Retrospective study to estimate the prevalence and describe the clinicopathological characteristics, treatments received, and outcomes of HER2-low breast cancer.

BACKGROUND: Approximately 80% of all breast cancers (BCs) are currently categorized as human epidermal growth factor receptor 2 (HER2)-negative [immunohistochemistry (IHC) 0, 1+, or 2+/in situ hybridization (ISH) negative]; approximately 60% of BCs traditionally categorized as HER2-negative express low levels of HER2. HER2-low (IHC 1+ or IHC 2+/ISH-) status became clinically actionable with approval of trastuzumab deruxtecan to treat unresectable/metastatic HER2-low BC. Greater understanding of patients with HER2-low disease is urgently needed. PATIENTS AND METHODS: This global, multicenter, retrospective study (NCT04807595) included tissue samples from patients with confirmed HER2-negative unresectable/metastatic BC [any hormone receptor (HR) status] diagnosed from 2014 to 2017. Pathologists rescored HER2 IHC-stained slides as HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2 IHC 0 after training on low-end expression scoring using Ventana 4B5 and other assays at local laboratories (13 sites; 10 countries) blinded to historical scores. HER2-low prevalence and concordance between historical scores and rescores were assessed. Demographics, clinicopathological characteristics, treatments, and outcomes were examined. RESULTS: In rescored samples from 789 patients with HER2-negative unresectable/metastatic BC, the overall HER2-low prevalence was 67.2% (HR positive, 71.1%; HR negative, 52.8%). Concordance was moderate between historical and rescored HER2 statuses (81.3%; κ = 0.583); positive agreement was numerically higher for HER2-low (87.5%) than HER2 IHC 0 (69.9%). More than 30% of historical IHC 0 cases were rescored as HER2-low overall (all assays) and using Ventana 4B5. There were no notable differences between HER2-low and HER2 IHC 0 in patient characteristics, treatments received, or clinical outcomes. CONCLUSIONS: Approximately two-thirds of patients with historically HER2-negative unresectable/metastatic BC may benefit from HER2-low-directed treatments. Our data suggest that HER2 reassessment in patients with historical IHC 0 scores may be considered to help optimize selection of patients for treatment. Further, accurate identification of patients with HER2-low BC may be achieved with standardized pathologist training.

Intervention for Cognitive Reserve Enhancement in Delaying the Onset of Alzheimer's Symptomatic Expression (INCREASE) Study: Results from a Randomized Controlled Study of Medication Therapy Management Targeting a Delay in Prodromal Dementia Symptom Progression.

BACKGROUND: Cognitive reserve has been hypothesized as a mechanism to explain differences in individual risk for symptomatic expression of Alzheimer's Disease (AD). Inappropriate medications may diminish cognitive reserve, precipitating the transition from preclinical AD (pAD) to a symptomatic state. To date, there is limited data on the potential impact of medication optimization as a potential tool for slowing the symptomatic expression of AD. OBJECTIVES: (1) To test the efficacy of a medication therapy management intervention designed to bolster cognitive reserve in community-dwelling older adults without dementia. (2) To evaluate the efficacy of intervention by baseline pAD status. DESIGN: A 1-year randomized controlled trial was conducted in community-dwelling older adults without dementia. Randomization was stratified by amyloid ß positron emission tomography levels. SETTING: Community-based, Lexington, Kentucky. PARTICIPANTS: Adults 65 years or older with no evidence of dementia and reporting at least one potentially inappropriate medication as listed in the Beers 2015 criteria were recruited. The study aimed to enroll 90 participants based on the a priori sample size calculation. INTERVENTION: Medication therapy management versus standard of care. MEASUREMENTS: Primary outcomes were: (1) one-year changes in the Medication Appropriateness Index; (2) one-year changes in Trail Making Test B under scopolamine challenge. RESULTS: The medication therapy management intervention resulted in significant improvement in Medication Appropriateness Index scores. Overall, there was no beneficial effect of the medication therapy management on Trail Making Test B scores, however stratified analysis demonstrated improvement in Trail Making Test B challenged scores associated with the medication therapy management for those with elevated amyloid ß positron emission tomography levels consistent with pAD. CONCLUSIONS: Medication therapy management can reduce inappropriate medication use in older adults at risk for AD. Our study indicated beneficial cognitive effects in those with preclinical Alzheimer's Disease. No statistically significant effects were evident in the study group as a whole, or in those without preclinical cerebral amyloidosis. Further work designed to improve the effectiveness of the medication therapy management approach and defining other preclinical pathologic states that may benefit from medication optimization are readily achievable goals for promoting improved cognitive health and potentially delaying the onset of symptomatic AD.

