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1.
Z Rheumatol ; 79(9): 865-872, 2020 Nov.
Article in German | MEDLINE | ID: mdl-32845394

ABSTRACT

Children and adults with rheumatic diseases (RD) have a higher risk to contract infections due to the underlying disease and the frequently necessary immunosuppressive treatment (IT). The quality of life of the majority of patients with RD has remarkably improved due to IT-related reduction of inflammation. Therefore, RD patients usually have an international travel behavior similar to healthy individuals. An investigation indicated that patients with RD and IT have lower travel vaccination rates and are often less well-prepared for their trip in comparison to healthy travelers, even when visiting high risk destinations. As the risk for general and travel-acquired infections is increased for patients with RD with and without IT, pretravel consultations are important. These pretravel consultations should include recommendations addressing travel cancellation, travel modification and travel vaccinations depending on the patient's risk. Travel vaccinations include vaccinations against hepatitis A, typhoid fever, rabies, cholera, meningococcal diseases, tick-bone encephalitis, Japanese encephalitis, seasonal influenza, poliomyelitis and yellow fever. In patients with RD the indications for vaccination depend on the exposure risks, disease severity, individual travel behavior, and possible complications associated with vaccination. In the further evaluation process it is crucial to include the general health condition of the patient, the underlying RD (type and activity), duration and intensity of the IT. In general, live-attenuated vaccines are contraindicated under IT. In contrast, inactivated vaccines may be administered although reduced immunogenicity with the need for antibody measurement, special vaccine schedules or additional booster vaccinations should be considered under IT.


Subject(s)
Immunocompromised Host , Rheumatic Diseases , Travel , Vaccination , Adult , Child , Humans , Meningococcal Infections/prevention & control , Quality of Life , Rheumatic Diseases/immunology , Yellow Fever/prevention & control
2.
Radiat Oncol ; 15(1): 143, 2020 Jun 05.
Article in English | MEDLINE | ID: mdl-32503580

ABSTRACT

BACKGROUND: Desmoid-type fibromatosis is a rare, potentially locally aggressive disease. Herein we present our experience in the treatment with radiotherapy. METHODS AND MATERIALS: In total 40 patients who received 44 treatments from 2009 to 2018 at the Heidelberg University Hospital with photons (N = 28) as well as protons (N = 15) and carbon ions (N = 1) were investigated. The median age at radiotherapy was 41 years [range 8-78]. Familial adenomatous polyposis (FAP) was confirmed for nine patients and 30 had a unifocal desmoid tumor. The localizations were abdominal wall, abdominopelvic cavity, thoracic wall, extremity, head and neck and trunk. The median prescribed dose was 54 Gy/ Gy (RBE) [range 39.6-66, IQR 50-60]. Eleven treatments were performed at the time of first diagnosis; 33 at the time of progression or recurrence. Post-operative radiotherapy was performed in 17 cases. The median planning target volume was 967 ml [84-4364 ml, IQR 447-1988]. Survival analysis was performed by the Kaplan-Meier Method. RESULTS: The median follow-up time was 32 months [1-153]. At the end of the follow-up interval all patients but one were alive. The estimated local progression free survival of the treated lesion in 3 and 5 years was 76.4% and 63,8%, respectively. The progression-free survival in 3 and 5 years was 72.3 and 58.4% and the overall survival was 97.4 and 97.4%, respectively. In case of macroscopic tumor (N = 31) before radiotherapy a partial remission was observed in 12 cases (38.7%) and a complete remission in 4 cases (12.9%). Progression was observed in 13 (29.5%) cases, predominantly at the margin of the planning target volume (PTV, N = 5, 38,4%) followed by progression within the PTV (N = 4, 30.8%). In univariate analysis multifocal localization was associated with impaired progression-free survival (p = 0.013). One patient developed a grade V gastrointestinal bleeding, otherwise no acute toxicity >°III was observed. Late toxicity was depending on the localization of the desmoid tumor and was especially severe in patients with FAP and abdominopelvine desmoids including gastrointesinal fistula, perforation and abscess. CONCLUSION: Radiotherapy in the treatment of desmoids can lead to long term control. Treatment of patients with abdominopelvine desmoids should be avoided, as the risk of higher-grade complications is substantial.


Subject(s)
Fibromatosis, Aggressive/radiotherapy , Adolescent , Adult , Aged , Child , Female , Heavy Ion Radiotherapy/methods , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young Adult
3.
Radiologe ; 58(8): 754-761, 2018 Aug.
Article in German | MEDLINE | ID: mdl-29947933

