Thomas P. Graeter

18F-FDG PET for Mediastinal Staging of Lung Cancer: Which SUV Threshold Makes Sense?

18F-FDG PET is the most accurate noninvasive modality for staging mediastinal lymph nodes in lung cancer. Besides using visual image interpretation, some institutions use standardized uptake value (SUV) measurements in lymph nodes. Mostly, an SUV of 2.5 is used as the cutoff, but this choice was never deduced from respective studies. Receiver operating characteristic (ROC) analyses demonstrated that SUV thresholds of more than 4 resulted in the highest accuracy. But these high cutoffs imply high false-negative rates (FNRs). The aim of our evaluation was to determine an optimal SUV threshold and to compare its diagnostic performance with the results of visual interpretation. Methods: This retrospective study included 95 patients with suspected lung cancer who underwent mediastinoscopy/mediastinal lymphadenectomy after 18F-FDG PET (90–150 min after 250 MBq of 18F-FDG). Maximum SUV was measured in 371 lymph node regions biopsied afterward and visually interpreted using a 6-level score (− − − through + + +). Diagnostic performance was assessed by ROC analysis. FNR and false-positive rate (FPR), the sum of both error rates (FNR + FPR), and diagnostic accuracy were plotted against a hypothetical SUV threshold to determine the optimum SUV threshold. Results: SUVs in metastatic lymph nodes were higher (mean ± SD, 7.1 ± 4.5; range, 1.4–26.9; n = 70) than in tumor-free lymph node stations (2.4 ± 1.7; range, 0.6–14.9; n = 301; P < 0.01). Inflammatory lymph nodes exhibited slightly increased SUVs (2.7 ± 2.0; range, 0.8–14.9; n = 146). The plot of error rates featured a minimum of the sum FNR + FPR for an SUV of 2.5. With increasing SUV threshold, the FPR decreased most prominently up to that value whereas a continuous rise of FNR was noticed. Highest diagnostic accuracy was achieved with an SUV of 4.5. The areas under the ROC curves demonstrated that visual interpretation tends to be more accurate than SUV quantification (visual, 0.930 ± 0.022; SUV, 0.899 ± 0.025; P = 0.241). Using an SUV of 2.5 as the threshold, the resulting sensitivity, specificity, and negative predictive value were 89%, 84%, and 96%, respectively. Conclusion: For mediastinal staging, the choice of an SUV of 2.5 as the threshold is justified because FNR + FPR is minimized. The resulting high negative predictive value of 96% allows the omission of mediastinoscopy in patients with negative mediastinal findings on 18F-FDG PET images. For the experienced observer, visual analysis should be relied on primarily, with calculation of the SUV used, at most, as a secondary aid. For the less experienced observer, the SUV may be of greater value.

Mediastinal lymph node staging in suspected lung cancer: comparison of positron emission tomography with F-18-fluorodeoxyglucose and mediastinoscopy

BACKGROUND In patients with bronchogenic carcinoma, mediastinal lymph node staging is essential for determining treatment options. In this retrospective analysis we compared the results of positron emission tomography (PET) using F-18 fluorodeoxyglucose with those of mediastinoscopy in nodal staging for suspected bronchogenic carcinoma. METHODS From March 1997 to June 2001, 102 patients (86 male,16 female, age 62 +/- 9 years) underwent both PET and mediastinoscopy for radiologically suspected mediastinal lymph node disease in bronchogenic carcinoma. Total body emission scans were acquired 90 to 150 minutes after injection of 230 MBq of F-18 fluorodeoxyglucose. Mediastinoscopic evaluation of lymph node stations was performed according to the method of Mountain and Dresler (1R, 1L, 2L, 2R, 4L, 4R,7). Patients were eligible if surgical staging was performed within 6 weeks after the PET scan. RESULTS. Of the 102 patients, benign lesions were diagnosed in 15. In 87 patients malignant disease was proven by histology, and bronchogenic carcinoma was found in 82. Of 469 nodal stations analyzed, malignancy was documented by histology in 84. In PET analysis 79 true-positive and 304 true-negative samples were found. Five lymph node stations were false negative, and 81 samples were false positive. False-positive findings in PET frequently were seen in inflammatory lung disease. The sensitivity of PET was 94.1%, specificity was 79% with a diagnostic accuracy of 81.6%. The positive predictive value of PET was 49.3%, and the negative predictive value was 98.4%. CONCLUSIONS In patients with positive PET scan results histologic verification appears necessary for exact lymph node staging. In view of the negative predictive value mediastinoscopy can be omitted in patients with bronchogenic carcinoma whose PET scan results were negative.

