Endoscopic ultrasound-guided elastography in the nodal staging of oesophageal cancer

AIM: To assess quantitative endoscopic ultrasound (EUS)-guided elastography in the nodal staging of oesophago-gastric cancers.METHODS: This was a single tertiary centre study assessing 50 patients with established oesophago-gastric cancer undergoing EUS-guided fine needle aspiration biopsy (FNAB) of lymph nodes between July 2007 and July 2009. EUS-guided elastography of lymph nodes was performed before EUS-FNAB. Standard EUS characteristics were also described. Cytological determination of whether a lymph node was malignant or benign was used as the gold standard for this study. Comparisons of elastography and standard EUS characteristics were made between the cytologically benign and malignant nodes. The main outcome measure was the accuracy of elastography in differentiating between benign and malignant lymph nodes in oesophageal cancers.RESULTS: EUS elastography and FNAB were performed on 53 lymph nodes. Cytological malignancy was found in 23 nodes, one was indeterminate, one was found to be a gastrointestinal stromal tumor and 25 of the nodes were negative for malignancy. On 3 occasions insufficient material was obtained for analysis. The area under the curve for the receiver operating characteristic curve for elastography strain ratio was 0.87 (P < 0.0001). Elastography strain ratio had a sensitivity 83%, specificity 96%, positive predictive value 95%, and negative predictive value 86% for distinguishing between malignant and benign nodes. The overall accuracy of elastography strain ratio was 90%. Elastography was more sensitive and specific in determining malignant nodal disease than standard EUS criteria.CONCLUSION: EUS elastography is a promising modality that may complement standard EUS and help guide EUS-FNAB during staging of upper gastrointestinal tract cancer.     

Differential expression of the TL1A/DcR3 system of TNF/TNFR-like proteins in large vs. small intestinal Crohn's disease

Background

TNF-like cytokine 1A provides co-stimulatory signals to activated lymphocytes through binding to death-domain receptor-3. Decoy receptor-3 inhibits death-domain receptor-3 signalling, rendering immunocytes resistant to apoptosis. These functions may be important for the pathogenesis of Crohn's disease.

Aims

To study the mucosal and systemic expression of Decoy receptor-3 and TNF-like cytokine 1A in Crohn's disease, in relation to disease activity, localization, and response to treatment.

Methods

Soluble Decoy receptor-3 and TNF-like cytokine 1A were measured by ELISA in active or quiescent Crohn's disease. Relative mRNA expression in non-affected and inflamed intestinal mucosa was determined by real-time RT-PCR.

Results

We found significant upregulation of Decoy receptor-3 and its ligands TNF-like cytokine 1A and FasL in inflamed intestinal mucosa of Crohn's disease patients. During active disease, Decoy receptor-3 and TNF-like cytokine 1A were detected in the serum in the majority of patients. Intestinal inflammation was strongly associated with these elevations as they were absent during remission and significantly reduced with anti-inflammatory treatment. Regional diversity was observed as Decoy receptor-3 was upregulated in colonic and ileal sites, whereas TNF-like cytokine 1A was preferentially induced in the large bowel mucosa and systemic circulation of patients with colonic involvement.

Conclusions

TNF-like cytokine 1A and Decoy receptor-3 are upregulated during active Crohn's disease and may participate in disease pathogenesis and offer novel therapeutic opportunities.     

A systematic review and meta-analysis of biological treatments targeting tumour necrosis factor α for sciatica

Purpose

Systematic review comparing biological agents, targeting tumour necrosis factor α, for sciatica with placebo and alternative interventions.

Methods

We searched 21 electronic databases and bibliographies of included studies. We included randomised controlled trials (RCTs), non-RCTs and controlled observational studies of adults who had sciatica treated by biological agents compared with placebo or alternative interventions.

Results

We pooled the results of six studies (five RCTs and one non-RCT) in meta-analyses. Compared with placebo biological agents had: better global effects in the short-term odds ratio (OR) 2.0 (95 % CI 0.7–6.0), medium-term OR 2.7 (95 % CI 1.0–7.1) and long-term OR 2.3 [95 % CI 0.5 to 9.7); improved leg pain intensity in the short-term weighted mean difference (WMD) −13.6 (95 % CI −26.8 to −0.4), medium-term WMD −7.0 (95 % CI −15.4 to 1.5), but not long-term WMD 0.2 (95 % CI −20.3 to 20.8); improved Oswestry Disability Index (ODI) in the short-term WMD −5.2 (95 % CI −14.1 to 3.7), medium-term WMD −8.2 (95 % CI −14.4 to −2.0), and long-term WMD −5.0 (95 % CI −11.8 to 1.8). There was heterogeneity in the leg pain intensity and ODI results and improvements were no longer statistically significant when studies were restricted to RCTs. There was a reduction in the need for discectomy, which was not statistically significant, and no difference in the number of adverse effects.

