Accuracy of CT parameters for assessment of tumour size and aggressiveness in lung adenocarcinoma with bronchoalveolar elements.

Accurate determination of tumour size in lung adenocarcinoma with bronchoalveolar features (BAC) is important for the determination of TNM (tumour, nodes, metastasis) scores used in staging, prognosis and therapy response assessment. However, tumour sizes derived using lung window (LW) CT or soft-tissue/mediastinal window (MW) CT often give different results. This study examines which measurement correlates best with actual tumour size and which best identifies advanced disease. This retrospective study included 43 BAC patients who underwent surgical resection with mediastinal lymphadenectomy <4 weeks post CT scan. The largest unidimensional tumour diameter on each CT window was compared with actual histopathological tumour size (HP). LW, MW and HP size measurements and a recently described CT parameter - the modified tumour shadow disappearance rate (mTDR) = (1 - [MW/LW]) - were then used to determine which parameter best discriminated between the presence or absence of advanced disease. There was no difference between HP and LW sizes, but MW significantly underestimated HP size (p<0.0001). Unlike MW (p = 0.01) and mTDR (p = 0.001), neither HP (p = 0.14) nor LW (p = 0.10) distinguished between patients with or without advanced disease. On receiver operating characteristic (ROC) analysis at a cut-off of ≤0.13, the sensitivity and specificity of mTDR for detecting advanced disease were 69% and 89%, respectively. In patients with tumours ≤3 cm, only mTDR remained a significant predictor of advanced disease (p = 0.017), with best cut-off at ≤0.20, giving a sensitivity and specificity of 71% and 94%, respectively. MW better predicts advanced disease than LW and might also need to be recorded for RECIST (response evaluation criteria in solid tumours) assessment for T staging of BAC; however, mTDR appears to be an even better predictor and should also be used.

[PET/CT in lymphoma patients]. / PET-CT bei Lymphompatienten.

PURPOSE: First results of PET/CT in Hodgkin's disease (HD) and aggressive non-Hodgkin's lymphoma (NHL) are reported. PATIENTS AND METHODS: From March 2001 to August 2004 822 PET/CT were performed at our clinic in lymphoma patients for primary staging, restaging after therapy, and diagnosis of recurrence. For coregistration non contrast-enhanced low-dose CT were used. RESULTS: Due to the exact anatomic localization of (18)F-FDG accumulating lesions equivocal or false positive PET findings are avoided. In comparison to contrast enhanced CT, PET/CT has a higher sensitivity and specificity in patients with HD and aggressive NHL. Integration of PET/CT in treatment planning of radiation therapy optimizes the field volume. CONCLUSION: Even in the initial phase of clinical evaluation, PET/CT has proven useful in staging and restaging of lymphoma. The exact anatomic localization of the PET findings is essential for a precise report, for treatment planning of radiation therapy, and for planning surgical biopsy.

Bronchoscopic radioisotope injection for sentinel lymph-node mapping in potentially resectable non-small-cell lung cancer.

OBJECTIVE: Prospective study to evaluate the feasibility of a preoperative bronchoscopic radioisotope application, followed by conventional sentinel lymph-node (SLN) identification and to investigate the occurrence and distribution of micrometastases in relation to SLN activity. METHODS: Twenty patients with a mean age of 63 years and proven clinical stage T1-3 N0-1 non-small-cell lung cancer (NSCLC) were included. A dosage of 80MBq radiolabeled technetium-99m nanocolloid was endoscopically administrated on intubated patients in the operation theatre. At thoracotomy, scintigraphic readings of both the primary tumor and hilar and mediastinal lymph-node stations were obtained with a hand-held gamma-counter. Patients underwent lung resection and mediastinal lymphadenectomy. Radiolabeled nodes were also examined separately on back-table. SLNs were defined as the hottest nodes or nodes with at least one-tenth of the radioactivity of the hottest nodes. SLNs pathologic assessment included standard examination using hematoxylin and eosin staining on step sections and immunohistochemistry (ICH) for cytokeratins. RESULTS: Identification of SLNs was possible in 19/20 (95%) patients after bronchoscopic radioisotope application. In 7/19 (37%) patients, a unique SLN was identified, whereas in 12/19 (63%) patients, nodes from two different stations could be classified as SLNs. Metastatic nodal disease was found in 9/19 (47%) patients. ICH revealed micrometastases in 2/12 (17%) patients, initially classified nodal negative. Pathologic negative SLNs were a predictor for absence of metastatic nodal disease after mediastinal lymphadenectomy. No complication related to the procedure was observed. CONCLUSION: Our preliminary results suggest that preoperative bronchoscopic radioisotope injection for SLN identification is a safe and simple method, improving accuracy of SLN detection in comparison to intraoperative technique. The absence of metastases in the SLNs seems to predict a negative nodal status accurately.

