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Background: 18-Fluoride labeled sodium fluoride (Na-18-F) positron emission tomography with computer tomography (PET/CT) has a better sensitivity and specificity than whole body bone scan (WBBS) in detecting osseous metastatic prostate cancer. We performed a pilot study of 20 men to examine what level of impact Na-18-F PET/CT has on management plans when used for staging newly diagnosed prostate cancer. Materials and methods: Twenty men were prospectively enrolled into the study in South Australia. Men were eligible if they had newly diagnosed, untreated, and biopsy-confirmed intermediate- or high-risk prostate cancer (D'Amico classification). WBBS and Na-18-F PET/CT scans were performed within 1 week of each other. Following review of the WBBS, treatment type and intent was documented by the treating urologist. The Na-18-F PET/CT scan was then reviewed. The impact of the Na-18-F PET/CT was measured on whether treatment modality or intent was subsequently altered: high impact = treatment intent or modality was changed; medium impact = treatment modality was modified; low impact = no change in treatment. Results: In 18 men (90%), the WBBS and Na-18-F PET/CT were negative for osseous metastases. In one man (5%), the WBBS demonstrated widespread osseous metastases which were similarly demonstrated on the Na-18-F PET/CT. One man (5%) had a normal WBBS; however, the Na-18-F PET/CT demonstrated widespread osseous metastases. Subsequently, in 19 men (95%), the results of the two scans were congruent and the addition of the Na-18-F PET/CT scan demonstrated a low impact on management. In one man (5%), the addition of the Na-18-F PET/CT had a high impact as treatment type and intent was altered. Conclusions: Our pilot study is the first of its kind in Australia, and our findings suggest that Na-18-F PET/CT is a safe and feasible modality for staging prostate cancer. However, its true impact on prostate cancer management warrants further investigation. Keywords: Metastases, Positron emission tomography with computer tomography, Prostate cancer, Sodium fluoride, Whole body bone scan

Objectives: We aimed to establish the typical rate of skeletal mineralisation in the growing sheep. The sheep (size, ease of handling, cost and bone physiology) is establishing itself as an appropriate model for bone research. Materials and Methods: Body composition including bone density at 4 time points in the first two years was performed using DXA on a cohort of 14 developing lambs, as well as measurements in comparable adult sheep. Results: Adult levels of bone density are reached by 18 months and lean body mass by 2 years in sheep. Conclusions: Depending on the indications for studying bone and other metabolism in sheep, the rate of development should be considered in selecting the age group of experimental animals.

Objective Despite better disease suppression with combination disease-modifying antirheumatic drugs (DMARDs), some patients with rheumatoid arthritis (RA) have progressive erosive disease. The objective of this study was to determine whether hand bone mineral density (BMD) loss in the first 6 months of treatment indicates increased risk of erosions at 12 months. Methods Patients with DMARD-naive early RA receiving treat-to-target therapy were studied (n = 106). Hand BMD was measured at baseline and 6 months by dual x-ray absorptiometry. Hand and feet radiographs were performed at baseline and 12 months and scored using the van der Heijde modification of the Sharp method. A K-means clustering algorithm was used to divide patients into 2 groups: the BMD loss group or the no loss group, according to their absolute change in BMD from baseline to 6 months. Multiple regression analysis (hurdle model) was performed to determine the risk factors for both erosive disease and erosion scores. Results Hand BMD loss at 6 months was associated with erosion scores at 12 months (P = 0.021). In a multiple regression analysis, hand BMD loss (P = 0.046) and older age at onset (≥50 years; P = 0.014) were associated with erosive disease, whereas baseline erosion scores (P = 0.001) and anti–cyclic citrullinated peptide (P = 0.024) were correlated with erosion severity/progression. Conclusion In RA patients receiving treat-to-target therapy, early hand BMD loss could identify patients who are at risk of developing erosive disease at 12 months, potentially allowing intensification of treatment to prevent erosive damage.

Catherine L. Hill, Christopher G. Schultz, Rodney Wu, Barry E. Chatterton and Leslie G. Cleland

We describe a prospective study in which bone mineral density (BMD) was measured in total body and regions, proximal femur, lumbar spine, and forearm in 84 apparently normal postmenopausal women with normal spinal radiographs and in 47 women with 1-10 wedged or compressed vertebrae. There was a history of peripheral fracture in 35 of the 84 controls and 30 of the 47 osteoporotics (p < 0.02) but there was no association between vertebral fracture and wrist fracture. At all sites and regions, the differences in BMD between the "normal"and "osteoporotic" women was highly significant and all but "ribs" and "arms" remained significant after correction for menopausal age. In the whole set, and in both subgroups, the coefficients of correlation between sites and regions were all highly significant (p < 0.001). Nonetheless, some sites discriminated better between the two groups than others. Standardized odds ratios (OR) for vertebral fracture versus no-fracture were calculated by logistic regression and expressed as the rise in OR for each standard deviation (SD) fall in bone density. This ratio was greatest (3.4) in "pelvis" and weakest (1.7) in "ribs" but all were statistically significant. Geometric mean regression equations were calculated for all the 78 possible pairs of sites and regions in the 84 normal subjects and the deviations of the osteoporotic women from these normal slopes calculated. In most pairs of sites and regions, the vertebral fracture cases were scattered around the normal group's slope but fell lower down on both axes. The bone deficits in the osteoporotics compared with young normal women ranged from -14% in "head" to -40% in Ward's triangle and the T-scores ranged from -1.9 in "ribs" to -3.9 in the forearm. Sensitivity ranged from 17% in "ribs" to 36.2% in Ward's triangle. Specificity varied between 88 and 94% and the percent correctly classified ranged from 62.6% in "ribs" to 72.5% in Ward's triangle. We conclude that primary postmenopausal osteoporosis affects the entire skeleton but that some sites discriminate better between vertebral fracture and nonfracture cases regardless of whether they represent cortical or trabecular bone.

Background 99m Tc-Evans blue is a 'single dose' agent for lymphatic mapping combining radioactivity and blue dye for sentinel node identification. The mechanism and distribution of blue dye retention in the lymph node is not clearly understood. Objective To demonstrate the cellular distribution of 99m Tc-Evans blue in sheep sentinel lymph nodes by measuring the radioactivity of different tissue components and correlating this with pathological examination. Methods 99m Tc-Evans blue was used to identify sheep lymph nodes. Part of each node was sent for pathological examination including imprint cytology, and frozen and permanent section examination. Sections were examined without stains, with only red stains and conventional haematoxylin & eosin staining. The remaining nodal tissue was homogenized and components separated by enzymatic digestion and density gradient centrifugation. Fractions representing each tissue component were counted in a gamma counter and the distribution of 99m Tc-Evans blue calculated. Results A dispersed population of blue staining cells was found. Their distribution, number and size indicated that they were histiocytes such as macrophages or antigen presenting cells. Radioactivity was distributed throughout the lymph node. Over 70% remained in the plasma, 19% in the leukocyte layer, and 10% was associated with erythrocytes and undigested tissue. Conclusion The accumulation of radioactivity and blue colour in the lymph nodes indicates the mechanism of retention is a result of the binding interaction between 99m Tc-Evans blue-protein and lymph node histiocytes including macrophages and antigen presenting cells.

