Georges Deneffe

Prognostic Importance of the Standardized Uptake Value on 18F-Fluoro-2-Deoxy-Glucose–Positron Emission Tomography Scan in Non–Small-Cell Lung Cancer: An Analysis of 125 Cases

PURPOSE The amount of radio-labeled (18)F-fluoro-2-deoxy-glucose (FDG) uptake, a measurement of the increased glucose metabolism of non-small-cell lung cancer (NSCLC) cells, has recently been correlated with proliferation capacity. The Standardized Uptake Value (SUV), a semi-quantitative measurement of FDG uptake on positron emission tomography (PET) scan, could thus be of prognostic significance. PATIENTS AND METHODS We analyzed the follow-up of 125 potentially operable NSCLC patients, previously included in three of our prospective PET protocols. Performance status, maximal tumor diameter, tumor-cell type, SUV, and final staging were analyzed for their possible association with survival. RESULTS Sixty-five patients had stage I or II NSCLC, 37 had stage IIIA, and 23 had stage IIIB. Treatment was complete resection in 91 cases. In a univariate analysis, performance status (P =.002), stage (P =.001), tumor diameter (P =.06), tumor-cell type (P =.03), and SUV greater than 7 (P =.001) were correlated with survival. For SUV, group dichotomy with a cut-off SUV of 7 had the best discriminative value for prognosis, both in the total and surgical cohort. A multivariate Cox analysis identified performance status (P =.02), stage (P =.01), and SUV (P =.007) as important for the prognosis. In the surgical group, patients with a resected tumor less than 3 cm had an expected 2-year survival of 86%, if the SUV was below 7, and 60%, if above 7. Nearly all resected tumors larger than 3 cm had SUVs greater than 7 and an expected 2-year survival of 43%. CONCLUSION We conclude that the FDG uptake in primary NSCLC on PET has an important prognostic value and could be complementary to other well-known factors in the decision on adjuvant treatment protocols.

Histopathologic validation of lymph node staging with FDG-PET scan in cancer of the esophagus and gastroesophageal junction : a prospective study based on primary surgery with extensive lymphadenectomy

ObjectiveTo assess the value of positron emission tomography with 18fluorodeoxyglucose (FDG-PET) for preoperative lymph node staging of patients with primary cancer of the esophagus and gastroesophageal junction. Summary Background DataFDG-PET appears to be a promising tool in the preoperative staging of cancer of the esophagus and gastroesophageal junction. Recent reports indicate a higher sensitivity and specificity for detection of stage IV disease and a higher specificity for diagnosis of lymph node involvement compared with the standard use of computed tomography and endoscopic ultrasound. MethodsForty-two patients entered the prospective study. All underwent attenuation-corrected FDG-PET imaging of the neck, thorax, and upper abdomen, a spiral computed tomography scan, and an endoscopic ultrasound. The gold standard consisted exclusively of the histology of sampled nodes obtained by extensive two-field or three-field lymphadenectomies (n = 39) or from guided biopsies of suspicious distant nodes indicated by imaging (n = 3). ResultsThe FDG-PET scan had lower accuracy for the diagnosis of locoregional nodes (N1–2) than combined computed tomography and endoscopic ultrasound (48% vs. 69%) because of a significant lack of sensitivity (22% vs. 83%). The accuracy for distant nodal metastasis (M+Ly), however, was significantly higher for FDG-PET than the combined use of computed tomography and endoscopic ultrasound (86% vs. 62%). Sensitivity was not significantly different, but specificity was greater (90% vs. 69%). The FDG-PET scan correctly upstaged five patients (12%) from N1–2 stage to M+Ly stage. One patient was falsely downstaged by FDG-PET scanning. ConclusionsFDG-PET scanning improves the clinical staging of lymph node involvement based on the increased detection of distant nodal metastases and on the superior specificity compared with conventional imaging modalities.

Value of computed tomography and mediastinoscopy in preoperative evaluation of mediastinal nodes in non-small cell lung cancer. A study of 569 patients.

