The use of sentinel node sampling in vulval cancer.

Between March 2007 and December 2009, 38 patients underwent sentinel lymph node biopsy (SLNB) sampling, along with vulvectomy, in their management of vulval cancer. A review has been conducted to establish the reliability and accuracy of the new procedure compared with the traditional total inguinofemoral lymphadenectomy. We also aimed to establish both the short- and long-term morbidities of both total inguinofemoral lymphadenectomy and SLNB and to assess the duration of hospital stay in both groups. Our data have shown a reduced short- and long-term morbidity and reduced length of hospital stay for the SLNB procedure. We conclude that it is a reliable and safe procedure, however it should only be conducted in cancer centres.

Preoperative Scintigrams to Identify the Sentinel Lymph Node in Breast Cancer: a Waste of Time?

Sentinel lymph node biopsy (SLNB) remains the gold standard for assessing axillary node status in breast cancer. Preoperative scintigrams have been used to identify the sentinel lymph node (SLN); however, their use is controversial. Studies suggest they add little to successful SLN detection in theatre, immediately prior to node excision. They have been associated with high false negatives, time expense, patient dissatisfaction, and unnecessary costs. The aim of the present study was to evaluate the diagnostic accuracy of scintigrams in comparison to intraoperative SLN identification techniques. This study included all patients undergoing a SLNB for breast cancer from April 2010 to 2011. Scintigram reports, operation notes, and histology results were analyzed. Mann-Whitney U and chi-squared tests were used for statistical analysis of data. Two hundred nineteen female patients with a median age of 59.6 years (24.0-89.9 years) were included in this study. Scintigram was performed in 185 and not in 34 patients due to time constraints. Combined γ-probe and Isosulfan blue dye for SLN detection (intraoperative methods) have an identification rate of 98.2 % (p = 0.005), compared to 92.4 % (p = 0.088) from scintigrams alone. Scintigrams confer no additional advantage to the operating surgeon for successful SLN detection and excision in theatre. Intraoperative SLN identification is more accurate and reliable. Routine scintigram use is unjustified and should be withdrawn from current practice.

Effect of pindolol versus atenolol on lipid profile in hypertensive patients.

The effect of pindolol (a beta-blocker with intrinsic sympathomimetic activity, ISA) on fasting plasma lipid profile in 30 hypertensive patients was compared with atenolol (without ISA) in a crossover single blind study. Both drugs lowered blood pressure. HDL-cholesterol increased significantly with pindolol (from 1.15 +/- 0.05 to 1.34 +/- 0.05 mmol/l at 12 weeks, P less than 0.001), but not with atenolol. VLDL-cholesterol increased with atenolol (from 0.57 +/- 0.09 to 0.86 +/- 0.14 mmol/l at 12 weeks, P less than 0.002), while there was no change with pindolol. These changes in lipoprotein profile suggest a more favourable effect of pindolol than of atenolol on lipid profile.

The influence of major histocompatibility complex class II genes and T-cell Vbeta repertoire on response to immunization with HBsAg.

Nonresponsiveness to HBsAg vaccination is observed in 5-10% of vaccine recipients and is possibly caused by a defect in the T helper cell compartment. The immune response to HBsAg is influenced by genes of the major histocompatibility complex. We have investigated MHC class I and class II antigens in 53 adult responders and 73 nonresponders. Results obtained in this first study were tested in a second study with 56 responders and 62 nonresponders from an infant vaccination trial. In addition, the peripheral Vbeta-chain T-cell receptor repertoire was investigated using monoclonal antibodies and flow-cytometry in 26 adult responders and 38 nonresponders. As previously reported, nonresponsiveness to HBsAg vaccination was associated with DRB1*3 and DRB1*7. In addition, DRB1*13 was significantly increased among vaccine responders (35.2% vs 5.4%;p < 0.0001) suggesting an immune response promoting effect for this allele whereas the closely related allele DRB1*14 was associated with nonresponse in the infant study. There was no evidence for a hole in the T cell receptor Vbeta repertoire. In conclusion, in agreement with results obtained in mice there appears to be a hierarchy of DRB1* genes in the HBsAg immune response. The possible differential association of DRB1*13 and DRB1*14 may allow the identification of differences between responsiveness and nonresponsiveness to a few amino acid differences in the beta1-domain of the class II heterodimer.

