Intestinal permeability tests in coeliac disease

Intestinal permeability tests have been used to screen for a wide range of small intestinal diseases, including coeliac disease and enteric infections. Several probe molecules have been used to investigate intestinal permeability including monosaccharides, disaccharides, 51Cr-EDTA and polyethyleneglycol. While many factors may affect intestinal permeability tests, the use of two probe molecules, for example, lactulose and mannitol, and the expression of the result as a ratio minimises the effects of these extraneous factors. Rendering the test solution hyperosmolar was also found to increase the sensitivity of the test in detecting coeliac disease. Intestinal permeability is characteristically elevated in untreated coeliac disease, with a sensitivity of up to 96% for the dual sugar techniques. The reason for this is a consistent increase in the absorption of lactulose (via the paracellular route) due to increased "leakiness" of the intestine and a reduction in the absorption of mannitol (via the transcellular route) due to a reduction in surface area as a result of villous atrophy. The intestinal permeability test allows subjects to be selected for jejunal biopsy in whom the clinical features are compatible with coeliac disease and in timing a follow-up biopsy. It has been postulated that raised intestinal permeability may be involved in the pathogenesis of coeliac disease. Recently, serum measurements of the probe molecules may have a valuable role, particularly in paediatric patients. Sucrose permeability has also been proposed as an accurate marker of adult coeliac disease and shows promise as a noninvasive test.

EXPERT-SYSTEM SUPPORT USING BAYESIAN BELIEF NETWORKS IN THE DIAGNOSIS OF FINE-NEEDLE ASPIRATION BIOPSY SPECIMENS OF THE BREAST

Aim-To develop an expert system model for the diagnosis of fine needle aspiration cytology (FNAC) of the breast.

Methods-Knowledge and uncertainty were represented in the form of a Bayesian belief network which permitted the combination of diagnostic evidence in a cumulative manner and provided a final probability for the possible diagnostic outcomes. The network comprised 10 cytological features (evidence nodes), each independently linked to the diagnosis (decision node) by a conditional probability matrix. The system was designed to be interactive in that the cytopathologist entered evidence into the network in the form of likelihood ratios for the outcomes at each evidence node.

Results-The efficiency of the network was tested on a series of 40 breast FNAC specimens. The highest diagnostic probability provided by the network agreed with the cytopathologists' diagnosis in 100% of cases for the assessment of discrete, benign, and malignant aspirates. A typical probably benign cases were given probabilities in favour of a benign diagnosis. Suspicious cases tended to have similar probabilities for both diagnostic outcomes and so, correctly, could not be assigned as benign or malignant. A closer examination of cumulative belief graphs for the diagnostic sequence of each case provided insight into the diagnostic process, and quantitative data which improved the identification of suspicious cases.

Conclusion-The further development of such a system will have three important roles in breast cytodiagnosis: (1) to aid the cytologist in making a more consistent and objective diagnosis; (2) to provide a teaching tool on breast cytological diagnosis for the non-expert; and (3) it is the first stage in the development of a system capable of automated diagnosis through the use of expert system machine vision.

Dual-colour HER2/chromosome 17 chromogenic in situ hybridisation assay enables accurate assessment of HER2 genomic status in gastric cancer and has potential utility in HER2 testing of biopsy samples

Determination of HER2 protein expression by immunohistochemistry (IHC) and genomic status by fluorescent in situ hybridisation (FISH) are important in identifying a subset of high HER2-expressing gastric cancers that might respond to trastuzumab. Although FISH is considered the standard for determination of HER2 genomic status, brightfield ISH is being increasingly recognised as a viable alternative. Also, the impact of HER2 protein expression/genomic heterogeneity on the accuracy of HER2 testing has not been well studied in the context of gastric biopsy samples.

