T O Nunan

Comparison of Positron Emission Tomography Scanning and Sentinel Node Biopsy in the Detection of Micrometastases of Primary Cutaneous Malignant Melanoma

PURPOSE Sentinel node biopsy (SNB) is a surgical technique for detecting micrometastatic disease in the regional draining nodes. 2-fluorine-18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) scanning is an imaging technique that can detect clinically undetectable metastases. This prospective study was undertaken to compare the sensitivity of FDG-PET scanning with SNB in the detection of micromatastatic malignant melanoma. PATIENTS AND METHODS Fifty consecutive patients (23 women, 27 men; mean age, 53 years) with primary melanoma >1 mm thick or lymphatic invasion were recruited (mean, 2.41 mm). Primary lesions had been narrowly excised (<1 cm). Patients underwent PET scanning followed by SNB, using a dual technique. Preoperative lymphoscintigraphy was used to identify the draining basin. Lymph nodes were examined histologically and immunostained for S100 and HMB 45. RESULTS The sentinel node (SN) was identified in all patients. Fourteen patients (28%) had positive SNBs, including eight patients with melanoma <1.5 mm thick. In none of these 14 patients did PET scans identify metastatic disease in the SN or draining basin. In seven patients, the PET scans were positive in other locations, and in four cases, this was suspicious of metastatic disease. However, no patient has developed recurrent melanoma (mean follow-up, 15 months). All patients with positive SNBs underwent therapeutic lymph node dissection. Further lymph node involvement was found in two patients (primary lesions, 1.3 mm and 3.5 mm thick). CONCLUSION This study demonstrates the limitations of FDG-PET scanning in staging patients with primary melanoma. SNB is the only reliable method for identifying micrometastatic disease in the regional draining node.

Pulmonary deposition of a nebulised aerosol during mechanical ventilation.

BACKGROUND: There is increasing use of therapeutic aerosols in patients undergoing mechanical ventilation. Few studies have measured aerosol delivery to the lungs under these conditions with adequate experimental methods. Hence this study was performed to measure pulmonary aerosol deposition and to determine the reproducibility of the method of measurement during mechanical ventilation. METHODS: Nine male patients were studied during mechanical ventilation after open heart surgery and two experiments were performed in each to determine the reproducibility of the method. A solution of technetium-99m labelled human serum albumin (99mTc HSA (50 micrograms); activity in experiment 1, 74 MBq; in experiment 2, 185 MBq) in 3 ml saline was administered with a Siemens Servo 945 nebuliser system (high setting) and a System 22 Acorn nebuliser unit. Pulmonary deposition was quantified by means of a gamma camera and corrections derived from lung phantom studies. RESULTS: Pulmonary aerosol deposition was completed in 22 (SD 4) minutes. Total pulmonary deposition (% nebuliser dose (SD)) was 2.2 (0.8)% with 1.5% and 0.7% depositing in the right and left lungs respectively; 0.9% of the nebuliser activity was detected in the endotracheal tube or trachea and 51% was retained within the nebuliser unit. Considerable variability between subjects was found for total deposition (coefficient of variation (CV) 46%), but within subject reproducibility was good (CV 15%). CONCLUSIONS: Administration of aerosol in this way is inefficient and further research is needed to find more effective alternatives in patients who require mechanical respiratory support. This method of measurement seems suitable for the assessment of new methods of aerosol delivery in these patients.

Effect of a spacer on pulmonary aerosol deposition from a jet nebuliser during mechanical ventilation.

BACKGROUND--Several factors have been identified which improve nebulised aerosol delivery in vitro. One of these is the addition of a spacer to the ventilator circuit which improves aerosol delivery from a jet nebuliser to a model lung by approximately 30%. The current study was designed to demonstrate whether similar improvements could be demonstrated in vivo. METHODS--Ten patients (seven men) were studied during mechanical ventilation (Siemens Servo 900C) after open heart surgery. Aerosol was delivered using a Siemens Servo 945 nebuliser system (high setting) driving a System 22 Acorn jet nebuliser (Medic-Aid) containing 3 ml technetium-99m labelled human serum albumin (99mTc-HSA (50 micrograms); activity in the first nebulisation, 90 MBq; in the second nebulisation, 185 MBq). Central and peripheral lung aerosol deposition and the time to complete deposition were measured using a gamma camera and compared when the nebuliser was connected to the inspiratory limb using a simple T-piece or a 600 ml spacer. RESULTS--The addition of the spacer increased total lung deposition (mean (SD) percentage initial nebuliser activity) from 2.2 (0.7)% to 3 (0.8)%. There was no difference in the time required to complete nebulisation (18.2 min v 18.3 min respectively for T-piece and spacer) or in the retention of activity in the nebuliser (46.2% v 47.1% respectively). CONCLUSIONS--The combination of a spacer with a jet nebuliser increased lung deposition by 36% in mechanically ventilated patients and is a simple way of increasing drug deposition or reducing the amount of an expensive drug required for nebulisation.