ABSTRACT

BACKGROUND: Peritumoral normal tissue is inevitably also irradiated during radiotherapy, depending on the location and size of the target volume as well as the cumulative dose. Depending on the temporal course after irradiation acute, subacute, and chronic alterations are described in co-irradiated normal tissue that can be detected by imaging. Radiation damage can be transient or persistent. OBJECTIVE: This article gives an overview of the most important signs of radiation-induced radiogenic alterations to tissue in various organ systems. FINDINGS: Frequent radiation-induced tissue alterations found by imaging are pneumonitis, disturbance of the blood-brain barrier, radionecrosis of brain tissue, radiogenic liver damage, mucositis, colitis, osteitis, osteoradionecrosis and myositis. The combination with systemic chemotherapy or immunotherapy can increase the severity of radiogenic reactions of normal tissue. RECOMMENDATIONS FOR AFTERCARE: The most important differential diagnosis for radiogenic alterations to normal tissue is post-therapeutic tumor recurrence. Besides typical latency periods, location and matching with the radiation field are important differentiation criteria, depending on the tumor biology and the radiation technique. The follow-up schedule should follow the current guidelines and the clinical condition of the patient should be additionally considered. The radiologist needs to be familiar with the typical imaging morphology of radiogenic tissue changes to avoid false interpretation during follow-up investigations.


Subject(s)
Neoplasms , Radiation Injuries , Humans , Neoplasms/etiology
4.
Aliment Pharmacol Ther ; 47(2): 259-267, 2018 01.
Article in English | MEDLINE | ID: mdl-29181842

ABSTRACT

BACKGROUND: Chronic hepatitis C infection leads to impairment of patient-reported outcomes (PROs). Treatment with direct-acting antiviral regimens results in short- and long-term improvement of these outcomes. AIM: To assess PROs in patients treated with a newly developed direct-acting antiviral, a fixed-dose combination of sofosbuvir/velpatasvir (SOF/VEL) with/without voxilaprevir (VOX). METHODS: The PRO data were collected from participants of POLARIS-2 and POLARIS-3 clinical trials (DAA-naïve, all HCV genotypes). Participants self-administered SF-36v2, FACIT-F, CLDQ-HCV and WPAI:SHP instruments at baseline, during treatment, and in follow-up. RESULTS: Of 1160 patients, 611 received SOF/VEL/VOX and 549 received SOF/VEL (52.8 ± 11.0 years, 55.9% male, 75.4% treatment-naïve, 33.9% cirrhotic). The sustained viral response at 12 weeks (SVR12) rates were 95%-98%. During treatment, improvements in most PRO scores were significant (all but one P < .01) and ranged from, on average, +2.3 to +15.0 points (on a 0-100 scale) by the end of treatment. These improvements were similar between SOF/VEL/VOX and SOF/VEL arms (all P > .05). After treatment discontinuation, patients treated with both regimens achieved significant and clinically meaningful PRO gains (+2.7 to +16.7 by post-treatment week 12, +3.9 to +20.1 by post-treatment week 24; all but one P < .001). Multivariate analysis showed that depression, anxiety and cirrhosis were the most consistent independent predictors of PRO impairment while no association of PROs with the treatment regimen choice was found (all P > .05). CONCLUSIONS: The pan-genotypic regimens with SOF/VEL with or without VOX not only have excellent efficacy and safety, but also significantly positively impact patients' experience both during treatment and after achieving sustained virologic response in DAA-naïve patients with HCV.


Subject(s)
Antiviral Agents/administration & dosage , Carbamates/administration & dosage , Hepatitis C, Chronic/drug therapy , Heterocyclic Compounds, 4 or More Rings/administration & dosage , Macrocyclic Compounds/administration & dosage , Sofosbuvir/administration & dosage , Sulfonamides/administration & dosage , Adult , Aminoisobutyric Acids , Antiviral Agents/adverse effects , Carbamates/adverse effects , Clinical Trials, Phase III as Topic , Cyclopropanes , Drug Therapy, Combination , Female , Follow-Up Studies , Genotype , Hepatitis C, Chronic/genetics , Hepatitis C, Chronic/virology , Heterocyclic Compounds, 4 or More Rings/adverse effects , Humans , Lactams, Macrocyclic , Leucine/analogs & derivatives , Liver Cirrhosis/drug therapy , Liver Cirrhosis/genetics , Liver Cirrhosis/virology , Macrocyclic Compounds/adverse effects , Male , Middle Aged , Multicenter Studies as Topic , Patient Reported Outcome Measures , Proline/analogs & derivatives , Quinoxalines , Randomized Controlled Trials as Topic , Self Report , Sofosbuvir/adverse effects , Sulfonamides/adverse effects , Sustained Virologic Response , Treatment Outcome
5.
Aliment Pharmacol Ther ; 46(4): 432-439, 2017 08.
Article in English | MEDLINE | ID: mdl-28627791