ACCIDENTAL FINDING OF SYNCHRONOUS BILATERAL DUCTAL CARCINOMA IN SITU IN A YOUNG MAN REFERRED TO MASTECTOMY DUE TO GYNECOMASTIA - AND WHAT IF LIPOSUCTION HAVE BEEN USED? CASE REPORT.

Breast male cancer is a rare condition. We report a case of a synchronous bilateral ductal carcinoma in situ (DCIS) which developed in a 26-year-old man with long-standing gynecomastia. He underwent bilateral subcutaneous mastectomy. Histology revealed bilateral pure DCIS. There was no identifiable causative factor for the development of bilateral DCIS, and there was no family history of the disease. No other treatment was required, and after 18 months there were no signs of local recurrence. This case highlights the importance of staying vigilant regarding the presence of malignancy in normally benign conditions. Liposuction has become a very useful technique for gynecomastia correction, however, there is a risk of dissemination of an unknown malignant tumor. In atypical cases, en bloc surgical excision should be performed.

Effects of magnesium sulfate and dioctyl sodium sulfosuccinate on fecal hydration, output and systemic hydration in healthy horses / [Efeitos do sulfato de magnésio e do dioctil-sulfossuccinato de sódio na hidratação e eliminação fecal e sobre a hidratação sistêmica de cavalos saudáveis]

Magnesium sulphate (MS) and dioctyl sodium sulphosuccinate (DSS) are laxative drugs frequently used for the treatment of impactions. The aim of this study was to compare the effects of MS and DSS in fecal hydration, output and systemic hydration in healthy horses. Five healthy horses received 3 treatments with a 21-day interval. Treatment 1 was performed with administration of 4 liters of warm water; treatment 2: administration of 4 liters of warm water associated with 1g/kg of MS; and treatment 3: administration of 4 liters of warm water associated with 20mg/kg DSS. General and specific physical examination of the digestive system were performed, alongside with packed cell volume and total plasma protein measurement, abdominal ultrasonography and quantification of the amount and hydration of feces, before and 6, 12, 24, 36 and 48 hours after the treatments. No adverse effects were observed. The administration of laxatives promoted greater fecal output and hydration without resulting in systemic dehydration, yet no differences were observed between treatments. The absence of adverse effects of DSS demonstrates the safety of its use as a laxative drug at a dose of 20mg/kg. Studies comparing the effects of the laxative drugs in horses with large colon impaction are needed.(AU)

O sulfato de magnésio (SM) e o dioctil-sulfossuccinato de sódio (DSS) são drogas laxativas frequentemente utilizadas no tratamento da compactação. O objetivo deste estudo foi comparar os efeitos do SM e do DSS na hidratação e eliminação fecal, e na hidratação sistêmica de cavalos saudáveis. Cinco cavalos receberam três tratamentos, com intervalo de 21 dias. O tratamento 1 consistiu na administração de quatro litros de água morna; o tratamento 2: administração de quatro litros de água morna associada a 1g/kg de SM; e o tratamento 3: administração de quatro litros de água morna associada a 20mg/kg de DSS. Foram realizados exames físicos gerais e específicos do trato digestivo, hematócrito e proteína plasmática total, ultrassonografia abdominal e mensuração da quantidade e hidratação das fezes antes e após seis, 12, 24, 36 e 48 horas dos tratamentos. Não foram observados efeitos adversos. A administração de ambos os laxantes promoveu maior produção fecal e hidratação, sem resultar em desidratação sistêmica, entretanto não houve diferença entre os tratamentos. A ausência de efeitos adversos do DSS demonstra a segurança de seu uso como medicamento laxante na dose de 20mg/kg. São necessários estudos que comparem o efeito dos laxantes em equinos portadores de compactação de cólon.(AU)

