Parameters assessing neurological status in malignant glioma patients: prognostic value for survival and relapse-free time

Malignant gliomas are the commonest primary brain tumours in adults and harbour a dismal prognosis. So far, established parameters with predictive significance for prognosis do not include the neurological functional assessment of patients. The aim of this study was to investigate the prognostic value of parameters assessing neurological status in malignant glioma patients for outcome and survival. Evaluation of neurological status included the Sawaya Functional Grade (SFG) and the Neurological Performance Scale (NPS). Moreover, the Karnofsky Performance Status (KPS), medical risk factors, extension of resection, postoperative complications, and the predictive value of these variables for outcome and survival were studied. For this purpose, we have analysed 110 consecutive patients with malignant gliomas who were treated at our institution. As expected, age (p <0.001), KPS (p = 0.003) and extent of resection (p <0.001) were good predictors of survival. Strikingly, SFG and NPS showed the highest significant correlation with survival (both p <0.0001) and, furthermore, they were the only predictors of the relapse-free time (p = 0.035 and p = 0.004, respectively). Our data strongly suggests that SFG and NPS accurately predict both survival and relapse-free time, which may add a valuable tool for tailoring individual therapy strategies.     

Long-term results after microsurgery for Cushing disease: experience with 426 primary operations over 35 years

OBJECTIVES: The aim of this paper was to demonstrate the long-term results following microsurgery in a single surgeon's continuous series of patients with Cushing disease (CD), to assess the influence of changes in surgical procedures, and to compare the results with those of other treatment modalities. In particular, preoperative diagnosis, tumor size, results of histological examination, and complications were considered. METHODS: Between 1971 and 2004, 426 patients suffering from newly diagnosed CD underwent primary surgery. Pre-operative measures included clinical examination, endocrinological workup (testing of the hypothalamic-pituitary-adrenal axis, and 2- and 8-mg dexamethasone overnight suppression tests), sellar imaging (polytomography, computed tomography, and magnetic resonance [MR] imaging), and in patients with negative results on imaging studies, inferior petrosal sinus sampling. Follow-up examinations consisting of endocrinological workup, and imaging took place 1 week and 3 months after surgery and then at yearly intervals. RESULTS: During microsurgery as first treatment, the adenoma finding rate was 86.6%. After selective adenomectomy, the remission rate was 75.9%, and this rate showed no improvement over the years. The best results were achieved in microadenomas confirmed on MR imaging or histopathological investigation. The recurrence rate (15%) and the complication rate (5.9%) declined over the years. If no adenoma was found, exploration of the sella turcica was performed in 45.6%, hypophysectomy in 3.5%, and hemihypophysectomy in 50.9% of these patients, leading to an early remission in 37.9%. In case of persistence or recurrence, further treatment (repeated operation, adrenalectomy, radio-therapy, or medical treatment) was used to control the disease. CONCLUSIONS: Microsurgery remains the treatment of first choice in CD, even though no improvement in remission rates was observed over the years, because complication or remission rates for other treatment options are comparable or worse.     

Probing the bioactive constituents from chemotypes of the sponge Psammocinia aff. bulbosa

Since the report of (+)-psymberin (2) in 2004, many synthetic groups have pursued the synthesis of this compound, and our group has further collected Psammocinia aff. bulbosa to successfully isolate more 2. With more (+)-psymberin (2) in hand, additional clonogenic studies, a therapeutic efficacy assessment, and the hollow fiber assay have been completed. The inconsistent production of (+)-psymberin (2) and the classification of six Psammocinia species are further discussed herein. The most recent of these six collections resulted in the isolation of a new brominated cyclic peptide, (-)-psymbamide A (4), which is the first report of a Psammocinia-derived compound in this peptide class. The planar structure was solved via dereplication with Marinlit, HRESIMS, and 1D and 2D NMR techniques, and the absolute configuration determined using Marfey's method.     

