PET-CT in the assessment of lung cancer at Rikshospitalet from 2007-2011.

BACKGROUND: PET-CT is an aid in the assessment of lung cancer for identifying operable patients. The examination is recommended for most patients with non-small cell lung cancer whom the primary assessment has indicated may have a curable disease. The aim was to assess the usefulness of PET-CT for patients assumed to be operable who underwent an examination at Rikshospitalet. MATERIAL AND METHOD: Patients admitted for lung cancer assessment are registered consecutively in the department's quality database. We analysed data for the period 2007-2011 for patients whom a primary assessment had revealed to have a potentially operable tumour. For capacity reasons, some patients underwent surgery without a prior PET-CT. RESULTS: Of 651 potentially operable patients, 533 had had a PET-CT scan of which 403 (76%) had undergone surgery. We calculated that the examination had a sensitivity of 78% (95% CI 70-86) and specificity 88% (95% CI 85-91%), positive predictive value 64% (95% CI 55-72) and negative predictive value 94% (95% CI 91-96) for spreading to mediastinal lymph nodes. Diagnostic accuracy was 86% (95% CI 83-89) with kappa agreement 0.61 (95% CI 0.53-0.69) between PET-CT and actual findings of malignant or benign mediastinal lymph nodes. INTERPRETATION: PET-CT was a useful tool for selecting potentially operable lung cancer patients at Rikshospitalet in the period 2007-2011. Provided that the population we scan with PET-CT does not change, patients with a negative PET-CT can with few exceptions be referred directly for surgery without further invasive assessment.

Systemic biomarkers of inflammation and haemostasis in patients with chronic necrotizing pulmonary aspergillosis.

BACKGROUND: The purpose of this study was to investigate mediators of inflammation and haemostasis in patients with chronic necrotizing pulmonary aspergillosis (CNPA), a locally, destructive process of the lung due to invasion by Aspergillus species. METHODS: Measurements of selected biomarkers in 10 patients with CNPA and 19 healthy, matched controls were performed with enzyme-linked immunosorbent assay (ELISA) and multiplex methodology. The gene expressions of relevant biomarkers were analyzed with real-time quantitative RT-PCR. RESULTS: Increased concentrations of circulating mediators of inflammation interleukin (IL)-6, IL-8, RANTES, TNF-α, ICAM-1 and mediators involved in endothelial activation and thrombosis (vWF, TF and PAI-1) were observed in patients with CNPA. The concentration of the anti-inflammatory cytokine IL-10 was increased both in plasma and in PBMC in the patient population. The gene expression of CD40L was decreased in PBMC from the patient group, accompanied by decreased concentrations of soluble (s) CD40L in the circulation. CONCLUSIONS: The proinflammatory response against Aspergillus may be counteracted by reduced CD40L and sCD40L, as well as increased IL-10, which may compromise the immune response against Aspergillus in patients with CNPA.

Diagnostic accuracy of computed tomography and histopathology in the diagnosis of usual interstitial pneumonia.

BACKGROUND: The relative clinical benefit of histopathology and computed tomography (CT) in patients with idiopathic interstitial pneumonia (IIP) is under debate. PURPOSE: To analyze thin-section CT features and histopathologic findings in patients with usual interstitial pneumonia (UIP) in the clinical context of idiopathic pulmonary fibrosis (IPF), and to evaluate and compare diagnostic accuracy of the two methods among patients with an appropriate spectrum of IIP. MATERIAL AND METHODS: The study included 91 patients (49 men; mean age 53.2 years; median follow-up 7.2 years) with clinically suspected interstitial lung disease. All underwent surgical lung biopsy and thin-section CT. Two independent readers retrospectively assessed the CT images for the extent and pattern of abnormality and made a first-choice diagnosis. Two pathologists retrospectively assessed the histopathologic slides. In 64 patients with IIP, a retrospective composite reference standard identified 41 patients with UIP. CT characteristics of UIP and IIPs other than UIP were compared with univariate and multivariate analyses. RESULTS: There was good agreement between the readers for the correct first-choice CT diagnosis of UIP (κ = 0.79). The sensitivity, specificity, and positive predictive value of the CT diagnosis of UIP were 63%, 96%, and 96%, respectively. The sensitivity, specificity, and positive predictive value of the histological diagnosis of UIP were 73%, 74%, and 83%, respectively. The CT feature that best differentiated UIP from IIPs other than UIP was the extent of reticular pattern (odds ratio, 5.1). CONCLUSION: Surgical lung biopsy may not be warranted in patients with thin-section CT diagnosis of UIP.

[Lung cancer without metastases--are all patients with resectable tumor operated?]. / Lungekreft uten spredning--blir alle pasienter med resektabel tumor operert?