The efficacy of computed tomography (CT) and mediastinoscopy as staging modalities to assess mediastinal lymph node status was evaluated in 569 patients with a presumed resectable non-small cell lung cancer (NSCLC). Computed tomography scan was performed in every patient and followed by mediastinoscopy in 331 and by thoracotomy in 477 patients. Mediastinal lymph nodes on CT larger than 1.5 cm were considered pathological. Overall, CT had a sensitivity of 69%, a specificity of 71% and an accuracy of 71% in identifying mediastinal lymph node metastases. For mediastinoscopy these figures were 72%, 100% and 89%, respectively. Computed tomography accuracy was distinctly lower in squamous cell carcinomas and in central tumors, as CT sensitivity was significantly lower in left-sided tumors. The positive predictive value (PPV) of CT in T1 lesions (29%) and PPV and negative predictive value (NPV) of CT in T2 squamous cell carcinomas (30% and 83%, respectively) were low, so questioning its use in those instances. We perform a mediastinoscopy in every situation except for squamous cell carcinomas or small (less than 3 cm) peripheral tumors in the absence of enlarged mediastinal lymph nodes. This selective attitude is rewarding since a) the number of pN2 in the straight thoracotomy group was only 16% versus 41% in the mediastinoscopy group, b) the exploratory thoracotomy rate in the straight thoracotomy group was low (4.6%).

Tumors of the esophagogastric junction: long-term survival in relation to the pattern of lymph node metastasis and a critical analysis of the accuracy or inaccuracy of ptnm classification

From 1983 to 1989, 95 patients with carcinoma of the esophagogastric junction underwent resection. Overall hospital mortality rate was 6.2% (6/95). Actuarial survival analysis showed 5- and 10-year survivals of 33% and 31%, respectively. Five- and 10-year survivals of patients according to TNM stages were as follows: stage I (n = 13), 90% at both 5 and 10 years; stage II (n = 13), 70% at both intervals; stage III (n = 28), 28% at both intervals; and stage IV (n = 40), 11% and 8%, respectively. For patients with undiseased nodes (n = 26), 5- and 10-year survivals were 72% and 72%, compared with 18% and 16% for patients with diseased nodes (n = 68; p < 0.005). In patients who had involvement of both the abdominal and thoracic lymph nodes (n = 28), 5- and 10-year survivals were 13% and 13%, compared with 26% and 26% if metastases were confined to the abdomen (n = 37; p > 0.05). Grouping patients with diseased intrathoracic nodes together with patients with N2 abdominal nodes showed survivals of 14% at both 5 and 10 years. When tumors were staged as an esophageal carcinoma, classification of individual patients changed, as did the 5- and 10-year survivals. Five- and 10-year survivals were as follows: stage I (n = 8), 100% for both 5 and 10 years; stage II (n = 18), 68% for both 5 and 10 years; stage III (n = 27), 37% for both 5 and 10 years; and stage IV (n = 41), 10% for 5 years and 6% for 10 years. These data indicate that tumors of the esophagogastric junction tend to spread to both abdominal and thoracic nodes. However, reasonably good 5- and 10-year survivals can be obtained even in patients with nodal metastases in both areas. We suggest that N2 labeling be included for thoracic node metastases instead of the actual M+Ly label, because the N2 label better reflects the potential for curative surgery. Finally, staging tumors as gastric or esophageal carcinoma makes no significant difference in survival analysis, which raises the question whether these tumors behave more like esophageal carcinoma than gastric carcinoma.

Pulmonary sequestration: a comparison between pediatric and adult patients.

OBJECTIVE Modern large single institutional reports on pulmonary sequestration (PS) are extremely rare. We were interested in comparing patients with PS referred by our pediatric versus adult pulmonologists. METHODS Hospital notes of all patients operated on between 1978 and 1997 for a congenital broncho-pulmonary malformation were reviewed. In 28 patients, the parenchymal lesion was vascularized by a systemic artery and was separated from the bronchial tree, thus matching the strict definition of PS. Patient characteristics and outcome were analyzed comparing the pediatric group (< or =16 years: n=13; mean age, 3+/-5 years) versus the adult group (>16 years: n=15; mean age, 33+/-13 years). RESULTS No significant differences between both groups were observed in sex, side, type of sequestration, pulmonary venous drainage, associated anomalies, hospital and late outcome, and patients overall score. Patients (n=21) with the intralobar type of sequestration presented significantly more often with an infection when compared with patients (n=7) with the extralobar type (91 versus 14%; P=0.0033). When compared with the pediatric group, patients in the adult group had significantly more respiratory infections (87 versus 38%; P=0.016), and also required a lobectomy more often (67 versus 31%; P=0.056). CONCLUSIONS The extralobar type of sequestration often remains asymptomatic, and is usually an incidental finding during infancy. The intralobar type mostly presents with recurrent infections in adulthood resulting in more lobectomies. We believe these findings support our current policy to remove any pulmonary malformation whenever diagnosed in order to: (1), prevent infection and other potentially serious late complications which may compromise the surgical outcome; and (2), enhance the chance of a parenchymal-sparing resection.