To confirm the pharmacokinetics and biodistribution of 99mTc aprotinin in normal volunteers and to determine the optimum time for scanning post-injection, prior to further investigations of 99mTc aprotinin as an imaging agent for amyloidosis.Five patients (three men and two women, average age 49 years, age range 38-66 years) without a history of amyloidosis or any of the associated diseases, were included in this prospective study. Blood and urine were collected and images were performed of the whole body and wrists.Normal biodistribution of 99mTc aprotinin includes early cardiac and lung activity in the blood pool phase with subsequent hepatic activity and renal excretion with variable splenic activity. There is variable bowel uptake on later images. The best quality images were obtained 90 min post-intravenous administration, and this is likely to be the optimum time for clinical imaging.

The penetration and permeation of the recombinant protein plasminogen activator inhibitor type 2 (PAI-2) in two formulations, one containing a penetration enhancer, into the psoriatic and uninvolved skin of eight patients with plaque-type psoriasis were investigated. Penetration and permeation of PAI-2 were measured by gamma counting and imaging following radiolabelling of a fraction of the applied PAI-2 with (123)I. The feasibility of topical delivery of drug to psoriatic plaques was confirmed by the finding that the permeability of psoriatic plaques to radiolabelled PAI-2 (P=0.007) and free (123)I (P=0.001) was approximately tenfold higher than the permeability of uninvolved skin. The addition of a penetration enhancer improved the permeation of PAI-2 into psoriatic plaques from an average of 35% to 46% (P=0.005). Occlusion decreased the permeation amount of PAI-2 from 46% to 15% due to losses on the occlusive dressing (P=0.001).

Patients with beta-Thalassemia Major have a requirement for repeated blood transfusion, which ultimately results in liver iron- and whole body iron-overload. These patients are also at risk of reduced bone mineral density (BMD). Seventeen patients (9 female, age 19-32 yr) were referred for bone density estimations of the hip, spine, and whole body. As well as calculating the usual indices of body composition, we superimposed regions of interest over the liver, and expressed the result as "BMD" (g/cm2). This was compared with the serum ferritin as a noninvasive indication of total body iron status. Twelve patients were studied at least twice, more than 18 mo apart. This group showed a significantly below average BMD (T-spine -2.1, T-femoral neck -1.2, T-whole body -1.7, p < 0.001). The group's hepatic density correlated significantly with initial serum ferritin (r = 0.90, p < 0.001). Changes in individual liver density did not correlate significantly with changes in ferritin levels (p = 0.15), possibly due to wide variability in individual results. DEXA may be a useful noninvasive technique for estimating liver-iron concentration.

Impaired lymphatic drainage in human limbs causes the debilitating swelling termed lymphoedema. In mammals, known growth factors involved in the control of lymphangiogenesis (growth of new lymph vessels) are vascular endothelial growth factors-C and -D (VEGF-C/D). Here we characterize a model of lymphangiogenesis in which the tail of lizards is regenerated without becoming oedematous. Three weeks after the tail is shed (autotomy), there are a small number of large diameter lymphatic vessels in the regenerated tail. Thereafter, the number increases and the diameter decreases. A functional lymphatic network, as determined by lymphoscintigraphy, is established 6 wk after autotomy. The new network differs morphologically and functionally from that in original tails. This lymphatic regeneration is associated with an up-regulation of a reptilian homologue of the VEGF-C/D protein family (rVEGF-C/D), as determined by Western blot analysis using a human reactive VEGF-C polyclonal antibody. Regenerating lizard tails are potentially useful models for studying the molecular basis of lymphangiogenesis with a view to developing possible treatments for human lymphoedema.

BACKGROUND: Port-site recurrences have delayed the uptake of laparoscopic colectomy, but the etiology of these is incompletely understood. These studies were designed to investigate variables such as the size of the tumor inoculum and the volume and pressure of the insufflated gas during operative laparoscopy that might affect the deposition of these cells in relation to trocars and port sites. METHODS: Radiolabeled human colon cancer cells were injected into the peritoneal cavity of pigs. Three trocars were inserted, and the abdomen was insufflated with carbon dioxide. The movement of cells within the abdomen was traced on a gamma camera. After 2 h, the trocars were removed and the port sites excised. Two studies were performed. In the first study, tumor inocula were varied from 1.5 × 105 to 120 × 105. In the second study, insufflation pressure was varied, with pressures 0, 4, 8 and 12 mmHg were studied. RESULTS: When larger tumor inocula were injected, the contamination of both trocars (p = 0.005, Kendall's rank correlation) and trocar sites (p = 0.04, Kendall's rank correlation) increased. The deposition of cells on a trocar site was linked to contamination of its trocar (p = 0.03, chi-square), but the contamination of trocars did not always result in trocar-site contamination (p = 0.5, chi-square). Increased volumes of gas insufflation caused increased intraabdominal movement of tumour cells (p = 0.01, Kendall's rank correlation), although this did not lead to greater contamination of trocars or port sites (p = 0.82, Kendall's rank correlation). Decreased insufflation pressures resulted in increased contamination of trocars and port sites (p = 0.01, Kendall's rank correlation). CONCLUSIONS: If clinical situations parallel this study, strategies such as increasing insufflation pressure, reducing episodes of desufflation and gas leaks, and using frequent intraabdominal lavage may help to reduce the numbers of viable tumor cells displaced to port sites during laparoscopic surgery for intraabdominal malignancy. This may reduce the rate of port-site metastases.

Background: Lymphoscintigraphy and sentinel node biopsy are currently being assessed as an alternative to axillary dissection for staging in early breast cancer. However, little is known about the optimum timing of surgery following injection of the radio­isotope into the breast. The aim of the present study was to establish whether lymphoscintigraphy on the morning of surgery allowed efficacious and accurate sentinel node identification and biopsy. Methods: We reviewed our experience of 216 consecutive cases of lymphoscintigraphy in early breast cancer using peritumoural injections of technetium99m antimony sulphide colloid and subsequent sentinel node biopsy using a hand-held gamma probe and blue dye. The time interval between radioisotope injection and successful intraoperative identification of the sentinel node was assessed and whether this was associated with certain clinical and histological variables. Results: The sentinel node was identified by lymphoscintigraphy in 160 cases (74%) at a median time duration of 40 min post injection. The median time duration between isotope injection and surgery was 5 h. Of the 160 cases where the sentinel node was visualized at lymphoscintigraphy, sentinel node biopsy was successfully performed in 155 cases (97%). This compares with 25/56 (45%) cases where lymphoscintigraphy failed to localize the sentinel node (P < 0.0001). There was no association found between the injection of the radioisotope greater or less than 5 h before surgery and the successful intraoperative identification of the sentinel node. Failure to identify the sentinel node at lymphoscintigraphy beyond 3 h was associated with a low intraoperative identification rate. There was no correlation found between intraoperative identification of the sentinel node according to the duration of isotope injection in relation to surgery and the various clinical and histological factors assessed. Conclusions: In our experience, the chance of identifying the sentinel node at the time of surgery does not increase with longer isotope injection duration using technetium99m antimony sulphide colloid. As soon as a sentinel node is identified at lymphoscintig­raphy, one can proceed to surgery. Scanning beyond 3 h does not appear to be effective in sentinel node localization. Given that the median time for successful lymphoscintigraphic mapping was only 40 min, lymphoscintigraphy can easily be completed during the morning to allow surgery to take place the same day.