ABSTRACT

BACKGROUND: Hepatitis B virus (HBV) reactivation has been observed following interferon (IFN)-based treatment in HBV/hepatitis C virus (HCV) co-infected patients. Recent reports suggest that reactivation may also occur in both hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative patients during HCV treatment with direct-acting antivirals (DAAs). AIM: To investigate the rate of patients with HBV reactivation during IFN-based and IFN-free HCV treatment in a large real-world cohort. METHODS: A total of 848 patients with chronic hepatitis C were treated with different combinations of DAAs. Among patients with available outcome and HBV data, there were 272 patients hepatitis B core antibody (HBcAb)-positive (HBsAg-positive, n=9; HBsAg-negative, n=263), and 536 were HBcAb-negative. All HBcAb-positive patients were tested for HBV DNA at the end of DAA therapy and alanine transaminase (ALT) levels were frequently measured during therapy and follow-up. RESULTS: Seventy-three percent (n=192/263) of HBsAg-negative/HBcAb-positive patients had elevated ALT levels at baseline, which declined to normal values in all but 18 patients, and no HBV reactivation was observed. Eight patients had detectable but not quantifiable HBV DNA (<20 IU/mL) at end of treatment, but none were associated with elevated ALT. Five of nine HBsAg-positive/HBcAb-positive patients experienced transient or permanent HBV reactivation, three of whom required nucleos(t)ide treatment during (n=1) or after (n=2) DAA therapy. CONCLUSIONS: HBV reactivation was not observed in HBsAg-negative/HBcAb-positive patients but common in HBsAg-positive/HBcAb-positive patients treated with different combinations of DAAs for HCV.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B virus/isolation & purification , Hepatitis B/epidemiology , Hepatitis C, Chronic/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Hepatitis B Antibodies/isolation & purification , Hepatitis B Surface Antigens/immunology , Humans , Interferons/therapeutic use , Male , Middle Aged , Retrospective Studies , Virus Activation , Young Adult
6.
J Viral Hepat ; 24(10): 840-849, 2017 10.
Article in English | MEDLINE | ID: mdl-28342229

ABSTRACT

Real-world studies are relevant to complement clinical trials on novel antiviral therapies against chronic hepatitis C; however, clinical practice data are currently limited. This study investigated effectiveness and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r)±dasabuvir (DSV)±ribavirin (RBV) for treatment of HCV genotype (GT) 1 and GT4 infection in a large real-world cohort. The German Hepatitis C Registry is an observational cohort study prospectively collecting clinical practice data on direct-acting antiviral therapies. Patients with GT1/4 infection treated with OBV/PTV/r±DSV±RBV were analysed. Effectiveness was assessed by sustained virologic response in 558 patients who reached post-treatment week 12 (SVR12). Safety is reported in 1017 patients who initiated treatment. Of the patients, 892 (88%) had GT1 and 125 (12%) had GT4 infection. Prior treatment experience and cirrhosis were reported in 598 (59%) and 228 (22%) patients, respectively. Overall, SVR12 (mITT) was 96% (486/505) in GT1- and 100% (53/53) in GT4 patients. SVR12 rates were high across subgroups including patients with cirrhosis (95%, 123/129), patients with moderate to severe renal impairment (100%, 34/34), and subgroups excluded from registrational trials like patients ≥70 years (96%, 64/67) and failures to prior protease inhibitor treatment (96%, 46/48). Adverse events (AEs) and serious AEs were reported in 52% (525/1017) and 2% (21/1017) of patients, respectively, and led to treatment discontinuation in 1.5% (15/1017) of patients. OBV/PTV/r±DSV±RBV was effective and generally well tolerated for treatment of HCV infection in clinical practice.


Subject(s)
Anilides/administration & dosage , Carbamates/administration & dosage , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/virology , Macrocyclic Compounds/administration & dosage , Ritonavir/administration & dosage , Sulfonamides/administration & dosage , Uracil/analogs & derivatives , 2-Naphthylamine , Adult , Aged , Anilides/adverse effects , Carbamates/adverse effects , Cohort Studies , Cyclopropanes , Drug Therapy, Combination , Female , Genotype , Germany , Hepacivirus/genetics , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/diagnosis , Humans , Lactams, Macrocyclic , Liver Cirrhosis/diagnosis , Liver Cirrhosis/etiology , Macrocyclic Compounds/adverse effects , Male , Middle Aged , Proline/analogs & derivatives , Ritonavir/adverse effects , Severity of Illness Index , Sulfonamides/adverse effects , Treatment Outcome , Uracil/administration & dosage , Uracil/adverse effects , Valine , Viral Load
7.
J Viral Hepat ; 23(12): 994-1002, 2016 12.
Article in English | MEDLINE | ID: mdl-27500382

