Quality of life of caregivers of breast cancer patients: a cross-sectional evaluation.

BACKGROUND: The aim of this study was to evaluate the care-related quality of life in caregivers of breast cancer patients, to assess its association with breast cancer patients' health-related quality of life (HRQoL), and to identify its potential predictors. METHODS: Caregivers of breast cancer patients at six and twelve months follow up were identified through the institutes electronic patient reported outcome measurement collection tool. The Care-related Quality of Life Instrument (CarerQoL) was used to obtain CarerQoL utility scores by applying a pre-existent set of Dutch tariffs and the CarerQoL VAS score, which represented the overall happiness of caregivers. The associations between breast cancer patients' EQ-5D-5L and EORTC QLQ-C30 scores and caregivers' CarerQoL scores was determined with Spearman's correlation coefficients. Associations between log transformed CarerQol scores and patient and caregiver characteristics were analyzed with multivariable linear regression analyses. RESULTS: A total of 116 completed CarerQoL questionnaires were analyzed. Most caregivers were male spouses or partners (81.4%) with a mean age of 55.7 ± 16.4. The median CarerQoL utility score was 92.4/100 and median CarerQoL VAS was 8.0/10. We found weak correlations between CarerQoL VAS scores and patients' EQ-5D-5L utility score (0.301, p = 0.002) and EQ VAS score (0.251, p = 0.009), and between EORTC QLQ-C30 scores and CarerQol VAS (0.339, p < 0.001) and utility score (0.236, p = 0.015). There was a negative association between chemotherapy and log-transformed CarerQoL utility score (B = - 0.063, p = 0.001) and VAS score (B = - 0.044, p = 0.038) at six months follow-up. CONCLUSIONS: This study provides the first evaluation of the CarerQoL in caregivers of Dutch breast cancer patients. Caregivers' happiness was associated with breast cancer patients' HRQoL. Our results can be used as reference values for future care-related quality of life evaluations. Breast cancer patients face many difficulties during their cancer journey and often need the support of their caregivers. Despite the fact that successfully providing informal care can have positive effects on caregivers' wellbeing, it may also have a negative impact on their quality of life. Monitoring the quality of life using a standardized questionnaire, such as the CarerQoL questionnaire, may result in early detection of possible quality of life issues. In this study, we evaluated 116 caregivers and found overall high CarerQoL scores. The scores showed a positive relation to the patients' quality of life. Lower CarerQoL scores at six months after surgery were found in caregivers of patients who received chemotherapy. Our research underlines the importance to include caregivers of breast cancer patients in clinical practice, provides reference values for future research, and the results can be used to manage the caregivers' expectations prior to treatment.

Importance of patient reported and clinical outcomes for patients with locally advanced rectal cancer and their treating physicians. Do clinicians know what patients want?

INTRODUCTION: Several factors are included in decision making for treatment of patients with locally advanced rectal cancer, including a trade-off between risks and gains of both clinical and functional outcomes. However, it is largely unknown which outcomes are most important to patients and whether this differs between patients and clinicians. METHODS: Both clinicians and patients treated for locally advanced rectal cancer were invited to fill out an online questionnaire, including a choice-based conjoint experiment. Participants were presented 14 comparisons of two hypothetical case presentations, characterized by different treatments and outcomes of care (6 attributes) and were asked to select the case with the best outcome at that moment. Hierarchical Bayes Estimation was used to calculate the relative importance (RI) of each of the six attributes. RESULTS: In total, 94 patients and 128 clinicians completed the questionnaire. For patients, avoiding surgery with permanent stoma was most important (RI 24.4, 95%CI 21.88-26.87) and a 2-year difference in disease-free survival was least important (RI 5.6, 95%CI 4.9-6.2). Clinicians assigned highest importance to avoiding severe and daily worries about cancer recurrence (RI 30.7, 95%CI 29.1-32.4), while this was ranked 4th by patients (RI 17.9, 95%CI 16.5-19.4, p < 0.001). CONCLUSION: When confronted with different outcomes within one case description, patients find the duration of disease free survival the least important. In addition, considerable differences were found between the importance assigned by patients and clinicians to clinical and functional outcomes, most notably in avoiding surgery with permanent stoma and worries about recurrence.