Conclusions

There was insufficient evidence to recommend these agents when treating sciatica, but sufficient evidence to suggest that larger RCTs are needed.

Electronic supplementary material

The online version of this article (doi:10.1007/s00586-013-2739-z) contains supplementary material, which is available to authorized users.     

Fulminant falciparum malaria

A case of fulminant falciparum malaria with a 35% parasitaemia, shock and subcoma was treated successfully by using parenteral chemotherapy, exchange transfusion, dexamethasone, circulatory support and mechanical ventilation. Pathophysiology and complications of falciparum malaria are discussed. The treatment of severe malaria should aim for a fast reduction in parasitaemia and toxic products. An exchange transfusion can be additive to parenteral chemotherapy. Blocking the over-reacting cell-mediated immune response, aggressive shock treatment, prevention of secondary infections and maintaining normoglycaemia might reduce morbidity and mortality of fulminant falciparum malaria.     

Cushing’s disease: A single centre’s experience using the linear accelerator (LINAC) for stereotactic radiosurgery and fractionated stereotactic radiotherapy

Cushing’s disease is hypercortisolaemia secondary to an adrenocorticotrophic hormone secreting pituitary adenoma. Primary management is almost always surgical, with limited effective medical interventions available. Adjuvant therapy in the form of radiation is gaining popularity, with the bulk of the literature related to the Gamma Knife. We present the results from our own institution using the linear accelerator (LINAC) since 1990. Thirty-six patients who underwent stereotactic radiosurgery (SRS), one patient who underwent fractionated stereotactic radiotherapy (FSRT) and for the purposes of comparison, 13 patients who had undergone conventional radiotherapy prior to 1990, were included in the analysis. Serum cortisol levels improved in nine of 36 (25%) SRS patients and 24 hour urinary free cortisol levels improved in 13 of 36 patients (36.1%). Tumour volume control was excellent in the SRS group with deterioration in only one patient (3%). The patient who underwent FSRT had a highly aggressive tumour refractory to radiation.     

Applications of positron emission tomography in neuro-oncology: A clinical approach

The field of neuro-oncology is concerned with some of the most challenging and difficult to treat conditions in medicine. Despite modern therapies patients diagnosed with primary brain tumours often have a poor prognosis. Imaging can play an important role in evaluating the disease status of such patients. In addition to the structural information derived from MRI and CT scans, positron emission tomography (PET) provides important quantitative metabolic assessment of brain tumours. This review describes the use of PET with radiolabelled glucose and amino acid analogues to aid in the diagnosis of tumours, differentiate between recurrent tumour and radiation necrosis and guide biopsy or treatment. [¹⁸F]Fluorodeoxyglucose (FDG) is the tracer that has been used most widely because it has a 2 h half life and can be transported to imaging centres remote from the cyclotron and radiochemistry facilities which synthesise the tracers. The high uptake of FDG in normal grey matter however limits its use in some low grade tumours which may not be visualised. [¹¹C] methionine (MET) is an amino acid tracer with low accumulation in normal brain which can detect low grade gliomas, but its short 20 min half life has limited its use to imaging sites with their own cyclotron. The emergence of new fluorinated amino acid tracers like [¹⁸F]Fluoroethyl-l-tyrosine (FET) will likely increase the availability and utility of PET for patients with primary brain tumours. PET can, further, characterise brain tumours by investigating other metabolic processes such as DNA synthesis or thymidine kinase activity, phospholipid membrane biosynthesis, hypoxia, receptor binding and oxygen metabolism and blood flow, which will be important in the future assessment of targeted therapy.     

Melanocortin 1 Receptor-derived peptides are efficiently recognized by cytotoxic T lymphocytes from melanoma patients

Background

Melanocortin 1 Receptor (MC1R) is expressed in a majority of melanoma biopsies and cell lines. We previously demonstrated that three hydrophobic low-affinity HLA-A2-restricted MC1R-derived peptides: MC1R_291–298, MC1R_244–252 and MC1R_283–291 can elicit cytotoxic T-lymphocytes (CTL) responses from normal donor peripheral blood lymphocytes (PBL). Moreover, peptide-specific CTL recognized a panel of MHC-matched melanomas, demonstrating that human melanoma cell lines naturally present MC1R epitopes. However, the natural presence of MC1R-specific T cells in melanoma patient's tumour and blood remains unknown.