Heparan sulfate proteoglycan expression in human lung-cancer cells

Heparan sulfate (HS) functions as a co‐factor in several signal‐transduction systems that affect cellular growth, differentiation, adhesion and motility. HS, therefore, may also play a role in the malignant transformation of cells, tumor growth, cell invasiveness and the formation of tumor metastases. To explore this hypothesis, we analyzed the expression of HS and heparan sulfate proteoglycan (HSPG) in histological sections of human lung‐cancer tissues and assayed for the presence of HSPGs in extracts of human lung‐cancer cell lines, using a panel of native HS‐, Δ‐HS‐ and HSPG (syndecan, glypican, CD44 and perlecan) core protein–specific monoclonal antibodies. Compared to normal epithelia, non‐small‐cell lung carcinomas, particularly poorly differentiated tumors, often expressed reduced amounts of the major cell surface–associated HSPGs (most consistently of syndecan‐1). CD44 or CD44‐variant proteins, in contrast, were found on all tumor cells, irrespective of their differentiation. Perlecan, a matrix‐associated HSPG found in the basement membrane of normal bronchial epithelium, was consistently undetectable in invasive bronchogenic carcinomas. Staining reactions for native HS were consistently reduced in squamous‐cell lung carcinomas, in the cells in contact with the stroma and in the less differentiated areas of these tumors. Reactions for Δ‐HS, however, were not reduced, suggesting a structural change in the HS of these tumor cells. Poorly differentiated adenocarcinomas, in contrast, yielded strong HS and Δ‐HS reactions. Marked differences in HSPG expression also were observed among various non‐small‐cell lung carcinoma cell lines. Our results suggest that poorly differentiated lung tumors have markedly altered patterns of HSPG expression, which may contribute to their invasive phenotype. Int. J. Cancer 74:335–345, 1997.

Role of cervical mediastinoscopy in staging of non-small cell lung cancer without enlarged mediastinal lymph nodes on CT scan

OBJECTIVE The results of primary surgery for non-small cell lung cancer (NSCLC) with involved ipsilateral mediastinal or subcarinal lymph nodes (N2 disease) remains poor. However, several studies suggest that induction chemotherapy could increase long-term survival in patients with N2 disease. Therefore, accurate preoperative staging of the mediastinum remains of paramount importance for the treatment policy in patients with NSCLC. Enlarged mediastinal lymph nodes (MLN) on CT scan are positive in only half of the patients. Small lymph nodes can contain metastatic deposits of clinical importance. However, many surgeons believe that a normal mediastinum at computed tomography allows them to cancel their preoperative mediastinal exploration. It was the aim of this study to evaluate the results of cervical mediastinoscopy in patients without enlarged MLN on CT scan. METHODS Between January 1990 and June 1994, 235 patients with potentially operable NSCLC underwent a cervical mediastinoscopy despite the absence of enlarged MLN on CT scan. MLN were considered enlarged if they were equal to or larger than 15 mm at their maximal cross-sectional diameter. RESULTS Cervical mediastinoscopy was positive in 47 patients (20%). In 21 patients, N2 disease was extranodal and in 16 patients more than one level was involved. Mediastinoscopy was positive in 9.5% of the cT1N0 cases, in 17.7% of the cT2N0 lesions, in 31.2 and 33.3% of cT3N0 or cT4N0 tumors, respectively. After a negative cervical mediastinoscopy, resectability for unforeseen N2 disease was as high as 95%. CONCLUSION We recommend a cervical mediastinoscopy in every patient with potentially operable NSCLC.