Carboxymethylcellulose and psyllium effects in sand output of horses with asymptomatic sand accumulation / [Efeitos da carboximetilcelulose e do psyllium sobre a eliminação de areia de cavalos com sablose assintomática]

The aim of this study was to evaluate the effects of Psyllium (PSY) and Carboxymethylcellulose (CMC) administration on fecal elimination of sand in horses with asymptomatic sand accumulations. Eight horses were selected from sandy areas and randomly divided into 2 groups of four animals. The subjects were treated either with CMC or PSY. The presence of intestinal sand was confirmed through radiography and glove sedimentation test. The study was performed in two phases, with a 7-day interval. In phase I, all the animals received 8 liters of warm water; in phase II, the CMC group received 8 liters of water + 1g/kg of CMC, whereas the PSY group received 8 liters of water + 1g/kg of PSY. All administrations were performed through nasogastric intubation and fractionated in 2 equal volume administrations with an interval of two hours. General and specific physical examination of the digestive system were performed in conjunction with abdominal ultrasonography before the administrations and after 6, 12, 24, 36 and 48 hours, aiming to evaluate intestinal motility and presence of sand. All the feces eliminated by the animals within the 72 hours following the administrations were quantified, diluted and sedimented in order to calculate the sand output (g/kg of feces). All the animals were also subjected to radiographic examination to quantify sand accumulation prior to phase I and after 72 hours of phases I and II. No adverse effects were observed after the treatments. It was possible to notice higher sand elimination in both groups during the phase I, whereas no difference was observed in sand elimination rates between the groups in phase II. The radiographic scores presented differences between the initial timepoint and 72h in phases I and II for both groups. Based on the sand elimination rates and radiographic score, this study demonstrated that sand output was greater after administration of water alone, compared to CMC and Psyllium, leading to the inference that removal of the sandy environment and prevention of sand re-ingestion are effective measures for the elimination of sand from the colon of horses with asymptomatic sand accumulations.(AU)

O objetivo deste estudo foi avaliar os efeitos da administração do psyllium (PSY) e da carboximetilcelulose (CMC) sobre a eliminação fecal de areia em equinos com sablose assintomática. Oito equinos com confirmação radiográfica de sablose assintomática foram divididos em dois grupos (grupo CMC e grupo PSY). O estudo foi realizado em duas fases, com intervalo de sete dias. Na fase 1, todos os animais receberam 8L de água; na fase 2, o grupo CMC recebeu 8L de água + 1g/kg de CMC e o grupo PSY recebeu 8L de água + 1g/kg de PSY. Antes da administração de cada solução e após seis, 12, 24, 36 e 48 horas, foram realizados exame físico e ultrassonografia abdominal. Todas as fezes eliminadas em 72 horas foram avaliadas para quantificar a eliminação de areia (g/kg de fezes). Antes da fase 1 e após 72 horas das fases 1 e 2, o exame radiográfico foi realizado para quantificar o escore de acúmulo de areia. Houve maior eliminação de areia após a administração de água em comparação com a administração de CMC, e não se observou diferença entre a CMC e o PSY. Uma redução significativa nos escores radiográficos de acúmulo de areia foi observada após a administração de água, bem como a manutenção dos escores após a administração da CMC e do PSY. Com base na produção de areia e no escore radiográfico, este estudo sugere que a remoção do ambiente arenoso, impedindo a reingestão de areia, é uma medida eficaz para a eliminação da areia do cólon de cavalos com acúmulos de areia assintomáticos.(AU)

Thyroid FNAC: Causes of false-positive results.

In this paper, we aim to focus on false positive results in the evaluation of thyroid aspirations, covering cystic, inflammatory, follicular and oncocytic lesions, papillary carcinoma, and medullary carcinoma of thyroid. The recently described entity noninvasive follicular thyroid neoplasm with papillary-like nuclear features is also discussed detailing the impact of its introduction on the sensitivity and specificity of thyroid FNA, as well as the use of molecular tests for diagnostics. Medicolegal issues in relation to current practice in English law are also described.

