ABSTRACT
Hepatocellular carcinoma (HCC) comprises 75 to 85% of all primary liver cancers. Current guidelines recommend a biannual HCC surveillance using ultrasound (US) for high-risk patients. However, due to its low sensitivity for detection of early-stage HCC lesions, there is an urgency for more sensitive surveillance tools. Here, we describe the potential of a short MRI surveillance (SMS) protocol for HCC, including axial T1-weighted in-out phase, fat-saturated T2-weighted, and diffusion-weighted sequences. In this prospective, multicenter, patient cohort study, patients will be recruited from existing HCC surveillance cohorts of six medical centers in The Netherlands. Surveillance patients who undergo biannual US, will be invited for SMS on the same day for 3 years. In case of a suspicious finding on either US or SMS, patients will be invited for a full MRI liver protocol including gadolinium-based contrast agent intravenous injection within 2 weeks. To our knowledge, this will be the first study to perform a head-to-head comparison with a paired US-MRI design. We hypothesize that the sensitivity of SMS for detection of early-stage HCC will be higher than that of US leading to improved survival of surveillance patients through timely HCC diagnosis. Furthermore, we hypothesize that the SMS-HCC protocol will prove cost-effective.Relevance statement The US sensitivity for detecting early-stage HCC has been reported to be less than 50%. We expect that the proposed SMS will detect at least twice as many early-stage HCC lesions and therefore prove to be cost-effective. Key points ⢠The low sensitivity of US necessitates better imaging tools for HCC screening.⢠This is the first study with a paired US-MRI design.⢠This design will allow a head-to-head comparison in both diagnostics and patient-acceptance.⢠We expect that SMS can contribute to a higher survival rate.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Prospective Studies , Magnetic Resonance Imaging/methods , Contrast Media , Multicenter Studies as TopicABSTRACT
BACKGROUND & AIMS: Sub-Saharan African (SSA) ethnicity has been associated with a higher risk of hepatocellular carcinoma (HCC) among individuals with chronic hepatitis B in cross-sectional studies. However, the incidence of HCC and performance of HCC risk scores in this population are unknown. METHODS: We conducted an international multicenter retrospective cohort study of all consecutive HBV-monoinfected individuals of SSA or Afro-Surinamese (AS) ethnicity managed at sites in the Netherlands, the United Kingdom and Spain. We assessed the 5- and 10-year cumulative incidences of HCC in the overall study population, among different clinically relevant subgroups and across (m)PAGE-B subgroups. Next, we explored the different risk factors for HCC. RESULTS: During a median follow-up of 8 years, we analyzed 1,473 individuals of whom 34 developed HCC. The 5- and 10-year cumulative incidences of HCC were 1% and 2.4%. The 10-year cumulative incidence of HCC was 0.7% among individuals without advanced fibrosis at baseline, compared to 12.1% among individuals with advanced fibrosis (p <0.001). Higher age (adjusted hazard ratio [aHR] 1.05), lower platelet count (aHR 0.98), lower albumin level (aHR 0.90) and higher HBV DNA log10 (aHR 1.21) were significantly associated with HCC development. The 10-year cumulative incidence of HCC was 0.5% among individuals with a low PAGE-B score, compared to 2.9% in the intermediate- and 15.9% in the high-risk groups (p <0.001). CONCLUSIONS: In this unique international multicenter cohort of SSA and AS individuals with chronic hepatitis B, we observed 5- and 10-year cumulative HCC risks of 1% and 2.4%, respectively. The risk of HCC was negligible for individuals without advanced fibrosis at baseline, and among individuals with low baseline (m)PAGE-B scores. These findings can be used to guide HCC surveillance strategies. IMPACT AND IMPLICATIONS: Sub-Saharan African ethnicity has been associated with a higher risk of hepatocellular carcinoma among individuals with chronic hepatitis B. In this international multicenter cohort study of sub-Saharan African and Afro-Surinamese individuals living with chronic hepatitis B in Europe, we observed 5- and 10-year cumulative incidences of hepatocellular carcinoma of 1% and 2.4%, respectively. The risk was negligible among individuals without advanced fibrosis and a low baseline (m)PAGE-B score. These findings can be used to guide HCC surveillance strategies in this population.
