Determining clinically important differences in health-related quality of life in older patients with cancer undergoing chemotherapy or surgery.

PURPOSE: Using the EORTC Global Health Status (GHS) scale, we aimed to determine minimal clinically important differences (MCID) in health-related quality of life (HRQOL) changes for older cancer patients with a geriatric risk profile, as defined by the geriatric 8 (G8) health screening tool, undergoing treatment. Simultaneously, we assessed baseline patient characteristics prognostic for HRQOL changes. METHODS: Our analysis included 1424 (G8 ≤ 14) older patients with cancer scheduled to receive chemotherapy (n = 683) or surgery (n = 741). Anchor-based methods, linking the GHS score to clinical indicators, were used to determine MCID between baseline and follow-up at 3 months. A threshold of 0.2 standard deviation (SD) was used to exclude MCID estimates too small for interpretation. Logistic regressions analysed baseline patient characteristics prognostic for HRQOL changes. RESULTS: The 15-item Geriatric Depression Scale (GDS15), Visual Analogue Scale (VAS) for Fatigue and ECOG Performance Status (PS) were selected as clinical anchors. In the surgery group, MCID estimates for improvement and deterioration were ECOG PS (5*, 11*), GDS15 (5*, 2) and VAS Fatigue (3, 9*). In the chemotherapy group, MCID estimates for improvement and deterioration were ECOG PS (8*, 7*), GDS15 (5, 4) and VAS Fatigue (5, 5*). Estimates with * were > 0.2 SD threshold. Patients experiencing pain or malnutrition (surgery group) or fatigue (chemotherapy group) at baseline showed a significantly stable or improved HRQOL (p < 0.05) after their treatment. CONCLUSION: The reported MCID for improvement and deterioration depended on the anchor used and treatment received. The estimates can be used to evaluate significant changes in HRQOL and to determine sample sizes in clinical trials.

Adherence to geriatric assessment-based recommendations in older patients with cancer: a multicenter prospective cohort study in Belgium.

Background: In the general older population, geriatric assessment (GA)-guided treatment plans can improve overall survival, quality of life and functional status (FS). In GA-related research in geriatric oncology, studies mainly focused on geriatric screening and GA but not on geriatric recommendations, interventions and follow-up. The aim of this study was to investigate the adherence to geriatric recommendations and subsequent actions undertaken in older patients with cancer. Patient and methods: A prospective Belgian multicenter (N = 22) cohort study included patients ≥70 years with a malignant tumor upon oncologic treatment decision. Patients with an abnormal result on the geriatric screening (G8 ≤14/17) underwent GA. Geriatric recommendations were formulated based on GA results. At follow-up the adherence to geriatric recommendations was documented including a description of actions undertaken. Results: From November 2012 till February 2015, G8 screening was carried out in 8451 patients, of which 5838 patients had an abnormal result. Geriatric recommendations data were available for 5631 patients. Geriatric recommendations were made for 4459 patients. Geriatric interventions data were available for 4167 patients. A total of 12 384 geriatric recommendations were made. At least one different geriatric recommendation was implemented in 2874 patients. A dietician, social worker and geriatrician intervened most frequently for problems detected on the nutritional, social and functional domain. A total of 7569 actions were undertaken for a total of 5725 geriatric interventions, most frequently nutritional support and supplements, extended home care and psychological support. Conclusions: This large-scale Belgian study focuses on the adherence to geriatric recommendations and subsequent actions undertaken and contributes to the optimal management of older patients with cancer. We identified the domains for which geriatric recommendations are most frequently made and adhered to, and which referrals to other health care workers and facilities are frequently applied in the multidisciplinary approach of older patients with cancer.

A Belgian Survey on Geriatric Assessment in Oncology Focusing on Large-Scale Implementation and Related Barriers and Facilitators.

OBJECTIVES: The aim of this study is to describe a large-scale, Belgian implementation project about geriatric assessment (=GA) in daily oncology practice and to identify barriers and facilitators for implementing GA in this setting. Design / setting / participants: The principal investigator of every participating hospital (n=22) was invited to complete a newly developed questionnaire with closed- and open-ended questions. The closed-ended questions surveyed how GA was implemented. The open-ended questions identified barriers and facilitators for the implementation of GA in daily oncology practice. Descriptive statistics and conventional content analysis were performed as appropriate. RESULTS: Qualifying criteria (e.g. disease status and cancer type) for GA varied substantially between hospitals. Thirteen hospitals (59.1%) succeeded to screen more than half of eligible patients. Most hospitals reported that GA data and follow-up data had been collected in almost all screened patients. Implementing geriatric recommendations and formulating new geriatric recommendations at the time of follow-up are important opportunities for improvement. The majority of identified barriers were organizational, with high workload, lack of time or financial/staffing problems as most cited. The most cited facilitators were all related to collaboration. CONCLUSION: Interventions to improve the implementation of GA in older patients with cancer need to address a wide range of factors, with organization and collaboration as key elements. All stakeholders, seeking to improve the implementation of GA in older patients with cancer, should consider and address the identified barriers and facilitators.

Hypertrophic lymphocytic gastritis with a gastric carcinoma.