Diagnostic and therapeutic impact of whole body positron emission tomography using fluorine-18-fluoro-2-deoxy-D-glucose in children with chronic granulomatous disease.

AIMS: To compare whole body positron emission tomography (PET) using fluorine-18-fluoro-2-deoxy-D-glucose (FDG) with computed tomography (CT) in detecting active infective foci in children with chronic granulomatous disease. METHODS: We performed 22 whole body FDG PET studies in seven children with X linked (n = 6) or autosomal recessive (n = 1) CGD. All had clinical signs of infection and/or were evaluated prior to bone marrow transplantation (BMT). Nineteen PET studies were also correlated with chest and/or abdominal CT. All PET scans were interpreted blinded to the CT findings. Diagnoses were confirmed histologically and bacteriologically. RESULTS: We detected 116 lesions in 22 FGD PETs and 126 lesions on 19 CTs. Only two of the latter could be classified reliably as active lesions by virtue of contrast enhancement suggesting abscess formation. PET excluded 59 lesions suspicious for active infection on CT and revealed 49 infective lesions not seen on CT. All seven active infective lesions were identified by PET, allowing targeted biopsy and identification of the infective agent followed by specific antimicrobial treatment, surgery, or subsequent BMT. CONCLUSIONS: Identification of infective organisms is more precise if active lesions are biopsied. CT does not discriminate between active and inactive lesions. Whole body FDG PET can be used to screen for active infective lesions in CGD patients.

[The impact of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) on planning of radiotherapy]. / Vliianie pozitronnoi émissionnoi tomografii s 18F-ftorodeoksigliukozoi na planirovanie luchevoi terapii.

AIM: To determine the impact of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) on patient management in radiotherapy. MATERIAL AND METHODS: One hundred sixty-nine consecutive patients with different malignant tumors were analyzed. Whole-body FDG-PET was performed for staging before radiotherapy. The strategy of radiotherapy before and after PET scanning was compared and the change in the treatment management determined. RESULTS: In 47(28%) of 169 patients PET results changed patient management in radiotherapy. In 19 patients (11%) radiotherapy was not performed after PET. In 16 patients (10%) PET results changed the intention of radiation treatment (curative/palliative). Correction of radiation dose was made in 16 patients (10%). Correction of the volume of the exposure area was made in 12 patients (7%). Tumor outside the field of view was missed in only 2 patients with a regional PET scan. CONCLUSION: In this retrospective analysis the information provided by FDG-PET contributes to a substantial change in radiotherapy strategy.

Value of (18F)-FDG positron emission tomography, computed tomography, and magnetic resonance imaging in diagnosing primary and recurrent ovarian carcinoma.

The aim of this study was to compare prospectively the accuracy of whole-body positron emission tomography (PET), CT and MRI in diagnosing primary and recurrent ovarian cancer. Nineteen patients (age range 23-76 years) were recruited with suspicious ovarian lesions at presentation (n = 8) or follow-up for recurrence (n = 11). All patients were scheduled for laparotomy and histological confirmation. Whole-body PET with FDG, contrast-enhanced spiral CT of the abdomen, including the pelvis, and MRI of the entire abdomen were performed. Each imaging study was evaluated separately. Imaging findings were correlated with histopathological diagnosis. The sensitivity, specificity and accuracy for lesion characterization in patients with suspicious ovarian lesions (n = 7) were, respectively: 100, 67 and 86% for PET; 100, 67 and 86% for CT; and 100, 100 and 100% for MRI. For the diagnosis of recurrent disease (n = 10), PET had a sensitivity of 100%, specificity of 50% and accuracy of 90%. The PET technique was the only technique which correctly identified a single transverse colon metastasis. Results for CT were 40, 50 and 43%, and for MRI 86, 100 and 89%, respectively. No statistically significant difference was seen. Neither FDG PET nor CT nor MRI can replace surgery in the detection of microscopic peritoneal disease. No statistically significant difference was observed for the investigated imaging modalities with regard to lesion characterization or detection of recurrent disease; thus, the methods are permissible alternatives. The PET technique, however, has the drawback of less accurate spatial assignment of small lesions compared with CT and MRI.

St John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4.

