The role of breast FNAC in diagnosis and clinical management: a survey of current practice.

Most participating countries have now adopted a triple assessment approach, i.e. clinical,imaging and pathology, to breast diagnosis, with FNAC as the first-line pathological investigation in both screening and symptomatic populations, with the exception of microcalcifications. Pathologists specialized in cytopathology are best qualified to collect and interpret FNAC samples, but this is not always possible or practical. Radiologists involved in breast imaging should ensure that they have the necessary skills to carry out FNAC under all forms of image guidance. Best results are achieved by a combination of both techniques, as shown in the image-guided FNAC in the presence of the cytopathologist. The majority of European countries use similar reporting systems for breast FNAC (C1-C5), in keeping with European Guidelines for Quality Assurance in Breast Cancer Screening and Diagnosis, although some still prefer descriptive reporting only. When triple assessment is concordant, final treatment may proceed on the basis of FNAC, without a tissue biopsy. ER and PR assessment can be done safely on FNAC material. However, not all institutions may have expertise in doing this. HER-2 protein expression on direct cytological preparations is insufficiently reliable for clinical use, although its use for FISH is possible, if expertise is available. The majority of participants practise a degree of one-stop diagnosis with a cytopathologist present in the out-patient clinic. Formal recognition of the importance of the time spent outside the laboratory, both for cytopathologist and cytotechnologist, is necessary in order to ensure appropriate resourcing. The use of core biopsy (CB) has increased, although not always for evidence-based reasons. CB and FNAC are not mutually exclusive. FNAC should be used in diagnosis of benign, symptomatic lesions and CB in microcalcifications, suspicious FNAC findings and malignancies where radiology cannot guarantee stromal invasion.

The future of cytopathology in Europe. Will the wider use of HPV testing have an impact on the provision of cervical screening?

The emphasis of the EFCS Congress held in Venice in October 2006 was on the future of Cytopathology in relation to events in Europe. Much of the discussion centred on the role of human papilloma virus testing and its impact on the provision of cervical screening. The following is a transcript of the discussion that took place at the Advisory Board Meeting for the journal Cytopathology, with some additional written comments received prior to the meeting. A brief summary has been provided as a conclusion by Dr A. Herbert.

Fine needle aspiration cytology: a survey of current European practice.

Fine needle aspiration cytology (FNAC) is practised widely throughout Europe. The majority of countries have dedicated cytopathologists as well as histopathologists practicing cytology. Despite this, FNAC is performed mostly by clinicians and radiologists except in the larger centres with dedicated staff with a special interest in cytopathology. The advent of One-Stop diagnostic services and image-guided procedures are prompting further development of FNAC clinics where cytopathologists take their own samples, issue reports in the same clinical session and take extra material for ancillary tests to complete the diagnosis. The volume of FNAC work varies accordingly; in dedicated centres FNAC represents up to 80% of the workload whilst, in the majority of countries, it represents one quarter or less. Hence, the rate of inadequate FNAC varies widely, depending on the local sampling policies and the organ, but does not exceed 25% in any of the countries. The most sampled organs are breast and thyroid, followed by lymph nodes. Most countries have dedicated training in cytopathology for pathology trainees, the duration varying between 6 months and 2 years of the total training time. This discussion, focusing on European practices, highlights the heterogeneity of FNAC activity but also its success in many centres where it is practiced to a high standard, particularly in breast, thyroid and lymph node pathology. The relatively high rate of inadequate material in some centres reflects local policies and calls for greater uniformity of FNAC practice, particularly specimen sampling. To achieve this, the future direction should concentrate on specialist training, to include performing as well as interpreting FNAC, as part of the curriculum. Current emphasis on web-based training may not provide first hand experience of the FNAC procedure and should be supplemented by attending FNAC clinics and developing the technique to its full potential.

Polyethylene glycol versus sodium phosphate in bowel cleansing for colonoscopy: a randomized trial.