Epileptogenicity and pathology - Under consideration of ablative approaches.

Besides resective epilepsy surgery, minimally invasive ablation using new diagnostic and therapeutic techniques recently became available. Optimal diagnostic approaches for these treatment options are discussed. The pathophysiology of epileptogenic networks differs depending on the lesion-types and location, requiring a differential use of non-invasive or invasive functional studies. In addition to the definition of epileptogenic zones, a challenge for pre-surgical investigation is the determination of three-dimensional epileptic networks to be removed.

Radiofrequency-thermoablation: General principle, historical overview and modern applications for epilepsy.

Stereotactically guided radiofrequency thermoablation (RFTA) for epilepsy has been frequently applied over the last 40 years. Radiofrequency electrodes with temperature control function generate a coagulation lesion with clearly defined borders. In combination with high-resolution MRI imaging, this technique allows minimally-invasive ablation of periventricular nodular heterotopias, small focal type II dysplasias, and hypothalamic hamartomas. This review summarises the literature addressing this topic mainly regarding technical aspects. In essence, RFTA is a safe treatment option for patients suffering from epileptogenic pathologies visible on MRI-images.

Laparoscopic adjustable gastric banding in adolescents with severe obesity: Psychological aspects, decision makers of surgery, and 2-year outcomes. A case series.

BACKGROUND: The results of medical treatment of severe obesity in the adolescent population (balanced diet and physical activity) are often unsatisfactory, and bariatric surgery is questioned. The psychological determinants for requesting bariatric surgery in these adolescents are unclear. The objective of this study was to report the psychiatric and psychological aspects as well as the determinants of the medical decision for surgery in a cohort of obese adolescents requesting bariatric surgery by laparoscopic adjustable gastric banding. METHODS: Thirty-five adolescents (12.3-17.7 years of age), were recruited from January 2007 to December 2012. Semistructured interviews were conducted. RESULTS: Fifty-four percent of the adolescents had a psychiatric history and 85% had psychiatric comorbidities. In adolescents undergoing surgery, excess weight loss was 46% after 1 year and 51% after 2years. For patients not receiving surgery, excess weight loss was 0.43% after 1 year (P=0.001). Compliance with medical treatment was the only significant element contributing to the decision to perform surgery. Results in terms of satisfaction and perception 1 and 2years after surgery were encouraging. CONCLUSION: Bariatric surgery is feasible in young patients and produces good results in terms of excess weight loss. We argue that compliance with medical treatment is probably one of the most important elements for making the decision to perform bariatric surgery and in excess weight loss after surgery. We probably need to focus on the compliance of young patients and evaluate how this can be improved.

Skills improvement after observation or direct practice of a simulated laparoscopic intervention.

BACKGROUND: Laparoscopic skills are more and more often being learned on simulators. PURPOSE: To assess the respective roles of observation and direct practice in the retention of laparoscopic procedural skills. BASIC PROCEDURES: Twelve surgical residents were included in a two-session laparoscopic training course. During the first session (S1), one participant completed a cholecystectomy on the Simbionix LAPMentor™ and then observed his colleague carrying out a total hysterectomy and vice versa. During the second session (S2), each participant completed both interventions. Skills evaluation was assessed using the Objective Structured Assessment of Technical Skills (OSATS) global rating scale and LAPMentor™ metrics. MAIN FINDINGS: Mean OSATS score during the first session was 19.3±5.1, and increased by 37% in the group of former observer students (S2O, P=0.003), and by 54% in the group of former practising students (S2A, P=0.001). Self- and peer-grading results were concordant with the supervisor's evaluation. Detailed analysis of LAPMentor™ metrics showed a trend toward more parameters being improved in group S2A as compared to group S2O on both interventions. The most significant improvements concerned the time of completion for the hysterectomy and the efficiency of cautery for the cholecystectomy. CONCLUSIONS: Observation of laparoscopic skills still allows for surgical improvement, but direct practice on a virtual reality trainer provides better results. Self- and peer-grading were concordant with the supervisor's evaluation. This work may advocate the integration of both personal training on simulators and surgical observation into residents' surgical curricula.