Performance of Contrast-Enhanced Sonography Versus MRI With a Liver-Specific Contrast Agent for Diagnosis of Hepatocellular Adenoma and Focal Nodular Hyperplasia.

OBJECTIVE. The purpose of this article is to compare contrast-enhanced sonography (CEUS) with sulfur hexafluoride with MRI with the liver-specific contrast agent gadobenate dimeglumine in the diagnosis of hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH) in a cohort of consecutive patients. MATERIALS AND METHODS. Patients referred to a tertiary center for hepatobiliary disease who had suspected HCA or FNH on MRI performed with an extracellular gadolinium-based contrast agent underwent a prospective workup including CEUS and MRI with a liver-specific contrast agent. Diagnosis was definite when the findings of CEUS and MRI with a liver-specific contrast agent were concordant; histopathologic examination (HPE) was performed for cases with discordant findings. Descriptive statistics and the association between categoric variables were presented as numbers and percentages and were assessed using the Fisher exact test. The primary analysis was patient based. Sensitivity, specificity, and AUC and predictive values for the diagnosis of HCA and FNH were calculated separately for CEUS and MRI with a liver-specific contrast agent. RESULTS. A total of 181 patients were selected for the first analysis. Findings from CEUS and MRI with a liver-specific contrast agent were concordant for 132 patients (73%) and discordant for 49 (27%). HPE was performed for 26 of the 49 patients with discordant findings (53%), with findings indeterminate for two of these patients, the findings of MRI with a liver-specific contrast agent correct for 21 of the remaining 24 patients (87.5%), and the findings of CEUS correct for three of these 24 patients (12.5%) (p < 0.05). For further analysis, 156 patients with concordant findings or HPE-proven cases were included. For CEUS, the sensitivity and specificity for the diagnosis of HCA and FNH were 85% and 87%, respectively; the ROC AUC value was 0.856; and the positive predictive value and negative predictive value were 79% and 90%, respectively. For MRI with a liver-specific contrast agent, the sensitivity and specificity were 95% each, the ROC AUC value was 0.949, and the positive predictive value and negative predictive value were 92% and 97%, respectively, for the diagnosis of HCA and FNH. CONCLUSION. The findings of CEUS and MRI with a liver-specific contrast agent showed fair agreement for the diagnosis of HCA and FNH. MRI with a liver-specific contrast agent is diagnostically correct significantly more often than CEUS in cases with discordant findings that are HPE proven.

Growth of Focal Nodular Hyperplasia is Not a Reason for Surgical Intervention, but Patients Should be Referred to a Tertiary Referral Centre.

BACKGROUND: When a liver lesion diagnosed as focal nodular hyperplasia (FNH) increases in size, it may cause doubt about the initial diagnosis. In many cases, additional investigations will follow to exclude hepatocellular adenoma or malignancy. This retrospective cohort study addresses the implications of growth of FNH for clinical management. METHODS: We included patients diagnosed with FNH based on ≥2 imaging modalities between 2002 and 2015. Characteristics of patients with growing FNH with sequential imaging in a 6-month interval were compared to non-growing FNH. RESULTS: Growth was reported in 19/162 (12%) patients, ranging from 21 to 200%. Resection was performed in 4/19 growing FNHs; histological examination confirmed FNH in all patients. In all 15 conservatively treated patients, additional imaging confirmed FNH diagnosis. No adverse outcomes were reported. No differences were found in characteristics and presentation of patients with growing or non-growing FNH. CONCLUSION: This study confirms that FNH may grow significantly without causing symptoms. A significant increase in size should not have any implications on clinical management if confident diagnosis by imaging has been established by a tertiary benign liver multidisciplinary team. Liver biopsy is only indicated in case of doubt after state-of-the-art imaging. Resection is deemed unnecessary if the diagnosis is confirmed by multiple imaging modalities in a tertiary referral centre.

A Model-Based Prediction of the Probability of Hepatocellular Adenoma and Focal Nodular Hyperplasia Based on Characteristics on Contrast-Enhanced Ultrasound.