BACKGROUND: St John's Wort (hypericum perforatum) is an herbal medicine that is frequently used for therapy of mild depression. Recently, St John's Wort was reported to substantially decrease blood/plasma concentrations and efficacy of cyclosporine (INN, ciclosporin), indinavir, and digoxin. In this study we investigated the mechanisms of these St John's Wort-induced drug interactions. METHODS AND RESULTS: In a preclinical study, the administration of St John's Wort extract to rats during 14 days resulted in a 3.8-fold increase of intestinal P-glycoprotein/Mdrl expression and in a 2.5-fold increase in hepatic CYP3A2 expression (Western blot analyses). In a clinical study, the administration of St John's Wort extract to 8 healthy male volunteers during 14 days resulted in an 18% decrease of digoxin exposure after a single digoxin dose (0.5 mg), in 1.4- and 1.5-fold increased expressions of duodenal P-glycoprotein/MDR1 and CYP3A4, respectively, and in a 1.4-fold increase in the functional activity of hepatic CYP3A4 (14C-erythromycin breath test). CONCLUSIONS: These results indicate direct inducing effects of St John's Wort on intestinal P-glycoprotein/MDR1 (in rats and humans), hepatic CYP3A2 (in rats), and intestinal and hepatic CYP3A4 (in humans). Therefore the results provide a mechanistic explanation for the previously observed drug interactions in patients and support the importance of intestinal P-glycoprotein/MDR1 in addition to intestinal and hepatic CYP3A4 for overall drug absorption and disposition in humans.

Non-invasive assessment of tumour cell proliferation with positron emission tomography and [76Br]bromodeoxyuridine.

In oncology, a number of new potential therapeutic modalities, including gene targeting, are currently under investigation. To evaluate their response at a preclinical level, a non-invasive method providing information about cell proliferation would be highly valuable. The growth fraction can be assessed by the incorporation of thymidine into the DNA of S-phase cells. We report the use of the thymidine analogue bromodeoxyuridine (BrUdR) labelled with bromide-76 (76Br) in positron emission tomography (PET). PET scans using [76Br]BrUdR were performed in seven patients with metastatic melanoma. The in vitro cell proliferation in these metastases (n = 7) was compared with immunohistochemically evaluated cell proliferation using anti-bromo-deoxyuridine and MIB-1 antibodies after excision. Blood samples were taken to analyse the kinetics of the radiopharmaceutical. The accumulation of [76Br]BrUdR in PET correlated significantly with the immunohistochemically assessment of S-phase and cycling cells. In one patient a clinically unexpected metastases was found on [76Br]BrUdR-PET which became evident 4 weeks later. Analysis of blood samples showed a fast disappearance of [76Br]BrUdR; 30 min after injection free bromide was the main form of radioactivity, resulting in a high background activity. Assessment of cell proliferation using [76Br]BrUdR is hampered because of fast debromation and high background activity. The results are thus rather the effect of the increased circulation in more rapidly proliferating metastases than Incorporation of [76Br]BrUdR into proliferating cells.

Planar coincidence scintigraphy and PET in staging malignant melanoma.

UNLABELLED: This study describes a comparison of simulated planar positron coincidence scintigraphy (PCS) with PET in the whole-body staging of patients with malignant melanoma using 2-18F-fluoro-2-deoxy-D-glucose (FDG). METHODS: In 55 patients with either known metastatic or newly diagnosed malignant melanoma, whole-body PET scanning was performed on a conventional full-ring dedicated PET tomograph, and multiaxial sections were obtained. Furthermore, anteroposterior projection images simulating images of a dual-head Anger camera operating in coincidence mode were obtained from the PET raw data. Each study was evaluated separately and blindly. Imaging findings were confirmed by biopsy or by at least one imaging modality in addition to PET. RESULTS: A total of 108 lesions were evaluated, of which 76 proved to be melanoma metastases. Whole-body PET correctly demonstrated 68 metastases, 6 lesions were classified as questionable metastases and 2 were missed. Whole-body PCS correctly demonstrated 14 metastases, 22 lesions were classified as questionable metastases and 40 metastases were missed. The sensitivities of whole-body PET and whole-body PCS were 89% and 18%, respectively. In PCS lesions in regions of high background activity, such as in the abdomen, were missed more often than in PET (p < 0.05). The tumor-to-background contrast was generally lower in PCS than in PET. A further decrease in PCS detection was found in lesions of < 22 mm in diameter. CONCLUSION: The lack of sensitivity precludes the clinical use of whole-body PCS in staging malignant melanoma.

Successful treatment of invasive aspergillosis in chronic granulomatous disease by bone marrow transplantation, granulocyte colony-stimulating factor-mobilized granulocytes, and liposomal amphotericin-B.