Incentive spirometry does not enhance recovery after thoracic surgery

Objective: To investigate the additional effect of incentive spirometry to chest physiotherapy to prevent postoperative pulmonary complications after thoracic surgery for lung and esophageal resections. Design: Randomized controlled trial. Setting: University hospital, intensive care unit, and surgical department. Patients: Sixty‐seven patients (age, 59 ± 13 yrs; forced expiratory volume in 1 sec, 93% ± 22% predicted) undergoing elective thoracic surgery for lung (n = 40) or esophagus (n = 27) resection. Interventions: Physiotherapy (breathing exercises, huffing, and coughing) (PT) plus incentive spirometry (IS) was compared with PT alone. Measurements and Main Results: Lung function, body temperature, chest radiograph, white blood cell count, and number of hospital and intensive care unit days were all measured. Pulmonary function was significantly reduced after surgery (55% of the initial value) and improved significantly in the postoperative period in both groups. However, no differences were observed in the recovery of pulmonary function between the groups. The overall score of the chest radiograph, based on the presence of atelectasis, was similar in both treatment groups. Eight patients (12%) (three patients with lobectomy and five with esophagus resection) developed a pulmonary complication (abnormal chest radiograph, elevated body temperature and white blood cell count), four in each treatment group. Adding IS to regular PT did not reduce hospital or intensive care unit stay. Conclusions: Pulmonary complications after lung and esophagus surgery were relatively low. The addition of IS to PT did not further reduce pulmonary complications or hospital stay. Although we cannot rule out beneficial effects in a subgroup of high‐risk patients, routine use of IS after thoracic surgery seems to be ineffective.

Congenital Parenchymatous Malformations of the Lung

Abstract. Congenital lung malformations, primary and secondary, contribute to an important portion of pediatric thoracic surgery. One purpose of this report is to outline the close relation in terms of embryology and clinical presentation of congenital parenchymatous pulmonary malformations. In a retrospective study we also aim to evaluate our experience with the diagnosis and surgical management of congenital parenchymatous bronchopulmonary malformations and to compare our data with the literature. From January 1979 to December 1996 a series of 48 patients, 30 males (62.5%) and 18 females (37.5%), were operated on for congenital bronchopulmonary malformations. Pulmonary sequestration, bronchogenic cysts, congenital lobar emphysema, and congenital cystic adenomatoid malformation were seen in 16, 13, 5, and 14 patients, respectively. The first clinical symptoms occurred at a mean age of 8.8 years (1 day to 62 years), and the mean age at the time of surgical intervention was 9.3 years (1 day to 62 years). The maximum time between first symptoms and surgical treatment was 27 years. A lobectomy was performed in 22 cases; in the other patients more lung-preserving surgery such as enucleation or sequestrectomy was performed. Only one postoperative death occurred following lobectomy for pulmonary sequestration, and it was due to pulmonary hypoplasia and pulmonary hypertension. Eleven other patients presented with postsurgical complications: pneumothorax (n= 5), pleural effusion (n= 3), prolonged air leak (n= 2), portal vein thrombosis (n= 1), and hemorrhage requiring reintervention (n= 1). We conclude that any thoracic cystic lesion expanding on chest radiography should be an indication for surgical resection, even if asymptomatic, because of the risk of pulmonary compression, infection, or malignant degeneration. In the few cases of a fetal intrathoracic mass, prenatal diagnosis and intrauterine intervention may be indicated, and these indications are also discussed.

Surgical treatment of bronchogenic carcinoma: A retrospective study of 720 thoracotomies

Seven hundred and twenty patients with primary bronchogenic carcinoma were operated on at the Pellenberg Clinic, K.U. Leuven, Belgium, between January 1, 1970, and January 1, 1985. Almost 45% of the resections were pneumonectomies and 47% were lobectomies. Mortality was 6.9% and 2.9%, respectively. Patients with squamous cell carcinoma (Stages I and II) who underwent lobectomy or pneumonectomy had an absolute 5-year survival rate of 52.8% (93/176); it was 21% (4/19) in the T3 N0/N1 subgroup. Patients with adenocarcinoma who underwent a lobectomy had a 5-year survival rate of 49% (26/53) in the T1/T2 N0 group and of 27% (3/11) in the T1/T2 N1 group. Only 13.6% (3/22) of patients survived 5 years if a pneumonectomy had to be performed. Only 1 in 22 N2 patients survived 5 years after resection.