A neurologist's perspective on serum neurofilament light in the memory clinic: a prospective implementation study.

BACKGROUND: Neurofilament light in serum (sNfL) is a biomarker for axonal damage with elevated levels in many neurological disorders, including neurodegenerative dementias. Since within-group variation of sNfL is large and concentrations increase with aging, sNfL's clinical use in memory clinic practice remains to be established. The objective of the current study was to evaluate the clinical use of serum neurofilament light (sNfL), a cross-disease biomarker for axonal damage, in a tertiary memory clinic cohort. METHODS: Six neurologists completed questionnaires regarding the usefulness of sNfL (n = 5-42 questionnaires/neurologist). Patients that visited the Alzheimer Center Amsterdam for the first time between May and October 2019 (n = 109) were prospectively included in this single-center implementation study. SNfL levels were analyzed on Simoa and reported together with normal values in relation to age, as part of routine diagnostic work-up and in addition to cerebrospinal fluid (CSF) biomarker analysis. RESULTS: SNfL was perceived as useful in 53% (n = 58) of the cases. SNfL was more often perceived as useful in patients < 62 years (29/48, 60%, p = 0.05) and males (41/65, 63%, p < 0.01). Availability of CSF biomarker results at time of result discussion had no influence. We observed non-significant trends for increased perceived usefulness of sNfL for patients with the diagnosis subjective cognitive decline (64%), psychiatric disorder (71%), or uncertain diagnosis (67%). SNfL was mostly helpful to neurologists in confirming or excluding neurodegeneration. Whether sNfL was regarded as useful strongly depended on which neurologist filled out the questionnaire (ranging from 0 to 73% of useful cases/neurologist). DISCUSSION: Regardless of the availability of CSF biomarker results, sNfL was perceived as a useful tool in more than half of the evaluated cases in a tertiary memory clinic practice. Based on our results, we recommend the analysis of the biomarker sNfL to confirm or exclude neurodegeneration in patients below 62 years old and in males.

The use of cerebrospinal fluid in biomarker studies.

Cerebrospinal fluid (CSF) is an extremely useful matrix for biomarker research for several purposes, such as diagnosis, prognosis, monitoring, and identification of prominent leads in pathways of neurologic diseases. Such biomarkers can be identified based on a priori hypotheses around prominent protein changes, but also by applying -omics technologies. Proteomics is widely used, but metabolomics and transcriptomics are rapidly revealing their potential for CSF studies. The basis of such studies is the availability of high-quality biobanks. Furthermore, profound knowledge and consequent optimization of all aspects in biomarker development are needed. Here we discuss current knowledge and recently developed protocols for successful biomarker studies, from collection of CSF by lumbar puncture, processing, and biobanking protocols, preanalytic confounding factors, and cost-efficient development and validation of assays for implementation into clinical practice or research.

Recurrent invasive thymoma with pleural dissemination : disease management and treatment possibilities.

Thymoma is the most common benign neoplasm of the anterior mediastinum presenting often an agressive behaviour typical for the malignants tumors. The rate of invasive thymoma recurrency is relatively high. We present the case of a 55-year old man with a recurrent invasive thymoma with a pleural dissemination, detected on CT-imaging 2 years following his primary surgery. Since the first pre-operative imaging studies showed no invasion of the adjacent organs and a thymoma was suspected, a surgical resection was decided as a first line treatment. Per-operatively a number of adjacent structures were invaded and despite a macroscopical RO resection, the margins were microscopically positive. An invasive thymoma, WHO classification B3, Masaoka stage IVb was diagnosed and the patient received adjuvant radiotherapy. We highlight the role of multimodality treatement and disscus the potential of surgical, radiotherapeutical and systemic therapy in stage IV thymoma as well as in recurrent disease.

[Thyroid cancers]. / Les cancers thyroïdiens.

During the last two decades, the incidence of thyroid cancer has doubled, mainly do to the early detection of small papillary tumors. However, mortality stayed stable (0.05/100.000). Well differentiated cancers (papillary and follicular) demonstrated a excellent survival prognosis (95 % at 30 years for the majority of the patients), factors of prognosis: age, size of the initial tumor, presence (or not) of distant metastases, lymph node involvement (only in patients 45 year or older). Surgery is the main treatment and should be with curative intent, hence the importance of a thorough preoperative work-up: sonography, needle aspiration cytology and MRI of cervicomediastinum for large tumors and/or suspected lymph nodes. Total thyroidectomy is mandatory, excepted for well selected patients with small (pT1) unilateral tumors under the age of 45. Central compartment lymph node clearance is advocated (but not evidence based) with presentation of the recurrent laryngeal nerves and of the parathyroids. Ablation of residual thyroid tissue (Iode 131) should be advocated for patients at high (or intermediary) risk of recurrence, only after multidisciplinary concertation. Unlimited follow-up checking the thyroglobulin serum local after the total thyroidectomy and radioactive ablation, the availability of recombinant rhTSH avoids the withdrawal of thyroid hormones (hypothyroid period). Anaplastic carcinomas are very aggressive, no therapeutic solution, excepted in some selected case for when radical surgery is possible (flap reconstruction) followed by chemoradiation. Calcitoninenia to detect and to follow medullary thyroid cancer after total thyroidectomy and lymph node clearance.