Background: Abdominal lavage is a common surgical practice, but few studies have been conducted to assess its efficacy at removing cells from the abdominal cavity, particularly during laparoscopic surgery. Methods: After three 12-mm trocars were inserted into six female 30-kg pigs at the umbilicus left and right iliac fossae, the abdomen was insufflated with carbon dioxide. The pelvis of each pigs was injected with 6 million radiolabeled LIM 1215 cells. Then the abdominal cavity was irrigated with either 500 ml 0.9% saline, 500 ml 10% betadine solution, or 1 L 0.9% saline. A maximum of 5 L of solution was used for each animal. The lavage fluid was suctioned into separate containers after each aliquot, and each container was measured for radioactivity. Results: Significantly greater numbers of cells were removed by lavage by the first to third lavage cycle; however, after four lavage cycles, relatively few cells were removed by each further cycle. No difference was observed between 500-ml and 1-L aliquots. Additionally, the mechanical efficacy of 0.9% saline and 10% betadine solution appeared similar. Conclusion: These findings suggest that optimal lavage consists of four irrigation/suction cycles utilizing 500-ml aliquots.

Background. Lymphatic mapping for sentinel node biopsy in breast cancer and melanoma usually involves initial peritumoral injection of a radioisotope, gamma camera detection of the sentinel lymph node several hours prior to the operation, and separate perioperative injection of a blue dye. We have developed a combined approach using technetium 99m labeled blue dye (Evans Blue) for use in lymphoscintigraphy that may be injected as a single dose just prior to the operation. Methods. In an anesthetized rabbit model we dissected a hind limb to display the popliteal node and afferent lymphatic. Technetium 99m Evans Blue (99mTc-EB) (22 MBq; 0.5 mL) was injected subdermally in the dorsum of the paw. Simultaneous digital and gamma camera images were obtained at 14 time intervals to 30 minutes post injection. For each of these time intervals the percentage of radioactivity and percentage blueness of the popliteal node were determined. Urine and afferent lymphatic fluid were analyzed by chromatography. The popliteal node was excised post mortem, placed into solvent solutions and analyzed for blueness and radioactivity. Results. Time-activity curves for radioactivity and time-blueness curves for Evans Blue uptake showed strong correlation (r = 0.958). Lymph analysis suggested 99mTc-EB is mainly bound to endogenous proteins. Urine was radioactive but not colored, 99mTc-EB being metabolized and excreted in the urine as 1,7-diamino-8-naphthol-2,4-disulfonic acid. Prolonged exposure of node to solvents did not dissociate any blue coloration or radioactivity. Conclusions.99mTc-EB and Evans Blue are simultaneously retained and concentrated in the sentinel lymph node. This process is rapid and reproducible. 99mTc-EB migrates at the same rate as Evans Blue in lymph, where it is transported as bound to endogenous proteins. These dye molecules are metabolized by reductive cleavage in the liver and then excreted renally as colorless, radioactive metabolites. This novel agent has the potential to facilitate lymphatic mapping and subsequent sentinel node biopsy for a range of solid malignancies including breast cancer and melanoma. (Surgery 2002;131:44-9.)

A 43-year-old man with liver failure caused by alcohol abuse and congenital hepatic fibrosis was examined for intermittent fever of unknown origin. He had portal hypertension, which was complicated in the past by bleeding varices that required a portocaval shunt. There were no localizing symptoms or signs for the fever, and, apart from an elevated leukocyte count, results of investigations including urine and blood cultures, abdominal ultrasound, abdominal magnetic resonance imaging, and endoscopic retrograde cholangiopancreatography were not helpful. A labeled leukocyte scan was obtained with Tc-99m stannous colloid. The 1-, 3-, and 24-hour images showed marked reduction in tracer uptake within the liver, with increased tracer accumulation in an enlarged spleen and marrow. Marked margination of labeled leukocytes in the lungs was also evident, which subsided on the 24-hour image. The focus of inflammation was not identified, and instead the tracer distribution pattem was similar to that on a Tc-99m sulfur colloid scan in a patient with liver failure. The scan appearances presumably represent reduced uptake of free Tc-99m stannous colloid by Kuppfer cells of the failing liver, with a shift in uptake to the reticuloendothelial system of the spleen and marrow.

Background: Although sentinel lymph node biopsy is likely to be offered as a method of assessing nodal status in primary breast cancer, the inability to identify the sentinel node at the time of surgery will limit the number of patients who may benefit from the procedure. The purpose of the present study was to identify factors that are associated with intraoperative identification of the sentinel node(s). Methods: Between September 1995 and May 1999, lymphatic mapping using a combination of preoperative lymphoscintigraphy and/or blue dye was performed on 169 consecutive patients with clinically lymph node-negative primary operable breast cancer. Clinical and histological factors were assessed using univariate and multivariate analysis to determine those that were associated with intraoperative identification of the sentinel node. Results: The sentinel node was identified at the time of surgery in 142 cases (84%). Of the clinical factors assessed, preoperative identification of the sentinel node on lymphoscintigraphy (P < 0.0001), use of blue dye in combination with isotope (P = 0.001), symptomatic palpable tumours (P < 0.05) and the experience of the surgeon (P = 0.03) were significant in identifying the sentinel node at operation. No histological factor was associated with intraoperative identification of the sentinel node. Using multivariate analysis, positive identification of the sentinel node on lymphoscintigram, the experience of the surgeon and the use of both blue dye and isotope for sentinel node mapping were independent factors associated with intraoperative sentinel node identification. The lymphoscintigram result was the strongest independent factor according to its β value, a measure of the weight of significance. Conclusion: Patients undergoing sentinel lymph node mapping and biopsy should be warned of the possibility of failure of sentinel node identification at operation. Our results suggest that the best predictor of intraoperative sentinel node identification is the visualization of the sentinel node on preoperative lymphoscintigraphy. The result of the lymhoscintigram may allow for additional preoperative counselling of the patient regarding the success or failure of sentinel node biopsy. Technical factors such as the experience and diligence of the surgeon, as well as the sentinel node mapping technique, are also important in determining the success of the procedure.

The cause of age-related bone loss in men is poorly understood. Previous studies of the relationship between bone density and serum androgens have yielded inconsistent results, perhaps partly because age is a determinant of both. Recent studies suggest that serum estrogen levels influence bone density in adult men. In order to determine whether bone mineral density (BMD) and bone turnover are associated with serum sex steroids, we investigated 37 normal men within a narrow age range (60-70 years). Bone mineral density at the forearm, hip, and spine, testosterone, sex hormone binding globulin (SHBG), free androgen index (FAI:T/SHBG), estradiol (E), free estradiol index (FEI:E/SHBG), and markers of bone formation (alkaline phosphatase, osteocalcin, procollagen type I C-terminal extension peptide) and bone resorption (hydroxyproline/creatinine [OHPr/Cr], deoxypyridinoline/creatinine [Dpd/Cr], pyridinoline/creatinine, collagen type I cross-linked telopeptide) were measured. Bone mineral density was positively related (r0.35, p0.05 at all sites) to log FAI, whereas there was no significant relationship between BMD and either serum total testosterone, serum E, or FEI. Bone density at the spine and hip were inversely related to both OHPr/Cr (r-0.41, p0.05 for all sites) and Dpd/Cr (r-0.36, p0.05 for all sites). OHPr/Cr (r = -0.41, p0.05) and Dpd/Cr (r = -0.41, p0.05) were both inversely related to log FAI. We conclude that BMD and bone turnover in adult men are related to plasma free androgens.