BACKGROUND AND STUDY AIMS: There have been conflicting results regarding the adverse effects of established bowel cleansing regimens. The aim of the present study was to compare the effects of three bowel cleansing regimens on subjective well-being, electrolyte balance, cardiac arrhythmia, and the microscopic post-cleansing appearance of the colonic mucosa. PATIENTS AND METHODS: A total of 231 consecutive outpatients were randomly assigned to receive bowel preparation for colonoscopy with either 4 l polyethylene glycol (PEG; group I, n = 76); 2 l PEG plus 10 mg Bisacodyl (group II, n = 71); or 90 ml sodium phosphate (group III, n = 84). After bowel preparation, the participants completed a questionnaire on symptoms. Endoscopists blinded to the regimen used gave scores for the quality of cleansing at endoscopy, ranging from poor (0) to very good (5). Blood samples were taken before and after bowel cleansing, electrocardiographic monitoring was used during colonoscopy, and mucosal biopsy samples were taken in the sigmoid colon. RESULTS: Bowel preparation in group II was poorer (mean score 3.26) than in groups I (3.88) and III (4.01); P < 0.001 (II vs. III), P < 0.001 (I vs. II). The frequency of arrhythmias and post-cleansing mucosal inflammation was similar in all three groups. Lower serum potassium and higher serum phosphate concentrations were found in group III in comparison with the other groups ( P < 0.001). CONCLUSIONS: No differences were detected regarding the effectiveness and safety of bowel preparation with PEG alone and sodium phosphate in individuals without cardiac, renal, or hepatic failure, despite a significantly stronger alteration of the electrolyte balance with sodium phosphate.

Smoking, folate and methylenetetrahydrofolate reductase status as interactive determinants of adenomatous and hyperplastic polyps of colorectum.

Most studies demonstrate increased risk of colorectal cancer (CRC) and adenomas in folate-deficient subjects or that high folate intake may afford some protection. Smoking increases such risk in some but not all studies. We investigated whether smoking, folate status and methylenetetrahydrofolate reductase (MTHFR) genotype predict the risk of adenomatous and hyperplastic polyps of colorectum. By colonoscopy, the type, number, size and extent of dysplasia of colorectal polyps were assessed in 443 subjects aged 63-72 years. We also determined RBC folate and the C667T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. Smoking, folate status and the C677T MTHFR polymorphism were strong, interactive determinants of high-risk adenomas (HRAs, defined as adenomas > or =10 mm in diameter, adenomas with villous components or with severe dysplasia). The risk was particularly high in smokers with low folate and the CT/TT genotype (risk category T) and in smokers with high folate and the CC genotype (risk category C). With non-smokers with low folate and the CC genotype as reference, the odds ratios (OR, 95% CI) were 8.7 (2.5-29.7) in category T and 9.9 (2.6-38.4) in category C. Notably, this risk pattern was also observed for hyperplastic polyps. In conclusion, in smokers, high folate status may confer increased or decreased risk for HRAs, depending on the MTHFR genotype. These data demonstrate the strong gene-nutrition interaction involving the C677T MTHFR polymorphism.

The effect of attending a flexible sigmoidoscopic screening program on the prevalence of colorectal adenomas at 13-year follow-up.

OBJECTIVES: Understanding the epidemiology of colorectal adenomas is a prerequisite for designing follow-up programs after polypectomy. The aim of the study was to investigate the effect of polypectomy on the long-term prevalence of adenomas. METHODS: In 1983, a total of 799 men and women aged 50-59 yr were drawn from the general population register. Of these, 400 comprised a screening group and 399 a matched control group. The screenees were invited to undergo a once-only flexible sigmoidoscopy. Persons with polyps had a baseline colonoscopy with follow-ups in 1985 and 1989. In 1996, both the screenees and the controls were invited to a colonoscopic examination. RESULTS: In 1996, a total of 451 (71%) individuals attended. Adenomas were found in 78 (37%) individuals in the screening group and 103 (43%) in the control group, relative risk (95% confidence interval): 0.9 (0.7-1.1), p = 0.3, and high-risk adenomas (severe dysplasia, adenomas > or = 10 mm, villous components) were found in 16 (8%) and 32 (13%), respectively; relative risk (95% confidence interval): 0.6 (0.3-1.0), p = 0.07. CONCLUSIONS: There was no significant difference in adenoma prevalence between the group after the screening program and the controls after the usual care. There was a trend toward more high-risk adenomas in the control group. This suggests a very limited effect of one-time screening sigmoidoscopy with surveillance colonoscopy on the prevalence of adenomas, but a preventive effect on the development of high-risk adenomas consistent with the reported effect on cancer prevention.