Fatal Stevens-Johnson syndrome in a patient on captopril and allopurinol

tumorous tissues, by Victoria-blue staining.8 The maternal serum was also negative for HBsAg and HBsAb by reverse phase and passive haemagglutination tests done twice before and after the delivery. The route of HBV infection in the baby is thus not clear. This case is important not only because it strengthens the hypothesis of a direct causal role for HBV in the induction of HCC (including hepatoblastomas) but also because it raises the possibility of transplacental transmission of HBV to the hepatocyte during embryogenesis.

Observer Variation in Interpreting 18F-FDG PET/CT Findings for Lymphoma Staging

Many studies demonstrate a high accuracy for PET in staging lymphoma, but few assess observer variation. This study quantified agreement for staging lymphoma with PET/CT. Methods: The PET/CT images of 100 patients with lymphoma who had been referred for staging were reviewed by 3 experienced observers, with 2 observers reviewing each series a second time. Ann Arbor stage and individual nodal and extranodal regions were assessed. Weighted κ (κw) and intraclass correlation coefficient were used to compare ratings. Results: Intra- and interobserver agreement was high for Ann Arbor stage (κw = 0.79–0.91), number of nodal regions involved (intraclass correlation coefficient, 0.83–0.93), and presence of extranodal disease (κ = 0.74–0.86). High agreement was also observed for all nodal regions (κw > 0.60) except hilar (κw = 0.56–0.82) and infraclavicular (κw = 0.14–0.55). Lower agreement was observed for bowel involvement (κw = 0.37–0.71). Conclusion: Experienced observers had a high level of agreement using PET/CT for lymphoma staging, supporting its use as a robust noninvasive staging tool. Further research is needed to evaluate observer variability for restaging during and after chemotherapy.

Lung deposition of nebulised pentamidine in children

BACKGROUND: Nebulised pentamidine is effective for preventing Pneumocystis carinii pneumonia in adults with acquired immunodeficiency syndrome. The nebuliser dose required to produce equivalent lung concentrations of pentamidine in children is unknown. This study was performed to measure pulmonary pentamidine deposition in children and to relate this to age, ventilation pattern, and body size. METHODS: Nebulised pentamidine (50 mg in 6 ml saline) was administered to 12 children (including one with lymphocytic interstitial pneumonitis) and to six adults with human immunodeficiency virus infection using a Respirgard II nebuliser. Technetium-99m labeled colloidal human serum albumin was used as an indirect marker for pentamidine and deposition in the lungs was detected by a gamma camera. RESULTS: Absolute deposition of pentamidine was not related to age, height, weight, spirometry, or ventilation characteristics. Deposition, as a mean (SD) percentage of nebuliser output, was similar in children aged 8-11 years (5.5(2.4)%), teenagers aged 12-15 years (7.2(2.2)%) and adults (7.1(2.6)%). Aerosol concentration within the lungs (% nebuliser output deposited/predicted total lung capacity) was therefore higher in children (1.9(1.5)%/1) and teenagers (1.9(0.7)%/1) than in adults (1.0(0.7%)/1), and was negatively correlated with height (r = -0.69) and weight (r = -0.50). Deposition of aerosol in the region of the large central airways was particularly marked in children. Small reductions in forced expiratory volume in one second and forced vital capacity after treatment did not differ significantly between adults and children and visual analogue scores of subjective adverse effects did not vary with age. CONCLUSIONS: These results suggest that children probably require lower nebuliser pentamidine doses to produce lung pentamidine concentrations equivalent to those found to be effective for preventing P carinii pneumonia in adults using the Respirgard II nebuliser.

Pulmonary deposition of nebulised pentamidine isethionate: effect of nebuliser type, dose, and volume of fill.