Subject(s)
Carcinoma, Hepatocellular , Hepatitis B, Chronic , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/drug therapy , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/epidemiology , Hepatitis B, Chronic/drug therapy , Liver Neoplasms/epidemiology , Liver Neoplasms/etiology , Liver Neoplasms/drug therapy , Cohort Studies , Retrospective Studies , Cross-Sectional Studies , Antiviral Agents/therapeutic use , Risk Factors , Europe , Fibrosis , Africa South of the Sahara/epidemiology , Hepatitis B virus/geneticsABSTRACT
RATIONALE AND OBJECTIVES: Distinguishing malignant from benign liver lesions based on magnetic resonance imaging (MRI) is an important but often challenging task, especially in noncirrhotic livers. We developed and externally validated a radiomics model to quantitatively assess T2-weighted MRI to distinguish the most common malignant and benign primary solid liver lesions in noncirrhotic livers. MATERIALS AND METHODS: Data sets were retrospectively collected from three tertiary referral centers (A, B, and C) between 2002 and 2018. Patients with malignant (hepatocellular carcinoma and intrahepatic cholangiocarcinoma) and benign (hepatocellular adenoma and focal nodular hyperplasia) lesions were included. A radiomics model based on T2-weighted MRI was developed in data set A using a combination of machine learning approaches. The model was internally evaluated on data set A through cross-validation, externally validated on data sets B and C, and compared to visual scoring of two experienced abdominal radiologists on data set C. RESULTS: The overall data set included 486 patients (A: 187, B: 98, and C: 201). The radiomics model had a mean area under the curve (AUC) of 0.78 upon internal validation on data set A and a similar AUC in external validation (B: 0.74 and C: 0.76). In data set C, the two radiologists showed moderate agreement (Cohen's κ: 0.61) and achieved AUCs of 0.86 and 0.82. CONCLUSION: Our T2-weighted MRI radiomics model shows potential for distinguishing malignant from benign primary solid liver lesions. External validation indicated that the model is generalizable despite substantial MRI acquisition protocol differences. Pending further optimization and generalization, this model may aid radiologists in improving the diagnostic workup of patients with liver lesions.
Subject(s)
Liver Neoplasms , Radiomics , Humans , Retrospective Studies , Magnetic Resonance Imaging/methods , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathologyABSTRACT
PURPOSE: To compare transarterial chemoembolization delivered with drug eluting beads (TACE-DEB) with stereotactioc body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC) in a multicenter randomized trial. METHODS AND MATERIALS: Patients were included if they were eligible for TACE. They could also be recruited if they required treatment prior to liver transplantation. A maximum of four TACE-DEB procedures and ablation after incomplete TACE-DEB were both allowed. SBRT was delivered in six fractions of 8-9Gy. Primary end point was time to progression (TTP). Secondary endpoints were local control (LC), overall survival (OS), response rate (RR), toxicity, and quality of life (QoL). The calculated sample size was 100 patients. RESULTS: Between May 2015 and April 2020, 30 patients were randomized to the study. Due to slow accrual the trial was closed prematurely. Two patients in the SBRT arm were considered ineligible leaving 16 patients in the TACE-DEB arm and 12 in the SBRT arm. Median follow-up was 28.1 months. Median TTP was 12 months for TACEDEB and 19 months for SBRT (p=0.15). Median LC was 12 months for TACE-DEB and >40 months (not reached) for SBRT (p=0.075). Median OS was 36.8 months for TACEDEB and 44.1 months for SBRT (p=0.36). A post-hoc analysis showed 100% for SBRT 1- and 2-year LC, and 54.4% and 43.6% for TACE-DEB (p=0.019). Both treatments resulted in RR>80%. Three episodes of possibly related toxicity grade ≥3 were observed after TACE-DEB. No episodes were observed after SBRT. QoL remained stable after both treatment arms. CONCLUSIONS: In this trial, TTP after TACE-DEB was not significantly improved by SBRT, while SBRT showed higher local antitumoral activity than TACE-DEB, without detrimental effects on OS, toxicity and QoL. To overcome poor accrual in randomized trials that include SBRT, and to generate evidence for including SBRT in treatment guidelines, international cooperation is needed.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Radiosurgery , Humans , Radiosurgery/adverse effects , Carcinoma, Hepatocellular/radiotherapy , Quality of Life , Liver Neoplasms/radiotherapyABSTRACT
