Positron emission tomography for staging of oesophageal and gastroesophageal malignancy.

Positron emission tomography (PET) with [18F]-fluoro-2-deoxy-D-glucose (FDG) was prospectively investigated as a means of detecting metastatic disease in patients with oesophageal tumours and compared with computerized tomography (CT), with the surgical findings as a gold standard. Twenty-six patients with a malignant tumour of the oesophagus or gastroesophageal junction underwent CT and PET of the chest and the abdomen. Seven patients underwent laparoscopy to establish resectability. Fifteen patients underwent laparotomy without prior laparoscopy. Four patients did not undergo surgery. The primary tumour was visualized in 81% of patients with CT and in 96% with PET. Neither CT nor PET were suited to assess the extent of wall invasion. Surgically assessed nodal status corresponded in 62% with CT and in 90% with PET. Distant metastases were found in five patients with CT and in eight with PET. The diagnostic accuracy of CT in determining resectability was 65% and for PET 88%. For CT and PET together this was 92%. The present study indicates that FDG-PET can be of importance for staging patients with oesophageal tumours. PET has a higher sensitivity for nodal and distant metastases and a higher accuracy for determining respectability than CT. PET and CT together would have decreased ill-advised surgery by 90%

Hypofractionated or Conventionally Fractionated Adjuvant Radiotherapy After Regional Lymph Node Dissection for High-Risk Stage III Melanoma

Aims: Adjuvant radiotherapy can be beneficial after regional lymph node dissection for high-risk stage III melanoma, as it has been shown to reduce the risk of recurrence in the node field. However, the optimal fractionation schedule is unknown and both hypofractionated and conventionally fractionated adjuvant radiotherapy are used. The present study examined the oncological outcomes of these two approaches in patients treated in an era before effective systemic immunotherapy became available. Materials and methods: This retrospective cohort study involved 335 patients with stage III melanoma who received adjuvant radiotherapy after therapeutic regional lymph node dissection for metastatic melanoma between 1990 and 2011. Information on tumour characteristics, radiotherapy doses and fractionation schedules and patient outcomes was retrieved from the institution's database and patients' medical records. Results: Hypofractionated radiotherapy (median dose 33 Gy in six fractions over 3 weeks) was given to 95 patients (28%) and conventionally fractionated radiotherapy (median dose 48 Gy in 20 fractions over 4 weeks) to 240 patients (72%). Five-year lymph node field control rates were 86.0% (95% confidence interval 78.4–94.4%) for the hypofractionated group and 85.5% (95% confidence interval 80.5–90.7%) for the conventional fractionation group (P = 0.87). There were no significant differences in recurrence-free survival (RFS) (41.7%, 95% confidence interval 32.5–53.5 versus 31.9%, 95% confidence interval 26.1–38.9; P = 0.18) or overall survival (41.2%, 95% confidence interval 32.1–52.8 versus 45.0%, 95% confidence interval 38.7–52.4; P = 0.77). On multivariate analysis, extranodal spread was associated with decreased RFS (P = 0.04) and the number of resected lymph nodes containing metastatic melanoma was associated with decreased RFS (P = 0.0006) and overall survival (P = 0.01). Conclusion: Lymph node field control rates, RFS and overall survival were similar after hypofractionated and conventionally fractionated adjuvant radiotherapy. The presence of extranodal spread and an increasing number of positive lymph nodes were predictive of an unfavourable outcome

Sentinel Node Detection in Head and Neck Malignancies: Innovations in Radioguided Surgery

Sentinel node mapping is becoming a routine procedure for staging of various malignancies, because it can determine lymph node status more precisely. Due to anatomical problems, localizing sentinel nodes in the head and neck region on the basis of conventional images can be difficult. New diagnostic tools can provide better visualization of sentinel nodes. In an attempt to keep up with possible scientific progress, this article reviews new and innovative tools for sentinel node localization in this specific area. The overview comprises a short introduction of the sentinel node procedure as well as indications in the head and neck region. Then the results of SPECT/CT for sentinel node detection are described. Finally, a portable gamma camera to enable intraoperative real-time imaging with improved sentinel node detection is described

