Long-term follow-up of high-dose chemotherapy with autologous stem-cell transplantation and response-adapted whole-brain radiotherapy for newly diagnosed primary CNS lymphoma: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study

Introduction: We previously reported the results of a phase II study for patients with newly diagnosed primary CNS lymphoma (PCNSL) treated with autologous peripheral blood stem-cell transplantation (aPBSCT) and responseadapted whole brain radiotherapy (WBRT). The purpose of this report is to update the initial results and provide long-term data regarding overall survival, prognostic factors, and the risk of treatment-related neurotoxicity.Methods: A long-term follow-up was conducted on surviving primary central nervous system lymphoma patients having been treated according to the ,,OSHO-53 study", which was initiated by the Ostdeutsche Studiengruppe Hamatologie-Onkologie. Between August 1999 and October 2004 twentythree patients with an average age of 55 and median Karnofsky performance score of 70% were enrolled and received high-dose mthotrexate (HD-MTX) on days 1 and 10. In case of at least a partial remission (PR), high-dose busulfan/ thiotepa (HD-BuTT) followed by aPBSCT was performed. Patients without response to induction or without complete remission (CR) after HD-BuTT received WBRT. All patients (n=8), who are alive in 2011, were contacted and Mini Mental State examination (MMSE) and the EORTC QLQ-C30 were performed.Results: Eight patients are still alive with a median follow-up of 116,9 months (79 - 141, range). One of them suffered from a late relapse eight and a half years after initial diagnosis of PCNSL, another one suffers from a gall bladder carcinoma. Both patients are alive, the one with the relapse of PCNSL has finished rescue therapy and is further observed, the one with gall baldder carcinoma is still under therapy. MMSE and QlQ-C30 showed impressive results in the patients, who were not irradiated. Only one of the irradiated patients is still alive with a clear neurologic deficit but acceptable quality of life.Conclusions: Long-term follow-up of our patients, who were included in the OSHO-53 study show an overall survival of 30 percent. If WBRT can be avoided no long-term neurotoxicity has been observed and the patients benefit from excellent Quality of Life. Induction chemotherapy with two cycles of HD-MTX should be intensified to improve the unsatisfactory OAS of 30 percent.

Endoscopic and surgical treatment of vesico-ureteral reflux in children. Comparative long-term follow-up.

PRINCIPLES: This retrospective study analyzes the long-term results of endoscopic and surgical treatment of vesico-ureteral reflux in children. METHODS: A cohort of 130 patients, 67 girls and 63 boys with a mean age of 30 months were treated either by endoscopic subureteral collagen injection (SCIN) in 92 and by Cohen reimplantation surgery in 123 refluxing ureteral units. Mean follow-up was 4.2 years varying from 1 to 8.7 years. Reflux recurrence, urinary tract infection (UTI) and renal function were evaluated. RESULTS: After SCIN reflux was absent in 64% at 6 months. 20% of the initially 92 refluxing ureters were injected twice. After one or two injections reflux was absent in 71%. In 21% recurrent reflux was of grade I or II, not requiring further treatment. UTI was observed in 27%. After Cohen ureteral reimplantation reflux was absent in 96% at 6 months. UTI was observed in 23%. Renal function at diagnosis and follow-up was compared in children with bilateral grade III reflux only. In patients treated with SCIN it was normal in 77% preoperatively and in 90% at follow-up. In patients treated by open surgery it was normal in 47% preoperatively and in 76% at follow-up. CONCLUSION: For high-grade vesico-ureteral reflux re-implantation surgery remains the gold standard. SCIN is indicated for low and medium grade reflux. Recurrent bacteriuria was observed more often after SCIN and pyelonephritis more often after open surgery. The renal function seems to be preserved with both techniques.

Long-term close follow-up of chorioretinal lesions in presumed ocular tuberculosis.