PURPOSE: A porcine model has been developed to allow the real-time imaging of radiolabeled tumor cell movement throughout the peritoneal cavity, both at rest and during carbon dioxide insufflation. METHODS: Fifteen 30-kg domestic white female pigs were used. Under anesthesia, 15 to 20 million radiolabeled human colorectal tumor cells (LIM1215) were introduced into the peritoneal cavity under laparoscopic vision into the pelvis. Radiolabeled tumor cell movement was examined by using a 25-cm-diameter, low-energy mobile gamma camera with high resolution collimator. Tumor cell movement and distribution during two hours without insufflation was examined in four pigs. Then tumor cell movement and distribution during two hours with CO2 insufflation was examined in four pigs. In a further four pigs, tumor cells were then mixed with blood and injected into the peritoneal cavity and the effect of no insufflationvs. insufflation was noted. A further three pigs were examined with manipulation of the intra-abdominal contents after injection of LIM1215 cells into the peritoneal cavity. Venting insufflating CO2 was filtered for tumor cells. RESULTS: Widespread intraperitoneal distribution of tumor cells from the pelvis was identified both with CO2 insufflation of the peritoneal cavity and without insufflation. Tumor cells dispersed throughout the peritoneal cavity at a slower rate without carbon dioxide insufflation. There was a differential rate of tumor cell movement to the left upper quadrant and right upper quadrant with insufflation and without insufflation. Blood within the peritoneal cavity and an extended contact of the laparoscopic trocars with the peritoneal cavity in this setting increased contamination of the trocars and trocar sites with tumor cells. Tumor cells were identified on laparoscopic instruments in all experiments. No evidence of aerosolization of tumor cells was found. CONCLUSION: Tumor cells move throughout the peritoneal cavity both at rest and during CO2 insufflation. The pattern of tumor cell dispersion differs with CO2 insufflation. The presence of blood and extended contact of trocars with peritoneal contents are a major factor in trocar and trocar site tumor cell contamination.

Loss of bone is an almost universal accompaniment of aging that proceeds at an average rate of 0.5-1% per annum from midlife onwards. There are at least four nutrients involved in this process: calcium, salt, protein, and vitamin D, at least in women. The pathogenesis of osteoporosis in men is more obscure. Calcium is a positive risk factor because calcium requirement rises at the menopause due to an increase in obligatory calcium loss and a small reduction in calcium absorption that persist to the end of life. A metaanalysis of 20 calcium trials shows that this process can generally be arrested by calcium supplementation, although there is some doubt about its effectiveness in the first few years after menopause. Salt is a negative risk factor because it increases obligatory calcium loss; every 100 mmol of sodium takes 1 mmol of calcium out of the body. Restricting salt intake lowers the rate of bone resorption in postmenopausal women. Protein is another negative risk factor; increasing animal protein intake from 40 to 80 g daily increases urine calcium by about 1 mmol/day. Low protein intakes in third world countries may partially protect against osteoporosis. Vitamin D (sometimes called a nutrient and sometimes a hormone) is important because age-related vitamin D deficiency leads to malabsorption of calcium, accelerated bone loss, and increased risk of hip fracture. Vitamin D supplementation has been shown to retard bone loss and reduce hip fracture incidence in elderly women.

A 39-year-old man presented to the emergency department with an ischemic left hand after inadvertent injection of amphetamine into the left radial artery 4 days before presentation. Examination revealed a gangrenous left thumb and index finger without clear demarcation and a weak radial pulse. Brachial angiography demonstrated absent blood flow to the digital arteries of the distal left thumb and entire left index finger. A 3-phase Tc-99m MDP (methylene diphosphonate) bone scan was performed 6 days later, which demonstrated nonviability of the distal phalanx of the left thumb and left index finger, distal to the midportion of the proximal phalange. The patient subsequently underwent amputation of the left thumb and index finger at these levels with the bone scan accurately reflecting the operative findings. The 3-phase bone scan was useful in determining the need for and extent of amputation in this case.

The factors influencing appetite in humans are poorly understood. There is a weak relation between appetite and gastric emptying in normal subjects. Recent studies have shown that fasting and postprandial antral areas increase in patients with functional dyspepsia compared with normal subjects. We evaluated the hypothesis that antral area, and hence antral distention, is a significant determinant of postprandial fullness. Fourteen normal subjects had simultaneous measurements of gastric emptying by scintigraphy and antral area by ultrasound after ingestion of 350 mL 20% glucose. Fullness and hunger were assessed by visual analog scales. Measurements of the gastric-emptying half time (t1/2) by scintigraphy and ultrasound were not significantly different (129.6 +/- 11.8 min compared with 115.6 +/- 11.4 min). Fullness increased (P0.001) and hunger decreased (P0.001) after the drink. Both fullness and the magnitude of the increase in fullness after the drink were related to antral area (r0.56, P0.05), the increase in antral area (r0.59, P0.05), and the scintigraphic content of the distal stomach (r0.57, P0.05), but not to the ultrasound or scintigraphic t1/2 values. In contrast, hunger and the magnitude of the decrease in hunger after the drink were not related to either antral area, the increase in antral area, or the rate of gastric emptying. We conclude that postprandial fullness, but not hunger, was closely related to antral distention in normal subjects.

Use of illicit stimulants such as methamphetamine, cocaine, and ecstasy is an increasing health problem. Chronic use can cause neurotoxicity in animals and humans but the long-term consequences are not well understood. The aim of the current study was to investigate the long-term effect of stimulant use on the morphology of the human substantia nigra. We hypothesised that history of illicit stimulant use is associated with an abnormally bright and enlarged substantia nigra (termed 'hyperechogenicity') when viewed with transcranial sonography. Substantia nigra morphology was assessed in abstinent stimulant users (n = 36; 31±9 yrs) and in two groups of control subjects: non-drug users (n = 29; 24±5 yrs) and cannabis users (n = 12; 25±7 yrs). Substantia nigra morphology was viewed with transcranial sonography and the area of echogenicity at the anatomical site of the substantia nigra was measured at its greatest extent. The area of substantia nigra echogenicity was significantly larger in the stimulant group (0.273±0.078 cm2) than in the control (0.201±0.054 cm2; P

Three restriction fragment length polymorphisms in the vitamin D receptor gene have been associated with a low bone density in twin and female population studies, but no studies have been conducted exclusively in men. We studied 146 normal men aged 20-83 years. Bone density was measured in the spine, hip, whole body and forearm, and the Bsm polymorphism for the vitamin D receptor was detected by the polymerase chain reaction. Men with genotype BB tended to have a lower bone density at all but one site than the other genotypes. In the men < or = 50 years of age bone density in the forearm was 7% lower in the BB than the Bb and bb groups (P = 0.030) but bone mineral content did not differ between the groups. Bone area was greater in the BB genotype at all sites. This was statistically significant in the forearm (P = 0.026). We conclude that BB genotype is associated with lower bone density in men, which may be due to larger bone size rather than reduced bone mass.