Temozolomide followed by combined immunotherapy with GM-CSF, low-dose IL2 and IFNα in patients with metastatic melanoma

The purpose of this study is to determine the toxicity and efficacy of temozolomide (TMZ) p.o. followed by subcutaneous (s.c.) low-dose interleukin-2 (IL2), granulocyte-monocyte colony stimulating factor (GM-CSF) and interferon-alpha 2b (IFN alpha) in patients with metastatic melanoma. A total of 74 evaluable patients received, in four separate cohorts, escalating doses of TMZ (150-250 mg m(-2)) for 5 days followed by s.c. IL2 (4 MIU m(-2)), GM-CSF (2.5 microg kg(-1)) and IFN alpha (5 MIU flat) for 12 days. A second identical treatment was scheduled on day 22 and cycles were repeated in stable or responding patients following evaluation. Data were analysed after a median follow-up of 20 months (12-30 months). The overall objective response rate was 31% (23 out of 74; confidence limits 20.8-42.9%) with 5% CR. Responses occurred in all disease sites including the central nervous system (CNS). Of the 36 patients with responding or stable disease, none developed CNS metastasis as the first or concurrent site of progressive disease. Median survival was 252 days (8.3 months), 1 year survival 41%. Thrombocytopenia was the primary toxicity of TMZ and was dose- and patient-dependent. Lymphocytopenia (grade 3-4 CTC) occurred in 48.5% (34 out of 70) fully monitored patients following TMZ and was present after immunotherapy in two patients. The main toxicity of combined immunotherapy was the flu-like syndrome (grade 3) and transient liver function disturbances (grade 2 in 20, grade 3 in 15 patients). TMZ p.o. followed by s.c. combined immunotherapy demonstrates efficacy in patients with stage IV melanoma and is associated with toxicity that is manageable on an outpatient basi

Impact of non-axillary sentinel node biopsy on staging and treatment of breast cancer patients

The purpose of this study was to evaluate the occurrence of lymphatic drainage to non-axillary sentinel nodes and to determine the implications of this phenomenon. A total of 549 breast cancer patients underwent lymphoscintigraphy after intratumoural injection of 99mTc-nanocolloid. The sentinel node was intraoperatively identified with the aid of intratumoural administered patent blue dye and a gamma-ray detection probe. Histopathological examination of sentinel nodes included step-sectioning at six levels and immunohistochemical staining. A sentinel node outside level I or II of the axilla was found in 149 patients (27%): internal mammary sentinel nodes in 86 patients, other non-axillary sentinel nodes in 44 and both internal mammary and other non-axillary sentinel nodes in nineteen patients. The intra-operative identification rate was 80%. Internal mammary metastases were found in seventeen patients and metastases in other non-axillary sentinel nodes in ten patients. Staging improved in 13% of patients with non-axillary sentinel lymph nodes and their treatment strategy was changed in 17%. A small proportion of clinically node negative breast cancer patients can be staged more precisely by biopsy of sentinel nodes outside level I and II of the axilla, resulting in additional decision criteria for postoperative regional or systemic therapy

Roles of glial cells in synapse development

Brain function relies on communication among neurons via highly specialized contacts, the synapses, and synaptic dysfunction lies at the heart of age-, disease-, and injury-induced defects of the nervous system. For these reasons, the formation—and repair—of synaptic connections is a major focus of neuroscience research. In this review, I summarize recent evidence that synapse development is not a cell-autonomous process and that its distinct phases depend on assistance from the so-called glial cells. The results supporting this view concern synapses in the central nervous system as well as neuromuscular junctions and originate from experimental models ranging from cell cultures to living flies, worms, and mice. Peeking at the future, I will highlight recent technical advances that are likely to revolutionize our views on synapse–glia interactions in the developing, adult and diseased brain