Philip C. Goodman

Treatment of Tuberculosis in Patients with Advanced Human Immunodeficiency Virus Infection

BACKGROUND AND METHODS Infection with the human immunodeficiency virus (HIV) increases the risk of tuberculosis and may interfere with the effectiveness of antituberculosis chemotherapy. To examine the outcomes in patients with both diagnoses, we conducted a retrospective study of all 132 patients listed in both the acquired immunodeficiency syndrome (AIDS) and tuberculosis case registries in San Francisco from 1981 through 1988. RESULTS At the time of the diagnosis of tuberculosis, 78 patients (59 percent) did not yet have a diagnosis of AIDS, 18 patients (14 percent) were given a concomitant diagnosis of AIDS (as determined by the presence of an AIDS-defining disease other than tuberculosis), and the remaining 36 patients (27 percent) already had AIDS. The manifestations of tuberculosis were entirely pulmonary in 50 patients (38 percent), entirely extrapulmonary in 40 patients (30 percent), and both pulmonary and extrapulmonary in 42 patients (32 percent). The treatment regimens were as follows: isoniazid and rifampin supplemented by ethambutol for the first two months, 52 patients; isoniazid and rifampin supplemented by pyrazinamide and ethambutol for the first two months, 39 patients; isoniazid and rifampin, 13 patients; isoniazid and rifampin supplemented by pyrazinamide for the first two months, 4 patients; and other drug regimens, 17 patients. The intended duration of treatment for patients whose regimen included pyrazinamide was six months, and for patients who did not receive pyrazinamide, nine months. Seven patients received no treatment because tuberculosis was first diagnosed after death. Sputum samples became clear of acid-fast organisms after a median of 10 weeks of therapy. Abnormalities on all chest radiographs taken after three months of treatment were stable or improved except for those of patients who had new nontuberculous infections. The only treatment failure occurred in a man infected with multiple drug-resistant organisms who did not comply with therapy. Adverse drug reactions occurred in 23 patients (18 percent). For all 125 treated patients, median survival was 16 months from the diagnosis of tuberculosis. Tuberculosis was a major contributor to death in 5 of the 7 untreated patients and 8 of the 125 treated patients. Three of 58 patients who completed therapy had a relapse (5 percent); compliance was poor in all 3. CONCLUSIONS Tuberculosis causes substantial mortality in patients with advanced HIV infection. In patients who comply with the regimen, conventional therapy results in rapid sterilization of sputum, radiographic improvement, and low rates of relapse.

Carcinoids associated with multiple endocrine neoplasia syndromes

Carcinoids occur in association with MEN types 1 and 2. To determine the relationship between carcinoids and MEN, we reviewed nine patients with carcinoids and other endocrine tumors. Analyzing these 9 patients and 56 other patients previously described in the literature, we found several clinically important relationships. In contrast to the usual midgut and hindgut origin, most carcinoids associated with MEN (69 percent) are of foregut origin (thymus 24 percent, bronchus 27 percent, stomach 3 percent, and duodenum 14 percent). Carcinoids are more commonly associated with MEN type 1 than MEN type 2 (59 patients and 6 patients, respectively). Thymic carcinoids associated with MEN are more common in men (15 versus 2), and most (82 percent) are malignant. Bronchial carcinoids associated with MEN are more common in women (15 versus 4), and most (74 percent) are benign. There is a strong association between thymic carcinoids and parathyroid tumors and between bronchial carcinoids and pituitary tumors. Most patients with carcinoids and hyperparathyroidism (82 percent) have had parathyroid hyperplasia or multiple parathyroid adenomas. Thus, carcinoids may occur in association with both MEN type I and MEN type II. MEN should be suspected in patients with foregut carcinoids. Patients with MEN and ectopic ACTH production should be considered to have bronchial carcinoids if they are female and thymic carcinoid if they are male. The thymus should be routinely removed in patients with MEN type I because of the possible presence of an ectopic parathyroid gland in this tissue and to prevent subsequent development of a carcinoid tumor.

FDG-PET finding in early-phase Takayasu arteritis.

We report a unique case of early-phase Takayasu arteritis in which the vessels demonstrated accumulation of [18F]fluorodeoxyglucose (FDG) on PET scanning. This observation suggests the possible use of FDG-PET for the diagnosis of vasculitis. Early diagnosis of Takayasu arteritis may permit early treatment and possibly could prevent progression to the occlusive or pulseless phase of this disease.

