imProving Outcomes after STroke clinical pilot trial protocol.

RATIONALE: One in three patients experience depression after stroke and this risk is consistent over time. A strategy to prevent depression that could be economically delivered to most stroke patients and ideally which also has a low likelihood of adverse events needs to be developed and evaluated. Aims POST aims to determine whether a simple intervention (postcards) prevents depression (Hospital Anxiety and Depression rating Scale, HADS depression subscale score > or =8) in patients with a recent stroke. Secondary end-points include reduced anxiety (HADS anxiety subscale score > or =8) and improved health-related quality of life in patients with a recent stroke. DESIGN: A single-centre randomised, double-blind, pilot trial to prevent depression in patients with a recent (within 8 weeks) stroke presenting to hospital. Patients will be enrolled over 12 months and randomised to receive three trial-specific assessments (baseline, 3- and 6-month assessments of mood, HRQoL and social functioning), or three trial-specific assessments plus a postcard sent centrally in a sealed envelope at 1, 2, 3, 4 and 5 months after discharge from hospital. Blinded follow-up telephone assessments will be conducted for both groups. STUDY OUTCOMES AND SAMPLE SIZE: For the primary end-point the POST trial will have 80% power to detect a relative risk of 0.4 given an incidence of depression of 30%. For the secondary aims POST has 90% power to detect a difference of 3 points on the HADS depression subscale (assuming a standard deviation of 6 points) between randomised groups. This includes an inflation factor of 15% to account for patients lost to follow-up. DISCUSSION: Evidence of efficacy will determine whether a multi-centre, international trial is warranted.

Venous and arterial thrombo-embolic complications of hormonal treatment in a male-to-female transgender patient.

We present a male-to-female (MTF) transgender patient admitted with a pulmonary embolism. The patient had been treated with high-dose oestrogens since the age of 16. Following a prolonged period of hypotension, our patient sustained cerebral border zone infarcts. There was evidence of bilateral carotid stenosis on Doppler ultrasound. We discuss the treatment and vascular complications of gender dysphoria.

Longitudinal prevalence and determinants of early mood disorder post-stroke.

BACKGROUND: Early identification of mood disorder post-stroke (MDPS) or its determinants could improve stroke outcomes. However, the natural history, prevalence and determinants of MDPS within the first weeks post-stroke require further investigation. METHODS: Consecutive hospitalised stroke survivors were assessed within 2-5 days of stroke, and at 1 and 3 months post-stroke. Baseline data included demographics, co-morbidities, stroke subtype, pre-stroke disability and cognition. At baseline, 1- and 3-month interviews physical impairment, disability, cognition and social support were assessed. MDPS was defined as a score of >8 on the depression subscale of the Hospital Anxiety Depression Scale. Factors independently associated with MDPS at each time-point were determined using regression analyses. RESULTS: One hundred and twenty-five subjects were included. The prevalence of MDPS within 5 days and at 1 and 3 months post-stroke was 5%, 16% and 21% respectively. The independent determinants for MDPS at 1 month were disability, social support and change in impairment score between initial and 1-month assessments; and at 3 months were disability, social support and institutionalisation. Individuals moved in and out of the subset of depressed patients over time. MDPS was independently associated with mortality at 3 months post-stroke. CONCLUSION: Mood disorder post-stroke increases in prevalence over the initial weeks post-stroke despite an improvement in disability, and is associated with mortality. Patients with MDPS at 1 month were not necessarily affected at 3 months and vice versa, indicating the dynamic nature of MDPS in the early stages.

Multimodal treatment of hepatocellular carcinoma (HCC).

Screening of patients at risk for hepatocellular carcinomas (HCC) and preventive virustatic therapy are the first steps in a multimodal treatment concept, because delayed detection leads to a poor prognosis with median survival of <10 months. Surgical resection of HCC is still the treatment of choice in patients with good residual liver function, however, recurrence-free 5-year survival after curative resection is low (33%). In patients with cirrhosis, only 25% of HCC are resectable, limited by low hepatic functional reserve. HCC in patients with non-cirrhotic livers are the domain of extended resections. In newer reports, transplantation in patients with cirrhosis is rated more positively when restricted to patients with solitary nodules <5 cm or up to 3 tumors <3 cm. A new option in HCC therapy are the local methods for tumor ablation, preferably radiofrequency ablation (RFA), especially in patients with limited liver function, non-resectable or multifocal tumors. A new horizon is opened combining these options and multimodal approaches with transarterial chemoembolisation (TACE). This trend to multimodal approaches promises a yet unknown improvement in the prognosis of patients with HCC. Controlled randomized studies comparing and validating the different methods and defining combined treatments according to liver function and tumor stage are eagerly awaited.

[Detection of micrometastases after curative resection for ductal adenocarcinoma of the pancreas]. / Detektion von Mikrometastasen nach kurativer Resektion duktaler Adenokarzinome des Pankreas.