PURPOSE: To evaluate the long-term outcome (up to 7 years) of presumed ocular tuberculosis (TB) when the therapeutic decision was based on WHO guidelines. METHODS: Twelve out of 654 new uveitic patients (1998-2004) presented with choroiditis and positive tuberculosis skin test (TST) (skin lesion diameter >15 mm). Therapy was administered according to WHO recommendations after ophthalmic and systemic investigation. The area size of ocular lesions at presentation and after therapy, measured on fluorescein and indocyanine green angiographies, was considered the primary outcome. Relapse of choroiditis was considered a secondary outcome. The T-SPOT TB test was performed when it became available. RESULTS: Visual acuity significantly improved after therapy (p=0.0357). The mean total surface of fluorescein lesions at entry was 44.8 ± 20.9 (arbitrary units) and decreased to 32.5 ± 16.9 after therapy (p=0.0165). The mean total surface of indocyanine green lesions at entry was 24.5 ± 13.3 and decreased to 10.8 ± 5.4 after therapy (p=0.0631). The T-SPOT TB revealed 2 false TST-positive results. The mean follow-up was 4.5 ± 1.5 years. Two relapses out of 10 confirmed ocular TB was observed after complete lesion healing, 2.5 years and 4.5 years after therapy, respectively. CONCLUSIONS: A decrease of ocular lesion mean size and a mean improvement of VA were observed after antituberculous therapy. Our long-term follow-up of chorioretinal lesions demonstrated relapse of ocular tuberculosis in 10% of patients with confirmed ocular TB, despite complete initial retinal scarring.

Long-term outcome after cognitive and behavioral regression in nonlesional epilepsy with continuous spike-waves during slow-wave sleep.

PURPOSE: To present the long-term follow-up of 10 adolescents and young adults with documented cognitive and behavioral regression as children due to nonlesional focal, mainly frontal, epilepsy with continuous spike-waves during slow wave sleep (CSWS). METHODS: Past medical and electroencephalography (EEG) data were reviewed and neuropsychological tests exploring main cognitive functions were administered. KEY FINDINGS: After a mean duration of follow-up of 15.6 years (range, 8-23 years), none of the 10 patients had recovered fully, but four regained borderline to normal intelligence and were almost independent. Patients with prolonged global intellectual regression had the worst outcome, whereas those with more specific and short-lived deficits recovered best. The marked behavioral disorders resolved in all but one patient. Executive functions were neither severely nor homogenously affected. Three patients with a frontal syndrome during the active phase (AP) disclosed only mild residual executive and social cognition deficits. The main cognitive gains occurred shortly after the AP, but qualitative improvements continued to occur. Long-term outcome correlated best with duration of CSWS. SIGNIFICANCE: Our findings emphasize that cognitive recovery after cessation of CSWS depends on the severity and duration of the initial regression. None of our patients had major executive and social cognition deficits with preserved intelligence, as reported in adults with early destructive lesions of the frontal lobes. Early recognition of epilepsy with CSWS and rapid introduction of effective therapy are crucial for a best possible outcome.

Suivi neurodéveloppemental de l'enfant né prématuré dans l'Arc lémanique [Neurodevelopmental follow-up of premature children in Lausanne and Geneva].

Preterm children born before 32 weeks of gestation represent 1% of the annual births in Switzerland, and are the most at risk of neurodevelopmental disabilities. A neurological surveillance is thus implemented in the neonatal units, and multidisciplinary neurodevelopmental follow-up is offered to all our preterm patients. The follow-up clinics of the University hospitals in Lausanne and Geneva follow the Swiss guidelines for follow-up. An extended history and neurological examination is taken at each appointment, and a standardized test of development is performed. These examinations, which take place between the ages of 3 months and 9 years old, allow the early identification and treatment of developmental disorders frequent in this population, such as motor, cognitive or behavioral disorders, as well as the monitoring of the quality of neonatal care.