Diabetes mitigates the role of memory complaint in predicting dementia risk: Results from the Prevention of Alzheimer's Disease with Vitamin E and Selenium Study.

BACKGROUND: Subjective memory complaints (SMCs) are associated with increased risk of dementia in older adults, but the role of comorbidities in modifying this risk is unknown. OBJECTIVES: To assess whether comorbidities modify estimated dementia risk based on SMCs. DESIGN: The Prevention of Alzheimer's Disease with Vitamin E and Selenium Study (PREADVISE) was designed as an ancillary study to the Selenium and Vitamin E Cancer Prevention Trial (SELECT), a randomized, multi-center prostate cancer prevention trial with sites in the Unites States, Puerto Rico, and Canada. In 2009, PREADVISE and SELECT were changed into cohort studies. SETTING: Secondary analysis of PREADVISE data. PARTICIPANTS: PREADVISE recruited 7,540 non-demented male volunteers from participating SELECT sites from 2002 to 2009. SMCs, demographics, and comorbidities including hypertension, diabetes, coronary artery bypass graft (CABG), stroke, sleep apnea, and head injury were ascertained by participant interview. MEASUREMENTS: Cox models were used to investigate whether baseline comorbidities modified hazard ratios (HR) for SMC-associated dementia risk using two methods: (1) we included one interaction term between SMC and a comorbidity in the model at a time, and (2) we included all two-way interactions between SMC and covariates of interest and reduced the model by "backward" selection. SMC was operationalized as any complaint vs. no complaint. RESULTS: Baseline SMCs were common (23.6%). In the first analyses, with the exception of stroke, presence of self-reported comorbidities was associated with lower estimated HR for dementia based on SMC status (complaint vs. no complaint), but this difference was only significant for diabetes. In the second analysis, the two-way interactions between SMC and race as well as SMC and diabetes were significant. Here, black men without diabetes who reported SMC had the highest estimated dementia risk (HR=5.05, 95% CI 2.55-10.00), while non-black men with diabetes who reported SMC had the lowest estimated risk (HR=0.71, 95% CI 0.35-1.41). CONCLUSIONS: SMCs were more common among men with comorbidities, but these complaints appeared to be less predictive of dementia risk than those originating from men without comorbidities, suggesting that medical conditions such as diabetes may explain SMCs that are unrelated to an underlying neurodegenerative process.

Morphological features that can predict BRAFV600E -mutated carcinoma in paediatric thyroid cytology.

OBJECTIVE: BRAFV600E represents the most common diagnostic marker in papillary thyroid carcinoma (PTC). A few papers have demonstrated the correlation between BRAFV600E and specific morphological findings on PTCs in the adult population. This is the first reported series investigating cytological morphological parameters in paediatric thyroid carcinoma. METHODS: One hundred and nineteen paediatric samples (56 male and 63 female patients), diagnosed in the period between April 2013 and July 2015, were enrolled in the study. Fifteen patients with inadequate results were excluded. Cytological cases were processed with liquid-based cytology (LBC). BRAFV600E and immunocytochemistry for the VE1 antibody were performed on LBC. RESULTS: The diagnostic series included 10 mutated and 94 wild-type (WT) cases. Twenty two percent surgical samples showed 96% cytohistological concordance. The morphological analysis revealed plump cells (abundant eosinophilic cytoplasm and PTC nuclei) in all 10 mutated cases with only four cases showing a focal (less than 20% of the cells) plump component. None of the WT showed plump cells. A sickle nuclear shape was seen only in the mutated cases. VE1 yielded 100% positivity on mutated cases with three cytohistological discrepancies. CONCLUSIONS: The BRAFV600E mutation is also seen in paediatric cytology and the morphological features showed a high accuracy as both predictive mutational parameters and a helpful aid in management mainly of the aggressive BRAFV600E mutated carcinomas.