OBJECTIVES: Despite apparently curative resection adenocarcinomas of the pancreas early recur. Thus, the pathological examination should be enriched by sensitive methods to detect minimal residual disease (MRD). Mutant K-ras is the most promising genetic alteration in ductal adenocarcinoma and may serve to detect malignant cells by polymerase chain reaction (PCR) based techniques. Therefore, we set out to detect K-ras mutations by PCR for evaluation of MRD in patients after curative resection of pancreatic adenocarcinoma. PATIENTS AND METHODS: Tumor tissue and corresponding paraaortic lymph nodes were obtained from 51 patients, who underwent surgery for pancreatic head tumors. The paraaortic lymph nodes were staged as tumor-free by routine histopathology in all cases diagnosed for ductal adenocarcinoma (study group, n = 40) or other tumors (control group, n = 11). Therefore, DNA of both primary tumors and lymph nodes was extracted and analysed by a PCR-based assay with respect to mutated K-ras. As a positive control the human pancreatic cancer cell line PaTu-8902 was used. RESULTS: K-ras mutations were detected in 73 % (29/40) of primary tumors of ductal adenocarcinomas and in 17 % (5/29) in the corresponding paraaortic lymph nodes, which were diagnosed as tumor-free by routine pathology. The identical type of point mutation was found in primary tumors and corresponding lymph nodes by use of sequence specific primers. In the control group no K-ras mutation was detected. CONCLUSION: Tumor cell DNA can be detected sensitively in tumor- and lymph node specimen with the described method. Routinely assessed, this method is able to detect MRD and could enrich the pathological examination, in order to determine prognostic relevant subgroups of patients.

Minimal residual disease in soft-tissue sarcomas.

Soft-tissue sarcomas are characterized by the development of disease recurrence in a distinct subgroup of patients. Despite intense efforts in applying multimodal treatment, the risk of local recurrence or distant metastases remains a considerable threat to patients with soft-tissue sarcoma. This review focuses on the efforts aimed at defining local and systemic tumor extent at the level of minimal residual disease (MRD) tumor cell detection. Examination of MRD in soft-tissue sarcomas has experienced a significant boost from the definition of fusion transcripts resulting from stable chromosomal translocations. The sensitivity and exclusive specificity of the reverse-transcription polymerase chain reaction (RT-PCR) protocols have given insights into tumor cell residues in nearly all body compartments. The accumulated data demonstrates that even after oncologic resections most patients will still harbor a significant tumor burden. Clinical concepts arising out of these new data are under way. One of these concepts is the targeting of the fusion transcript for therapy. However, this approach is still restricted to the experimental setting. The development of clinical applications remains a challenging task, requiring the treatment of as many patients as possible in centers specializing in all of the affected disciplines.

[Locally ablative therapies of hepatocellular carcinoma]. / Lokal ablative Therapien des hepatozellulären Karzinoms.

Locally Ablative Therapies of Hepatocellular Carcinoma Delayed diagnosis of hepatocellular carcinomas (HCC) leads to a poor prognosis with a median survival time of less than 10 months. Surgical resection of small HCCs is the treatment of choice in patients with good residual liver function. The recurrence-free 5-year survival rate after curative resection is 33%. Resectability of HCC is often limited by the low hepatic functional reserve. Only 20% of all HCC are resectable in spite of novel diagnostic tools, an intensified screening, and advances in surgical technique. Local methods for tumor ablation are promising extensions of tumor therapy, especially in patients with limited liver function, nonresectable tumors, or multifocal tumors. Vis-à-vis a change of therapeutic options, local methods of tumor ablation in combination with tumor resection promise a yet unknown improvement of the prognosis for patients with HCC. Controlled randomized studies comparing and validating these methods of local tumor ablation are eagerly awaited. In the following article different methods of tumor ablation are described. Percutaneous interventions can be distinguished into vascular regional (TAE = transarterial embolization and TACE = transarterial catheter embolization) and local ablative approaches like PEI (percutaneous ethanol instillation), LITT (laser-induced thermotherapy), Cryo (cryotherapy), and RFA (radio frequency ablation).

Ictal SPECT and interictal PET in the localization of occipital lobe epilepsy.

PURPOSE: To compare the localizing value of ictal single photon emission computed tomography (SPECT) and interictal fluorodeoxyglucose-positron emission tomography (FDG-PET) in refractory occipital lobe epilepsy. METHODS: Six patients who underwent surgery for refractory epilepsy associated with pathology in the occipital lobe were retrospectively selected from records of the Austin & Repatriation Centre Comprehensive Epilepsy Programme. Interictal SPECT and PET and ictal SPECT were obtained by standard methods. All studies were read by a nuclear medicine expert blinded to clinical data except the diagnosis of epilepsy. RESULTS: Ictal SPECT showed unilateral occipital hyperperfusion in five of six cases often accompanied by temporal lobe hyperperfusion. These patterns were seen in cases with or without magnetic resonance imaging (MRI) abnormality. Interictal SPECT was not localizing in any case, in contrast to PET, which showed occipital hypometabolism in three of five studies. CONCLUSIONS: Ictal SPECT can provide novel localizing data in MRI-negative occipital lobe epilepsy. Interictal PET can provide useful localizing information, but its role in providing novel information was not demonstrated. Interictal SPECT is useful only as a baseline to aid in interpretation of ictal studies.

"Pressure to laugh": an unusual epileptic symptom associated with small hypothalamic hamartomas.

Gelastic seizures are the hallmark of the epilepsy syndrome associated with hypothalamic hamartomas. Patients typically develop cognitive deterioration and refractory seizures. The authors describe three patients with small hypothalamic hamartomas without these features and thus identify a mild end to the clinical spectrum. All had the unusual symptom of "pressure to laugh," often without actual laughter. This symptom could be dismissed as psychogenic but should be recognized as a clue to the presence of this unusual lesion.

Diagnosis and investigation of headache.

BACKGROUND: Headache is one of the commonest medical complaints. It is usually benign but may be the first presentation of serious disease. OBJECTIVE: This article reviews the symptoms and signs that suggest the diagnosis of the common headaches and discusses which headache presentations require investigation. DISCUSSION: An accurate clinical history is the key to diagnosing the cause of a headache. A new headache of acute onset or progressing over days to weeks or associated with abnormal neurological signs requires investigation.