Y-90-Ibritumomab Tiuxetan (Zevalin (R)) Consolidation of First Remission In Advanced-Stage Follicular Non-Hodgkin's Lymphoma: Updated Results After a Median Follow-up of 66.2 Months From the International, Randomized, Phase III First-Line Indolent Trial (FIT) In 414 Patients

The FIT trial was conducted to evaluate the safety and efficacy of 90Y-ibritumomab tiuxetan (0.4 mCi/kg; maximum dose 32 mCi) when used as consolidation of first complete or partial remission in patients with previously untreated, advanced-stage follicular lymphoma (FL). Patients were randomly assigned to either 90Y-ibritumomab treatment (n = 207) or observation (n = 202) within 3 months (mo) of completing initial induction therapy (chemotherapy only: 86%; rituximab in combination with chemotherapy: 14%). Response status prior to randomization did not differ between the groups: 52% complete response (CR)/CR unconfirmed (CRu) to induction therapy and 48% partial response (PR) in the 90Y-ibritumomab arm vs 53% CR/CRu and 44% PR in the control arm. The primary endpoint was progression-free survival (PFS) of the intent-to-treat (ITT) population. Results from the first extended follow-up after a median of 3.5 years revealed a significant improvement in PFS from the time of randomization with 90Y-ibritumomab consolidation compared with control (36.5 vs 13.3 mo, respectively; P < 0.0001; Morschhauser et al. JCO. 2008; 26:5156-5164). Here we report a median follow-up of 66.2 mo (5.5 years). Five-year PFS was 47% in the 90Y-ibritumomab group and 29% in the control group (hazard ratio (HR) = 0.51, 95% CI 0.39-0.65; P < 0.0001). Median PFS in the 90Y-ibritumomab group was 49 mo vs 14 mo in the control group. In patients achieving a CR/CRu after induction, 5-year PFS was 57% in the 90Y-ibritumomab group, and the median had not yet been reached at 92 months, compared with a 43% 5-year PFS in the control group and a median of 31 mo (HR = 0.61, 95% CI 0.42-0.89). For patients in PR after induction, the 5-year PFS was 38% in the 90Y-ibritumomab group with a median PFS of 30 mo vs 14% in the control group with a median PFS of 6 mo (HR = 0.38, 95% CI 0.27-0.53). Patients who had received rituximab as part of induction treatment had a 5-year PFS of 64% in the 90Y-ibritumomab group and 48% in the control group (HR = 0.66, 95% CI 0.30-1.47). For all patients, time to next treatment (as calculated from the date of randomization) differed significantly between both groups; median not reached at 99 mo in the 90Y-ibritumomab group vs 35 mo in the control group (P < 0.0001). The majority of patients received rituximab-containing regimens when treated after progression (63/82 [77%] in the 90Y-ibritumomab group and 102/122 [84%] in the control group). Overall response rate to second-line treatment was 79% in the 90Y-ibritumomab group (57% CR/CRu and 22% PR) vs 78% in the control arm (59% CR/CRu, 19% PR). Five-year overall survival was not significantly different between the groups; 93% and 89% in the 90Y-ibritumomab and control groups, respectively (P = 0.561). To date, 40 patients have died; 18 in the 90Y-ibritumomab group and 22 in the control group. Secondary malignancies were diagnosed in 16 patients in the 90Y-ibritumomab arm vs 9 patients in the control arm (P = 0.19). There were 6 (3%) cases of myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) in the 90Y-ibritumomab arm vs 1 MDS in the control arm (P = 0.063). In conclusion, this extended follow-up of the FIT trial confirms the benefit of 90Y-ibritumomab consolidation with a nearly 3 year advantage in median PFS. A significant 5-year PFS improvement was confirmed for patients with a CR/CRu or a PR after induction. Effective rescue treatment with rituximab-containing regimens may explain the observed no difference in overall survival between both patient groups who were - for the greater part - rituximab-naïve.

A follow-up study on the quality of alcohol dependence-related information on the web.

