Reactivation of an occult hepatitis B virus escape mutant in an anti-HBs positive, anti-HBc negative lymphoma patient.

BACKGROUND: Hepatitis B virus (HBV) often persists after resolution, but its replication is suppressed by antiviral T cells. Immunosuppressive treatment may lead to viral reactivation and severe hepatitis. Early antiviral therapy prevents reactivation but some occult HBV infections are not easily detectable. RESULTS: Here we describe a patient with a progressive non-Hodgkin lymphoma who had probably not been vaccinated against HBV and, before immunosuppression, showed antibodies (anti-HBs) against the viral surface antigen (HBsAg) as the only possible marker of occult HBV infection. Under immunosuppression he developed viremia (>10(8)copies/mL). The virus exhibited three S gene mutations (L109R, C137W, G145R) which led to false negative HBsAg results and diminished binding of vaccine-induced anti-HBs. CONCLUSIONS: Reliable screening and monitoring of severely immunosuppressed patients for HBV should include, in addition to anti-HBc and HBsAg, anti-HBs and sensitive HBV DNA assays. Furthermore, active vaccination or hepatitis B immune globulin may not protect against such mutants.     

To Explore the Validity of Change Scores of the Children's Hand-use Experience Questionnaire (CHEQ) in Children with Unilateral Cerebral Palsy

Aims: To explore the validity of change scores of the Children's Hand-use Experience Questionnaire (CHEQ). Methods: Analysis of the CHEQ included 44 children (15 girls) between 6–16 years (median 9.0; IQR 8–11) with unilateral cerebral palsy, with baseline and post- (two-week intensive) intervention assessments using the Goal Attainment Scale (GAS) as external anchor for change. Hypotheses on the magnitude of expected change were formulated and correlation coefficients and effect sizes calculated. Receiver operating curve analysis was performed and the area under the curve (AUC) calculated to investigate the ability of CHEQ to discriminate between improvement and non-improvement according to GAS. Results: All hypotheses about the magnitude of change were confirmed supporting longitudinal validity of CHEQ scales to measure change in the perception of bimanual performance. AUCs for the Grasp efficacy and the Time utilization were slightly below, and for the Feeling bothered slightly above the threshold. The latter one accurately discriminating between children that improved and did not improve according to the GAS. Conclusions: Evidence was found that CHEQ scales capture change in bimanual performance but with limited accuracy for two out of three scales. The validity of CHEQ change scores needs to be further explored in a wider population.     

Quantity-guided drain management reduces seroma formation and wound infections after radical lymph node dissection: results of a comparative observational study of 374 melanoma patients

Background: Lymphatic fistulas are common complications after lymph node dissections in melanoma patients. We investigated whether drain management could improve the patient’s outcome.

Methods: Patients who underwent axillary or inguinal lymph node dissection (RALND or RILND) for malignant melanoma were recorded in a prospective database. Two different methods of drain management were compared. Either the drain was removed no later than the eighth postoperative day (period I, 2003–2007) or it was left in place until fluid flow was below 50?ml in 24?h for two consecutive days (period II, 2008–2011). The main outcome criterion was the incidence of seroma punctures after drain removal.

Results: 374 patients were analysed. The incidence of seroma punctures significantly decreased in period II. The number of patients with elevated lymphatic secretions rose by 41.3% (RALND) and 38.1% (RILND). With the exception of lymphatic fistulas, we observed significantly more local complications with need for treatment in period I (n?=?104, 52%) than in period II (n?=?31, 18%). In period II, the hospital stays after both procedures were significantly reduced.

Conclusions: We conclude that quantity-guided drain management leads to a prolonged interval of drainage but is associated with a lower incidence of seroma formation and shorter hospital stay.     

Fear of cancer recurrence in survivor and caregiver dyads: differences by sexual orientation and how dyad members influence each other

Purpose

The purpose of this study was to identify explanatory factors of fear of recurrence (FOR) in breast cancer survivors of different sexual orientations and their caregivers and to assess the directionality in the survivor and caregiver dyads’ FOR.