BACKGROUND & AIMS: Patients with chronic hepatitis B (CHB) are at increased risk of hepatocellular carcinoma and (liver-related) mortality. In addition to hepatitis B-related factors, metabolic comorbidities may contribute to the progression of fibrosis. Therefore, we studied the association between metabolic comorbidities and adverse clinical outcomes in patients with CHB. METHODS: We conducted a retrospective cohort study of CHB patients attending the Erasmus MC University Medical Center (Rotterdam, The Netherlands) and CHB patients who underwent liver biopsy at the Toronto General Hospital (Toronto, Canada). The presence of metabolic comorbidities (ie, overweight, diabetes mellitus, hypertension, and dyslipidemia) was assessed based on chart review. The primary end point was liver-related events, defined as the first composite of hepatocellular carcinoma, liver transplantation, or liver-related mortality. RESULTS: We analyzed 1850 patients, of whom 926 (50.1%) were overweight, 161 (8.7%) had hypertension, 116 (6.3%) had dyslipidemia, and 82 (4.4%) had diabetes. During a median follow-up period of 7.3 years (interquartile range, 2.9-11.5 y), a total of 111 first events were recorded. Hypertension (hazard ratio [HR], 8.3; 95% CI, 5.5-12.7), diabetes (HR, 5.4; 95% CI, 3.2-9.1), dyslipidemia (HR, 2.8; 95% CI, 1.6-4.8), and overweight (HR, 1.7; 95% CI, 1.1-2.5) were associated with an increased risk for liver-related events. The presence of multiple comorbidities further increased the risk. Findings were consistent for patients with and without cirrhosis, among noncirrhotic hepatitis B e antigen-negative patients with hepatitis B virus DNA less than 2000 IU/mL and in multivariable analysis adjusting for age, sex, ethnicity, hepatitis B e antigen status, hepatitis B virus DNA, use of antiviral therapy, and the presence of cirrhosis. CONCLUSIONS: Metabolic comorbidities in CHB patients are associated with an increased risk for liver-related events, with the highest risk observed in patients with multiple comorbidities. Findings were consistent in various clinically relevant subgroups, underscoring the need for thorough metabolic assessment in patients with CHB.
Subject(s)
Carcinoma, Hepatocellular , Diabetes Mellitus , Dyslipidemias , Hepatitis B, Chronic , Hypertension , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Hepatitis B, Chronic/drug therapy , Retrospective Studies , Hepatitis B e Antigens , Overweight/complications , Overweight/drug therapy , Antiviral Agents/therapeutic use , Liver Cirrhosis/complications , Liver Cirrhosis/epidemiology , Liver Cirrhosis/drug therapy , Diabetes Mellitus/epidemiology , DNA , Dyslipidemias/complications , Hepatitis B virus/geneticsABSTRACT
Background & Aims: Increased serum IgG and autoantibodies suggest involvement of B cells in autoimmune hepatitis (AIH). The aim of this study was to assess levels of B cell activating factor of the tumour necrosis family (BAFF), IL-21, and circulating B cell populations in AIH and correlate these to treatment response. Methods: BAFF and IL-21 levels were determined in 66 patients with AIH before treatment and 10 healthy controls. Flow cytometry was performed on circulating B cells of 10 patients with AIH and 12 healthy controls. Results: Based on BAFF and IL-21 levels, untreated patients with AIH were divided into 3 groups: 27 (41%) patients with normal BAFF and IL-21 (normal BAFF), 27 (41%) patients with elevated BAFF but normal IL-21 (high BAFF), and 12 (18%) patients with elevated IL-21 (high IL-21). The high BAFF group presented with higher bilirubin compared with the normal BAFF and high IL-21 groups (159 vs. 26 vs. 89 µmol/L; p = 0.001; Mann-Whitney U test). After 12 months of treatment, 54% of the high BAFF group reached remission compared with 34% of the normal BAFF group and 0% of the high IL-21 group (p = 0.006, Chi-square test). During follow-up, 3 patients (25%) with high IL-21 developed primary sclerosing cholangitis (PSC) variant syndrome. Autoimmune-associated B cells were increased in patients with AIH compared with healthy controls (4.4 vs. 1.4%; p = 0.003, Mann-Whitney U test). BAFF levels were correlated positively with naïve B cells (p = 0.01) and negatively with class-switched B cells (p = 0.003) and nonclass-switched B cells (p = 0.005, Spearman correlation). Discussion: Using BAFF and IL-21, we identified different immunological phenotypes of AIH with a different presentation, treatment response, and outcome. Patients with high IL-21 had the poorest treatment response and a risk of developing PSC variant syndrome. BAFF level was related to shifts in circulating B-cell populations. Lay summary: In patients with untreated autoimmune hepatitis (AIH), circulating B-cell activating factor of the tumour necrosis family (BAFF), IL-21, and B-cell populations were determined. Three subgroups were identified: with (1) normal BAFF and IL-21, (2) elevated BAFF and normal IL-21, and (3) elevated IL-21. Remission after 1-year treatment occurred in 54, 34, and 0% in Groups 1, 2, and 3, respectively. Group 2 had higher bilirubin, indicating more liver dysfunction. In 25% of patients with high IL-21, AIH-PSC variant syndrome developed, but none in the other groups. Autoimmune-associated B cells were elevated and BAFF levels correlated with certain B cells.