Effect of nifedipine and mefruside on renal function and platelet function in hypertensive patients.

A study was carried out in 16 patients with moderately severe hypertension to investigate the effects of nifedipine, given alone or combined with a diuretic, on blood pressure and on renal and platelet function. After 4 weeks on placebo, patients were randomized to receive treatment for 6 weeks with either 20 mg, nifedipine twice daily or 25 mg mefruside once daily on a double-blind, double-dummy basis. All patients then received treatment for a further 6 weeks with a combination of the two drugs in the same dosage as before. The results of blood pressure measurements and laboratory investigations during the three phases of the study showed that significantly better blood pressure control was achieved with nifedipine alone than with mefruside alone. Mefruside had an additional hypotensive effect when added to nifedipine. There was no significant change in the renal blood flow or glomerular filtration rate, with a satisfactory control of blood pressure. There was also no detectable change in platelet aggregation with increasing concentrations of ADP and ristocetin. An adaptive mechanism could be responsible for the apparent lack of change compared with single dose studies.

An evaluation of the efficacy and safety of doxazosin in the treatment of hypertension associated with renal insufficiency.

The efficacy, safety and potential effect on renal function of doxazosin were studied in hypertensive patients with renal impairment. Thirty adult patients with moderate hypertension (DBP between 95-114 mmHg and SBP less than 210 mmHg) and moderately impaired renal function of varying underlying pathology (serum creatinine between 220-640 mumol/l) were given doxazosin, either as monotherapy or part of polytherapy, in an open study. Their average duration of doxazosin therapy was 75 days and the median dose was 2 mg. With doxazosin treatment, the mean supine and standing SBPs were reduced by 15 mmHg and 13 mmHg, respectively. These changes were highly significant (P less than 0.0001). Supine and standing DBPs were also significantly reduced by 16 mmHg and 17 mmHg, respectively (P less than 0.0001). Heart rate was increased by 4 beats/min (mean maximum change); this was statistically, but not clinically, significant. There was a small but significant rise in serum creatinine (mean value, 35 mumol/l) in the group as a whole over a mean period of 75 days. This was considered to be compatible with the natural progression of the underlying renal pathology. Retrospective plotting of the reciprocal of available serum creatinine values against time during the months before doxazosin therapy yielded a linear relationship which supported this hypothesis. One patient withdrew from the study because of a rapid rise in serum creatinine concentration during the placebo run-in phase. Overall, side effects were minimal and did not necessitate reducing the dosage or discontinuing active therapy. The results of this study indicate that doxazosin is effective and well-tolerated in the treatment of hypertension with concomitant renal insufficiency and does not appear to compromise renal function.

A comparison of simplified and standard methods for the measurement of glomerular filtration rate and renal tubular function.

Two methods of measuring the clearance of 99Tcm DTPA, OIH and iothalamate were compared with standard techniques of measuring the clearance rates of inulin and sodium para-aminohippurate. The best correlation was between the clearance of subcutaneously injected radiolabelled iothalamate or 99Tcm DTPA and that of inulin. 99Tcm DTPA and 131I OIH clearances measured by a two blood sample technique did not give as good a correlation with inulin and PAH clearances respectively. When measurements of GFR and tubular function were repeated on the same patients the changes measured by inulin and PAH clearances did not correlate with those measured by the two blood sample technique using 99Tcm DTPA and OIH. Our results suggest that the clearance of subcutaneously injected iothalamate or DTPA can replace inulin clearance measurements. The two blood sample technique of measuring DTPA and OIH clearance does not directly reflect inulin and PAH clearance and is insufficiently reproducible to be used to follow changes in renal function.

Out-of-hours weekend scintigraphy: assessing/predicting the need.

We have assessed the potential impact of a regular half-day session on Saturday only, or Sunday only, and compared this with a whole weekend on-call service for lung scans. We predicted the effect of these services using the data gathered over 2 years (1992-94), looking at the results of lung scans and admission and discharge of patients. The on-call service in all three cases would be justified if resources from the savings on patient discharge and bed availability could be earmarked for the nuclear medicine service. The cost of introducing such an on-call service for the department would be Pounds 3000 per year per session at the weekend and up to Pounds 10,000 per year for a full weekend on-call service. The total cost to the hospital would be negligible.