Methods

The presence of anti-MC1R specific CD8⁺ T cells was established in a population of melanoma-specific T cells derived from peripheral blood mononuclear cells (PBMC) and tumour-infiltrating lymphocytes (TIL) from HLA-A2⁺ melanoma patients.

Results

CTLs specific for the three MC1R-derived peptides that lysed allogeneic HLA-A2⁺MC1R⁺ melanomas were elicited from PBMC, demonstrating the existence of an anti-MC1R T cell repertoire in melanoma patients. Moreover, TILs also recognized MC1R epitopes and HLA-A2⁺ melanoma cell lines. Finally, HLA-A2/MC1R₂₄₄-specific CD8⁺ T cell clones derived from TILs and a subset of MC1R₂₉₁ specific TILs were identified using HLA-A2/MC1R tetramers.

Conclusion

Our results demonstrate that MC1R-derived peptides are common immunogenic epitopes for melanoma-specific CTLs and TILs, and may thus be useful for the development of anti-melanoma immunotherapy.     

Long-term follow-up of transitional cell carcinoma of the bladder in childhood

BackgroundBladder tumours are rare in children, with only 0.38% of cases occurring in the first two decades of life.ObjectiveTo describe a long-term follow-up series of nine urothelial bladder tumours in children.Patients and methodsWe carried out a retrospective study covering the period from 1988 until 2005. We found that during this time, urothelial tumours had been diagnosed at our centre in eight patients (9 tumours) younger than 18 years old who reported an episode of haematuria. Diagnosis was attained through renal and bladder ultrasound in 85% of patients, and through cystoscopy under anaesthesia in 15%. All cases were treated by means of transurethral resection of the bladder, with ensuing follow-up using renal and bladder ultrasound and urinary cytology.MeasurementsPatients characteristics and outcome are evaluated.ResultsSingle exophytic tumours were present in seven (87.5%) of the patients, located either in the lateral wall or in the trigone; one patient showed two small tumours. The pathology was as follows: two G1Ta, one G1T1, one G2T1, and five G2Ta. There were no recurrences.ConclusionsTransitional cell carcinoma in childhood is of low grade and low aggressiveness. It has a good prognosis and recurrences are infrequent. We suggest performing a urinary cytology/cystoscopy every 6 months the first 2 years and urinary cytology/bladder ultrasound once a year.     

Gland-preserving robotic surgery for benign submandibular gland tumours: a comparison between robotic and open techniques

Benign tumours of the submandibular gland are usually treated surgically. Gland-preserving techniques, which can be used to completely remove the tumour, preserve the function of the gland and reduce complications, but conventional open operations result in obvious scars on the neck. We aimed to investigate the feasibility and efficacy of gland-preserving robotic surgery using a hairline approach. We compared robotic with open techniques for gland-preserving operations to remove benign tumours of the submandibular gland. Patients were matched for age and sex (4 in each group). All patients in the robotic surgery group had their tumours removed successfully through hairline approaches. No patient had operative complications or postoperative functional nerve deficit, and an aesthetically pleasing outcome was achieved by concealing the scars within the hairline. Robotic operations took longer than open operations. No recurrence was noted during follow-up. Gland-preserving robotic surgery is a feasible alternative to conventional techniques and has potential advantages for safety and aesthetic outcome.     

Co-occurrence in body site of malformations and cancer

In many malformation syndromes benign and malignant tumours develop more frequently than in the general population. Malformations result from an abnormal intrinsic developmental process. It can be hypothesised that disturbed regulation of cell growth as can become evident by the presence of benign and malignant tumours, which will occur at the same site of a malformation or at other sites at which the gene involved in the malformation is functioning.The present study aimed to compare the localisation of malignant and benign tumours to the localisation of major and minor characteristics of syndromes that have either of two malformations, i.e. microtia and hypospadias. To eliminate co-occurrence of a malformation syndrome and tumours by chance we confined evaluations to syndromes which have been described in >100 individuals. We identified 11 syndromes associated with microtia and 26 syndromes associated with hypospadias, for which co-localisation of (benign and malignant) tumours with (major and minor) syndrome characteristics was determined. In both groups of syndromes tumours were found to be localised at the same body site as the major and minor characteristics of the syndromes in two-third of the tumours. There was no significant difference in co-occurrence in site between benign and malignant tumours.We conclude that in two groups of malformation syndromes which go along with a different core malformation, benign and malignant tumours co-localise with the core malformation or with other sites at which the gene involved is functioning. This adds further proof that tumours in malformation syndromes can usually be explained by abnormal functioning of the same gene that has caused the malformation syndrome.