Radiation Dose Savings for Adult Pulmonary Embolus 64-MDCT Using Bismuth Breast Shields, Lower Peak Kilovoltage, and Automatic Tube Current Modulation

OBJECTIVE The purpose of this study was to assess whether radiation dose savings using a lower peak kilovoltage (kVp) setting, bismuth breast shields, and automatic tube current modulation could be achieved while preserving the image quality of MDCT scans obtained to assess for pulmonary embolus (PE). MATERIALS AND METHODS CT angiography (CTA) examinations were performed to assess for the presence or absence of pulmonary artery emboli using a 64-MDCT scanner with automatic tube current modulation (noise level=10 HU), two kVp settings (120 and 140 kVp), and bismuth breast shields. Absorbed organ doses were measured using anthropomorphic phantoms and metal oxide semiconductor field effect transistor (MOSFET) detectors. Image quality was assessed quantitatively as well as qualitatively in various anatomic sites of the thorax. RESULTS Using a lower kVp (120 vs 140 kVp) and automatic tube current modulation resulted in a dose savings of 27% to the breast and 47% to the lungs. The use of a lower kVp (120 kVp), automatic tube current modulation, and bismuth shields placed directly on the anterior chest wall reduced absorbed breast and lung doses by 55% and 45%, respectively. Qualitative assessment of the images showed no change in image quality of the lungs and mediastinum when using a lower kVp, bismuth shields, or both. CONCLUSION The use of bismuth breast shields together with a lower kVp and automatic tube current modulation will reduce the absorbed radiation dose to the breast and lungs without degradation of image quality to the organs of the thorax for CTA detection of PE.

Radiation Dose to the Female Breast from 16-MDCT Body Protocols

OBJECTIVE The objective of our study was to determine the radiation dose to the female breast from current 16-MDCT body examinations. MATERIALS AND METHODS Metal oxide semiconductor field effect transistor (MOSFET) detectors were placed in four quadrants of the breast of a female-configured anthropomorphic phantom to determine radiation dose to the breast. Imaging was performed on a 16-MDCT scanner (LightSpeed, GE Healthcare) using current clinical protocols designed to assess pulmonary embolus (PE) (140 kVp, 380 mA, 0.8-sec rotation, 16 x 1.25 mm collimation), appendicitis (140 kVp, 340 mA, 0.5-sec rotation, 16 x 0.625 mm collimation), and renal calculus (140 kVp, 160 mA, 0.5-sec rotation, 16 x 0.625 mm collimation). RESULTS Radiation dose to the breast ranged from 4 to 6 cGy for the PE protocol and up to 1-2 cGy in the inferior aspect of the right breast and lateral aspect of the left breast for the appendicitis protocol. The renal calculus protocol yielded less than 150 microGy absorbed breast dose. CONCLUSION Current clinical chest and abdomen protocols result in vairable radiation doses to the breast. The magnitude of exposure may have implications for imaging strategies.

Validation of Metal Oxide Semiconductor Field Effect Transistor Technology for Organ Dose Assessment During CT: Comparison with Thermoluminescent Dosimetry

OBJECTIVE The purposes of this study were to apply near-real-time dose-measurement technology with metal oxide semiconductor field effect transistors (MOSFETs) to the assessment of organ dose during CT and to validate the method in comparison with the thermoluminescent dosimeter (TLD) method. MATERIALS AND METHODS Dosimetry measurements were performed in two ways, one with TLDs and the other with MOSFETs. Twenty organ locations were selected in an adult anthropomorphic female phantom. High-sensitivity MOSFET dosimeters were used. For the reference standard, TLDs were placed in the same organ locations as the MOSFETs. Both MOSFET and TLD detectors were calibrated with an X-ray beam equivalent in quality to that of a commercial CT scanner (half-value layer, approximately 7 mm Al at 120 kVp). Organ dose was determined with a scan protocol for pulmonary embolus studies on a 4-MDCT scanner. RESULTS Measurements for selected organ doses and the percentage difference for TLDs and MOSFETs, respectively, were as follows: thyroid (0.34 cGy, 0.31 cGy, -8%), middle lobe of lung (2.4 cGy, 3.0 cGy, +26%), bone marrow of thoracic spine (2.2 cGy, 2.5 cGy, +11%), stomach (1.0 cGy, 0.93 cGy, -6%), liver (2.5 cGy, 2.6 cGy, +6%), and left breast (3.0 cGy, 2.9 cGy, -1%). Bland-Altman analysis showed that the MOSFET results agreed with the TLD results (bias, 0.042). CONCLUSION We found good agreement between the results with the MOSFET and TLD methods. Near-real-time CT organ dose assessment not previously feasible with TLDs was achieved with MOSFETs. MOSFET technology can be used for protocol development in the rapidly changing MDCT scanner environment, in which organ dose data are extremely limited.

Effective dose determination using an anthropomorphic phantom and metal oxide semiconductor field effect transistor technology for clinical adult body multidetector array computed tomography protocols.