Are MIBI/tetrofosmin heart studies a potential radiation hazard to technologists?

The number of nuclear medicine studies is increasing and they are becoming more complex and time-consuming. In particular, this is true of myocardial perfusion investigations. We use a one-day protocol for these studies, utilizing 99Tc(m)-MIBI or 99Tc(m)-tetrofosmin with tomographic rest images (250 MBq) acquired in the morning and exercise images (750 MBq) approximately 4 h later after pharmacological stress. Imaging technologists are concerned about continual exposure to 1000 MBq 99Tc(m) per study. Radiation doses were measured during rest (1.0 microSv, n = 18), exercise (2.5 microSv, n = 18) and stress administration (2.0 microSv, n = 16), giving a total dose of 5.5 microSv per combined cardiac study. We have previously shown that the average dose per radionuclide study (excluding myocardial perfusion studies) is 1.5 microSv. Although 5.5 microSv is higher, a technologist is highly unlikely to exceed current dose limits. New EC legislation, however, is expected to reduce these limits, which may lead to more classified workers. Pregnant technologists should avoid, if possible, combined cardiac studies, especially if performing other nuclear medicine duties.

Can reduced imaging times be used for scintimammography?

A reduction in acquisition times from 10 to 5 min for scintimammography does not reduce the diagnostic value of the study when imaging for detection of breast lesions. The test showed an overall sensitivity of 96%, specificity of 100% and accuracy of 98% for breast lesions visualized on both 5 and 10 min acquisitions. Even if lymph node detection is the primary concern of the study, longer scan times do not increase the sensitivity of the test (40% on both 5 and 10 min). Scintimammography is poor at detecting lymph nodes (sensitivity 40%, specificity 69-82%) and is not useful for assessing lymph node involvement. A reduction in imaging times appeared to be consistent on both camera systems tested, which have very different display outputs. This would indicate that other departments may be able to reduce times on their systems without affecting the quality of the study. The detection of breast lesions was also consistent between reporters.

Counting the cost of patients who do not attend nuclear medicine departments.

The mean rate of non-attendance at this hospital is 16%, with the Nuclear Medicine Department averaging 4%. Although only a small percentage, increasing demand for nuclear medicine studies has led to a need for greater efficiency to reduce financial losses. From April 1995 to March 1996, 104 patients did not attend over a range of 16 studies. We examined the types of study, patients and costs. The costs of wasted staff time, camera time and radiopharmaceutical ranged from pound sterling 24 (99Tc(m) thyroid) to pound sterling 470 (75Se cholesterol adrenal). This results in a loss equivalent to pound sterling 7258 over the year. There was no significant difference in non-attendance rates between different types of procedure, source and type of referral, or in the three age groups: children, working and retired population. Finally, we looked at cultural origins, segregating the groups into Asian and European origins based on surname. A significantly higher proportion of patients of Asian origin did not attend. This study has shown that it may be of benefit to target specific groups and tests. For example, at City Hospital, perhaps we should concentrate on our Asian community to ensure they understand fully what the study involves. It would also be worthwhile targeting the more expensive nuclear medicine studies.

Radiation doses from nuclear medicine patients to an imaging technologist: relation to ICRP recommendations for pregnant workers.

The ICRP has now recommended that the dose limit to the surface of the mother's abdomen during the declared term of pregnancy is reduced to 2 mSv. Direct measurements of the radiation dose to technologists carrying out a variety of imaging studies were made. The average dose ranged from 0.3 micro Sv for a liver scan to 5.3 micro Sv for a brain scan. Using national data for the frequency of nuclear medicine studies, a weighted average figure of 1.5 micro Sv per study was derived. A technologist could therefore perform approximately eight imaging studies per day during the declared term of her pregnancy and remain within the proposed limit. Generally, there should be no need to alter a technologist's duties during her pregnancy, and these findings should be helpful in allaying any anxiety.

Relationship between myocardial counts and patient weight: adjusting the injected activity in myocardial perfusion scans.