An estimate of the absolute pulmonary deposition of nebulised pentamidine isethionate was obtained in nine patients with AIDS. Two nebuliser systems were compared, System 22 Mizer (Medic-Aid) and Respirgard II (Marquest), with 50 and 150 mg doses of pentamidine in a 3 ml solution driven by an air flow of 6 l/min with the patient in the sitting position. The 50 mg pentamidine dose was repeated with a 6 ml fill with both devices. The nebuliser cloud was labelled with technetium-99m human serum albumin (Ventocol) and lung deposition was measured with a gamma camera. Of the two nebulisers studied, System 22 Mizer delivered more drug to the lungs as a whole and to each individual lung region, including the peripheral and upper zones. For the 50 mg dose the mean (SEM) total pulmonary deposition with the 3 and the 6 ml fill respectively was 2.63 (0.34) and 3.71 (0.41) mg for the System 22 Mizer and 1.37 (0.26) and 1.45 (0.18) mg for the Respirgard II. For the 150 mg dose the System 22 Mizer delivered 7.16 (1.02) mg and the Respirgard II 4.34 (0.57) mg. Increasing the volume of fill from 3 to 6 ml increased pulmonary deposition with System 22 Mizer, and this was related to an increase in nebuliser output. Neither pulmonary deposition nor nebuliser output was increased by using a 6 ml solution in the Respirgard II. Increasing the volume of fill prolonged the time required for nebulisation with both nebulisers. The System 22 Mizer produced more nonpulmonary (gastric and oropharyngeal) deposition of drug, more frequent local adverse effects (cough, burning in the throat, and a metallic taste), and small reductions in lung function, particularly with the 150 mg pentamidine dose. Thus nebuliser type, volume of fill, and nebuliser dose affect the pulmonary deposition of pentamidine. A 300 mg dose of pentamidine via a Respirgard II is generally recommended as providing effective prophylaxis; our results suggest that similar pulmonary deposition can be produced with System 22 Mizer and 150 mg pentamidine. A clinical trial would be needed to show whether this regimen provides similar prophylactic benefit.

The place of lung 99mTc DTPA aerosol transfer in the investigation of lung infections in HIV positive patients

Pneumocystis carinii pneumonia (PCP) is the most common cause of pneumonia in HIV antibody positive patients, but other pneumonias remain important, i.e. streptococcal and mycobacterial infections. A definitive diagnosis relies on obtaining samples from the lung either noninvasively (induced sputum), or invasively (bronchoalveolar lavage, transbronchial or open lung biopsy). We have used the noninvasive technique of nebulized 99mTc DTPA transfer, to assess patients with PCP (n = 30) and other lung infections (n = 20) to see whether this test will distinguish between the various infections. The presence of a biphasic, rapid transfer curve indicates severe extensive alveolar damage and is seen in PCP or legionella pneumonia. The mean transfer time (T50 +/- SEM) for patients with PCP (whether smokers or nonsmokers) was 2.1 +/- 0.2 min, and for two of the patients with legionella 3.2 min. In PCP effective treatment causes the transfer to slow (mean T50 22.7 +/- 3.3 min, n = 24) and become monoexponential. Other causes of these changes in transfer are discussed. The other pneumonias (streptococcal, mycobacterial, and staphylococcal) did not result in biphasic curves or very rapid times, their T50 values are indistinguishable from cigarette smokers. In this patient group the DTPA transfer is a useful noninvasive investigation with a very rapid, biphasic curve indicating a high probability of PCP.

Use of splenic volume estimation to distinguish primary thrombocythaemia from reactive thrombocytosis

Splenic volume was measured by visual assessment of planar images of the spleen, and also by single photon emission computerised tomography (SPECT) using 99mtechnetium tin colloid, in a group of 33 patients with primary thrombocythaemia (PT) or reactive thrombocytosis. Volumes greater than 337 cm3 correlated strongly though not absolutely with PT, all patients with volumes greater than this figure being in the PT group. Simple visual assessment of planar images by an experienced observer matched measured splenic volumes very closely.

Radionuclides and therapy of thyroid cancer

The majority of thyroid carcinomas are removed surgically. The appropriate surgical technique is still debated. After surgery the amount of residual thyroid or tumour and the presence of local or distant metastases is often in doubt, particularly if it is not detectable clinically. Therefore, methods for determining the presence of disease or the later recurrence of disease are needed. They commonly include serum thyroglobulin and imaging after diagnostic or therapeutic doses of 131I. Other techniques are used such as 131I whole body retention (using a whole body counter), 201Tl and 99Tcm-sestamibi imaging. The place of these diagnostic methods in the management of thyroid cancer is reviewed in this article. Radioiodine would seem an ideal treatment for recurrence of functioning thyroid carcinoma as 131I targets the lesion and has minimal side effects. However, the indolent nature of well-differentiated thyroid carcinomas makes it difficult to assess the benefits of radioiodine therapy both in its ability to ablate the normal thyroid and to treat recurrent and metastatic disease. However, the addition of radioiodine therapy to local surgical removal reduces both the occurrence of metastases and the morbidity with prolonged follow-up. Unresolved issues that remain concern the activities of radioiodine needed to achieve adequate ablation of residual thyroid tissue and to treat residual and recurrent cancer. There is also debate as to exactly which patients require radioiodine therapy. This review also considers radiation protection and the side effects of 131I therapy.