ABSTRACT
As pegylated interferon alpha (PEG-IFN-α) is increasingly used in combination regimens of novel drugs, we aimed to characterize ALT flares and their relationship with serum HBsAg and HBV RNA kinetics in a large combined cohort of chronic hepatitis B (CHB) patients on PEG-IFN-α-based therapy. In this post hoc analysis of four international randomized trials, 269/130/124/128 patients on PEG-IFN-α monotherapy, PEG-IFN-α plus nucleos(t)ide analogue (NA) de novo combination, PEG-IFN-α add-on to NA or NA monotherapy were included, respectively. A flare was defined as an episode of ALT ≥5 × ULN. The association between flares and HBsAg and HBV RNA changes were examined. On-treatment flares occurred in 83/651 (13%) patients (median timing/magnitude: week 8 [IQR 4-12], 7.6 × ULN [IQR 6.2-10.5]). Flare patients were more often Caucasians with genotype A/D and had higher baseline ALT, HBV DNA, HBV RNA and HBsAg levels than the no-flare group. More flares were observed on PEG-IFN-α monotherapy (18%) and PEG-IFN+NA de novo combination (24%) vs. PEG-IFN-α add-on (2%) or NA monotherapy (1%) (p < .001). On-treatment flares were significantly and independently associated with HBsAg and HBV RNA decline ≥1 log10 at the final visit declines started shortly before the flare, progressing towards 24 weeks thereafter. On-treatment flares were seen in 16/22 (73%) patients who achieved HBsAg loss. In conclusion, ALT flares during PEG-IFN-α treatment are associated with subsequent HBsAg and HBV RNA decline and predict subsequent HBsAg loss. Flares rarely occurred during PEG-IFN-α add-on therapy and associated with low HBsAg loss rates. Combination regimens targeting the window of heightened response could be promising.
Subject(s)
Hepatitis B virus , Hepatitis B, Chronic , Antiviral Agents/therapeutic use , DNA, Viral , Hepatitis B Surface Antigens , Hepatitis B e Antigens , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Humans , Polyethylene Glycols/therapeutic use , RNA , Recombinant Proteins/therapeutic useABSTRACT
BACKGROUND: Treatment with immunosuppressive drugs (IS) after transplantation is accompanied by severe side effects. A limited number of studies have investigated the effect of IS withdrawal on IS-related comorbidities after liver transplantation (LTx) and the results are contradictory. PATIENTS AND METHODS: We determined in a retrospective case-control study the clinical effects of complete IS withdrawal in operationally tolerant (TOL) LTx recipients who discontinued IS 10.8 ± 5.1 years after LTx (n = 13) compared with a completely matched control (CTRL) group with a regular IS regimen (n = 22). TOL recipients have been IS and rejection free for 4.0 ± 2.8 years. RESULTS: IS withdrawal in TOL recipients resulted in lower low-density lipoprotein levels (P = 0.027), whereas this was not observed in the CTRL group. Furthermore, persistent infections in individual recipients were resolved successfully by IS withdrawal. TOL recipients also had significantly fewer de novo infections after IS withdrawal (TOL pre vs. post withdrawal P = 0.0247) compared with recipients continued on IS during the same follow-up period (post withdrawal TOL vs. CTRL P = 0.044). Unfortunately, no improvement in kidney function, and lower rates of de novo occurrences of diabetes, hypertension, cardiovascular diseases, and malignancies were observed in the TOL group after IS withdrawal compared with the CTRL group during the same follow-up time period. CONCLUSION: IS withdrawal late after LTx reduces infection rates and low-density lipoprotein levels, but other IS-related side effects persist late after LTx. An accurate tolerance immune profile enabling identification of tolerant LTx recipients eligible for safe IS withdrawal earlier after transplantation is needed to prevent the development of irreversible IS-related side effects.