It is generally accepted that the quality of myocardial images deteriorates with increasing patient weight. This is attributed to a reduction of counts detected from the myocardium. In this paper we have looked at the count reduction in obese patients and suggest a workable algorithm to increase the injected activity to compensate for this loss of count. In this prospective study, 64 consecutive patients with normal myocardial images were selected to include a weight range of 50-120 kg. The height, weight and gender of patients were noted. Each patient had two studies (total of 128 studies), one at rest and one following stress with adenosine and 20-40 W bicycle exercise. Total myocardial counts were calculated from the back-projected views. The total myocardial counts per MBq of the injected activity were calculated. There was no significant difference in the injected activity and the size of the heart (pixel length of heart) between stress and rest, or gender of the patient. The normalized myocardial counts were not different between men and women, but the counts were slightly, although not significantly, higher ( P=NS) with adenosine and exercise (mean of 243 x 10(3) counts) compared to rest images (229 x 10(3) counts). There was a significant progressive loss of counts in patients with increasing weight, body mass index or body surface area ( P<0.001). There was no significant difference in the changes in counts with weight between male and female, or rest and stress studies. The combined data from all the studies were used to calculate the correlation coefficient and the slope of the line for reduction of cardiac counts with a patient's weight, body mass index, and body surface area. The best correlation was with patient weight ( r=0.58, P<0.001). This was used to calculate the increase in injection activity with increasing weight to maintain the same average counts as achieved in a 70 kg patient with a 400 MBq injection. We suggest that the injection activity should increase from 100% for a 70 kg patient to 140% for 110 kg, 200% for 140 kg, and 250% for a 150 kg patient.

Adsorption of radiopharmaceuticals to syringes leads to lower administered activity than intended.

In this study we examined the delivered activity of radiopharmaceuticals injected into patients and the various factors which lead to incomplete delivery. Four commonly used 99Tcm radiopharmaceuticals were included, namely pertechnetate, methylene diphosphonate (MDP), macro-aggregated albumin (MAA) and tetrofosmin. There was no appreciable residual activity after injection of pertechnetate and MDP other than that due to the dead space in syringes (0.06 ml, 4% of measured activity). However, there was considerable residual activity following an MAA injection. This was particularly dependent on the radiopharmaceutical residence time in the syringe prior to injection. If MAA was pre-dispensed there was up to 80% of activity remaining in the syringe following injection. We have shown that this activity is not bound and can be decreased by agitating the syringe prior to the injection. For tetrofosmin, the activity remaining in the syringe was shown to be mostly due to adsorption of the tetrofosmin onto the plastic syringe (up to 30% of the activity); in particular, onto the rubber plunger. The amount of binding probably depends on the formulation of the rubber plunger and the plastic barrel, which varies between manufacturers. Of the three commonly used syringe brands (Becton-Dickinson, Sherwood, and Braun syringes) the Braun syringes were shown to have the least binding (6%) and would be most suitable for tetrofosmin injection. We recommend the use of Braun syringes for tetrofosmin. We also recommend that pre-dispensed MAA injections should be gently agitated before injection into the patient. No special precautions are necessary for pertechnetate or MDP injections.

Estimation of ascitic fluid volume using 99Tcm labelled macroaggregated albumin.

We have assessed the usefulness of a radionuclide dilution method for estimation of ascitic fluid volume. 99Tc(m) macroaggregated albumin (10 MBq) was injected into the peritoneal fluid. Multiple samples were taken using a trocath peritoneal dialysis catheter over a 4-h period. Blood samples were taken at the same time and a 4-h urine collection was made during the study. At 4 h a controlled drainage of ascitic fluid, followed by suction drainage, was used and a total drained volume measured. For comparison, peritoneal volumes were measured from the radioactivity of peritoneal fluid activity samples using dilution techniques. The estimated peritoneal fluid volume using the radionuclide method was consistently higher than the drained volume. This was attributed to either a lack of uniform distribution of the activity in the peritoneal cavity by 4 h or early breakdown and absorption of activity from the peritoneal cavity. In two patients it was not possible to measure a volume due to poor distribution of the radionuclide in the peritoneal fluid. We found that in our group of patients the radionuclide dilution is of little value in estimating the peritoneal fluid volume.

Closing the audit loop: a patient satisfaction survey.