Observation of universal strong orbital-dependent correlation effects in iron chalcogenides.

Establishing the appropriate theoretical framework for unconventional superconductivity in the iron-based materials requires correct understanding of both the electron correlation strength and the role of Fermi surfaces. This fundamental issue becomes especially relevant with the discovery of the iron chalcogenide superconductors. Here, we use angle-resolved photoemission spectroscopy to measure three representative iron chalcogenides, FeTe0.56Se0.44, monolayer FeSe grown on SrTiO3 and K0.76Fe1.72Se2. We show that these superconductors are all strongly correlated, with an orbital-selective strong renormalization in the dxy bands despite having drastically different Fermi surface topologies. Furthermore, raising temperature brings all three compounds from a metallic state to a phase where the dxy orbital loses all spectral weight while other orbitals remain itinerant. These observations establish that iron chalcogenides display universal orbital-selective strong correlations that are insensitive to the Fermi surface topology, and are close to an orbital-selective Mott phase, hence placing strong constraints for theoretical understanding of iron-based superconductors.

Guidelines for time-to-event end point definitions in breast cancer trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

BACKGROUND: Using surrogate end points for overall survival, such as disease-free survival, is increasingly common in randomized controlled trials. However, the definitions of several of these time-to-event (TTE) end points are imprecisely which limits interpretation and cross-trial comparisons. The estimation of treatment effects may be directly affected by the definitions of end points. The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for randomized cancer clinical trials (RCTs) in breast cancer. PATIENTS AND METHODS: A literature review was carried out to identify TTE end points (primary or secondary) reported in publications of randomized trials or guidelines. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points based on a validated consensus method that formalize the degree of agreement among experts. RESULTS: Recommended guidelines for the definitions of TTE end points commonly used in RCTs for breast cancer are provided for non-metastatic and metastatic settings. CONCLUSION: The use of standardized definitions should facilitate comparisons of trial results and improve the quality of trial design and reporting. These guidelines could be of particular interest to those involved in the design, conducting, reporting, or assessment of RCT.

Training and practice of cytotechnologists: a discussion forum focused on Europe.

OBJECTIVES: To discuss the role and training of cytotechnologists (CTs) in Europe, to identify areas of good practice and to provide an informed opinion to those providing guidelines for training and practice in Europe. METHODS: All members of the Editorial Advisory Board of Cytopathology were invited to take part in a 'discussion forum' for which six topics were circulated in advance concerning the roles of CTs with regard to: (1) pre-screening slides; (2) 'signing out' reports; (3) carrying out ancillary techniques; (4) supervising laboratory staff; (5) taking part in rapid on-site evaluation (ROSE) of fine needle aspirates (FNAs); and (6) whether CTs were trained specifically in cytopathology or in general histopathology. Notes of the meeting were circulated by email and a final report was agreed by 22 participants from 17 predominantly European countries. RESULTS: Training for CTs throughout Europe was variable, especially for non-gynaecological cytology, which was inconsistent with the range of activities required. The participants recommended graduate entry, preliminary training in general laboratory technology, and subsequent training to take account of the probability and, in some centres, the reality of primary cervical cancer screening changing from cytology to human papillomavirus (HPV) testing. They further recommended that CTs should perform HPV tests and take part in ROSE for FNAs, and they supported the European Federation of Cytology Societies developing guidelines for training and practice. CONCLUSION: With CT training added to a university-based education in laboratory or biomedical science, a career in cytotechnology should be an attractive option involving a diverse range of laboratory and clinically based activities.

Metastatic breast cancer: mechanisms and opportunities for cytology.