Osteoporosis can be defined in terms of apparent bone density and can be determined by densitometry. But differences between reference standards and instruments make standardization difficult. Conventional classification schemes are not applicable but analysis by risk factors does permit a systematic approach.

To evaluate the long-term effects of abdominal irradiation for the treatment of seminoma of the testis on gastrointestinal function, 15 randomly selected patients who had been treated for stage I seminoma of the testis 2-10 years previously had the following parameters of gastrointestinal function evaluated: gastrointestinal symptoms; absorption of bile acid; vitamin B12; lactose and fat; gastric emptying; small intestinal and total gut transit; and intestinal permeability. Results were compared to those obtained in 18 normal volunteers. There was an increased prevalence of gastrointestinal symptoms (P < 0.01) in the patients and stool frequency was above the control range in two of them. Gastric emptying was faster (P < 0.01) in the patients. There were no significant differences in vitamin B12, bile acid, lactose or fat absorption, small intestinal transit or whole gut transit between the two groups, although faecal fat excretion was greater than the control range in three of the patients. At least one parameter of gastrointestinal function was abnormal in 11 of the 15 patients. Patients with right-sided seminoma had a greater bowel frequency when compared to those with left-sided seminoma (P < 0.05). We conclude that mild abnormalities in gastrointestinal function occur frequently when abdominal irradiation is used to treat stage I seminoma.

Accurate and reliable staging of disease extent in patients with malignant MM is essential to ensure appropriate treatment planning. The detection of recurrent or residual malignancy after primary treatment is important to allow for early intervention and to optimise patient survival. 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) PET or PET computed tomography (PET/CT) is indicated for surveillance of malignant MM due to its high sensitivity and specificity for soft-tissue or nodal recurrences and metastases. It has been claimed that including lower extremities and skull in addition to 'eyes to thigh' images in PET/CT evaluation of metastatic MM routinely is warranted. We have studied retrospectively the reports of whole-body PET/CT scans in all patients with MM scanned in our Department from April 2005 to December 2010. All PET abnormalities in the brain/scalp and lower extremities were tabulated by location and whether they were 'expected' or 'unexpected'. Findings were correlated with pathology, other imaging studies, and clinical follow-up. In this study, 398 PET/CT examinations in 361 patients with MM were included. Results showed that twelve of the 398 (3%) scans had brain/scalp abnormalities, with only 4 (1.0%) showing unexpected abnormalities. Twenty nine of the 398 (7.2%) scans showed lower extremity abnormalities, with only 5 (1.2%) showing unexpected abnormalities. In no case was an isolated unexpected malignant lesion identified in the brain/scalp or lower extremities. In conclusion, whole body PET/CT scan showed about 1% unexpected primary or metastatic MM lesions involving the head or lower extremities, which seldom offered significant additional clinical benefit and were unlikely to change clinical management. No clinically significant change in staging would have occurred. Routine 'eyes to thighs' images were adequate for this subset of patients.

Objective: It is assumed that delayed gastric emptying (GE) occurs frequently in critical illness; however, the prevalence of slow GE has not previously been assessed using scintigraphy. Furthermore, breath tests could potentially provide a convenient method of quantifying GE, but have not been validated in this setting. The aims of this study were to (i) determine the prevalence of delayed GE in unselected, critically ill patients and (ii) evaluate the relationships between GE as measured by scintigraphy and carbon breath test. Design: Prospective observational study. Setting: Mixed medical/surgical intensive care unit. Patients: 25 unselected, mechanically ventilated patients (age 66 years (49-72); and 14 healthy subjects (age 62 years (19-84)). Interventions: GE was measured using scintigraphy and 14C-breath test. A test meal of 100 ml Ensure (standard liquid feed) labelled with 14C octanoic acid and 99mTechnetium sulphur colloid was placed in the stomach via a nasogastric tube. Main outcome measures: Gastric 'meal' retention (scintigraphy) at 60, 120, 180 and 240 min, breath test t50 (BTt50), and GE coefficient were determined. Results: Of the 24 patients with scintigraphic data, GE was delayed at 120 min in 12 (50%). Breath tests correlated well with scintigraphy in both patients and healthy subjects (% retention at 120 min vs BTt50; r 2=0.57 healthy; r2=0.56 patients; p≤0.002 for both). Conclusions: GE of liquid nutrient is delayed in approximately 50% of critically ill patients. Breath tests correlate well with scintigraphy and are a valid method of GE measurement in this group. Refereed/Peer-reviewed

To evaluate the prevalence of disordered gastrointestinal function following therapeutic irradiation.Gastrointestinal function was evaluated in 30 randomly selected patients who had received pelvic irradiation for treatment of carcinoma of the cervix between 1 and 6 years previously. Each patient underwent evaluations of (a) gastrointestinal symptoms (b) absorption of bile acid, vitamin B12, lactose and fat (c) gastrointestinal transit: gastric emptying, small intestinal transit and whole gut transit and (d) intestinal permeability. Results were compared with those obtained in 18 normal volunteers.Stool frequency was above the control range in five patients and had increased (p0.001) since radiotherapy treatment. Bile acid (p0.001) vitamin B12 (p0.01) and lactose (p0.01) absorption were less in the patients when compared with the control subjects. Bile acid absorption was below the control range in 14 of the 30 patients. Dietary calcium intake was lower (p0.05) in those patients with lactose malabsorption. Gastric emptying (p0.01) and small intestinal transit (p0.01) were more rapid in the patients. Both small intestinal (r = -0.39, p0.05) and whole gut (r = -0.45) transit were inversely related to stool frequency. Either bowel frequency, bile acid absorption, vitamin B12 absorption was outside the control range in 19 of the 30 patients.Abnormal gastrointestinal function is essentially an inevitable long-term sequel of pelvic irradiation.

The effects of loperamide-N-oxide, a new peripheral opiate agonist precursor, on gastrointestinal function were evaluated in 18 patients with diarrhoea caused by chronic radiation enteritis. Each patient was given, in double-blind randomised order, loperamide-N-oxide (3 mg orally twice daily) and placebo for 14 days, separated by a washout period of 14 days. Gastrointestinal symptoms; absorption of bile acid, vitamin B12, lactose, and fat; gastric emptying; small intestinal and whole gut transit; and intestinal permeability were measured during placebo and loperamide-N-oxide phases. Data were compared with those obtained in 18 normal subjects. In the patients, in addition to an increased frequency of bowel actions (p < 0.001), there was reduced bile acid absorption, (p < 0.001) a higher prevalence of lactose malabsorption (p < 0.05) associated with a reduced dietary intake of dairy products (p < 0.02), and faster small intestinal (p < 0.001) and whole gut transit (p < 0.05) when compared with the normal subjects. There was no significant difference in gastric emptying between the two groups. Treatment with loperamide-N-oxide was associated with a reduced frequency of bowel actions (p < 0.001), slower small intestinal (p < 0.001), and total gut transit (p < 0.01), more rapid gastric emptying (p < 0.01), improved absorption of bile acid (p < 0.01), and increased permeability to 51Cr EDTA (p < 0.01). These observations indicate that: (1) diarrhoea caused by chronic radiation enteritis is associated with more rapid intestinal transit and a high prevalence of bile acid and lactose malabsorption, and (2) loperamide-N-oxide slows small intestinal transit, increases bile acid absorption, and is effective in the treatment of diarrhoea associated with chronic radiation enteritis.