Contrast-enhanced ultrasound (CEUS) is an emerging imaging technique that is increasingly used to diagnose liver lesions. It is of the utmost importance to differentiate between the two most common solid focal liver lesions (i.e., hepatocellular adenoma [HCA] and focal nodular hyperplasia [FNH]), because their management and follow-up differ greatly. The main objective of this study was to determine how frequently the specific CEUS features of HCA and FNH are visible on CEUS and to define their predictive value for discrimination between HCA and FNH. We included 324 CEUS examinations performed on patients with FNH (n = 181) or HCA (n = 143). Patients with HCA and FNH significantly differed with respect to age and CEUS features of steatosis, echogenicity, homogeneity, the presence of a central scar, central artery, arterial enhancement pattern, necrosis or thrombus and enhancement in the late venous phase.

Inflammatory and multiple hepatocellular adenoma are associated with a higher BMI.

AIM: To identify patient and lesion characteristics associated with the occurrence of single or multiple hepatocellular adenoma (HCA). PATIENTS AND METHODS: Using a tertiary centre database, we retrospectively collected information on patient and lesion characteristics, management and follow-up of all patients with HCA included between 2001 and 2016. Patients were classified into three groups; patients with a single HCA, 2-9 HCA and at least 10 HCA. RESULTS: A total of 458 patients were diagnosed with HCA, including 121 (26.4%) with single HCA, 235 (51.3%) with 2-9 HCA and 102 (22.3%) with at least 10 HCA. Significant differences in the mean BMI were found, with the highest BMI in patients with more than 10 HCA (P<0.05). The mean BMI was significantly higher in patients with inflammatory HCA compared with steatotic HCA (31 vs. 26, respectively, P<0.05). Steatotic HCA were more often single lesions (22/55, 40%), whereas patients with inflammatory HCA were often diagnosed with multiple lesions (122/166, 73%). CONCLUSION: Our series show a significantly higher BMI and frequency of inflammatory HCA in patients with multiple HCA compared with single HCA.

The predictive value of Golgi protein 73 in differentiating benign from malignant liver tumors.

INTRODUCTION: In the work up of primary solid liver lesions it is essential to differentiate correctly between benign and malignant tumors, such as hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC) respectively. A promising new marker to detect HCC is Golgi Protein 73 (GP73). Studies comparing patients with HCC and cirrhosis with normal controls suggested that GP73 is specific for patients with HCC; however, patients with other liver tumors were not included. We therefore studied the predictive value of GP73 in differentiating between solid benign and malignant liver tumors. MATERIALS AND METHODS: This study included 264 patients: 88 patients with HCC, 88 with hepatocellular adenoma (HCA), and 88 with focal nodal hyperplasia (FNH). A blood sample was collected from each patient to measure GP73 levels using a quantitative ELISA assay and differences in outcome between subgroups were compared. The receiver operating characteristic (ROC) curve, sensitivity and specificity of GP73 were calculated and compared to alpha-fetoprotein (AFP) levels. RESULTS: When comparing malignant and benign liver tumors the area under ROC was 0.701 and 0.912 for GP73 and AFP respectively. Test characteristics revealed a sensitivity of 60% for GP73 and 65% for AFP; in addition the specificity was 77% for GP73 and 96% for AFP. CONCLUSION: Although the literature suggests that GP73 is a valuable serum marker in patients with HCC, the serum concentration may also be increased in patients with solid benign liver tumors. Therefore, a GP73 assay is less suitable for discriminating between primary malignant and benign tumors of the liver.

Collagen peptides in urine: a new promising biomarker for the detection of colorectal liver metastases.