Suspected giant cell arteritis:A study of referrals for temporal artery biopsy

Background: The purpose of this study is to describe the nature of cases undergoing temporal artery biopsy (TAB) for suspected giant cell arteritis (GCA). Methods: A retrospective review of case notes was undertaken for all patients on whom ophthalmologists had performed TAB in 2 teaching hospitals between 1995 and 2001. Presenting symptoms, referring specialty, TAB result, treatment, and discharge diagnosis were recorded. Results: Ophthalmologists performed TAB on 110 patients for suspected GCA. A variety of specialties referred patients to ophthalmology for TAB; presenting symptoms varied with referral source. Of the 110 TABs, 21 (19%) were reported as positive for GCA, 84 (76%) were negative, and 5 (4.5%) were reported as inadequate. The symptoms most commonly associated with a positive TAB were visual disturbance (15/21) and headache (15/21).The odds ratios for having a positive TAB result rather than a negative result were 1.0 for the presence of headache, 4.1 for visual disturbance, and 6.7 for jaw claudication. Interpretation: Physicians were faced with a different population of GCA suspects than ophthalmologists. While physicians should be alert to the significance of visual symptoms or jaw claudication, ophthalmologists should be ready to facilitate prompt TABs when appropriate. TAB should be performed promptly and an adequate length of artery taken for biopsy. An argument can be made that TAB is not needed in cases of suspected GCA. However, a positive result provides firm justification for the use of steroids. We feel that TAB has a useful role and we make reference to methods to maximize its usefulness.

Freehand core biopsy in breast cancer: an accurate predictor of tumour grade following neoadjuvant chemotherapy?

Core biopsy is an increasingly used technique in the pre-operative diagnosis of breast carcinoma, as it provides useful prognostic information with respect to tumour type and grade. Neoadjuvant chemotherapy is being used in the treatment of large and locally advanced breast cancers but little is known regarding the correlation between tumour histology on pre-treatment core biopsy and that in residual tumour following primary chemotherapy and surgery. This study aimed to evaluate the accuracy of core biopsy in predicting these features in patients treated with primary chemotherapy. One hundred and thirty-three patients with carcinoma of the breast diagnosed on clinical, radiological and cytological examination underwent core biopsy, followed by primary chemotherapy (with cyclophosphamide, vincristine, doxorubicin and prednisolone) and surgery. The false-negative rate for pre-treatment core biopsy was 14%, with 91% agreement between the grade demonstrated on core biopsy and that in the residual tumour following completion of chemotherapy. Tumour type in the residual post-chemotherapy tumour was predicted by core biopsy in 84%. This study suggests that pre-treatment core biopsy histology accurately predicts residual tumour histology following primary chemotherapy and surgery in patients with breast cancer. (C) 2002 Elsevier Science Ltd. All rights reserved.

Sentinel lymph node biopsy in breast cancer - is lymphoscintigraphy really necessary?

The role of lymphoscintigraphy in sentinel node biopsy in breast cancer remains debatable. This study assesses the value of lymphoscintigraphy in axillary sentinel node biopsy in women undergoing surgery for breast cancer. Sixty-two patients underwent sentinel node biopsy using a combination of technetium-label led nanocolloid, lymphoscintigraphy and patent blue dye. Lymphoscintigraphy was successful in 84% of patients. Axillary sentinel nodes were identified intraoperatively in all these patients. Internal mammary nodes were identified on lymphoscintigraphy in 19%. Despite lymphoscintigraphy being unsuccessful in 10 patients, axillary sentinel nodes were found intraoperatively in eight of these patients. Lymphoscintigraphy did not increase the detection rate of axillary sentinel nodes and a negative scan did not preclude identification of an axillary sentinel node intraoperatively. This study questions the contribution of lymphoscintigraphy in axillary sentinel node biopsy, however its value may lie in the detection of extra-axillary nodes. (C) 2002 Published by Elsevier Science Ltd.

Sentinel lymph node biopsy in impalpable breast cancer

Sentinel lymph node biopsy has been investigated using combined radioactive colloid and supra vital blue dye in 27 patients with impalpable breast cancers. Sentinel nodes were identified in 25 cases (93%). Seven patients had involved nodes of whom all had a positive sentinel node. Sentinel node biopsy is ideally suited for use in impalpable breast cancers. (C) 2000 Harcourt Publishers Ltd.

Lymphatic mapping and sentinel node biopsy in breast cancer

Background Sentinel lymph node biopsy is a recently developed, minimally invasive technique for staging the axilla in patients with breast cancer. It has been suggested that this technique will avoid the morbidity associated with more extensive axillary dissection. A wide range of different methods and materials has been employed for lymphatic mapping, but there has been little consensus on the most reliable and reproducible technique.

Methods This is a comprehensive review of all published literature on sentinel node biopsy in breast cancer, using the Medline and Embase databases and cross-referencing of major articles on the subject.

Results and conclusion Sentinel node biopsy is a valid technique in breast cancer management, providing valuable axillary staging information. The optimal technique of lymphatic mapping utilizes a combination of vital blue dye and radiolabelled colloid. However, there remain controversial issues which require to be resolved before sentinel node biopsy becomes a widely accepted part of breast cancer care.