The earliest radiological change in rheumatoid arthritis (RA) is periarticular osteopenia, which occurs prior to the appearance of erosions and clinically apparent deformities. The aim of the study was to measure periarticular bone mineral density (BMD) in the hands of patients with early RA, using dual energy X-ray absorptiomentry (DEXA) and to correlate this with markers of disease activity and radiological progression.The study population (n = 50) of patients with RA of3 years duration underwent measurement of BMD of the non-dominant hand, femoral neck and lumbar spine and clinical assessment at baseline, 6 and 12 months. Hand radiographs were performed at baseline and 12 months. Thirty age- and sex-matched controls also underwent measurement of BMD of the non-dominant hand, femoral neck and lumbar spine.Hand BMD correlated strongly with sex, height, weight and lumbar and femoral neck BMD in both RA subjects and controls. Baseline hand BMD in RA subjects correlated with baseline serum C-reactive protein (r = -0.36, P = 0.01) and 12-month radiographic score (r = 0.36, P = 0.02). There were small non-significant decreases in hand, femoral neck and lumbar spine BMD over the 12-month period.Hand BMD measurement using DEXA is a reproducible, well-tolerated procedure that warrants further investigation as a component of routine assessment in early RA.

This report describes single photon emission tomography (SPECT) evidence of transient, relative hypoperfusion of the right basal ganglia and left temporal lobe in a 60-year-old man studied during the acute phase of classical transient global amnesia (TGA). The findings are interpreted in the light of previous reports indicating that involvement of the right hemisphere or both cerebral hemispheres consistently predicts severe retrograde amnesia, in addition to the typical loss of anterograde memory observed during TGA. These deficits involving the right hemisphere and left temporal lobe may reflect disruption of circuits mediating episodic memory retrieval and memory encoding, respectively.

The aims of this study were (1) to determine the incremental information provided by 18F-FDG positron emission tomography (PET) in staging patients with oesophageal cancer, and (2) to determine the impact of PET staging on post-PET clinical management of oesophageal cancer, and on prognosis. In a multicentre, single-arm open study, patients with proved oesophageal cancer without definite distant metastases and regarded as suitable for potentially curative treatment were examined by PET. Clinicians were requested to supply a management plan before and another plan after being supplied with the PET scan results. Patients were followed for at least 1 year for outcome analysis. A total of 129 patients (104 men, mean age 67 y) were recruited. PET detected additional sites of disease in 53 patients (41%). Significant changes in management (high or medium impact) were observed in 38% of patients, primarily as a result of identifying additional sites of disease and/or confirming previously equivocal regional and distant metastases. Progression-free survival was significantly shorter in patients found to have additional lesions on PET (p

99mTc-Evans Blue (EB) is an agent that contains both radioactive and color signals in a single dose. Earlier studies in animal models have suggested that this agent when compared with the dual-injection technique of radiocolloid/blue dye can successfully discriminate the sentinel lymph node. The aim of this study was to investigate the potential of 99mTc-EB as an agent to map the lymphatic system in an ovine model.Doses of 99mTc-EB (23 MBq) containing EB dye (4 mg) were administered intradermally to the limbs of four anesthetized sheep, and they were then imaged over 20-30 min using a gamma camera. The study protocol was repeated using 99mTc-antimony trisulfide colloid (ATC) and Patent Blue V dye. The lymph nodes (popliteal, inguinal, and iliac for hind limbs or prescapular for fore limbs) were identified with a gamma probe during the operative exposure, then dissected and counted in a large volume counter.Simple and complex (dual) drainage patterns were visible on the scans, and the sentinel node was more radioactive than higher tier nodes in a chain, for both radiotracers. For 99mTc-EB, maximum radioactive uptake was achieved at 3-6 min for popliteal lymph nodes, 12-14 min for iliac nodes, and 13-14 min for prescapular nodes. 99mTc-ATC resulted in maximum radioactive uptake at 4-6 min for popliteal lymph nodes, 13 min for an inguinal node, 13-20 min for iliac nodes, and 18 min for a prescapular node. Following 99mTc-EB injection, 15/15 lymph nodes harvested were all radioactive and blue. For 99mTc-radiocolloid/Patent Blue V injection, 8/14 nodes were radioactive and blue, and 6/14 nodes were radioactive only.The soluble radiotracer 99mTc-EB appeared to be a useful lymphoscintigraphic agent in sheep, in which radioactive counts from superficial lymphatic channels and lymph nodes were sufficient for planar imaging. In comparison with 99mTc-antimony trisulfide colloid, both tracers discriminated the sentinel lymph node up to 50 min after administration; however, 99mTc-EB had the advantage of providing radioactive (gamma probe) and color signals simultaneously during the operative exposure.

We have estimated the relative contributions of age and menopause to forearm mineral density in 485 normal postmenopausal women up to age 75 yr. In 87 pairs matched for years since menopause, in which 1 member was below 61 yr and the other was 61 yr or older, the mean bone density was significantly lower in the older than in the younger subjects despite their identical years since menopause (P less than 0.001). Further analysis suggested a model for bone loss after the menopause which comprises a menopausal component of exponential type and an age-related component which is linear and starts in the mid-50s. According to this model, a 70-yr-old woman has lost 11% of her bone due to menopause and 18% as a function of age. Thereafter, the age-related function is dominant. Early menopause is associated with a self-limiting loss of bone which does not progress further until aging exerts its effect. The main conclusion is that the significance of early menopause as a risk factor for osteoporosis has been overstated.

Dual radionuclide parathyroid scintigraphy with Tc-99m pertechnetate and TI-201 was performed before surgery in a 52-year-old woman with primary hyperparathyroidism and a nontoxic multinodular goiter. The study did not locate a parathyroid adenoma, but it detected an autonomous thyroid adenoma. A parathyroid exploration and a total thyroidectomy did not cure the hyperparathyroidism. Two occult papillary thyroid carcinomas were removed. Subsequently, Tc-99m sestamibi, CT, and MRI visualized an ectopic parathyroid adenoma overlying the ascending aorta missed with TI-201. This case shows the superiority of Tc-99m sestamibi to TI-201 in localizing an ectopic parathyroid adenoma and exemplifies the pitfalls in dual radionuclide subtraction parathyroid scintigraphy caused by coexisting benign or malignant thyroid disease.

The aim of this study was to investigate the potential of (99m)Tc-Evans blue for discriminating the sentinel lymph node in multitiered lymph node sequences by using an ovine model. (99m)Tc-Evans blue is an agent that has both radioactive and color signals in a single dose. Previous studies in smaller animal models suggested that this agent could have advantages over the dual-injection technique of radiocolloid/blue dye.Doses of (99m)Tc-Evans blue ( approximately 21 MBq) containing Evans blue dye (approximately 4 mg) were administered to the hind limbs or fore limbs of sheep to map the lymphatic drainage patterns, validate its ability to identify the sentinel lymph node, and examine the reproducibility of the technique. The study protocol was repeated with (99m)Tc-antimony trisulfide colloid and Patent Blue V dye. After the operative exposure, lymph nodes were identified with the gamma probe and then excised and analyzed for radioactivity (percentage of injected dose) and blue color.After the administration of (99m)Tc-Evans blue, all lymph nodes harvested (35 of 35) in either short chains or long basins were hot and blue. The sentinel lymph nodes concentrated more radioactivity than the second-tier nodes to the extent of 2:1 to 215:1. For radiocolloid/Patent Blue V, the ratios were lower, at 2:1 to 3:1.(99m)Tc-Evans blue was found to better discriminate the sentinel lymph node than (99m)Tc-antimony trisulfide colloid/Patent Blue V in variable multitier lymph node anatomy, and it is an agent that promises to have positive clinical applications.