ABSTRACT: In order to evaluate the one-year evolution of web-based information on alcohol dependence, we re-assessed alcohol-related sites in July 2007 with the same evaluating tool that had been used to assess these sites in June 2006. Websites were assessed with a standardized form designed to rate sites on the basis of accountability, presentation, interactivity, readability, and content quality. The DISCERN scale was also used, which aimed to assist persons without content expertise in assessing the quality of written health publications. Scores were highly stable for all components of the form one year later (r = .77 to .95, p &lt; .01). Analysis of variance for repeated measures showed no time effect, no interaction between time and scale, no interaction between time and group (affiliation categories), and no interaction between time, group, and scale. The study highlights lack of change of alcohol-dependence-related web pages across one year.

Behavioral and psychological symptoms and cognitive decline in patients with amnestic MCI and mild AD: a two-year follow-up study.

BACKGROUND: Mild cognitive impairment (MCI) has been defined as a transitional state between normal aging and dementia. In many cases, MCI represents an early stage of developing cognitive impairment. Patients diagnosed with MCI do not meet the criteria for dementia as their general intellect and everyday activities are preserved, although minor changes in instrumental activities of daily living (ADL) may occur. However, they may exhibit significant behavioral and psychological signs and symptoms (BPS), also frequently observed in patients with Alzheimer's disease (AD). Hence, we wondered to what extent specific BPS are associated with cognitive decline in participants with MCI or AD. METHODS: Our sample consisted of 164 participants, including 46 patients with amnestic (single or multi-domain) MCI and 54 patients with AD, as well as 64 control participants without cognitive disorders. Global cognitive performance, BPS, and ADL were assessed using validated clinical methods at baseline and at two-year follow-up. RESULTS: The BPS variability over the follow-up period was more pronounced in the MCI group than in patients with AD: some BPS improve, others occur newly or worsen, while others still remain unchanged. Moreover, specific changes in BPS were associated with a rapid deterioration of the global cognitive level in MCI patients. In particular, an increase of euphoria, eating disorders, and aberrant motor behavior, as well as worsened sleep quality, predicted a decline in cognitive functioning. CONCLUSIONS: Our findings confirm a higher variability of BPS over time in the MCI group than in AD patients. Moreover, our results provide evidence of associations between specific BPS and cognitive decline in the MCI group that might suggest a risk of conversion of individuals with amnestic MCI to AD.

Antecedents, psychiatric characteristics and follow-up of adolescents hospitalized for suicide attempt of overwhelming suicidal ideation.

To evaluate the socio-demographic as well as the health and psychiatric profiles of adolescents hospitalised for suicide attempt or overwhelming suicide ideation and to assess repetition of suicide attempt over a period of 18 months. Between April 2000 and September 2001, all patients aged 16 to 21 years admitted to the University Hospitals of Geneva and Lausanne for suicide attempt or ideation were included in the study. At this time (T0) semi-structured face to face interviews were conducted to identify socio-demographic data, mental health and antecedents regarding suicidal conducts. Current psychiatric status was assessed with the MINI (Mini International Neuropsychiatric Instrument). At T1 and T2, reassessments included psychiatric status (MINI) as well as lifestyles, socio-professional situation and suicidal behaviours. At T0, 269 subjects met the study criteria, among whom 83 subjects (56 girls and 27 boys) left the hospital too quickly to be involved or refused to participate in the study (final sample at T0: 149 girls; 37 boys). The participation rate at T1 and T2 was respectively 66% and 62% of the original sample. The percentage of adolescents meeting the criteria for psychiatric diagnoses (91%) was high: affective disorder (78%); anxiety disorder (64%); substance use disorder (39%); eating disorder (9%); psychotic disorder (11%); antisocial personality (7%) with most subjects (85%) having more than one disorder. Around 90% of the subjects interviewed at T1, and/or T2, had received follow-up care after their hospitalisation, either by a primary care physician or a psychotherapist or both. Two subjects died of violent death and 18% made a further suicide attempt. Most adolescents hospitalised for suicidal episodes suffer from psychiatric problems which should be addressed by a careful psychiatric assessment, followed up if needed by a structured after care plan.