A patient satisfaction survey was carried out in a nuclear medicine department of a large acute hospital. Surveys were initially carried out by interview and postal techniques, with approximately 100 responders in each category. The responses to each question were not significantly different for the two types of survey, although overall there was a significantly larger number of dissatisfied responses in the postal survey (22%) compared with the interview study (12%). The postal survey was repeated after 1 year, thus completing the audit loop. A significant reduction in dissatisfied responses has occurred in those areas which had been addressed following the criticisms revealed by the first survey.

Measurement of colonic transit time using radionuclide imaging: analysis by condensed images.

A polymer-coated capsule has been used in eight volunteer subjects to deliver 111In-resin into the ileocaecal region. The images were acquired for up to 3 days to follow transit through the colon. Expressing the results of individual studies is difficult and time-activity curves for each region are confusing. Calculation of the geometric centre indicates only where the middle of the activity has reached. We describe a new method of presenting colonic transit data as parametric images. The parametric images show the amount of activity in each area of interest as the study progresses. This is readily understood and allows segmental movement of the isotope, either forward or retrograde, to be examined. The geometric mean of activity in four areas of the colon were also calculated. Four hours after reaching the ileocaecal region, 65% (S.D. 24%) of the activity was in the caecum and 26% (S.D. 20%) in the transverse colon. By 24 h three controls had excreted most of the activity, in two the activity was mainly in the rectum and in two there was still some activity in the transverse colon. A protocol for colonic transit studies, problems with analysis and a new method of presentation of data are discussed.

Radioimmunoscintigraphy of recurrent colorectal carcinoma using 111In-labelled murine monoclonal antibody B72.3: a comparison with contrast-enhanced computed tomography.

Ten patients underwent contrast-enhanced abdominal computed tomographic (CT) carcinoembryonic antigen (CEA) measurement and murine 111In-B72.3 monoclonal antibody radioimmunoscintigraphy for recurrent or residual colorectal carcinoma. All patients had undergone primary colorectal tumour resection at a median of 3 (range 1-18) months previously. Histological analysis of pelvic tissue biopsies confirmed that six patients had recurrent or residual colorectal cancer and that four were tumour free. Whilst scintigraphy correctly showed all six patients with recurrent or residual disease, both CT and CEA measurement were correct in only four patients. In the four patients without recurrent cancer, CT was correct in two patients whilst scintigraphy and CEA measurement were accurate in three patients. Six out of the 10 patients showed marked nonspecific colonic excretion of radiolabelled antibody which was correctly interpreted in five patients. Future prospective studies comparing CT scans, CEA estimation and B72.3 radioimmunoscintigraphy in a larger group of patients with suspected residual or recurrent colorectal adenocarcinoma may help to define the respective sensitivity and specificity of these techniques.

Procedure guidelines for radionuclide myocardial perfusion imaging.

Radionuclide myocardial perfusion imaging (MPI) is an established and non-invasive imaging technique with diagnostic and prognostic efficacy in the investigation of coronary artery disease. It is the only widely available test for assessing myocardial perfusion directly but there are variations in the way it is performed in different centres. Harmonization of practice, at least at a national level, is therefore essential, and clinical governance now makes it mandatory for practice to be based upon evidence whenever possible [ 1]. This is best achieved by expert analysis of the evidence and to this end the British Nuclear Cardiology Society (BNCS) in association with the British Cardiac Society (BCS) and the British Nuclear Medicine Society (BNMS) have developed procedure guidelines for tomographic myocardial perfusion imaging. A systematic literature search was performed and every effort was made to conform with the AGREE recommendations [ 2]. All recommendations are therefore based on either evidence from clinical studies, previous published guidelines or expert consensus of the writing and advisory groups. The guidelines cover the clinical indications of MPI, the methods used for stress testing, the radiopharmaceuticals and the injected activities and also issues related to acquisition, processing and interpretation of images. They do not cover the benefits or drawbacks of the technique in specific circumstances; neither do they address its cost effectiveness in clinical diagnosis and management nor its potential impact on clinical outcomes. The guidelines aim to assist medical practitioners and other health care professionals in recommending, performing, interpreting and reporting single photon emission computed tomography (SPECT) of myocardial perfusion.