Despite significant advances in diagnosis, surgical techniques, general patient care, and local and systemic adjuvant therapies, metastatic disease remains the most critical condition limiting the survival of patients with breast cancer. Therefore, the development of effective treatment against late-arising metastasis has become the centre of clinical attention and is one of the current challenges in cancer research. A deeper understanding of the metastatic cascade is fundamental, and the need for repetitive tumour assessments for the evaluation of tumour evolution is a relatively new practice in routine medical care. As such, fine needle aspiration cytology (FNAC) is ideally placed to monitor biological changes in metastasis that may affect treatment and response. As FNAC is a minimally invasive method, it can be performed repeatedly with relatively little trauma, and selective ancillary tests can be applied to FNAC specimens, including for tumour whose primary nature is known. Herein, we review how the linear and parallel models explain metastatic dissemination, thus influencing therapeutic and clinical decisions, and how cytology, together with immunocytochemistry and molecular analysis, can be a tool for routine clinical practice and clinical trials aimed at metastatic disease with a special emphasis on breast cancer.

Chemosaturation with percutaneous hepatic perfusions of melphalan for hepatic metastases: experience from two European centers.

PURPOSE: Chemosaturation with percutaneous hepatic perfusion (PHP; Hepatic CHEMOSAT(®) Delivery System; Delcath Systems Inc, USA) is a minimally invasive, repeatable regional therapy for unresectable hepatic metastases. It uses a system of catheters and filters to isolate hepatic venous blood from the systemic circulation, allowing delivery of high-dose chemotherapy to the hepatic artery. Effluent hepatic venous blood is filtered before being returned to the systemic circulation, thereby reducing exposure to chemotherapy. We describe our experiences with chemosaturation-PHP at 2 European centers. MATERIALS AND METHODS: 14 patients presented unresectable hepatic metastases from solid tumors; 13 received 1 - 3 sessions of chemosaturation-PHP. Melphalan 2.0 (n = 1) or 3.0 (n = 12) mg/kg was given as a 30-minute infusion into the hepatic artery. 12 patients were evaluable for tumor response. RESULTS: One complete (cholangiocarcinoma, n = 1) and 6 partial responses (ocular, n = 3 or cutaneous melanoma, n = 3) were observed, 5 patients had stable disease (ocular melanoma, n = 3; breast cancer, n = 1; gastric cancer, n = 1). Mild to moderate filter-related toxicity (i. e. thrombocytopenia, anemia) was observed immediately post-procedure. Grade 3/4 melphalan-related pancytopenia developed after 1 - 2 weeks. All hematological events were managed effectively with transfusions and/or other supportive measures. The new high-efficiency filter showed milder toxicity and faster recovery. In one case, chemosaturation-PHP was abandoned prematurely due to heparin-induced vaginal bleeding, and one patient died due to retroperitoneal hemorrhage from heparin anti-coagulation. CONCLUSION: Chemosaturation-PHP for non-resectable liver metastases is a feasible treatment option when performed by an experienced multi-disciplinary team. It may be a promising regional therapy for patients with no effective treatment options.

Case report: practicability of functionally based tractography of the optic radiation during presurgical epilepsy work up.

Pre-operative tractography of the optic radiation (OR) has been advised to assess the risk for postoperative visual field deficit (VFD) in certain candidates for resective epilepsy surgery. Diffusion tensor imaging (DTI) tractography relies on a precise anatomical determination of start and target regions of interest (ROIs), such as the lateral geniculate nucleus (LGN) and the primary visual cortex (V1). The post-chiasmal visual pathway and V1 show considerable inter-individual variability, and in epilepsy patients parenchymatous lesions might further complicate this matter. A functionally based tractography (FBT) seems beneficial for precise OR identification. We assessed practicability of FBT for OR identification in a patient with occipital lobe epilepsy due to a temporo-occipital maldevelopmental tumor. The MRI protocol at 3T included a T1-weighted sagittal 3D scan, a T2-weighted axial 2D scan and a DTI scan using an echo planar spin echo sequence. ROIs for fiber tracking of OR (LGN & V1) were determined with T2*-weighted fMRI-based retinotopic assessment. After DTI pre-processing and fiber tracking, paths with similar properties were combined in clusters for visual presentation and OR localization. Retinotopic phase maps allowed for the identification of V1 and LGN for a precise DTI-based reconstruction of OR, which was distant to the patient's tumor. Location and structure of ORs were comparable in each hemisphere. FBT could thus influence the human research of the extrastriate visual pathway and the risk management of post-operative VFD in epilepsy surgery.