Lymphocytic gastritis is a recently described gastric inflammation, characterized by an increased intraepithelial lymphocytic infiltrate mainly composed of T-lymphocytes. Endoscopically it correlates mainly with diffuse varioliform gastritis. Ménétrier's disease is a hypertrophic gastropathy with enlarged gastric folds. The histological picture is that of foveolar hyperplasia and glandular cysts of the mucosa. A few small series of lymphocytic gastritis with microscopic and endoscopic features of Ménétrier's disease have been published previously. We describe a similar case associated with a gastric adenocarcinoma.

VACTERL with hydrocephalus. A distinct entity with a variable spectrum of multiple congenital anomalies.

In this report we describe the experience and follow-up data in 4 patients presenting the "VACTERL-hydrocephaly association". A review of the literature and the present data show that the inheritance pattern of this association is not clear at the present time and that data on the long-term prognosis are scarse.

[Squamous esophageal papillomas]. / Squameuze slokdarmpapillomen.

In three patients, two women of 37 and 58 and a man of 68 years, a papillomatous lesion was incidentally detected in the distal part of the oesophagus. Microscopically a squamous papilloma was seen with parakeratosis and in two patients poikilocytosis, indicating an infection with human papilloma virus (HPV). The lesions were removed endoscopically, in one patient with laser photocoagulation. Squamous papillomas of the oesophagus are benign tumours with a very low incidence. The pathogenesis still remains unclear. Some authors suggest local irritation as a possible mechanism. On the other hand there is growing evidence of an aetiological role of HPV. In several studies the presence of viral antigen or DNA has been demonstrated. These papillomas may undergo malignant transformation, which means that they are best removed preventively.

Lymphocytic gastritis. Clinical and endoscopic presentation and long-term follow-up.

Lymphocytic gastritis is a histopathological entity corresponding with diffuse varioliform gastritis but also with other gastroscopic findings. Eighteen patients were followed over a mean period of 25 months. The symptoms, the endoscopic and histopathological abnormalities remained unchanged in the majority of the cases. Conventional peptic ulcer therapy failed to control symptoms or to normalize endoscopic alterations. Helicobacter pylori did not seem to play a role in the pathophysiology. Lymphocytic duodenitis was found in four patients. The relationship between lymphocytic gastritis, Ménétrier's disease and coeliac disease has further to be elucidated.

Human CTLA-4 is expressed in situ on T lymphocytes in germinal centers, in cutaneous graft-versus-host disease, and in Hodgkin's disease.

Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4, CD152) is a molecule expressed on in vitro activated T cells. CTLA-4 shares important sequence homology with CD28 and binds to the same ligands, CD80 (B7-1) and CD86 (B7-2). CTLA-4 probably functions as a negative regulator of T lymphocyte activation in the mouse, although this remains to be proven for human T lymphocytes. We have developed new monoclonal antibodies against human CTLA-4 and have investigated the in situ expression of CTLA-4 in a wide variety of normal and pathological human tissues expressing CD80 and CD86. As revealed in this study, CTLA-4 is expressed on thymocytes in thymic medulla, on a subset of CD4+ T lymphocytes in germinal centers of follicular hyperplasia, on T cells, mainly CD8+, infiltrating skin affected by graft-versus-host disease, and on T cells, mainly CD4+, infiltrating Hodgkin's disease lesions. In immunoelectron microscopy, CTLA-4 was found on the plasma membrane as well as in the hyaloplasm and cytoplasmic vesicles, in agreement with its pattern of expression on in vitro activated T cells. Interestingly, no or at most scarce expression of CTLA-4 was found in granulomatous lymph nodes, T-cell-mediated inflammatory diseases, or non-Hodgkin's lymphomas, regardless of their expression of CD80 or CD86. Thus, expression of CTLA-4 appears to be induced in selective pathological conditions in vivo. The pathways leading to selective induction of CTLA-4 and its role in the pathophysiology of these conditions need to be further investigated.

Interaction of CTLA-4 (CD152) with CD80 or CD86 inhibits human T-cell activation.

Occupancy of CTLA-4 (cytotoxic T-lymphocyte antigen-4 or CD152) negatively regulates the activation of mouse T lymphocytes, as indicated by the fate of CTLA-4-deficient mice, by the impact of anti-CTLA-4 monoclonal antibodies (mAbs) on mouse T-cell activation in vitro and by the impact of CTLA-4 blockade on the course of experimental tumoral, autoimmune, alloimmune or infectious disease in this animal. The function of human CTLA-4, however, remains less clear. The expression and function of human CTLA-4 were further explored. CTLA-4 was expressed under mitogenic conditions only, its expression being, at least partially, dependent on the secretion of interleukin-2. Memory T cells expressed CTLA-4 with faster kinetics than naive T cells. The functional role of human CTLA-4 was assessed utilizing a panel of four anti-CTLA-4 mAbs that blocked the interaction between CTLA-4 and its ligands. These mAbs, in immobilized form, profoundly inhibited the activation of T cells by immobilized anti-CD3 mAb in the absence of anti-CD28 mAb, but co-stimulated T-cell activation in the presence of anti-CD28 mAb. Finally, and importantly, blockade of the interaction of CTLA-4 with its ligands using soluble anti-CTLA-4 mAbs, in intact form or as Fab fragments, enhanced T-cell activation in several polyclonal or alloantigen-specific CD80- or CD80/CD86-dependent assays, as measured by cytokine production, cellular proliferation or cytotoxic responses. It is concluded that interaction of CTLA-4 with its functional ligands, CD80 or CD86, can down-regulate human T-cell responses, probably by intracellular signalling events and independent of CD28 occupancy.