Subject(s)
Deprescriptions , Dyslipidemias/chemically induced , Graft Rejection/prevention & control , Immune Tolerance/immunology , Immunosuppressive Agents/adverse effects , Infections/etiology , Liver Transplantation , Renal Insufficiency/chemically induced , Adolescent , Adult , Aged , Cardiovascular Diseases , Case-Control Studies , Cholesterol, LDL/metabolism , Diabetes Mellitus , Dyslipidemias/metabolism , Female , Glomerular Filtration Rate , Graft Rejection/immunology , Humans , Hypertension , Male , Middle Aged , Neoplasms , Renal Insufficiency/metabolism , Retrospective Studies , Treatment Outcome , Young AdultSubject(s)
Immunocompromised Host/immunology , Yellow Fever Vaccine/immunology , Adult , Contraindications, Drug , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/adverse effects , Female , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Male , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/adverse effects , Risk Assessment , Tacrolimus/administration & dosage , Travel , Vaccination/adverse effects , Yellow Fever Vaccine/administration & dosage , Yellow Fever Vaccine/adverse effectsABSTRACT
OBJECTIVE: To develop a feasible model for monitoring short-term outcome of clinical care trajectories for hospitals in the Netherlands using data obtained from hospital information systems for identifying hospital variation. STUDY DESIGN: Retrospective analysis of collected data from hospital information systems combined with clinical indicator definitions to define and compare short-term outcomes for three gastrointestinal pathways using the concept of Textbook Outcome. SETTING: 62 Dutch hospitals. PARTICIPANTS: 45 848 unique gastrointestinal patients discharged in 2015. MAIN OUTCOME MEASURE: A broad range of clinical outcomes including length of stay, reintervention, readmission and doctor-patient counselling. RESULTS: Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) for gallstone disease (n=4369), colonoscopy for inflammatory bowel disease (IBD; n=19 330) and colonoscopy for colorectal cancer screening (n=22 149) were submitted to five suitable clinical indicators per treatment. The percentage of all patients who met all five criteria was 54%±9% (SD) for ERCP treatment. For IBD this was 47%±7% of the patients, and for colon cancer screening this number was 85%±14%. CONCLUSION: This study shows that reusing data obtained from hospital information systems combined with clinical indicator definitions can be used to express short-term outcomes using the concept of Textbook Outcome without any excess registration. This information can provide meaningful insight into the clinical care trajectory on the level of individual patient care. Furthermore, this concept can be applied to many clinical trajectories within gastroenterology and beyond for monitoring and improving the clinical pathway and outcome for patients.
Subject(s)
Cholangiopancreatography, Endoscopic Retrograde/standards , Colonic Neoplasms/surgery , Gallstones/surgery , Inflammatory Bowel Diseases/surgery , Quality Indicators, Health Care/statistics & numerical data , Aged , Aged, 80 and over , Colonoscopy/methods , Female , Hospital Information Systems/statistics & numerical data , Humans , Male , Middle Aged , Netherlands , Quality Assurance, Health Care , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: A reduction in skeletal muscle mass (sarcopenia) independently predicts poor survival in patients with hepatocellular carcinoma (HCC) undergoing treatment with curative intent. Whether this is due to an increased risk of recurrence and disease specific death, or due to an increased risk of postoperative morbidity and mortality is currently unclear. In this study, we investigate the association between sarcopenia and death in a cohort of HCC patients undergoing treatment with curative intent. METHODS: Patients undergoing surgical resection or radiofrequency ablation for lesions ≤ 3 cm between 2002 and 2013 were identified. Clinicopathological characteristics, CT-assessed sarcopenia and outcomes were analyzed. RESULTS: Among 90 patients, 52 (57.8%) were found to be sarcopenic. Sarcopenic patients had a limited overall survival (median: 33 months vs. non-sarcopenic median: 105 months; P = 0.002), but not disease-free survival. Sarcopenia was an independent predictor for overall survival in multivariate Cox-regression analysis (HR 3.756; P = 0.001). Major complications (32.7% vs. 13.2%, P = 0.033) and treatment-related mortality (17.3% vs. 2.6%, P = 0.029) were more frequent in sarcopenic patients. CONCLUSION: Sarcopenia impairs survival in patients with potentially curable hepatocellular carcinoma, mainly due to an increase in treatment-related mortality.