ABSTRACT

It is still controversial, whether and to what amount cirrhosis and portal hypertension are reversible in patients with hepatitis C virus (HCV)-associated cirrhosis and sustained virologic response (SVR) after interferon-free antiviral therapy. In this study, we prospectively evaluated dynamics of liver and spleen stiffness in HCV-infected patients with advanced liver disease and SVR after interferon-free treatment. A total of 54 patients with HCV-associated cirrhosis and SVR were included. Liver and spleen stiffness was measured at therapy baseline (BL), end of treatment (EOT) and 24 weeks after EOT (FU24) by transient liver elastography (L-TE) as well as by acoustic radiation force impulse of the liver (L-ARFI) and spleen (S-ARFI), as well as biochemical, virologic and clinical data. Improvement of liver and spleen stiffness was found in 44 of 50 (88%), 31 of 54 (57%) and 25 of 54 (46%) of patients assessed by L-TE, L-ARFI and S-ARFI between baseline and FU24. Liver stiffness assessed by L-TE improved between BL [median (range), 32.5 (9.1-75) kPa] and EOT [median (range), 21.3 (6.7-73.5) kPa; (P<.0001)], and between BL and FU24 [median (range), 21.2 (5.4-70) kPa; (P<.0001)]. Liver stiffness assessed by L-ARFI improved between BL [median (range), 2.7 (1.2-4.1) m/s] and FU24 [median (range), 2.4 (1.2-3.9) m/s; P=.002), while spleen stiffness remained unchanged. Our data suggest that improvement of liver stiffness may be rather due to reduced necroinflammation and may be due to a less extent to regression of cirrhosis, as dynamics of liver stiffness improvement was more pronounced between BL and EOT than BL and FU24.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Hypertension, Portal/pathology , Liver Cirrhosis/pathology , Sustained Virologic Response , Adult , Aged , Aged, 80 and over , Female , Humans , Liver/pathology , Male , Middle Aged , Prospective Studies , Spleen/pathology , Treatment Outcome
8.
Aliment Pharmacol Ther ; 44(8): 856-65, 2016 10.
Article in English | MEDLINE | ID: mdl-27549000

ABSTRACT

BACKGROUND: Direct antiviral therapies for chronic hepatitis C virus (HCV) infection have expanded treatment options for neglected patient populations, including elderly patients who are ineligible/intolerant to receive interferon (IFN)-based therapy. AIM: To investigate the efficacy, tolerability and potential for drug-drug interactions (DDIs) of IFN-free treatment in patients aged ≥65 years in a large real-world cohort. METHODS: A total of 541 patients were treated with different combinations of direct antiviral agents (DAAs: ledipasvir/sofosbuvir ±ribavirin; daclatasvir/sofosbuvir ±ribavirin; paritaprevir/ombitasvir ±dasabuvir ±ribavirin or simeprevir/sofosbuvir ±ribavirin in genotype 1/4, and daclatasvir/sofosbuvir ±ribavirin or sofosbuvir/ribavirin in genotype 2/3). Efficacy, safety and potential DDIs were analysed and compared between patients aged <65 years (n = 404) and patients aged ≥65 years (n = 137) of whom 41 patients were ≥75 years. RESULTS: Sustained virological response rates were 98% and 91% in patients aged ≥65 years and <65 years, respectively. Elderly patients took significantly more concomitant medications (79% vs. 51%; P < 0.0001). The number of concomitant drugs per patient was highest in patients ≥65 years with cirrhosis (median, three per patient; range, 0-10). Based on the hep-druginteractions database, the proportion of predicted clinically significant DDIs was significantly higher in elderly patients (54% vs. 28%; P < 0.0001). The number of patients who experienced treatment-associated adverse events was similar between the two age groups (63% vs. 65%; P = n.s.). CONCLUSIONS: Elderly patients are at increased risk for significant DDIs when treated with DAAs for chronic HCV infection. However, with careful pre-treatment assessment of concomitant medications, on-treatment monitoring or dose-modifications, significant DDIs and associated adverse events can be avoided.


Subject(s)
Antiviral Agents/therapeutic use , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Aged , Drug Interactions , Female , Genotype , Humans , Liver Cirrhosis/drug therapy , Male , Treatment Outcome
9.
S Afr Med J ; 104(6): 424-7, 2014 May 12.
Article in English | MEDLINE | ID: mdl-25214252

ABSTRACT

BACKGROUND: Each year, ~89,000 (180/100,000) new cases of head injury are reported in South Africa (SA), with the majority of patients being in the economically active population. Hypotension and hypoxaemia significantly increase the morbidity and mortality in patients who have suffered a traumatic brain injury (TBI). Cerebral tissue is particularly vulnerable to these secondary insults in the period immediately following a TBI, emphasising the importance of prehospital care in TBI. OBJECTIVE: To establish the prevalence of prehospital hypotension and hypoxaemia in moderate to severe blunt TBI in greater Johannesburg, Gauteng, SA. METHODS: The records of adult patients who sustained a moderate to severe TBI between 1 January and 31 December 2011 were retrospectively reviewed for hypotension (systolic blood pressure <90 mmHg) and hypoxaemia (oxygen saturation <90%) during their prehospital phase of care. These results were subject to descriptive analysis. RESULTS: A total of 299 records were identified, 66 of which met the inclusion criteria. The prevalence of prehospital hypotension and hypoxaemia were 33.3% (n=22) and 37.9% (n=25), respectively, while 21.2% (n=14) of patients suffered double insults of hypotension and hypoxaemia. Hypotension and hypoxaemia were associated with haemorrhage (p=0.011) and chest injuries (p=0.001), respectively. CONCLUSION: The prevalence of hypotension in this study was similar to that observed in international studies, but the prevalence of hypoxaemia was much higher. There is a need for local guidelines to be developed to inform the quality of TBI care in the context of the developing world.