Flexible sigmoidoscopy or colonoscopy as a screening modality for colorectal adenomas in older age groups? Findings in a cohort of the normal population aged 63-72 years.

BACKGROUND: Most cases of colorectal cancer originate from adenomas. Removing adenomas has been shown to reduce the incidence of colorectal cancer. The design of cost effective endoscopic screening programmes requires a knowledge of the distribution of adenomas in different age groups. AIM: To investigate the distribution of colorectal adenomas in older age groups in the normal population. METHOD: A total of 356 men and women selected randomly from the population register were offered a colonoscopic screening examination to detect and remove polyps. RESULTS: In all, 241(68%) subjects, mean age 67.4 years (range 62-73), attended. The caecum was intubated in 193 (80%), and in this group 32 (38%) women and 51 (47%) men had adenomas. One hundred and ten (54%) of the adenomas and 11 (39%) of the "high risk adenomas" (adenomas larger than 10 mm in diameter, adenomas containing villous components, and adenomas with severe dysplasia) were found proximal to the sigmoid colon. In 36 (43%) of the subjects with adenomas, the adenomas were only found proximal to the sigmoid colon. Twenty two (11%) subjects had more than two adenomas. Of 203 adenomas discovered, 189 (93%) were less than 10 mm in diameter. CONCLUSION: More than half of the adenomas were localised proximal to the sigmoid colon, and, in nearly half of the adenoma bearing subjects examined, the adenoma was proximal to the descending colon. This indicates that a sigmoidoscopic screening examination in this age group would miss a substantial number of adenomas, but this may be acceptable as the vast majority of proximal adenomas do not progress to clinical cancer within the life expectancy of this age group.

Population-based surveillance by colonoscopy: effect on the incidence of colorectal cancer. Telemark Polyp Study I.

BACKGROUND: Most cases of colorectal cancer (CRC) develop from adenomas. Polypectomy is believed to reduce the incidence of CRC, but this effect has never been explored in prospective controlled studies. The aim of the present study was to evaluate the effect of polypectomy on colorectal cancer incidence in a population-based screening program. METHODS: In 1983, 400 men and women aged 50-59 years were randomly drawn from the population registry of Telemark, Norway. They were offered a flexible sigmoidoscopy and, if polyps were found, a full colonoscopy with polypectomy and follow-up colonoscopies in 1985 and 1989. A control group of 399 individuals was drawn from the same registry. In 1996 both groups (age, 63-72 years) were invited to have a colonoscopic examination. Hospital files and the files of The Norwegian Cancer Registry were searched to register any cases of CRC in the period 1983-96. RESULTS: At screening endoscopy 324 (81%) individuals attended in 1983 and 451 (71%) in 1996. From 1983 to 1996, altogether 10 individuals in the control group and 2 in the screening group were registered to have developed CRC (relative risk, 0.2; 95% confidence interval (CI), 0.03-0.95; P = 0.02). A higher overall mortality was observed in the screening group, with 55 (14%) deaths, compared with 35 (9%) in the control group (relative risk, 1.57; 95% CI, 1.03-2.4; P = 0.03). CONCLUSION: Endoscopic screening examination with polypectomy and follow-up was shown to reduce the incidence of CRC in a Norwegian normal population. The possible effect of screening on overall mortality should be addressed in larger studies.