INTRODUCTION: For both patients and the outpatient clinic the frequent follow-up visits after a resection of colorectal cancer (CRC) are time consuming and due to large patient numbers expensive. Therefore it is important to develop an effective non-invasive test for the detection of colorectal liver metastasis (CRLM) which could be used outside the hospital. The urine proteome is known to provide detailed information for monitoring changes in the physiology of humans. Urine collection is non-invasive and urine naturally occurring peptides (NOPs) have the advantage of being easily accessible without labour-intensive sample preparation. These advantages make it potentially useful for a quick and reliable application in clinical settings. In this study, we will focus on the identification and validation of urine NOPs to discriminate patients with CRLM from healthy controls. MATERIALS AND METHODS: Urine samples were collected from 24 patients with CRLM and 25 healthy controls. In the first part of the study, samples were measured with a nano liquid chromatography (LC) system (Thermo Fisher Scientific, Germaring, Germany) coupled on-line to a hybrid linear ion trap/Orbitrap mass spectrometer (LTQ-Orbitrap-XL, Thermo Fisher Scientific, Bremen, Germany). A discovery set was used to construct the model and consecutively the validation set, being independent from the discovery set, to check the acquired model. From the peptides which were selected, multiple reaction monitoring (MRM's) were developed on a UPLC-MS/MS system. RESULTS: Seven peptides were selected and applied in a discriminant analysis a sensitivity of 84.6% and a specificity of 92.3% were established (Canonical correlation:0.797, Eigenvalue:1.744, F:4.49, p:0.005). The peptides AGPP(-OH)GEAGKP(-OH)GEQGVP(-OH)GDLGA P(-OH)GP and KGNSGEP(-OH)GAPGSKGDTGAKGEP(-OH)GPVG were selected for further quantitative analysis which showed a sensitivity of 88% and a specificity of 88%. CONCLUSION: Urine proteomic analysis revealed two very promising peptides, both part from collagen type 1, AGPP(-OH)GEAGKP(-OH)GEQGVP(-OH)GDLGAP(-OH)GP and KGNSGEP(-OH)GAPGSKGDTGAKGEP(-OH)GPVG which could detect CRLM in a non-invasive manner.

Tumor promotion through the mesenchymal stem cell compartment in human hepatocellular carcinoma.

Although the infiltration of mesenchymal stem (stromal) cells (MSCs) into different tumors is widely recognized in animal models, the question whether these MSCs have a positive or negative effect on disease progression remains unanswered. The aim of this study is to investigate whether human hepatocellular carcinoma (HCC) harbors MSCs and whether these MSCs affect tumor growth. We observed that cells capable of differentiation into both adipocyte and osteocyte lineages and expressing MSC markers can be cultured from surgically resected HCC tissues. In situ staining of human HCC tissues with a STRO-1 antibody showed that the tumor and tumor-stromal region are significantly enriched with candidate MSCs compared with adjacent tissue (n = 12, P < 0.01). In mice, coengraftment of a human HCC cell line (Huh7) with MSCs resulted in substantially larger tumors compared with paired engraftment of Huh7 alone (n = 8, P < 0.01). Consistently, coculturing Huh7 with irradiated MSCs significantly increased the number and the size of colonies formed. This enhancement of Huh7 colony formation was also observed by treatment of MSC-conditioned medium (MSC-CM), suggesting that secreted trophic factors contribute to the growth-promoting effects. Genome-wide gene expression array and pathway analysis confirmed the upregulation of cell growth and proliferation-related processes and downregulation of cell death-related pathways by treatment of MSC-CM in Huh7 cells. In conclusion, these results show that MSCs are enriched in human HCC tumor compartment and could exert trophic effects on tumor cells. Thus, targeting of HCC tumor MSCs may represent a new avenue for therapeutic intervention.

[Hepatocellular adenomas and pregnancy]. / Leveradenomen en zwangerschap.

Hepatocellular adenomas are benign liver tumours which are mostly seen in young women. When women with such tumours attempt to become pregnant, they require special attention because of the risks of hormone-induced growth and spontaneous rupture of the tumour, which are caused by increased levels of steroid hormones during pregnancy. We present three patients with hepatocellular adenomas who were either pregnant or wished to become pregnant. These cases describe the complexity of the situation. The size of the hepatocellular adenoma increased during pregnancy in patient A and contrarily remained stable in patient B. Patient C was advised to not get pregnant before an intervention because of the tumour's central location within the liver. We also describe the general clinical presentation and treatment of patients with a hepatocellular adenoma.

Pregnancy and liver adenoma management: PALM-study.