Small-molecule Bcl-2 inhibitors sensitise tumour cells to immune-mediated destruction

The cytotoxic effects of anticancer immune cells are mediated by perforin/granzyme-B, Fas ligand and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), and therefore depend on intact apoptotic responses in target tumour cells. As killing by all three of these mechanisms is blocked by the frequently overexpressed antiapoptotic oncoprotein Bcl-2, we hypothesised that coexposure to a Bcl-2 inhibitor might enhance anticancer immune responses. We evaluated this in U937 lymphoma cells, and A02 melanoma cells, which both show strong Bcl-2 expression. Valpha24(+) Vbeta11(+) natural killer T (NKT) cells expanded from peripheral blood of normal donors (n=3) were coincubated with PKH26-labelled U937 cells, and cytotoxicity was determined by flow cytometry after annexin-V-FITC and 7-AAD staining. In all cases, addition of the HA14-1 small-molecule Bcl-2 inhibitor to the cocultures significantly increased apoptosis in the target U937 cells. Using a similar assay, killing of A02 cells by the cytotoxic T-lymphocyte clone 1H3 was shown to be amplified by coexposure to the potent small-molecule Bcl-2 inhibitor ABT-737. Experiments with immune effectors preincubated with concanamycin-A suggested that sensitisation to perforin/granzyme-B may underlie enhanced target-cell killing observed in the presence of Bcl-2 inhibitors. We conclude that immune destruction of malignant cells can be amplified by molecular interventions that overcome Bcl-2-mediated resistance to apoptosis.     

Treatment of anal stenosis: a 5-year review

BACKGROUND: Benign anal stenosis is an uncommon, disabling and incapacitating disease, occurring mainly after anorectal surgery. Both non-surgical and surgical treatments have been devised in the treatment of anal stenosis with good results. We described the results of the treatment of this disease in the Coloproctology Department of our institution. METHODS: A retrospective clinical study was undertaken over a 5-year period for consecutive patients operated on for anal stenosis. RESULTS: Twenty-three patients with benign anal stenosis were treated in our department. Haemorrhoidectomy was the most common cause of anal stenosis (74%). Nineteen patients with moderate to severe symptoms of anal stenosis underwent surgical treatment. Lateral mucosal advancement flap was the most frequently carried out operation (63.1%). Four patients were treated with anal dilatation (17.3%). All patients had remission of the preoperative symptoms. There was no re-operation and only minor complications were present in four patients: three patients with anal pruritus and one patient with temporary incontinence. CONCLUSION: The easy performance, the absence of major complications and the good results obtained confirm that these methods are effective and safe in the treatment of anal stenosis.     

Induction and exacerbation of psoriasis with Interferon‐alpha therapy for hepatitis C: A review and analysis of 36 cases

Background Interferon‐alpha (IFN‐α) therapy is used to treat hepatitis C infection. The exacerbation and occurrence of psoriasis in hepatitis C patients treated with IFN‐α is increasingly recognized, but the distinct associated features, aetiology and management have not been reviewed. Objective To review all published cases of hepatitis C patients who developed psoriasis while receiving IFN‐α therapy. Methods The review was conducted by searching the PubMed database using the keywords ‘hepatitis C’ AND ‘psoriasis.’ In addition, references to additional publications not indexed for PubMed were followed to obtain a complete record of published data. Results We identified 32 publications describing 36 subjects who developed a psoriatic eruption while receiving IFN‐α therapy for hepatitis C. Topical therapies were a commonly employed treatment modality, but led to resolution in only 30% of cases in which they were employed solely. Cessation of IFN‐α therapy led to resolution in 93% of cases. Hundred per cent of those who developed psoriasis while on IFN‐α therapy responded to systemic therapy and were able to continue the drug. Conclusion Further studies and analysis of IFN‐α‐induced lesions are necessary to clarify the role of IFN‐α and the hepatitis C virus in the development of psoriatic lesions.