Subject(s)
Brain Injuries/complications , Emergency Medical Services , Hypotension/epidemiology , Hypoxia/epidemiology , Urban Population , Adult , Cross-Sectional Studies , Female , Humans , Hypotension/etiology , Hypoxia/etiology , Male , Middle Aged , Retrospective Studies , South Africa/epidemiology
10.
Strahlenther Onkol ; 190(1): 59-63, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24052009

ABSTRACT

BACKGROUND AND PURPOSE: For palliative care of spinal bone metastases, stability assessment is of crucial importance. Pathological fractures, instability-related patient immobility and the extent of bone metastasis have been reported to affect patient outcome and these parameters have therefore been used for treatment stratification. We report on stability-dependent fracture and survival rates in over 300 non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: Data from 303 patients with 868 osteolytic metastases treated with radiotherapy (RT) between 2000 and 2012 were evaluated retrospectively. RESULTS: In NSCLC patients with bone metastases only, the retrospective 6- and 12-month overall survival (OS) rates were 76.7 and 47.2%, respectively. In patients with additional non-bone distant metastases, these values were 60.0 and 34.0%, respectively. Survival rates were significantly lower in patients with multiple bone metastases and in those suffering pathological fractures (p=0.017). No significant impact of histological type, location of spinal lesions or treatment regime was detected. Furthermore, stability assessment revealed no influence of vertebral column stability on patient outcome (p=0.739). CONCLUSION: Our analysis demonstrated a correlation between the pathological fractures of bone lesions, the number of bone metastases, additional distant metastases and survival. The results offer a rationale for future prospective investigations.


Subject(s)
Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/secondary , Lung Neoplasms/mortality , Radiotherapy, Conformal/mortality , Spinal Fractures/mortality , Spinal Neoplasms , Survival Rate , Carcinoma, Non-Small-Cell Lung/therapy , Comorbidity , Female , Germany/epidemiology , Humans , Incidence , Lung Neoplasms/therapy , Male , Middle Aged , Palliative Care/statistics & numerical data , Prognosis , Retrospective Studies , Risk Factors , Spinal Fractures/prevention & control , Spinal Neoplasms/mortality , Spinal Neoplasms/radiotherapy , Spinal Neoplasms/secondary
12.
Strahlenther Onkol ; 189(9): 745-52, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23896631

ABSTRACT

BACKGROUND: Cancer patients commonly suffer from weight loss since rapid tumor growth can cause catabolic metabolism and depletion of energy stores such as abdominal fat. In locally advanced pancreatic cancer this is even more pronounced due to abdominal pain, fatigue, nausea or malnutrition. In the present article, we quantify this frequently observed weight loss and assess its impact on outcome and survival. METHODS: Data on demographics, biometrics, toxicity and survival were collected for the last 100 patients treated with neoadjuvant chemoradiation for locally advanced pancreatic cancer at our department (45.0 Gy and boost up to 54.0 Gy plus concurrent and subsequent gemcitabine), and the subcutaneous fat area at the umbilicus level was measured by computer tomography before and after chemoradiation. RESULTS: After chemoradiation, patients showed a highly statistically significant weight loss and reduction of the subcutaneous fat area. We could determine a very strong correlation of subcutaneous fat area to patient BMI. By categorizing patients according to their BMI based on the WHO classification as slender, normal, overweight and obese, we found improved but not statistically significant survival among obese patients. Accordingly, patients who showed less weight loss tended to survive longer. CONCLUSIONS: In this study, patients with pancreatic cancer lost weight during chemoradiation and their subcutaneous fat diminished. Changes in subcutaneous fat area were highly correlated with patients' BMI. Moreover, obese patients and patients who lost less weight had an improved outcome after treatment. Although the extent of weight loss was not significantly correlated with survival, the observed trend warrants greater attention to nutritional status in the future.


Subject(s)
Chemoradiotherapy, Adjuvant/mortality , Neoadjuvant Therapy/mortality , Nutritional Status , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/therapy , Weight Loss , Adult , Aged , Aged, 80 and over , Comorbidity , Female , Germany/epidemiology , Humans , Male , Middle Aged , Prevalence , Risk Assessment , Statistics as Topic , Survival Analysis , Survival Rate , Treatment Outcome
13.
Br J Cancer ; 107(1): 195-200, 2012 Jun 26.
Article in English | MEDLINE | ID: mdl-22588556

ABSTRACT

BACKGROUND: Liver cancer incidence rates in the United States have increased for several decades for reasons that are not entirely clear. Regardless of aetiology, cirrhosis is a strong risk factor for liver cancer. As mortality from cirrhosis has been declining in recent decades, it is possible that the risk of liver cancer among persons with cirrhosis has been affected. METHODS: Data from the US Veterans Affairs medical records database were analysed after adjustment for attained age, race, number of hospital visits, obesity, diabetes, and chronic obstructive pulmonary disease. Hazard ratio (HR) and 95% confidence interval (95% CI) were calculated using Cox proportional hazards modelling. Survival analyses were conducted using age as the time metric and incidence of cirrhosis as a time-dependent covariate. RESULTS: Among 103 257 men with incident cirrhosis, 788 liver cancers developed. The HR of liver cancer was highest among men with viral-related cirrhosis (HR=37.59, 95% CI: 22.57-62.61), lowest among men with alcohol-related cirrhosis (HR=8.20, 95% CI: 7.55-8.91) and intermediate among men with idiopathic cirrhosis (HR=10.45, 95% CI: 8.52-12.81), when compared with those without cirrhosis. Regardless of cirrhosis type, white men had higher HRs than black men. The HR of developing liver cancer increased from 6.40 (95% CI: 4.40-9.33) in 1969-1973 to 34.71 (95% CI: 23.10-52.16) in 1992-1996 for those with cirrhosis compared with those without. CONCLUSION: In conclusion, the significantly increased HR of developing liver cancer among men with cirrhosis compared with men without cirrhosis in the United States may be contributing to the increasing incidence of liver cancer.