Subject(s)
Body Mass Index , Carcinoma, Hepatocellular/mortality , Liver Neoplasms/mortality , Sarcopenia/epidemiology , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/therapy , Female , Humans , Kaplan-Meier Estimate , Liver Neoplasms/complications , Liver Neoplasms/therapy , Male , Middle Aged , Muscle, Skeletal/diagnostic imaging , Netherlands/epidemiology , Sarcopenia/complications , Sarcopenia/diagnostic imaging , Tomography, X-Ray ComputedABSTRACT
BACKGROUND AND OBJECTIVE: Despite an increase in recent years, hepatocellular carcinoma remains uncommon in the Netherlands. The aim of the current study is to explore potential effects of hospital type and volume on outcomes after resection or sorafenib in patients with hepatocellular carcinoma. METHODS: Initial treatment and survival of patients with hepatocellular carcinoma diagnosed in the period 2005-2011 were based on data of the Netherlands Cancer Registration. Potential risk factors (including hospital type and volume) for 30-days postoperative and long-term mortality in patients who underwent resection and in patients treated with sorafenib were evaluated by uni- and multivariate analyses. RESULTS: In the period 2005-2011, 2402 patients were diagnosed with hepatocellular carcinoma: 12% received resection and 9% sorafenib. Postoperative mortality was higher in non-university hospitals (13% versus 4%; P=0.01). Resection in non-university hospitals was associated with higher postoperative mortality (odds ratio 3.38, 95% confidence interval 1.37-10.68) and long-term mortality (hazard ratio 1.21, 95% confidence interval 1.04-1.40). Sorafenib treatment in non-university hospitals was also associated with higher long-term mortality (hazard ratio 1.39, 95% confidence interval 1.06-1.82). Hospital volume was not independent predictor for outcome. CONCLUSION: In low incidence countries, outcome after resection or sorafenib for hepatocellular carcinoma may differ between various hospital types.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/therapy , Hepatectomy , Hospitals/classification , Liver Neoplasms/mortality , Liver Neoplasms/therapy , Niacinamide/analogs & derivatives , Phenylurea Compounds/therapeutic use , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Netherlands , Niacinamide/therapeutic use , Sorafenib , Survival RateABSTRACT
Patients with incurable esophageal cancer (EC) or pancreaticobiliary cancer (PBC) often have multiple symptoms and their quality of life is poor. We investigated which problems these patients experience and how often care is expected for these problems to provide optimal professional care. Fifty-seven patients with incurable EC (N = 24) or PBC (N = 33) from our outpatient clinic completed the validated "Problems and Needs for Palliative Care" (PNPC) questionnaire and two disease-specific quality of life questionnaires, European Organization for Research and Treatment in Cancer (EORTC). Although patients in general had several problems, physical, emotional, and loss of autonomy (LOA) problems were most common. For these physical and emotional problems, patients also expected professional care, although to a lesser extent for LOA problems. Inadequate care was received for fatigue, fear, frustration, and uncertainty. We conclude that an individualized approach based on problems related to physical, emotional, and LOA issues and anticipated problems with healthcare providers has priority in the follow-up policy of patients with incurable upper gastrointestinal cancer. Caregivers should be alert to discuss needs for fatigue, feelings of fear, frustration, and uncertainty.
Subject(s)
Biliary Tract Neoplasms/psychology , Esophageal Neoplasms/psychology , Esophageal Neoplasms/therapy , Palliative Care/methods , Pancreatic Neoplasms/psychology , Adaptation, Physiological , Adaptation, Psychological , Adult , Aged , Biliary Tract Neoplasms/physiopathology , Biliary Tract Neoplasms/therapy , Cohort Studies , Esophageal Neoplasms/mortality , Esophageal Neoplasms/physiopathology , Female , Humans , Interdisciplinary Communication , Male , Middle Aged , Needs Assessment , Netherlands , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/physiopathology , Pancreatic Neoplasms/therapy , Quality of Life , Risk Assessment , Survival Analysis , Terminally IllABSTRACT
BACKGROUND & AIMS: We aimed to assess the association between the patatin-like phospholipase domain-containing-3 (PNPLA3) I148M polymorphism, liver histology and long-term outcome in chronic hepatitis B (CHB) patients. METHODS: We enrolled 531 consecutive treatment naïve CHB patients diagnosed from 1985 to 2012 with an available liver biopsy for reassessment, and sample for genetic testing. Data on all-cause mortality and hepatocellular carcinoma (HCC) at long-term follow-up were obtained from national database registries. RESULTS: The prevalence of steatohepatitis increased with PNPLA3 CC (14%), CG (20%) and GG (43%) (P < 0.001). The association was altered by both gender (P = 0.010) and overweight (P = 0.015): the effect of PNPLA3 on steatohepatitis was most pronounced among non-overweight females (adjusted OR 13.4, 95%CI: 3.7-51.6, P < 0.001), and non-overweight males (adjusted OR 2.4, 95%CI: 1.4-4.3, P = 0.002). Furthermore, PNPLA3 GG genotype was associated with iron depositions (OR 2.8, 95%CI: 1.2-6.4, P = 0.014) and lobular inflammation (OR 2.2, 95%CI: 1.1-4.5, P = 0.032), but not with advanced fibrosis (OR 1.1, 95%CI: 0.7-1.8, P = 0.566). The median follow-up was 10.1 years (interquartile range 5.6 - 15.8), during which 13 patients developed HCC and 28 died. Steatohepatitis was associated with all-cause mortality [Hazard ratio (HR) 3.1, 95%CI: 1.3-7.3, P = 0.006] and HCC (HR 2.8, 95%CI: 0.9-9.2, P = 0.078), but no significant association was observed for PNPLA3. CONCLUSIONS: In this cohort of biopsied CHB patients, PNPLA3 was independently associated with steatosis, steatohepatitis, lobular inflammation and iron depositions, but not with advanced fibrosis, HCC development or all-cause mortality. The effect of PNPLA3 on steatohepatitis was particularly pronounced among female patients without severe overweight.