X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency with complete absence or malfunction of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the phagocytic cells. Life-threatening infections especially with aspergillus are common despite optimal antimicrobial therapy. Bone marrow transplantation (BMT) is contraindicated during invasive aspergillosis in any disease setting. We report an 8-year-old patient with CGD who underwent HLA-genoidentical BMT during invasive multifocal aspergillus nidulans infection, nonresponsive to treatment with amphotericin-B and gamma-interferon. During the first 10 days post-BMT, the patient received granulocyte colony-stimulating factor (G-CSF)-mobilized, 25 Gy irradiated granulocytes from healthy volunteers plus G-CSF beginning on day 3 to prolong the viability of the transfused granulocytes. This was confirmed in vitro by apoptosis assays and in vivo by finding nitroblue tetrazolium (NBT)-positive granulocytes in peripheral blood 12 and 36 hours after the transfusions. Clinical and biological signs of infection began to disappear on day 7 post-BMT. Positron emission tomography with F18-fluorodeoxyglucose (FDG-PET) and computed tomography (CT) scans at 3 months post-BMT showed complete disappearance of infectious foci. At 2 years post-BMT, the patient is well with full immune reconstitution and no sign of aspergillus infection. Our results show that HLA-identical BMT may be successful during invasive, noncontrollable aspergillus infection, provided that supportive therapy is optimal.

Detection of extrathoracic metastases by positron emission tomography in lung cancer.

BACKGROUND: Accurate staging of non-small cell lung cancer is essential for treatment planning. We evaluated in a prospective study the role of whole-body 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in mediastinal nodal staging with a positive predictive value of 96%. The study was continued to further evaluate the value of whole-body FDG PET in detecting unexpected extrathoracic metastases (ETMs) in patients qualifying for surgical treatment by conventional staging. METHODS: One hundred patients underwent clinical evaluation, chest and upper abdominal computed tomography scan, mediastinoscopy (lymph nodes greater than 1 cm on computed tomography), and routine laboratory tests. In 94 patients with stage IIIa or less and 6 with suspected N3 a whole-body FDG PET was performed. If clinical signs of ETMs were present additional diagnostic methods were applied. All findings in the FDG PET were confirmed histologically or radiologically. RESULTS: Unexpected ETMs were detected in 13 (14%) of 94 patients (stage IIIa or less) at 14 sites. In addition 6 of 94 patients were restaged up to N3 after PET. The suspected N3 disease (stage IIIb) on computed tomography was confirmed by PET in all 6 patients. There was no false positive finding of ETM. Weight loss was correlated with the occurrence of ETM: more than 5 kg, 5 of 13 patients (38%); more than 10 kg, 4 of 6 patients (67%). Pathologic laboratory findings were not predictive for ETM. CONCLUSIONS: Whole-body FDG PET improves detection of ETMs in patients with non-small cell lung cancer otherwise elegible for operation. In 14% of patients (stage IIIa or less), ETMs were detected, and in total, 20% of the patients were understaged.

Whole-body positron emission tomography using fluorodeoxyglucose for staging of lymphoma: effectiveness and comparison with computed tomography.

The purpose of this study was to evaluate whole-body positron emission tomography (WB-PET) as a staging modality in Hodgkin's disease (HD) and non-Hodgkin lymphoma (NHL) and to compare it with computed tomography (CT) in a retrospective study. Seventy-one WB-PET studies using fluorodeoxyglucose (FDG) and 49 CT examinations were performed in 19 women and 31 men. Transaxial images were acquired and reformatted coronally and sagittally in PET. CT sections were obtained from the skull base to the pelvic floor. The written reports of the imaging data were compared with a reference standard constructed on the basis of all the data on the individual patients, including clinical follow-up of at least 6 months. The sensitivity and specificity of PET were, respectively, 86% and 96% for HD (n=53), and 89% and 100% for NHL (n=18). For CT sensitivity and specificity were 81% and 41% for HD (n=33) and 86% and 67% for NHL (n=16). Differences between PET and CT sensitivities were not significant, while in HD there was a significant difference in the specificity of PET and CT examinations, mainly because CT was unable to distinguish between active or recurrent disease and residual scar tissue after therapy. FDG tumour uptake was found in high- as well as low-grade NHL patients. In conclusion, PET appears to be highly sensitive and specific for staging of lymphoma. It is at least as sensitive as CT, and more specific, particularly in patients undergoing restaging, where a well-recognized diagnostic dilemma in CT is the presence of a post-therapeutic residual mass.

[Detection of unexpected extrathoracic metastases in preoperative staging of non-small-cell bronchial carcinoma (NSCLC) with positron emission tomography (PET)]. / Nachweis unerwarteter extrathorakaler Metastasen beim präoperativen Staging des nicht kleinzelligen Bronchialkarzinoms (NSCLC) mittels Positronenemissionstomographie (PET).