Subject(s)
Liver Cirrhosis/complications , Liver Neoplasms/epidemiology , Veterans , Adolescent , Adult , Aged , Aged, 80 and over , Humans , Liver Cirrhosis/virology , Liver Neoplasms/etiology , Male , Middle Aged , Risk , Time Factors , United States/epidemiology , Young Adult
14.
Strahlenther Onkol ; 188(9): 795-801, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22526232

ABSTRACT

BACKGROUND: The purpose of this work was to determine efficacy, toxicity, and patterns of recurrence after concurrent chemoradiation (CRT) in patients with extrahepatic bile duct cancer (EHBDC) and hilar cholangiocarcinoma (Klatskin tumours) in case of incomplete resection or unresectable disease. PATIENTS AND METHODS: From 2003-2010, 25 patients with nonmetastasized EHBDC and hilar cholangiocarcinoma were treated with radiotherapy and CRT at our institution in an postoperative setting (10 patients, 9 patients with R1 resections) or in case of unresectable disease (15 patients). Median age was 63 years (range 38-80 years) and there were 20 men and 5 women. Median applied dose was 45 Gy in both patient groups. RESULTS: Patients at high risk (9 times R1 resection, 1 pathologically confirmed lymphangiosis) for tumour recurrence after curative surgery had a median time to disease progression of 8.7 months and an estimated mean overall survival of 23.2 months (6 of 10 patients are still under observation). Patients undergoing combined chemoradiation in case of unresectable primary tumours are still having a poor prognosis with a progression-free survival of 7.1 months and a median overall survival of 12.0 months. The main site of progression was systemic (liver, peritoneum) in both patient groups. CONCLUSION: Chemoradiation with gemcitabine is safe and can be applied safely in either patients with EHBDC or Klatskin tumours at high risk for tumour recurrence after resection and patients with unresectable tumours. Escalation of systemic and local treatment should be investigated in future clinical trials.


Subject(s)
Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/therapy , Bile Ducts/surgery , Cholangiocarcinoma/mortality , Cholangiocarcinoma/therapy , Neoplasm Recurrence, Local/prevention & control , Adult , Aged , Aged, 80 and over , Chemoradiotherapy, Adjuvant/mortality , Female , Germany/epidemiology , Hepatectomy/mortality , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Postoperative Care/mortality , Prevalence , Risk Factors , Survival Analysis , Survival Rate , Treatment Outcome
15.
J Viral Hepat ; 17(2): 115-22, 2010 Feb 01.
Article in English | MEDLINE | ID: mdl-19874478

ABSTRACT

The main objectives of this study were to define the occurrence and levels of hepatitis B virus (HBV) DNA in asymptomatic HBV carriers, cirrhosis patients and hepatocellular carcinoma (HCC) cases from The Gambia, and to evaluate the risk for cirrhosis or HCC associated with HBV viremia. We used sensitive real-time quantitative PCR assays to measure HBV DNA in samples from a case-control study consisting of 60 asymptomatic HBV carriers, 53 cirrhotic patients and 129 HCC cases. Logistic regression was used to estimate the risks of cirrhosis and HCC associated with HBV-DNA levels and HBV e antigenemia (HBeAg) detection (a surrogate marker for viral replication). Detectable HBV viremia and HBeAg positivity were both significantly associated with cirrhosis (increasing risk by fourfold and 11-fold respectively) and with HCC (increasing risk by sixfold and threefold respectively). HBV-DNA levels were significantly higher in both HCC cases and cirrhotic patients compared to asymptomatic carriers (P < 0.01 for both). High-level HBV DNA (>10,000 copies/mL) was strongly associated with both HCC and cirrhosis (17- and 39-fold increased risk). Lower level HBV viremia (200-10,000 copies/mL) conferred a significant risk of HCC, although the association with cirrhosis was not significant. In conclusion, we find that high HBV-DNA levels are strongly associated with the serious sequelae of HBV infection, independent of HBeAg status. While risk for cirrhosis and for HCC notably increases at HBV-DNA levels >or=10,000 copies/mL, low-level viremia was also associated with significant risk for HCC.