To objectively evaluate the performance of new vaginal dosage forms, it is important to determine their time of residence and their distribution. This paper describes the in vivo characteristics of a reference and test product in this situation. Method: A randomised cross-over study was performed in the same phase of the menstrual cycle in eight pre-menopausal women. The retention and distribution of a commercially available vaginal clotrimazole cream and a test gel product, each “labelled” with 99 m Tc -DTPA was assessed by gamma scintigraphy for 24 h after administration of the products. Mass balance analysis was attempted by collecting and counting sanitary napkins worn for the study time. Results: Within individuals there was little variation in the clearance of the formulations, but wide variation between individuals with a range between 81 and 1% of the administered doses retained by 24 h. The losses appeared to occur mainly at times of urination with 12±8% (cream) and 20±23% (gel) collected on the sanitary napkins, but 46±34% (cream) and 38±22% gel activity not accounted for by 24 h. The intravaginal distribution of activity was similar for each product. Conclusions: Radioactive tracer methods are useful in assessing and comparing vaginal dosage forms.

Lymphatic mapping and sentinel lymph node dissection (LM/SLND) for surgical staging of cutaneous primary melanoma is currently being evaluated, but the role of these techniques in recurrent (secondary) melanoma is largely unexplored. Our experience with 12 patients indicates the potential usefulness of LM/SLND in the management of locally recurrent melanoma at subcutaneous sites. We have even used mapping to localize the sentinel node draining a subcutaneous local recurrence after previous LM/SLND for primary melanoma. The application of LM/SLND may therefore be extended beyond primary melanoma management as we understand more about the technical issues and appropriate selection of patients.

To develop a simple method for simultaneous solid and liquid gastric emptying assessment using a dual isotope labelled breath test.13 patients were given 100 g ground beef labelled with 25 MBq (99m)Tc sulphur colloid and 74 KBq (14)C octanoic acid, and 150 ml 10% glucose drink labelled with 8 MBq (67)Ga citrate and 150 mg (13)C acetate. 10 normal volunteers were given the same test meals but labelled with (14)C and (13)C only. Breath was collected at baseline and regularly for 4 hours. The (14)CO(2) and (13)CO(2) activity was measured with liquid scintillation counting and mass spectroscopy. The times to maximum (14)CO(2) and (13)CO(2), were determined. Comparison was made between times to maximum (14)CO(2) with scintigraphic retention of (99m)Tc at 100 minutes and times to maximum (13)CO(2) with the scintigraphic half-clearance time of (67)Ga.For the solid meal, the times to maximum (14)CO(2) were: 60-120 minutes in the 8 patients with normal gastric emptying of (99m)Tc; 75-145 minutes for the 10 healthy volunteers; 75-180 minutes for the remaining 5 patients with abnormal gastric emptying of (99m)Tc. There was a weak but significant correlation (r = 0.56, p0.025) between the time to maximum (14)CO(2) and gastric retention of (99m)Tc at 100 minutes. For the liquid meal, times to maximum (13)CO(2) were: 20-35 minutes for the 4 with normal gastric emptying of (67)Ga; 15-40 minutes for the 10 healthy volunteers; 20-75 minutes for the remaining 9 patients with abnormal gastric emptying of (67)Ga. There was a strong and significant correlation (r = 0.88, p0.005) between times to maximum (13)CO(2) and gastric half-clearance time of (67)Ga.Breath tests utilising test meals labelled with *C isotopes are valid alternatives to scintigraphic studies using (99m)Tc and (67)Ga for the simultaneous assessment of gastric emptying of solids and liquids.

INTRODUCTION: A subset of patients undergoing elective resection for an intra-abdominal malignancy may have viable tumor cells present within the peritoneal cavity at the start of the procedure. The presence of these cells may alter the pattern of tumor recurrence. METHODS: Six million human colorectal tumor cells were radiolabeled and injected into the pelvis of eight pigs before the undertaking of a standardized laparoscopic-assisted sigmoid colectomy. In four pigs, a 1-liter saline lavage was performed before resection, and in the four remaining pigs, a similar lavage was performed after construction of the anastomosis. After completion of the sigmoid colectomy, pigs were killed, and the anastomosis was excised. Counting the radioactivity present on each sample and correlating this with the radioactivity present within the initial cell inoculum enabled the number of cells on each anastomosis to be calculated. Additional measurements were made of the number of cells on the resected bowel specimen, the stapling device, the resected anastomotic donuts, the trocars and abdominal wounds, and the lavage fluid. RESULTS: Significantly fewer cells were detected on the anastomosis, the resected bowel specimen, and the donut of resected tissue in the pigs that received a preresection lavage (P = 0.01). Significantly greater numbers of cells were retrieved in the lavage fluid in this group (P = 0.01). No differences were detected in the number of cells that contaminated the stapling device (P = 0.1), trocars (P = 0.47), or trocar sites (P = 0.27). CONCLUSION: The simple strategy of lavage at the commencement of resection for an intra-abdominal resection may reduce contamination of the anastomosis and effect a reduction of the total number of viable cells present within the abdominal cavity in patients with free intra-abdominal tumor cells.

To review clinical outcomes in patients referred for confirmation of brain death by (99m)Tc-labelled exametazime scintigraphy and to assess any tangible benefit.A retrospective casenote review in the intensive care unit and nuclear medicine department of a tertiary-level acute care hospital.66 consecutive patients, in whom a clinical diagnosis of brain death was not possible, undergoing (99m)Tc-labelled exametazime scintigraphy from February 1993 to March 2002, and for 56 of whom casenotes were available for review.Brain death was confirmed in 77% on the basis of absent supratentorial and infratentorial uptake. Where brain death was not confirmed, a normal scan was seen in 30%, the remainder showing patchy reduced infratentorial and/or supratentorial uptake. All patients with the scintigraphic appearance of brain death subsequently died. Even when brain death could not be confirmed, 11 of 13 patients died soon afterwards. Two patients with normal brain scintigraphy regained consciousness and survived for an extended period. When brain death was not confirmed by scintigraphy, elapsed time to certification of death was longer (44.7 vs. 7 h) and organ donation was less common even when a subsequent clinical diagnosis was made.The results indicate that patient prognosis remains poor regardless of the findings on (99m)Tc-labelled exametazime scintigraphy, but that the scan result influences the elapsed time to withdrawal of therapy or organ donation, providing a significant cost benefit, and occasionally a long-term survivor is seen.