Prognostic factors in muscle-invasive bladder cancer treated with radiotherapy: an immunohistochemical study.

OBJECTIVE: To determine the prognostic role of p53, Ki-67 and p21 for patients with muscle-invasive bladder cancer treated with curative intent by radiotherapy. PATIENTS AND METHODS: The study included 131 patients (24 women and 107 men, median age 72 years, range 40-86) with transitional cell carcinoma (T2-T4) treated with external definitive pelvic radiotherapy between 1985 and 1994. Paraffin-embedded pretreatment biopsies from the patients were examined for the presence of p53, p21 and Ki-67, detected by immunohistochemistry, and related to tumour stage, grade and patient survival. RESULTS: The expression of p53 protein correlated positively with the detection of Ki-67 (P < 0.05) but did not correlate with p21. None of the immunohistochemical variables (p53, p21 or Ki-67) correlated with T category and only Ki-67 correlated with histological grade. Patients with > 5% p21 expression tended to live longer than those with < 5% (P = 0.09). In a multivariate analysis, the T category (T2/T3 vs. T4), histological grade (2 vs. 3) and p21 expression (< or = 5% vs. > 5%) were independent prognostic factors for overall survival. CONCLUSION: Further investigation is warranted in patients with muscle-invasive bladder cancer undergoing different types of treatment p21 seems to play an independent prognostic role in these patients, in addition to T category and grade.

[Schistosomiasis of the urinary bladder]. / Urinblaereschistosomiasis.

A 12 year old male immigrant from Somalia was admitted to hospital after several years of haematuria and dysuria. Microscopic examination of the urine revealed eggs of the Schistosoma haematobium. Urine culture was negative. Cystoscopy showed a characteristic bilharzial tubercle, and numerous sandy patches were also seen. Mucosal biopsy showed schistosoma eggs, some with calcification. There was squamous cell metaplasia and infiltration of plasma cells and eosinofilic granulocytes. The patient was treated with praziquantel 600 mg x 4 for two days. Three months later no schistosoma eggs were seen in his urine and cystoscopy was negative. In immigrants from countries where bilharzia is endemic, it should be considered a differential diagnosis in patients with haematuria.

[Renal angiomyolipoma as a cause of acute retroperitoneal hemorrhage]. / Renalt angiomyolipom som årsak til akutt retroperitoneal blødning.

Angiomyolipoma is a mesenchymal tumor, usually found in the kidney. The pleomorphic appearance and involvement of regional lymph nodes may simulate malignancy, but angiomyolipomas are classified as benign. Renal angiomyolipomas are found in approximately 40% of tuberous sclerosis patients and are usually small, bilateral and asymptomatic nodules. Spontaneous rupture and retroperitoneal haemorrhage may be experienced with larger tumours. Although findings by ultrasonography and computerized tomography are specific for this lesion, histological examination is necessary for a final diagnosis. Small asymptomatic angiomyolipomas should be followed up with sequential CT scans and be removed by enucleation or partial nephrectomy when they reach a size of more than 4 cm in diameter. If the patient suffers from massive bleeding, it is very difficult to preserve the kidney. We report on a 61-year old women who experienced acute retroperitoneal haemorrhage. She was given ten blood transfusions before she was operated on with en bloc removal of the left kidney, an angiomyolipoma with a diameter of 10 cm and a large haematoma.

[Cystitis cystica--a premalignant condition?]. / Cystitis cystica--en premalign tilstand?

Although cystitis cystica is considered to be a premalignant disease of the urinary bladder, remarkably few reports document the progression from cystitis cystica and glandularis to carcinoma of the bladder. We describe three patients where cystitis cystica was demonstrated 12, three and one month before diagnosis of cancer. We believe cystitis cystica reflects mobilization of the humoral immune defence mechanism in response to various agents, among these a subclinical malignant tumour.