Subject(s)
Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/virology , Hepatitis B virus/isolation & purification , Hepatitis B, Chronic/complications , Liver Cirrhosis/epidemiology , Liver Cirrhosis/virology , Viral Load , Adult , Carrier State/virology , DNA, Viral/blood , Female , Gambia/epidemiology , Hepatitis B e Antigens/blood , Hepatitis B, Chronic/virology , Humans , Male , Middle Aged , Risk Factors
16.
Pancreatology ; 9(5): 621-30, 2009.
Article in English | MEDLINE | ID: mdl-19657217

ABSTRACT

OBJECTIVE: A prospective study to determine the value of multidetector CT (MD-CT) in assessing the course of nonresectable pancreatic carcinoma during therapy. MATERIAL AND METHODS: 26 patients with nonresectable pancreatic carcinoma underwent MD-CT before and after therapy. The examinations were evaluated with regard to tumor size and vascular invasion using an invasion score (IS) by 2 radiologists independently (kappa analysis). Diagnosis was confirmed surgically, by biopsy or clinical course. RESULTS: Sensitivity for the assessment of irresectability was 100%. Following therapy, 54% of all the tumors were smaller (14/26), 42% had increased in volume (11/26), and one tumor remained stable (1/26). The IS (veins) during follow-up changed in 26 patients (portal vein: 5 higher (mean score 10.4/16.2), 4 lower (mean score 17.5/11.5); superior mesenteric vein: 12 higher (11/14.4), 5 lower (16.2/14.6); p = 0.026). The IS (arteries) changed in 13 patients (celiac trunk: 3 higher (3.3/10); hepatic artery: 4 higher (5.7/10.2), 3 lower (11.6/10.3); superior mesenteric artery: 2 higher (4.5/9.5), 1 lower (12/11)). The kappa values were calculated between 0.56 and 0.87. CONCLUSION: MD-CT is suitable for evaluating tumor spread during therapy for nonresectable pancreatic carcinoma. The IS is useful for assessing the degree of change in vessel invasion.


Subject(s)
Neoadjuvant Therapy , Pancreatic Neoplasms/diagnostic imaging , Adult , Aged , Aged, 80 and over , Celiac Artery/diagnostic imaging , Female , Hepatic Artery/diagnostic imaging , Humans , Liver Neoplasms/secondary , Male , Mesenteric Artery, Superior/diagnostic imaging , Mesenteric Veins/diagnostic imaging , Middle Aged , Neoplasm Invasiveness/diagnostic imaging , Neoplasm Invasiveness/pathology , Neoplasm Staging , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/therapy , Portal Vein/diagnostic imaging , Sensitivity and Specificity , Tomography, X-Ray Computed
17.
J Viral Hepat ; 15(9): 690-8, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18507757

ABSTRACT

Infection with hepatitis C virus (HCV) may suppress co-infection with hepatitis B virus (HBV) during acute or chronic HBV infection. We examined relationships between HBV infection, HCV infection and other factors among injection drug users (IDUs) with antibodies to both viruses. Participants enrolled in a cross-sectional study during 1998-2000 were considered to have been infected with HBV if they had core antibody, to be chronically infected if they had hepatitis B surface antigen (HBsAg), to have been infected with HCV if they had HCV antibody and to be chronically infected if they had HCV RNA. Among 1694 participants with antibody to both viruses, HBsAg prevalence decreased with increasing age among those positive for HCV RNA [from 4.55% in those 18-29 years to 1.03% in those >or=50 years old (P(trend) = 0.02)], but not among those who were negative for HCV RNA. Chronic HBV infection was less common overall among those with chronic HCV infection (odds ratio [OR], 0.25; P < 0.0001), but this inverse relationship was much stronger in the oldest (>50 years; OR = 0.15) than the youngest (18-29 years; OR = 0.81) participants (P(trend) = 0.03). Similar results were obtained when duration of injection drug use was substituted for age (P(trend) = 0.05). Among IDUs who have acquired both HBV and HCV, chronic HBV infection is much less common among those with chronic HCV infection, but this inverse relationship increases markedly with increasing years of age and injection drug use. Co-infection with HCV may enhance the resolution of HBsAg during the chronic phases of these infections.


Subject(s)
Hepatitis B/epidemiology , Hepatitis C, Chronic/epidemiology , Substance Abuse, Intravenous/complications , Adolescent , Adult , Age Factors , Child , Cross-Sectional Studies , Female , Hepatitis B Antibodies/blood , Hepatitis B Surface Antigens/blood , Hepatitis C Antibodies/blood , Humans , Male , Middle Aged , Pharmaceutical Preparations , RNA, Viral/blood
18.
Br J Oral Maxillofac Surg ; 46(8): 639-44, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18490090

ABSTRACT

Digital volume tomography is a recently established imaging method that is based on the principle of cone beam computed tomography (CBCT). One of its main applications is imaging in dental and maxillofacial surgery. The objective of this study was to compare the geometric accuracy of digital volume tomographic imaging with that of conventional CT and to assess the suitability for image-guided operating. A calibration cube with a defined pattern of tubes inside was scanned using CT and digital volume tomography. Spatial accuracy was analysed with a software evaluation tool. The positions of the intersections of the tubes were detected in imaging data and registered to the real positions in the calibration body. The deviation was calculated and compared for CT and digital volume tomography. Resolution of spatial images was similar for both methods. However, the spatial accuracy in digital volume tomography was slightly lower than that of CT but still in the submillimetric range. The accuracy was better in the middle, but lower in the margins of the volume. This is a disadvantage in technical image quality, but does not affect the diagnostic image quality. The geometric accuracy is sufficient for digital volume tomography-based image-guided surgery.