Subject(s)
Fatty Liver/epidemiology , Hepatitis B, Chronic/genetics , Lipase/genetics , Liver/pathology , Membrane Proteins/genetics , Polymorphism, Single Nucleotide/genetics , Body Weight , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/genetics , Fatty Liver/genetics , Female , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/pathology , Humans , Iron/metabolism , Liver Neoplasms/epidemiology , Liver Neoplasms/genetics , Male , Odds Ratio , Prevalence , Proportional Hazards Models , Sex FactorsABSTRACT
PURPOSE: To evaluate the presentation of inflammatory hepatocellular adenomas (HCAs) on hepatocyte phase MRI. MATERIALS AND METHODS: We retrospectively reviewed the MRI features of histologically proven HCAs on hepatocyte phase imaging. Twenty-one lesions (17 with inflammatory subtype) were scanned with gadobenate dimeglumine. Signal intensities of the lesions were assessed in the hepatocyte phase and on the T1-weighted sequences before contrast. RESULTS: After gadobenate dimeglumine injection, 71% (12/17) of the inflammatory HCAs showed areas of iso- or hyperintensity to the surrounding liver in the hepatocyte phase. In 82% (10/12) of the iso- or hyperintense lesions, this was found over more than 75% of the lesion surface. None of the noninflammatory HCAs showed areas of iso- or hyperintensity to the surrounding liver in the hepatocyte phase. From these 12, 7 were hyperintense on T1-weighting before contrast due to liver steatosis, 2 due to intrinsic hyperintensity (on the in-phase sequence), and 3 were isointense. CONCLUSION: In contrast to noninflammatory HCAs, inflammatory HCAs can show areas of iso- to hyperintensity to the surrounding liver in the hepatocyte phase; therefore, other typical imaging features should also be used to distinguish between HCAs and FNHs.
Subject(s)
Adenoma, Liver Cell/pathology , Focal Nodular Hyperplasia/pathology , Hepatitis/pathology , Hepatocytes/pathology , Liver Neoplasms/pathology , Magnetic Resonance Imaging/methods , Meglumine/analogs & derivatives , Organometallic Compounds , Adult , Contrast Media , Diagnosis, Differential , Female , Hepatitis/complications , Humans , Image Enhancement/methods , Male , Middle Aged , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
CONTEXT: Upper gastrointestinal cancer is associated with a poor prognosis. The multidimensional problems of incurable patients require close monitoring and frequent support, which cannot sufficiently be provided during conventional one to two month follow-up visits to the outpatient clinic. OBJECTIVES: To compare nurse-led follow-up at home with conventional medical follow-up in the outpatient clinic for patients with incurable primary or recurrent esophageal, pancreatic, or hepatobiliary cancer. METHODS: Patients were randomized to nurse-led follow-up at home or conventional medical follow-up in the outpatient clinic. Outcome parameters were quality of life (QoL), patient satisfaction, and health care consumption, measured by different questionnaires at one and a half and four months after randomization. As well, cost analyses were done for both follow-up strategies in the first four months. RESULTS: In total, 138 patients were randomized, of which 66 (48%) were evaluable. At baseline, both groups were similar with respect to clinical and sociodemographic characteristics and health-related QoL. Patients in the nurse-led follow-up group were significantly more satisfied with the visits, whereas QoL and health care consumption within the first four months were comparable between the two groups. Nurse-led follow-up was less expensive than conventional medical follow-up. However, the total costs for the first four months of follow-up in this study were higher in the nurse-led follow-up group because of a higher frequency of visits. CONCLUSION: The results suggest that conventional medical follow-up is interchangeable with nurse-led follow-up. A cost utility study is necessary to determine the preferred frequency and duration of the home visits.