Diagnostic performance and prognostic impact of FDG-PET in suspected recurrence of surgically treated non-small cell lung cancer

PurposeThe differentiation of recurrent lung cancer and post-therapeutic changes remains a problem for radiological imaging, but FDG-PET allows biological characterisation of tissues by visualising glucose metabolism. We evaluated the diagnostic performance and prognostic impact of FDG-PET in cases of suspected relapse of lung cancer.MethodsIn 62 consecutive patients, 73 FDG-PET scans were performed for suspected recurrence after surgical therapy of lung cancer. FDG uptake by lesions was measured as the standardised uptake value (SUV). PET results were compared with the final diagnosis established by biopsy or imaging follow-up. SUV and clinical parameters were analysed as prognostic factors with respect to survival.ResultsFDG-PET correctly identified 51 of 55 relapses and gave true negative results in 16 of 18 remissions (sensitivity, specificity, accuracy: 93%, 89%, 92%). SUV in recurrent tumour was higher than in benign post-therapeutic changes (10.6±5.1 vs 2.1±0.6, p<0.001). Median survival was longer for patients with lower FDG uptake in recurrent tumour (SUV<11: 18 months, SUV≥11: 9 months, p<0.01). Long-term survival was observed mainly after surgical re-treatment (3-year survival rate 38%), even if no difference in median survival for surgical or non-surgical re-treatment was detected (11 vs 12 months, p=0.0627). For patients subsequently treated by surgery, lower FDG uptake predicted longer median survival (SUV<11: 46 months, SUV≥11: 3 months, p<0.001). SUV in recurrent tumour was identified as an independent prognostic factor (p<0.05).ConclusionFDG-PET accurately detects recurrent lung cancer. SUV in recurrent tumour is an independent prognostic factor. FDG-PET helps in the selection of patients who will benefit from surgical re-treatment.

Valve-preserving replacement of the ascending aorta: Remodeling versus reimplantation

OBJECTIVE Aortic valve regurgitation in combination with dilatation of the ascending aorta and root requires a combined procedure to restore valve function and eliminate pathologic dilatation of the proximal aorta. Two techniques have been proposed for this purpose; the aortic root may be either remodeled with an especially configured vascular graft or replaced with reimplantation of the aortic valve within the graft. We have used both techniques depending on the individual pathologic condition of the aortic root. METHODS Of 107 patients undergoing operation for proximal aortic disease between October 1995 and November 1997, 40 patients had morphologically intact aortic valve leaflets in conjunction with dilatation of the aortic root. Of these, 15 patients underwent an operation as a surgical emergency for acute aortic dissection type A. In 29 instances, root remodeling in conjunction with ascending aortic replacement was performed; 11 patients underwent radical replacement of the proximal aorta with reimplantation of the aortic valve. Partial or total arch replacement was performed additionally in 27 of these patients. Other concomitant procedures were coronary artery bypass grafts (n = 11) and mitral reconstruction (n = 1). RESULTS Two patients died after repair of acute aortic dissection, for a total operative mortality rate of 5%. No patient died after elective surgery. Aortic valve function could be effectively restored with both techniques. No patient underwent reoperation on the proximal aorta; freedom from aortic regurgitation of grade II or more at 1 year is 88% with both techniques. CONCLUSIONS Depending on individual root pathologic condition, both the remodeling and the reimplantation techniques appeared to have their individual merits. Both result in adequate restoration of aortic valve function and elimination of pathologic aortic dilatation.

Valve-preserving operation in acute aortic dissection type A

BACKGROUND The standard treatment in patients with acute aortic dissection type A (AADA) and aortic regurgitation is either supracommissural aortic or composite replacement of ascending aorta and valve. Valve-preserving surgical procedures provide a promising alternative. We retrospectively analyzed midterm results after these different approaches. METHODS From October 1995 to December 1999, 52 patients (35 men, 17 women) underwent repair of AADA. Patient ages ranged from 30 to 83 years. Composite replacement was chosen for degenerated aortic valves or prior valve replacement (group A; n = 8). With normal root diameter, supracommissural replacement of the ascending aorta was performed (group B; n = 22). For preexisting root dilatation the aortic root was either remodeled (root diameter 30 to 50 mm, group C; n = 17) or the valve reimplanted within a vascular graft (root diameter more than 50 mm, group D; n = 5). RESULTS All patients underwent either proximal (n = 46) or total (n = 6) arch replacement under circulatory arrest. Eight patients (15.4%) died (group A: n = 3; group B: n = 3; group C: n = 2). Freedom from aortic regurgitation of grade 2 or more at 2 years was 100% in groups A and D, 90.9% in group C, and 75% following supracommissural replacement. At 2 years freedom from proximal reoperation was 100% in groups A, C, and D and 84.5% in group B. CONCLUSIONS In AADA valve-preserving root replacement leads to improved stability of aortic valve function without an increased operative risk. Midterm results are promising and may show further superiority over supracommissural aortic replacement in the future.