Subject(s)
Cone-Beam Computed Tomography , Surgery, Computer-Assisted/methods , Tomography, X-Ray Computed , Algorithms , Calibration , Cone-Beam Computed Tomography/instrumentation , Humans , Models, Anatomic , Oral Surgical Procedures , Tomography Scanners, X-Ray Computed , Tomography, X-Ray Computed/instrumentation
19.
AJNR Am J Neuroradiol ; 29(2): 379-83, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17974610

ABSTRACT

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) will show abnormal fractional anisotropy (FA) in the normal-appearing brain after prophylactic cranial irradiation (PCI). These abnormalities will be more accentuated in patients with underlying vascular risk factors. MATERIALS AND METHODS: A prospective study by use of DTI and conventional T2-weighted MR images was performed with a 1.5T unit with 16 patients with small cell lung cancer and undergoing PCI. All of the T2-weighted images were evaluated with respect to abnormalities in signal intensity of white matter as markers of radiation damage. Measurements of FA were performed before, at the end of, and 6 weeks after radiation therapy. On the FA maps, the bifrontal white matter, the corona radiata, the cerebellum, and the brain stem were evaluated. FA values were compared with respect to age, demographic, and vascular risk factors. Statistical analyses (Friedman test, Wilcoxon test, and Mann-Whitney U test) were performed. RESULTS: Fractional anisotropy decreased significantly in supratentorial and infratentorial normal-appearing white matter from the beginning to the end of PCI (P < .01). A further decline in FA occurred 6 weeks after irradiation (P < .05). A stronger reduction in FA was observed in patients with more than 1 vascular risk factor. There was an age-related reduction of white matter FA. Patients 65 years and older showed a trend toward a stronger reduction in FA. CONCLUSION: During the acute phase, after PCI, patients with many vascular risk factors showed stronger damage in the white matter compared with patients with only 1 risk factor.


Subject(s)
Carcinoma, Small Cell/prevention & control , Carcinoma, Small Cell/radiotherapy , Diffusion Magnetic Resonance Imaging/methods , Lung Neoplasms/radiotherapy , Nerve Fibers, Myelinated/pathology , Nerve Fibers, Myelinated/radiation effects , Radiation Injuries/etiology , Radiation Injuries/pathology , Aged , Dose Fractionation, Radiation , Female , Humans , Lung Neoplasms/prevention & control , Magnetic Resonance Imaging/methods , Male , Middle Aged , Pilot Projects , Treatment Outcome
20.
Rofo ; 180(1): 42-7, 2008 Jan.
Article in German | MEDLINE | ID: mdl-18008195

ABSTRACT

PURPOSE: To test whether CT with low slice thickness and low tube current provides reliable attenuation measurements. MATERIALS AND METHODS: Using multi-slice CT and a phantom, we measured the attenuation values of thrombi with different proportions of erythrocytes, using a slice thickness of 1.25 mm, 2.5 mm, and 5 mm with tube currents of 200 mA, 300 mA, and 400 mA and a slice thickness of 0.625 mm with tube currents of 150 mA, 175 mA, and 200 mA. Differences in attenuation values and pixel noise between the three thrombi for tube current and slice thickness were statistically analyzed. RESULTS: The attenuation values of all thrombi increased (p<0.05) when the slice thickness decreased using a tube current of 200 mA or when the tube current decreased using a slice thickness of 1.25 mm. With higher tube currents and thicker slices, the CT values depended on the type of thrombus and the slice thickness. In slices with a thickness of 0.625 mm, the CT values decreased with the tube current in the mixed thrombus with a low proportion of erythrocytes and in the red thrombus (p<0.05). The maximal difference in mean attenuation values was 4.3 HU with a slice thickness of 0.625 mm and 2.2 HU with a slice thickness of 1.25 mm. The pixel noise increased as the slice thickness decreased (p<0.05) with the exception of the red thrombus, if reduced to 0.625 mm. The pixel noise also increased as the tube current decreased (p<0.05) except in mixed thrombi measured with 0.625 mm. The maximal difference in mean standard deviation was 1.8 HU with a slice thickness of 1.25 mm. CONCLUSION: The accuracy of attenuation values as determined by CT with low slice thickness and low tube current with a maximal difference of 4.3 HU suffices for the purposes of clinical routine. A reduction of slice thickness from 1.25 mm to 0.625 mm yields the greatest differences in CT values.


Subject(s)
Phantoms, Imaging , Thrombosis/diagnostic imaging , Tomography, Spiral Computed , Artifacts , Erythrocyte Count , Erythrocytes/pathology , Hemoglobinometry , Humans , In Vitro Techniques , Leukocyte Count , Sensitivity and Specificity , Thrombosis/pathology
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