An animal model of gastric emptying may have use in the study of gastric physiology and pharmacoscintigraphy. The pig has anatomy and physiology similar to that of humans. Our aim was to develop a model of gastric emptying in the pig. It was not possible to perform this study in conscious pigs; therefore, an anesthetic model was developed.Fifteen studies were performed on 4 pigs (age, 2-6 mo; weight, 20-100 kg). After acclimatization and training, pigs were fasted overnight before the study. Pigs were anesthetized using inhaled isoflurane without the use of injected premedication agents. An orogastric tube was inserted for the administration of a liquid meal, which consisted of (99m)Tc-diethylenetriaminepentaacetic acid either in water (nonnutrient) or with dextrose (nutrient meal). The pig was laterally positioned to enable right lateral dynamic acquisition to be performed. Anesthesia was maintained at 2% +/- 0.5% isoflurane in 4 studies and 0.8% +/- 0.5% in 11 studies (4 nutrient, 7 nonnutrient).With 2% +/- 0.5% isoflurane, there was delayed gastric emptying with a mean 50% emptying time (+/-SEM) of 141 +/- 14 min. With 0.8% +/- 0.5% isoflurane, the liquid meal emptied in an exponential manner similar to that of humans, with mean 50% emptying times (+/-SEM) of 30 +/- 7 min (nutrient) and 31 +/- 4 min (nonnutrient).The results indicate that high-dose anesthesia inhibits gastric emptying, but with low-dose anesthesia a useful pig model of liquid gastric emptying can be developed.

Background Laparoscopic resection of intra-abdominal malignancies has yet to be widely adopted, partly because of concerns over the possible increase in the rate of port-site metastasis. The aetiology of these is unclear, but the laparoscopic instrumentation used may influence the deposition of tumour cells at the port sites during operation. An in vitro model to examine tumour cell adherence to laparoscopic ports and to port sites was developed to examine this hypothesis. Methods A pilot study (study 1) was performed in which six smooth plastic, six ribbed plastic and six metal ports were introduced through the shaved abdominal wall of a cadaveric sheep and suspended in a water-bath containing radiolabelled LIM 1215 human colonic cancer cells for 30 min. Radioactivity on both ports and port sites was measured and the number of cells adherent to each structure was calculated. The study was expanded to include a further 36 smooth plastic ports and 36 metal ports (study 2). Results In study 1 metal ports were found to have significantly more adherent cells than plastic ports (P = 0·004), as did ribbed ports when compared with smooth ports (P < 0·05). In study 2 increased numbers of cells were again detected on metal ports (P < 0·001) when compared with plastic ports. Significantly greater numbers of cells were also detected on the sites through which metal ports had passed than on sites through which plastic ports had passed (P = 0·03). Conclusion In this model, the use of metal ports as opposed to plastic ports resulted in increased deposition of tumour cells on both ports and port sites.

Background Port-site metastases after laparoscopic surgery may occur with greater frequency than would be expected following open resection of intra-abdominal malignancies, but the causal mechanism for this is incompletely understood. The possibility that insufflation may increase peritoneal blood flow producing a wound environment conducive to the formation of metastases was investigated. Methods The effects of insufflation gas type and pressure were studied in 30-kg female pigs. Pigs were divided into five groups, which were subjected to insufflation at 12 mmHg pressure with helium, insufflation at 12, 8 or 4 mmHg pressure with carbon dioxide, or laparotomy. A microsphere technique utilizing two distinct radiotracers, 99mTc-labelled macroaggregated albumin (MAA) and 51Cr-labelled MAA, was used to study blood flow to the peritoneum, liver and kidneys. Results Insufflation with carbon dioxide or helium gases had no effect on renal (P < 0·09) or hepatic blood flow (P = 0·54). However, insufflation significantly increased peritoneal blood flow when carbon dioxide (P < 0·05), but not when helium (P = 0·99), was used as the insufflating gas. Conclusion These data suggest that blood flow within the peritoneum is influenced by insufflation with carbon dioxide. It is conceivable that such hyperaemia could increase the propensity for implanted tumour cells to metastasize in these sites following laparoscopy.

A 65-year-old man with several subcutaneous masses (clinically diagnosed as lipomata), underwent Tc-99m tetrofosmin scanning for chest pain. One of these masses (in the right thigh) was incidentally noted to take up tetrofosmin. Computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated a fat-containing lesion, and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET or C-PET) showed active uptake. Biopsy showed the lesion to be a hibemoma. Hibemoma is a benign but metabolically active tumor of brown fat origin. Brown fat is a major heat producer in the newborn and contains high levels of mitochondria. This high metabolic rate probably explains the uptake of Tc-99m tetrofosmin and F-18 FDG. Nevertheless, without a biopsy, the imaging studies could not exclude liposarcoma.

A 32-year-old woman with a 6-year history of benign intracranial hypertension was referred with headache symptoms for assessment of patency of a lumbopleural shunt. This had been inserted after failure of several previous lumboperitoneal shunts. Chest radiographs showed the shunt catheter to be in situ, but there was no evidence of pleural effusion. After intrathecal administration of Tc-99m DTPA, activity was seen in the right pleural space, confirming shunt patency.

Background: Assessment of axillary lymph node status is necessary for patients with invasive breast cancer. Sentinel node biopsy is a new minimally invasive technique that may provide accurate assessment of regional lymph node status while limiting the morbidity associated with axillary clearance. Methods: A workshop conducted in Adelaide in November 1998 aimed to assess current sentinel node mapping and biopsy techniques, and make recommendations regarding its application in the surgical management of early breast cancer in Australia and New Zealand. Results: At the conclusion of the workshop, a consensus was reached regarding indications, exclusions, sentinel node mapping/biopsy technique, nuclear medicine requirements, pathology and safety of sentinel node biopsy in breast cancer. It was agreed that a feasibility study according to an agreed prospective protocol was necessary to validate the technique by breast surgeons. Surgeons that satisfied validation criteria for the feasibility study could then consider a prospective randomized study comparing sentinel node biopsy with standard axillary dissection. Conclusions: Sentinel node biopsy in breast cancer involves close cooperation between members of a multidisciplinary team including surgeons, nuclear physicians, pathologists and radiologists. Although the technique has the potential to reduce morbidity associated with axillary surgery, surgical performance in this area will need to be closely monitored to ensure that the technique does not fall into disrepute by adversely affecting breast cancer prognosis.

OBJECTIVES To assess the reliability of determining sentinel node status in staging regional lymph nodes in breast cancer. DESIGN AND SETTING Prospective validation study in a major public teaching hospital, comparing histological sentinel node status with that of remaining axillary nodes. PATIENTS 117 women who underwent sentinel node biopsy and axillary dissection for primary breast cancer between 1995 and 1998. MAIN OUTCOME MEASURES Intraoperative success rate in sentinel node identification; false negative rate; predictive value of negative sentinel node status; overall accuracy of sentinel node status. RESULTS The sentinel node was identified at operation in 95 patients (81.2%). Tumour involvement of the sentinel node was demonstrated in 29 of 31 women (93.5%; 95% CI, 79%-99%). Sixty-four of the 66 women in whom the sentinel node was negative for tumour showed no further involvement of remaining axillary nodes (standard haematoxylin-eosin histological assessment), giving a predictive value of negative sentinel node status of 97% (95% CI, 89%-100%). The overall accuracy in 95 women in whom sentinel node status was compared with axillary node status was 97.9%. CONCLUSIONS Histopathological examination of the sentinel node is an accurate method of assessing axillary lymph node status in primary breast cancer and is likely to be incorporated into future surgical management of women with primary breast cancer.