The management of radial scars of the breast - does core biopsy help?

Purpose: To compare the effectiveness of fine needle aspiration cytology (FNAC) with core biopsy (CB) in the pre-operative diagnosis of radial scar (RS) of the breast.

Patients and methods: A retrospective analysis was made of all radial scars diagnosed on surgical histology over an 8-year period. Comparison was made between the results of different preoperative needle biopsy techniques and surgical histology findings.

Results: Forty of 47 patients with a preoperative radiological diagnosis of radial scar were included in this analysis. Thirty-eight patients had impalpable lesions diagnosed on mammography and two presented with a palpable lump. FNAC (n=17) was inadequate in 47% of patients, missed two co-existing carcinomas found in this group, and gave a false positive or suspicious result for malignancy in 4 patients. CB (n=23) suggested a RS in 15 patients, but only diagnosed 4 out of 7 co-existing carcinomas found in this group.

Conclusion: CB is more accurate than FNAC in the diagnosis of RS. However, these data demonstrate that CB may offer little to assist in the management of patients with RS. In summary, this paper advocates the use of CB in any lesion with a radiological suspicion of carcinoma and diagnostic excision of all lesions thought to be typical of RS on mammography.

Efficacy and safety of peri-prostatic local anaesthetic injection in tram-rectal biopsy of the prostrate:A prospective randomised study

Objective: To assess the efficacy and safety of periprostatic lignocaine injection in trans-rectal ultrasound (TRUS) -guided biopsy of the prostate gland.

Methods: Ninety- six men (mean age 65 years, range 47-74) undergoing TRUS biopsy were randomised into the local anaesthetic (LA) or placebo group. Six to twelve biopsy cores were taken, the majority being 10 cores. Patients were asked to fill in the expected pain score on a visual analogue scale (VAS) prior to the procedure. They also completed the actual pain experienced on VAS after the biopsy. The incidence of complications was documented.

Results: The age, mean prostate specific antigen (PSA) were comparable in both groups. The expected pain score was also comparable (5.2 +/- 1.6 in LA, 5.0 +/- 1.4 in Placebo). In the LA group, the mean actual pain score was 3.0 +/- 1.8 and in the placebo group it was 6.5 +/- 2.2 (P = 0.0001). When patients were asked whether they would undergo the procedure again in the same way, 100% of the LA group and only 64% of the placebo group responded 'yes'(P=0.002 using Fisher's test). The complication rates were not significantly different between the two groups.

Conclusion: Peri-prostatic injection of local anaesthetic is safe and reduces discomfort significantly, and should be routinely offered to patients.

Lifestyle factors and small intestine adenocarcinoma risk: a systematic review and meta-analysis.

Background: Although the incidence of small intestinal adenocarcinoma (SIA) is low, rates are increasing and little information regarding modifiable lifestyle risk factors is available.

Aim: To provide a systematic review of lifestyle factors and SIA risk.

Methods: Ovid MEDLINE, EMBASE and WEB OF SCIENCE were searched from inception to Week 1 October 2013. Nine publications that reported on SIA risk in relation to alcohol intake (n=6), tobacco smoking (n=6), diet (n=5), body mass (n=3), physical activity (n=1), hormone use (n=1) and/or socio-economic status (n=3) were retrieved. Results for alcohol, smoking and SIA risk were pooled using random-effects meta-analyses to produce relative risks (RR) and 95% confidence intervals (CI).

Results: The summary RR for individuals consuming the highest versus lowest category of alcohol intake was 1.51 (95% CI 0.83-2.75; n=5 studies) with significant increased risks emerging in sensitivity analysis with reduced heterogeneity (RR: 1.82, 95% CI: 1.05-3.15; n=4 studies). The pooled SIA RR for individuals in the highest versus lowest category of smoking was 1.24 (95% CI 0.71-2.17; n=5 studies). In relation to dietary factors, high fibre intakes and normal body weight may be protective, while high intakes of red/processed meat and sugary drinks may increase SIA risk. Evidence on socio-economic status and SIA risk was equivocal. Data on other factors were too sparse to draw any conclusions.

Conclusions: Alcohol may be associated with an increased risk of SIA. Further investigation of lifestyle factors, particularly alcohol, smoking and diet, in the aetiology of this cancer is warranted in large consortial studies.