Remodeling of the aortic root and reconstruction of the bicuspid aortic valve

BACKGROUND Currently, isolated reconstruction of a regurgitant bicuspid aortic valve can be performed with adequate early results. Dilatation of the proximal aorta is known to be associated with this valve anomaly and may be partially responsible for the development of primary regurgitation or secondary failure of valve repair. We have used repair of the bicuspid valve with remodeling of the aortic root as an alternative to insertion of a composite graft. METHODS Between October 1995 and May 1999, 16 patients (12 men, 4 women, aged 35 to 73 years) were seen with a regurgitant bicuspid aortic valve and dilatation of the proximal aorta of more than 50 mm. All patients underwent repair of the valve using either coapting sutures alone (n = 12) or in combination with triangular resection of a median raphe (n = 4). Using a Dacron graft, the aortic root was remodeled and the ascending aorta (n = 16) and proximal arch (n = 4) replaced. RESULTS No patient died. The postoperative degree of aortic regurgitation was less than grade II in all patients. Valve function has remained stable in all patients between 2 and 43 months postoperatively. CONCLUSIONS Reconstruction of the regurgitant bicuspid valve in the presence of proximal aortic dilatation is feasible with good results by combining the root remodeling technique with valve repair.

Bronchial and bronchovascular sleeve resection for treatment of central lung tumors.

BACKGROUND To improve postoperative pulmonary reserve, we have employed parenchyma-sparing resections for central lung tumors irrespective of pulmonary function. The results of lobectomy, pneumonectomy, and sleeve resection were analyzed retrospectively. METHODS From October 1995 to June 1999, 422 typical lung resections were performed for lung cancer. Of these, 301 were lobectomies (group I), 81 were sleeve resections (group II), and 40 were pneumonectomies (group III). RESULTS Operative mortality was 2% in group I, 1.2% in group II, and 7.5% in group III (group I and II vs. group III, p<0.03). Mean time of intubation was 1.0+/-4.1 days in group I, 0.9+/-1.3 days in group II, and 3.6+/-11.2 days in group III (groups I and II vs. group III, p<0.01). The incidence of bronchial complications was 1.3% in group I, none in group II, and 7.5% in group III (group I and II vs group III, p<0.001). After 2 years, survival was 64% in group I, 61.9% in group II, and 56.1% in group III (p = NS). Freedom from local disease recurrence was 92.1% in group I, 95.7% in group II, and 90.9% in group III after 2 years (p = NS). CONCLUSIONS Sleeve resection is a useful surgical option for the treatment of central lung tumors, thus avoiding pneumonectomy with its associated risks. Morbidity, early mortality, long-term survival, and recurrence of disease after sleeve resection are similar to those seen after lobectomy.

Prognostic value and therapeutic consequences of vascular invasion in non-small cell lung carcinoma

The prognostic relevance of blood vessel invasion (BVI) in non-small cell lung carcinoma (NSCLC) remains controversial, as is the question of whether its finding should influence therapeutic decisions after an R0 resection. One hundred and twelve cases of NSCLC were included in the study. All had been treated by potentially curative surgical resection of the primary tumor and systematic lymphadenectomy. In all cases, lymphatic metastatic spread was at its earliest stage and only one regional lymph node was involved, 27.0+/-8.9 nodes per patient being examined histologically. Most of the cases were pT2 (75.9%) and pN1 (81.3%), and all were MX/M0 and R0. 62.5% were at stage IIB, 25.9% at stage IIIA, and 9.8% at stage IIA. BVI was found in 45.5% of the tumors (V1), and 18.8% exhibited both lymphatic invasion and BVI (L1V1). Local recurrence occurred in 10.7% of the patients, distant metastasis in 24.1%, and both forms of tumor progression simultaneously in a further 7.1%. Thus 31.2% of the patients developed distant metastases by hematogenous spread (to the brain, bones, lung, adrenal, and liver, in descending order of frequency), mostly within two years of surgery. Late metastasis is not typical of NSCLC. Adenocarcinomas showed a strong tendency to be associated with a poorer prognosis than squamous cell carcinomas, probably because of their more frequent involvement of blood vessels. Five-year survival (Kaplan-Meier method) was significantly lower in V1 cases (37.2%) than in V0 cases (56.0%; p = 0.0249). Adjuvant mediastinal radiation in node-positive cases of NSCLC may prevent local recurrence but is unlikely to influence the development of distant metastases. The histological detection of BVI is of prognostic relevance and should be considered for inclusion in the staging criteria and indications for adjuvant chemotherapy.