Stromal tumour of the rectum: laparoscopic approach of a rare localization of GIST.

The authors present the case of a 60 year-old man known for a rectal polyp which was diagnosed in 1994 and since then followed-up by means of a colonoscopy associated with periodic biopsies. Recently, the results of a biopsy revealed positive markers for the diagnosis of Gastro-Intestinal Stromal Tumor (GIST). Despite the absence of malignant criteria, an anterior resection of the rectum was performed by laparoscopy and the patient rapidly recovered. Epidemiology, diagnosis and management of this rare location of GIST's are discussed.

At home management of aplastic phase following high-dose chemotherapy with stem-cell rescue for hematological and non-hematological malignancies.

BACKGROUND: After high-dose chemotherapy with autologous stem-cell support long hospital stays in the aplastic phase are expensive, lead to increased risk of hospital infections and to increasing pressure on available hospital beds. We developed a home care regimen that allows patients to be at home for most of the aplastic period, without daily hospital visits. PATIENTS AND METHODS: Between October 1995 and December 1997, transfer of supportive care to the home setting took place in three phases for patients undergoing high-dose chemotherapy with stem-cell transplant for malignant lymphoma (one course of BEAM), breast cancer or germ-cell cancer (three courses of tCTC). In the inpatient cohort, the supportive care designed for at home use was administered in the hospital until neutrophile recovery to 0.5 x 10(9)/l. In the second, outpatient cohort, patients were discharged the day after stem-cell reinfusion but the supportive care was delivered daily in hospital. The third, home care cohort, consisted of patients who were discharged the day after stemcell reinfusion, after which specialized home care professionals delivered all supportive care including transfusions and parenteral antibiotics at home, with once weekly check-up in hospital by the transplant physician. RESULTS: Forty-two patients were treated with 81 cycles of high-dose chemotherapy (11, 18 and 13 patients and 17, 40 and 24 courses in the inpatient, outpatient and home care cohorts respectively). Inpatients were hospitalized in the aplastic phase for a median of 14 days. Patients in the outpatient cohort were at home in the aplastic phase for a median of six days (with a median of six days in hospital), and in the home care cohort for a median of 10 days (with a median of 1.5 days in hospital). Unscheduled readmissions and hospital visits were frequent in the outpatient and home care cohorts, mostly due to fever, central indwelling catheter malfunctioning or chemotherapy-related toxicity. However, patients could usually be discharged again after observation and treatment. No infectious deaths or unexpected emergencies occurred in the outpatient or home care cohort. Neither was there any suggestion of an increased number of fevers, infections, or other complications. CONCLUSIONS: At home management in the aplastic phase after high-dose chemotherapy and stemcell transplant by community-based professionals is feasible without signs of increased toxicity or infections.

Diffuse large B-cell non-Hodgkin lymphomas: the clinical relevance of histological subclassification.

In the REAL classification the diffuse large B-cell non-Hodgkin lymphomas (NHL) are grouped together, because subclassifications are considered to lack both reproducibility and clinical significance. Others, however, claim that patients with an immunoblastic NHL have a worse prognosis than patients with other types of diffuse large B-cell NHL. Therefore, we investigated the prognostic and clinical significance of histological subclassification of diffuse large B-cell NHL in a uniformly treated series of patients. For this retrospective study, all patients diagnosed as having an immunoblastic (IB) B-cell NHL by the Lymphoma Review Panel of the Comprehensive Cancer Center Amsterdam (CCCA) between 1984 and 1994, and treated according to the guidelines of the CCCA, were analysed. Patients with a centroblastic polymorphic subtype (CB-Poly) or centroblastic (CB) NHL by the Lymphoma Review Panel who were treated in the Netherlands Cancer Institute during the same period according to CCCA guidelines were used as reference groups. All patients' records were reviewed. Clinical parameters at presentation, kind of therapy and clinical outcome were recorded. All available histological slides were separately reviewed by two haemato-pathologists. One hundred and seventy-seven patients were included in the study: 36 patients (20.3%) with an IB NHL, 69 patients (39%) with a CB-Poly NHL and 72 patients (40.7%) with a CB NHL. The patients with an IB NHL tended to be older and presented more often with stage I or II and one extranodal site than patients with a CB and CB-Poly NHL. None of the subtypes showed a clear preference for localization in a particular site. The patients with IB or CB-Poly NHL showed a significantly worse prognosis than patients with CB NHL, with a 5-year overall survival for patients with CB NHL of 56.3% and for patients with IB or CB-Poly NHL 39.1% and 41.6% respectively. The 5-year disease free survival was 53.2% for the patients with CB, 32% for the patients with CB-Poly and 26.9% for the patients with IB NHL. A multivariate analysis showed that histological subtyping was of prognostic significance independent of the International Prognostic Index. This finding merits further exploration in prospective studies in order to judge the value of subclassification of large B-cell NHL as a guideline in therapy choice.