Methods

We recruited survivors of non-metastatic breast cancer of different sexual orientations and invited their caregivers into this study. Using a telephone survey, we collected data from 167 survivor and caregiver dyads. Using simultaneous equation models and a stepwise selection process, we identified the significant determinants of survivors’ and caregivers’ FOR and determined the directionality of survivors’ and caregivers’ FOR. Weighting the model by the inverse propensity score ensured that differences by sexual orientation in age and proportion of life in the caregiver-survivor relationship were accounted for.

Results

Caregivers’ FOR predicted survivors’ FOR, and sexual orientation had a significant effect on survivors’ FOR, in that sexual minority women reported less FOR than heterosexual women. Other determinants of survivors’ FOR included their medical characteristics, coresidence with caregivers, and caregivers’ social support and use of counseling. Caregivers’ FOR was related to their social support and survivors’ medical characteristics.

Conclusions

This study suggests a need for caregiver interventions. Because survivors’ FOR is affected by caregivers’ FOR, caregiver interventions will likely benefit survivors’ FOR.

Implications for cancer survivors

Both sexual minority and heterosexual breast cancer survivors’ FOR are affected by their caregivers’ FOR, which suggests that the caregivers of breast cancer survivors are central for the survivors’ well-being and shall therefore be integrated into the care process.

     

Validity of self‐reported family history of cancer: A systematic literature review on selected cancers

Evidence regarding validity of self‐reported family history of cancer (FHC) has been reviewed only for breast, colorectal, prostate, ovarian, endometrial and uterine cancer. We aimed to systematically review studies assessing validity of self‐reported family history for the remaining cancer sites. We searched the Medline database for relevant studies published by January 2016. We extracted information on the study design and the positive predictive value (PPV) of self‐reported FHC, defined as the proportion of reported cancer diagnoses among relatives that was confirmed by a reference standard (as a measure of over‐reporting). We also extracted information on sensitivity of self‐reported FHC (as a measure of underreporting). Overall, 21 studies were included that provided information on the PPV of self‐reported FHC for relevant cancers and four studies also provided information on sensitivity. The PPV was highest (mostly >70%) for pancreatic, lung, thyroid and urinary system cancers and for leukemia and lymphoma, while it was lowest for stomach and liver cancer. Sensitivity was highest (>70%) for pancreatic cancer, lung cancer, brain cancer, melanoma, leukemia and lymphoma. For several cancers, sample sizes were low and the number of studies limited, particularly regarding sensitivity of self‐reported FHC. In conclusion, for some cancers (e.g., pancreatic cancer, lung cancer, leukemia, lymphoma) self‐reported FHC can be considered sufficiently valid to be useful, for example, in preventive counseling. For several cancers, it is not sufficiently studied or the pattern is inconsistent. This needs to be taken into account when using self‐reported information about FHC in clinical practice or epidemiological research.     

mTORC1 promotes survival through translational control of Mcl-1

Activation of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is a frequent occurrence in human cancers and a major promoter of chemotherapeutic resistance. Inhibition of one downstream target in this pathway, mTORC1, has shown potential to improve chemosensitivity. However, the mechanisms and genetic modifications that confer sensitivity to mTORC1 inhibitors remain unclear. Here, we demonstrate that loss of TSC2 in the E mu-myc murine lymphoma model leads to mTORC1 activation and accelerated oncogenesis caused by a defective apoptotic program despite compromised AKT phosphorylation. Tumors from Tsc2(+/-)E mu-Myc mice underwent rapid apoptosis upon blockade of mTORC1 by rapamycin. We identified myeloid cell leukemia sequence 1 (Mcl-1), a bcl-2 like family member, as a translationally regulated genetic determinant of mTORC1-dependent survival. Our results indicate that the extent by which rapamycin can modulate expression of Mcl-1 is an important feature of the rapamycin response.