Accurate staging of non-small cell lung cancer (NSCLC) is essential for subsequent treatment. This study was designed to evaluate the value of FDG-PET in detecting unexpected extrathoracic metastases (ETM) in patients with NSCLC qualifying for surgical treatment based on conventional staging. One hundred patients with stage IIIa or less were included and underwent clinical evaluation, chest and upper abdominal CT scan, mediastinoscopy, and routine laboratory tests. If clinical signs of EM were present additional diagnostic methods, were applied. A partial body FDG-PET was performed. All findings in the FDG-PET were confirmed histologically or radiologically. Unknown ETM were detected in 13 patients (14%) at 19 sites. Whole-body FDG-PET improves detection of unsuspected ETM in patients with NSCLC otherwise eligible for surgery. Fourteen percent of patients were understaged.

D1 dopamine receptors are not expressed in human melanoma.

D1 dopamine receptor mRNA has been demonstrated in mouse melanoma cells, and the expression of these G-protein-coupled receptors in human melanoma was therefore presumed when dopamine receptor binding radiopharmaceuticals were found to be useful for the detection of metastases in whole-body scintigraphy. The aim of this study was thus to investigate if D1 dopamine receptor mRNA or protein could be directly demonstrated in melanoma cells. The presence of D1 dopamine receptor mRNA was investigated in six human melanoma cell lines from metastases using reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, in vitro binding assays with the D1 dopamine receptor agonist 125I-Sch 23982 were performed in 19 melanoma metastases. No D1 dopamine receptor mRNA could be detected by RT-PCR. All melanotic metastases were found to accumulate 125I-Sch 23982, with the presence of binding sites and intensity of 125I-Sch 23982 labelling correlating to the amount of melanin present in the metastases. Two amelanotic melanomas did not accumulate 125I-Sch 23982. D1 dopamine receptors could not be detected by means of RT-PCR or in vitro binding assays in human melanomas. Detection of antagonists is best explained by non-specific binding to melanin.

Non-small cell lung cancer: nodal staging with FDG PET versus CT with correlative lymph node mapping and sampling.

PURPOSE: To prospectively compare the accuracy of positron emission tomography (PET) with 2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG) with that of computed tomography (CT) in the nodal staging of non-small cell lung cancer. MATERIALS AND METHODS: PET and contrast material-enhanced CT were performed in 47 patients suspected of having or with newly diagnosed non-small cell lung cancer. Each imaging study was evaluated separately, and nodal stations were localized according to the American Thoracic Society mapping system. Extensive lymph node sampling (599 nodes from 191 nodal stations) of the ipsi- and contralateral tracheobronchial and mediastinal nodal stations was performed at thoracotomy and/or mediastinoscopy. Imaging findings were correlated with histopathologic staging results. RESULTS: The sensitivity of PET and CT was 89% and 57%, respectively, for the staging of N2 or N3 disease in mediastinal nodes; specificity was 99% and 94%, respectively; positive predictive value was 96% and 76%, respectively; negative predictive value was 97% and 87%, respectively; and accuracy was 96% and 85%, respectively. In assigning the correct N stage, PET was correct in 96% and CT in 79% of cases. CONCLUSION: PET with FDG appears to be superior to CT for nodal staging of non-small cell lung cancer.

MR imaging versus alternative imaging techniques.

MR imaging is the method of choice in evaluating a large number of soft-tissue abnormalities; however, it has certain draw-backs, some of which may make other imaging methods more suitable. MR imaging is more expensive than alternative imaging methods; it may not be affordable for screening purposes and for diagnoses obtainable by less expensive imaging methods. In addition, immediate scheduling is not always possible for MR imaging, and an MR scanner may not be available close to the patient's home, which may be important for imaging follow-up. These factors support the use of other imaging modalities, with sonography frequently being the appropriate choice. In some situations, mainly in the presence of certain biomedical implants and devices, MR imaging is contraindicated. Additionally, under some circumstances patient access may be difficult during MR imaging; sonography and CT therefore are preferable (as for imaging guided biopsy). Moreover, some artifacts, such as motion artifacts, may have less relevance in other imaging methods (such as sonography), which may be important in noncooperative patients and children. MR imaging may not be specific in tumors and infection; this deficiency is shared with most alternative imaging methods, with the exception of scintigraphy in selected indications. Lastly, standard radiography and CT commonly are superior to MR imaging in diagnosing calcification and abnormalities of cortical bone. Consequently, in selected cases and for screening purposes, methods other than MR imaging should be considered for depicting soft-tissue structures.