremlin 1 (GREM1) is a bone morphogenetic protein antagonist and a novel proangiogenic factor. Our aim was to evaluate the prognostic value of GREM1 expression and GREM1-related factors in tumor-associated angiogenesis in pancreatic neuroendocrine tumors (NETs). Methods: The immunohistochemical expression of GREM1 and microvessel density (MVD) were examined in 35 patients with pancreatic NETs and then compared with other clinicopathologic characteristics, including the World Health Organization classification. Results: The presence of expression of GREM1 ( p = 0.016) and high MVD ( p = 0.020) were significant and favorable prognostic factors. Moreover, GREM1 expression was significantly associated with high MVD ( p = 0.011). MVD was significantly higher in well-differentiated NETs than in well-differentiated or poorly differentiated neuroendocrine carcinomas ( p < 0.001). Conclusions: GREM1 expression was correlated with tumor-associated angiogenesis and was found to be a novel prognostic marker in pancreatic NETS. Our data support a tumor suppressor role of GREM1 in pancreatic NETs. [ABSTRACT FROM AUTHOR]

Background: In Asian countries, transarterial chemoembolization (TACE) is widely applied in hepatocellular carcinoma (HCC) patients with extra-hepatic metastasis in the absence of main portal vein thrombosis. However, its survival benefit is unclear. The study aimed to analyze the role of TACE in patients with metastatic HCC. Methods: From 2002 to 2009, 2,165 consecutive HCC patients were retrospectively reviewed. Of the 893 Barcelona Clinic Liver Cancer stage C patients, 105 who had extra-hepatic metastasis on initial presentation without main portal vein thrombosis were enrolled, including 46 who received TACE (TACE group) and 59 who received supportive treatment (control group). Factors associated with survival were evaluated by multivariate analysis. Survival between the two groups was compared by propensity score matching analysis. Results: Median survival in the TACE and control groups was 6.6 and 3.2 months, respectively ( p < 0.001). By multivariate analysis, TACE [hazard ratio (HR) = 0.476, p = 0.002], tumor size >10 cm (HR = 1.606, p = 0.045), and alpha-fetoprotein (AFP) >2,000 ng ml (HR = 1.599, p = 0.037) were factors associated with survival. After propensity score matching analysis, a better survival was noted in the TACE group (median survival 4.0 vs. 3.0 months, p = 0.029). Subgroup analysis showed that patients with tumor size ≤10 cm and AFP levels ≤2,000 ng ml had the best survival from TACE. Smaller tumor size is the only independent predictor for survival longer than 6 months in patients receiving TACE. Conclusions: TACE provides survival benefit for metastatic HCC patients. Prospective randomized controlled trials are warranted to delineate the role of combining TACE with sorafenib or other treatment for metastatic HCC. [ABSTRACT FROM AUTHOR]

Purpose: The highest rates of gastric cancer occur in Eastern Asia. Fluoropyrimidine-based therapy is used initially in unresectable and metastatic disease, but no single standard of care exists following disease progression. Ixabepilone, an epothilone B analog, is a non-taxane microtubule-stabilizing agent with clinical activity across multiple tumor types approved by the United States Food and Drug Administration for treatment of metastatic breast cancer. Methods: Asian patients with unresectable or metastatic gastric adenocarcinoma who had failed fluoropyrimidine-based chemotherapy received ixabepilone 40 mg/m by 3-h intravenous infusion every 3 weeks. The primary endpoint was objective response rate (ORR). Results: Fifty-two patients were treated (65.4 % men; median age: 56.5 years). The ORR was 15.4 % (95 % confidence interval [CI] 6.9-28.1); 8 patients achieved partial responses for a median duration of 3.1 months (95 % CI 2.6-4.1 months) and 26 patients (50.0 %) had stable disease. Median progression-free survival was 2.8 months (95 % CI 2.1-3.5 months). The most common grade 3 non-hematological toxicities were fatigue (9.6 %), decreased appetite (7.7 %), sensory neuropathy (5.8 %), and diarrhea (5.8 %). Grade 3/4 neutropenia occurred in 46.2 % of patients. Conclusions: Ixabepilone is active in Asian patients with advanced gastric cancer and shows a toxicity profile similar to those previously reported in other tumor types. [ABSTRACT FROM AUTHOR]

Background: To investigate the therapeutic index of combining etoposide, doxorubicin (adriamycin), cisplatin, 5-fluorouracil (5-FU), and leucovorin (EAPFL) chemotherapy in the treatment of advanced HCC, a trial of a novel schedule of triweekly administration was conducted.Patients and Methods: Sixty-six patients with measurable advanced HCC, adequate liver and renal functions and adequate bone marrow reserves in whom local treatment was not indicated were studied. Triweekly EAPFL treatment consisted of a concomitant boost of etoposide 40 mg/m2 i.v. over 30 min on day 1, 2, and 3, doxorubicin 30 mg/m2 i.v. over 30 min on day 1 to a backbone regimen, triweekly PFL chemotherapy with cisplatin 60 mg/m2, 5-FU 1,200 mg/m2, and leucovorin 120 mg/m2 given simultaneously by a 72-h i.v. infusion. Response, survival, and toxicity were evaluated.Results: One patient had complete response (1%) and thirteen patients had partial response (20%). The objective response rate was 21% (95% confidence interval 11-31%). The median overall survival and median time to progression were 8.9 months and 3.3 months, respectively. Major treatment toxicities (grade 3-4) were neutropenia (28%), anemia (11%), thrombocytopenia (7%), hepatotoxicity (5%), vomiting (2%), and diarrhea (2%). There was no treatment-related death.Conclusion: Triweekly EAPFL chemotherapy is a moderately effective regimen with tolerable toxicities in the treatment of advanced HCC. [ABSTRACT FROM AUTHOR]

To investigate the postprandial gallbladder motility, including emptying and refilling, in cirrhotic patients and to evaluate the relationship to the presence of gallstones and various humoral mediators, 82 patients with liver cirrhosis and 40 age- and sex-matched healthy subjects were enrolled into this study. Postprandial gallbladder volumes were measured with ultrasonography every 15 min for 2 hr. Plasma levels of estradiol, testosterone, substance P, and nitrate/nitrite were also measured. Cirrhotic patients showed a higher prevalence of gallstones than healthy subjects (41% vs 15%, P = 0.003), and the prevalence increased with the progression of liver cirrhosis (Child-Pugh class A: 26%, B: 44%, and C: 65%, P = 0.02). Plasma levels of estradiol, testosterone, and substance P, and nitrate/nitrite and estradiol/testosterone ratios were not different between cirrhotic patients with and without gallstones. However, postprandial refilling of the gallbladders was significantly impaired in patients with cirrhosis, especially in those combined with gallstones. There was no significant difference in the postprandial gallbladder motility between cirrhotic patients with and without elevated plasma levels of estradiol, testosterone, and substance P and nitrate/nitrite, and estradiol/testosterone ratios. Gallstones were common in patients with liver cirrhosis and the prevalence increased with the progression of liver diseases. Sex hormones, substance P, and nitrate/nitrite did not play major roles in the formation of gallstones in cirrhotic patients. Refilling of the gallbladder was significantly impaired in patients with liver cirrhosis, especially in those with gallstones, and may play an important role in the pathogenesis of gallstones. [ABSTRACT FROM AUTHOR]