Amelioration of lung reperfusion injury by L- and E- selectin blockade

OBJECTIVE Reperfusion injury is the main reason for early graft failure after lung transplantation. Inhibition of the adherence of polymorphonuclear leukocytes to activated endothelium by blocking L- and E-selectins (antibody EL-246) could potentially inhibit reperfusion injury. METHODS Reperfusion injury was induced in a left lung autotransplant model in sheep. After hilar stripping the left lung was flushed with Euro-Collins solution and preserved for 2 h in situ at 15 degrees C. After reperfusion right main bronchus and pulmonary artery were occluded leaving the animal dependent on the reperfused lung (control, n = 6). Pulmonary function was assessed by alveolo-arterial oxygen difference (AaDO2) and pulmonary vascular resistance (PVR), the chemiluminescence of isolated neutrophils, as well as the release of beta-N-acetyl-glucosaminidase (beta-NAG) served as indicator of neutrophilic activation. Extravascular lung water was an indicator for pulmonary edema formation. EL-246 group animals (n = 6) were treated additionally with 1 mg/kg BW of EL-246 given prior and during reperfusion. RESULTS After 3 h of reperfusion five control animals developed alveolar edema compared to one animal in the EL-246 group (P = 0.08). AaDO2 (mm Hg) was significantly higher in the control compared to the EL-246 group (510 +/- 148 vs. 214 +/- 86). PVR (dyn x s x cm(-5)) was significantly increased in the control compared to the EL-246 group (656 +/- 240 vs. 317 +/- 87). Neutrophilic activation was significantly lower in the EL-246 group. Extravascular lung water was significantly lower compared to control (6.88 +/- 1.0 vs. 13.4 +/- 2.8 g/g blood-free lung weight). CONCLUSIONS Treatment with EL-246 results in improved pulmonary function and less in vivo PMN activation in this experimental model. Further studies are necessary to evaluate the possible role of selectin blockade in amelioration of reperfusion injury in human lung transplantation.

Unexpected Lymph Node Disease in Resections for Pulmonary Metastases

BACKGROUND Pulmonary metastasectomy is widely accepted for different malignant diseases. The role of mediastinal lymph node (LN) dissection in these procedures is discussed controversially. We evaluated our results of LN removal at the time of pulmonary metastasectomy with respect to the frequency of unexpected LN disease. METHODS This was a retrospective analysis of 313 resections performed in 209 patients. Operations were performed in curative intention. Patients with known thoracic LN involvement and those without lymphadenectomy (n = 43) were excluded. Patients were analyzed according the type of LN dissection. Subgroups of different primary cancers were evaluated separately. RESULTS Sublobar resections were performed in 256 procedures with lymphadenectomy, and 14 patients underwent lobectomy. Patients underwent radical lymphadenectomy (n = 158) or LN sampling (n = 112). The overall incidence of unexpected tumor in LN was 17% (radical lymphadenectomy, 15.8%; sampling, 18.8%). Unexpected LN involvement was found in 17 patients (35.5%) with breast cancer, in 120 (9.2%) with colorectal cancer, and in 53 (20.8%) with renal cell carcinoma. The 5-year survival was 30.2% if LN were tumor negative and 25% if positive (p = 0.19). LN sampling vs radical removal had no significant effect on 5-year survival (23.6% vs 30.9%; p = 0.29). CONCLUSIONS Dissection of mediastinal LN in resection of lung metastases will reveal unexpected LN involvement in a relevant proportion of patients, in particular in breast and renal cancer. Routine LN dissection appears necessary and may become important for further therapeutic decisions. On the basis of our data, LN sampling seems to be sufficient.