Subject(s)
Ambulatory Care/methods , Esophageal Neoplasms/therapy , Gastrointestinal Neoplasms/therapy , Home Care Services , Oncology Nursing/methods , Pancreatic Neoplasms/therapy , Aged , Ambulatory Care/economics , Ambulatory Care/psychology , Ambulatory Care Facilities/economics , Esophageal Neoplasms/economics , Esophageal Neoplasms/psychology , Female , Follow-Up Studies , Gastrointestinal Neoplasms/economics , Gastrointestinal Neoplasms/psychology , Home Care Services/economics , Humans , Male , Middle Aged , Nurses , Oncology Nursing/economics , Palliative Care/economics , Palliative Care/methods , Palliative Care/psychology , Pancreatic Neoplasms/economics , Pancreatic Neoplasms/psychology , Patient Satisfaction , Quality of Life , Surveys and QuestionnairesABSTRACT
BACKGROUND & AIMS: Current treatment strategies in autoimmune hepatitis (AIH) include long-term treatment with corticosteroids and/or azathioprine. Here we determined the risk of relapse after drug withdrawal in patients in long-term remission and factors associated with such a relapse. METHODS: A total of 131 patients (out of a cohort including 844 patients) from 7 academic and 14 regional centres in the Netherlands were identified in whom treatment was tapered after at least 2 years of clinical and biochemical remission. Relapse was defined as alanine-aminotransferase levels (ALT) three times above the upper limit of normal and loss of remission as a rising ALT necessitating the reinstitution of drug treatment. RESULTS: During follow-up, 61 (47%) patients relapsed and 56 (42%) had a loss of remission. In these 117 patients, 60 patients had fully discontinued medication whereas 57 patients were still on a withdrawal scheme. One year after drug withdrawal, 59% of the patients required retreatment, increasing to 73% and 81% after 2 and 3 years, respectively. Previous combination therapy of corticosteroids and azathioprine, a concomitant autoimmune disease and younger age at time of drug withdrawal were associated with an increased risk of relapse. Subsequent attempts for discontinuation after initial failure in 32 patients inevitably resulted in a new relapse. CONCLUSIONS: This retrospective analysis indicates that loss of remission or relapse occurs in virtually all patients with AIH in long-term remission when immunosuppressive therapy is discontinued. These findings indicate a reluctant attitude towards discontinuation of immunosuppressive treatment in AIH patients.
Subject(s)
Hepatitis, Autoimmune/drug therapy , Hepatitis, Autoimmune/epidemiology , Immunosuppressive Agents/adverse effects , Substance Withdrawal Syndrome/epidemiology , Adolescent , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/adverse effects , Adult , Aged , Azathioprine/administration & dosage , Azathioprine/adverse effects , Child , Female , Follow-Up Studies , Hepatitis, Autoimmune/immunology , Humans , Immunosuppressive Agents/administration & dosage , Kaplan-Meier Estimate , Male , Middle Aged , Recurrence , Remission Induction , Retrospective Studies , Risk Factors , Substance Withdrawal Syndrome/immunology , Young AdultABSTRACT
OBJECTIVES: We evaluated a new assessment technique for colonoscopy training. METHODS: We prospectively evaluated colonoscopy skills during training using the Rotterdam Assessment Form for colonoscopy. The questionnaire covers cecal intubation, procedural time, and subjective grading of performance. Individual learning curves are compared with a group reference. RESULTS: Nineteen trainees self-assessed 2,887 colonoscopies. The cecal intubation rate improved from 65% at baseline to 78% and 85% after 100 and 200 colonoscopies, respectively. In our training program the 90% threshold was reached after 280 colonoscopies on average. Cecal intubation time improved from 13:10 minutes at baseline to 9:30 and 8:30 after 100 and 200 colonoscopies, respectively. CONCLUSIONS: This novel self-assessment form allows individual learning curves to be compared with a group reference, provides data on the development of dexterity skills and individual training targets, and stimulates trainees to identify steps for self-improvement.
Subject(s)
Clinical Competence/standards , Colonoscopy/standards , Education, Medical, Graduate/methods , Educational Measurement , Gastroenterology/education , Self-Assessment , Analysis of Variance , Female , Humans , Internship and Residency , Male , Middle Aged , Netherlands , Practice Guidelines as Topic , Prospective Studies , Surveys and QuestionnairesABSTRACT
We screened 1,200 living heart, lung, liver, and kidney transplant recipients for hepatitis E virus infection by reverse transcription PCR. In 12 (1%) patients, hepatitis E virus infection was identified; in 11 patients, chronic infection developed. This immunocompromised population is at risk for hepatitis E virus infection.