Purpose: To determine the organ doses and total body effective dose (ED) delivered to an anthropomorphic phantom by multidetector array computed tomography (MDCT) when using standard clinical adult body imaging protocols. Materials and Methods: Metal oxide semiconductor field effect transistor (MOSFET) technology was applied during the scanning of a female anthropomorphic phantom to determine 20 organ doses delivered during clinical body computed tomography (CT) imaging protocols. A 16-row MDCT scanner (LightSpeed, General Electric Healthcare, Milwaukee, Wis) was used. Effective dose was calculated as the sum of organ doses multiplied by a weighting factor determinant found in the International Commission on Radiological Protection Publication 60. Volume CT dose index and dose length product (DLP) values were recorded at the same time for the same scan. Results: Effective dose (mSv) for body MDCT imaging protocols were as follows: standard chest CT, 6.80 ± 0.6; pulmonary embolus CT, 13.7 ± 0.4; gated coronary CT angiography, 20.6 ± 0.4; standard abdomen and pelvic CT, 13.3 + 1.0; renal stone CT, 4.51 + 0.45. Effective dose calculated by direct organ measurements in the phantom was 14% to 37% greater than those determined by the DLP method. Conclusions: Effective dose calculated by the DLP method underestimates ED as compared with direct organ measurements for the same CT examination. Organ doses and total body ED are higher than previously reported for MDCT clinical body imaging protocols.

Correlation of FDG-PET imaging with Glut-1 and Glut-3 expression in early-stage non-small cell lung cancer.

PURPOSE To correlate FDG activity on PET with the expression of glucose transporter proteins Glut-1 and Glut-3 in patients with early stage non-small cell lung cancer (NSCLC). METHODS Over a 5 year period, all patients with a PET scan and clinical stage I NSCLC underwent an immunohistochemical analysis of their tumor for Glut-1 and Glut-3 expression. The amount of FDG uptake in the primary lesion was measured by a standardized uptake ratio (SUR) and correlated with immunohistochemical results. RESULTS Seventy-three patients with a mean age of 66 years had clinical stage I disease. The final pathologic stage showed 64 patients with stage IA/B disease, eight with stage IIA disease, and one patient with pathologic stage IIIA (T1N2) disease. Glut-1 transporter expression was significantly higher than Glut-3 (P<0.0001), and although there was some association between the SUR and Glut-1 (P=0.085) and SUR and Glut-3 (P=0.074) expression, this did not reach statistical significance. CONCLUSIONS Glut-1 and Glut-3 transporter expression did not demonstrate a statistically significant correlation with FDG uptake in potentially resectable lung cancer. It appears that these transporters alone do not affect the variation in FDG activity in early stage NSCLC.

Fibrosing Alveolitis in Patients with Neurofibromatosis

Fibrosing alveolitis, or interstitial pulmonary fibrosis, is a common manifestation of neurofibromatosis, and was observed in 7 of 70 patients with the disease. Though neurofibromatosis is congenital, fibrosing alveolitis does not appear until adulthood, and occurs in 20% of patients with the disease who are over 30 years old. Characteristic radiographic findings include linear, interstitial density, and large upper lobe bullae; this combination limits the differential diagnosis. Pathological examination demonstrates alveolar wall thickening progressing to fibrosis and lung destruction. Pulmonary function tests can show obstructive or restrictive lung disease.

Identification of small lung nodules at autopsy: implications for lung cancer screening and overdiagnosis bias

PURPOSE Unsuspected cases of lung cancer are reported to be uncommon in autopsy series, and these data have been used to suggest that indolent tumors are rare and that overdiagnosis bias is not an important factor in lung cancer screening. The purpose of this study was to determine if a retrospective autopsy review is indeed accurate in identifying all small lung nodules on CT, and thus provide a true estimate of unsuspected lung tumors. MATERIALS AND METHODS We identified all 1047 patients who had an autopsy at our institution from 1994 to 1998. We then reviewed the patients radiology records and found 187 patients with a thoracic CT within 2 months of the postmortem examination. All 187 CT reports were reviewed in order to identify patients with at least one pulmonary nodule. CT studies with reports that described a nodule(s) were then re-reviewed to confirm presence and location of the nodule(s). The CT findings were than compared to the autopsy report to determine if the postmortem examination indeed found the nodule(s). RESULTS 28 autopsy patients had at least one pulmonary nodule identified on their thoracic CT no more than 2 months before death. Nineteen patients (68%) had nodule(s) recorded on the autopsy report, two ( approximately 10%) of which proved to have undiagnosed squamous cell carcinoma. Nine patients (22%) had no mention of pulmonary nodules seen on the CT recorded on their autopsy report. CONCLUSIONS This study suggests autopsies do not identify all small pulmonary nodules found at CT. The true incidence of clinically insignificant lung cancer is thus uncertain, and overdiagnosis bias in lung cancer screening may be more important than previously recognized.