BACKGROUND: Hepatocellular adenoma (HCA) in pregnant women requires special considerations because of the risk of hormone induced growth and spontaneous rupture, which may threaten the life of both mother and child. Due to scarcity of cases there is no evidence-based algorithm for the evaluation and management of HCA during pregnancy. Most experts advocate that women with HCA should not get pregnant or advise surgical resection before pregnancy. Whether it is justified to deny a young woman a pregnancy, as the biological behavior may be less threatening than presumed depends on the incidence of HCA growth and the subsequent clinical events during pregnancy.We aim to investigate the management and outcome of HCA during pregnancy and labor based on a prospectively acquired online database in the Netherlands. METHODS/DESIGN: The Pregnancy And Liver adenoma Management (PALM) - study is a multicentre prospective study in three cohorts of pregnant patients. In total 50 pregnant patients, ≥ 18 years of age with a radiologically and/or histologically proven diagnosis of HCA will be included in the study. Radiological diagnosis of HCA will be based on contrast enhanced MRI. Lesions at inclusion must not exceed 5 cm. The study group will be compared to a healthy control group of 63 pregnant patients and a group of 63 pregnant patients with diabetes mellitus without HCA. During their pregnancy HCA patients will be closely monitored by means of repetitive ultrasound (US) at 14, 20, 26, 32 and 38 weeks of gestation and 6 and 12 weeks postpartum. Both control groups will undergo US of the liver at 14 weeks of gestation to exclude HCA lesions in the liver. All groups will be asked to fill out quality of life related questionnaires. DISCUSSION: The study will obtain information about the behaviour of HCA during pregnancy, the clinical consequences for mother and child and the impact of having a HCA during pregnancy on the health related quality of life of these young women. As a result of this study we will propose a decision-making model for the management of HCA during pregnancy. TRIAL REGISTRATION: Dutch trial register: NTR3034.

Discriminating between simple and perforated appendicitis.

BACKGROUND: Several studies have been performed in order to diagnose an acute appendicitis using history taking and laboratory investigations. The aim of this study was to create a model for the identification of a perforated appendicitis. METHODS: All consecutive patients who have undergone an appendectomy in the Reinier de Graaf hospital between January 1, 2007 and July 31, 2009, were included in a retrospective cohort study. Baseline patient characteristics, history and laboratory data were collected. Variables discriminating perforated from non-perforated appendicitis were identified using univariate and multivariable analyses. RESULTS: A total of 498 patients were included in the study. In the univariate analysis leukocyte count, C-Reactive Protein levels, Erythrocyte Sedimentation Rate levels, days of symptoms and temperature were identified as predictors of perforated appendicitis. The predicted probability (P) of a perforated appendicitis can be calculated from the following model: (P)=1/(1+e(-(-2.788+0.012 * CRP+0.207 * days with complaints))). CONCLUSIONS: Perforation of appendicitis can be predicted from the CRP level and the duration of abdominal pain. These findings might influence the choice between conservative or surgical treatment of appendicitis, and could provide guidance in the early start of antibiotics.

The management of pregnancy in women with hepatocellular adenoma: a plea for an individualized approach.

Because of the risk of hormone-induced growth and spontaneous rupture of hepatocellular adenoma (HCA) during pregnancy, special considerations are required. Due to the scarcity of cases, there is no evidence-based algorithm for the evaluation and management of HCA during pregnancy. We think it should be questioned if it is justified to discourage pregnancy in all women with HCA. The biological behavior of this benign lesion might be less threatening than presumed and a negative advice concerning pregnancy has great impact on the lives of these young female patients. The balance between the pros and cons of hepatic adenomas and pregnancy should be reconsidered. In our center, pregnancy in women with an HCA up to 5 cm is no longer discouraged in close consultation with the patient, her partner, and members of the liver expert team.

[Breast cancer in an accessory breast]. / Mammacarcinoom in een accessoire borst.

BACKGROUND: There are two types of ectopic breast tissue: accessory breast (polymastia) and aberrant breast tissue. Breast cancer may arise in any type of ectopic breast tissue, although rarely. CASE DESCRIPTION: A 50-year old woman had a palpable mass near an accessory nipple. Physical and X-ray examination suggested a benign tumour, but after excision and pathological examination it turned out to be breast cancer. After follow-up examination a re-excision with a sentinel node procedure was performed. There was no indication for adjuvant therapy. CONCLUSION: Due to the atypical location, the diagnosis 'breast cancer in an accessory breast' is usually made in a late stage. Due to the small amount of breast tissue, invasion of skin or underlying tissue is more common. Drainage of lymph fluids may be different as well, which has to be taken into account when performing a sentinel node procedure. Also, lymph node metastases may present in the ipsilateral mamma. These particulars should be taken into account in the treatment of cancer in ectopic breast tissue.