The updated Swiss guidelines 2016 for the treatment and follow-up of cutaneous melanoma.

Cutaneous melanoma is the most deadly cutaneous neoplasm. In order to guide treatment decisions and follow-up of melanoma patients, guidelines for the management of melanoma in Switzerland were inaugurated in 2001 and revised in 2006 and 2016. Recent data on surgical and medical treatments from randomised trials necessitated modification of the treatment and follow-up recommendations.

Giant warts in a kidney transplant patient: regression with sirolimus.

Purpose: Recent reports have suggested that intraabdominal postoperative infection is associated with higher rates of overall and local recurrence and cancer-specific mortality. However, the mechanisms responsible for this association are unknown. We hypothesized that the greater inflammatory response in patients with postoperative intraabdominal infection is associated to an increase in local and systemic angiogenesis. Methods: We designed a prospective cohorts study with matched controls. Patients with postoperative intra-abdominal infection (abscess and/or anastomotic leakage) (group 1; n=17) after elective colorectal cancer resection operated on for cure were compared to patients with an uncomplicated postoperative course (group 2; n=17). IL-6 and VEGF levels were determined by ELISA in serum and peritoneal fluid at baseline, 48 hours and postoperative day 4 or at the time the peritoneal infection occurred. Results: No differences were observed in age, gender, preoperative CEA, tumor stage and location and type of procedure performed. Although there were no differences in serum IL-6 levels at 48 hours, this pro-inflammatory cytokine was higher in group 1 on postoperative day 4 (group 1: 21533 + 27900 vs. group 2: 1130 + 3563 pg/ml; p < 0.001). Serum VEGF levels were higher in group 1 on postoperative day 4 (group 1: 1212 + 1025 vs. group 2: 408 + 407 pg/ml; p < 0.01). Peritoneal fluid VEGF levels were also higher in group 1 at 48 hours (group 1: 4857 + 4384 vs. group 2: 630 + 461 pg/ml; p < 0.001) and postoperative day 4 (group 1: 32807 + 98486 vs. group 2: 1002 + 1229 pg/ml; p < 0.001). A positive correlation between serum IL-6 and VEGF serum levels was observed on postoperative day 4 (r=0.7; p<0.01). Conclusions: These results suggest that not only the inflammatory response but also the angiogenic pathways are stimulated in patients with intra-abdominal infection after surgery for colorectal cancer. The implications of this finding on long-term follow-up need to be evaluated.

Cancers de l'adulte jeune [Overview on cancer in young adults]

To make a diagnostic of cancer in a young adult (15-30 years of age) has important physical, psychological and social implications. The most frequent cancers seen at this age are cancer of the thyroid, testicular germ cell tumours, 'melanoma, Hodgkin's lymphoma, non-Hodgkin lymphoma, leukaemia, cerebral tumours and sarcomas. Even if the prognostic of most of these cancers is excellent, treatments are difficult and often associated with long-term side effects. A multidisciplinary approach of these patients is essential. A long-term follow-up by a general practicioner or an oncologist is indispensable.

Transcatheter renal denervation for the treatment of resistant arterial hypertension: the Swiss expert consensus.

Transcatheter (or percutaneous) renal denervation is a novel technique developed for the treatment of resistant hypertension. So far, only one randomised controlled trial has been published, which has shown a reduction of office blood pressure. The Swiss Society of Hypertension, the Swiss Society of Cardiology, The Swiss Society of Angiology and the Swiss Society of Interventional Radiology decided to establish recommendations to practicing physicians and specialists for good clinical practice. The eligibility of patients for transcatheter renal denervation needs (1.) confirmation of truly resistant hypertension, (2.) exclusion of secondary forms of hypertension, (3.) a multidisciplinary decision confirming the eligibility, (4.) facilities that guarantee procedural safety and (5.) a long-term follow-up of the patients, if possible in cooperation with a hypertension specialist. These steps are essential until long-term data on safety and efficacy are available.