BACKGROUND: Only 17% of patients with lung cancer are surgically resected, and the resection rate has not improved despite more attention about the disease. All patients with resectable disease should be offered operation and we wanted to investigate whether this is the case. MATERIAL AND METHODS: We assessed patients that received the diagnosis localized lung cancer in the period 2003-2005 and were not resected according to the Cancer Registry of Norway (n = 322). After exclusion of 40 patients, 282 remained for evaluation. RESULTS: The Cancer Registry of Norway had received clinical reports for 253 patients. Lung physicians had filled in less than half of these, and TNM was registered appropriately in 37% of all reports. Despite that all patients had been categorized in the Registry as having localized lung cancer, 55 patients had advanced disease. Poor lung function, high age and serious comorbidity were contraindications towards surgery for patients with localized disease. Of 282 patients, 258 were inoperable while nine had undergone resection. The remaining 15 cases were thus classified as being operable or possibly operable. INTERPRETATION: The proportion of patients who had not undergone resection and were assessed as operable has decreased. Legally required reporting to the Cancer Registry is still insufficient. Introduction of a specific report form for these patients may facilitate treatment evaluation and thereby treatment and ensure that the decision to not operate is well documented.

[Middle-aged man with fever, hypoxia and bilateral alveolar infiltrates]. / En middelaldrende mann med feber, hypoksi og bilaterale lungefortetninger.

Pulmonary alveolar proteinosis (PAP) is a rare condition characterized by excessive amounts of surfactant phospholipids and proteins within the pulmonary alveoli. Depending on the amount of surfactant in the alveoli, varying degrees of disturbed gas exchange develop. We report the case of a middle-aged man presenting with fever, dyspnoe, cough and bilateral alveolar infiltrates on chest X-ray. On the basis of pink staining periodic acid-Schiff (PAS) of the milky material recovered from the airways during bronchoscopy, and transbronchial biopsies demonstrating normal interstitial structures, a diagnosis of PAP was established. He has been repeatedly treated with whole lung lavage--totally eight treatments- during a 30-month-period. The effect of therapy was excellent initially, but his symptoms recur, and he now needs treatment with shorter time-intervals. On the basis of this case history, an overview of the pathogenesis, clinical presentation, diagnosis, existing treatment modalities and prognosis of PAP is given.

Lung cancer surgery: the first 60 days. A population-based study.

OBJECTIVE: The postoperative mortality following lung cancer surgery is relatively high. The purpose of the present study was to identify preoperative risk factors as well as fatal complications in 27 Norwegian hospitals. METHODS: In Norway, all clinical and pathologic departments submit reports on cancer patients to the Cancer Registry of Norway. The Registry also has a law-regulated authority to collect supplemental information regarding diagnosis, treatment, and outcome for all cancer patients from the hospitals in charge. This investigation included all patients who died within 30 and 60 days after resection of lung cancer in the period 1993-2002. RESULTS: During the investigation lung cancer was diagnosed in 19,582 patients, 3224 (16.5%) were treated by surgery. The resection rate was almost similar in the two sexes, but postoperative mortality in women was less than half compared to men. Total mortality was 5% and 8% after 30 and 60 days, respectively. Bilobectomy and pneumonectomy were most risky with a mortality rate of about 10% within 60 days. In patients more than 70 years of age, there was a considerably higher frequency of pneumonectomy in men compared to women. Dominating causes of death were pneumonia with respiratory failure and cardiac events. Other identifiable causes were surgical hemorrhage and bronchopleural fistula. CONCLUSIONS: In this population-based, unselected series, the postoperative mortality was relatively high, and increased markedly in patients older than 70 years. Pneumonectomy in patients older than 70 years should only be performed when heart-lung function is found to be acceptable following full pulmonary function testing and thorough preoperative assessment of cardiovascular risk factors.

Results of pulmonary resection for lung cancer in Norway, patients older than 70 years.

OBJECTIVE: Surgical resection for lung cancer is the mainstay of curative treatment, but studies regarding postoperative results and long term outcome in the elderly have differed. The purpose of the present study was to assess the early and long-term results of surgical resection in patients more than 70 years of age. METHODS: In Norway all clinical and pathologic departments submit reports on cancer patients to the Cancer Registry of Norway. This investigation included all patients more than 70 years of age resected for lung cancer in the time period 1993-2000. For results of long-time follow-up only patients operated on between 1993 and 1998 were included. RESULTS: A total of 763 patients (541 men) were identified aged 71-87 years. Postoperative mortality rate was 9%, highest after bilobectomy and pneumonectomy. The most commonly reported causes of postoperative death were pneumonia and cardiac complications. The majority of patients had tumor categorized as clinical stage (cStage) Ia and Ib. More than 100 in each of these groups proved to have more advanced disease postoperatively (pStage). The 5-year relative survival rate was significantly better in patients with disease in pStage I compared to higher stages. Women had a significantly better 5-year survival rate compared to men, 62.8 and 35.7%, respectively. CONCLUSIONS: Lung cancer surgery appears to be a relatively safe procedure even in the elderly. There is a high postoperative mortality after bilobectomy and pneumonectomy. However, when old people survive the postoperative period the long term prognosis seems favorable.

Diagnosis of biopsy verified usual interstitial pneumonia by computed tomography.

OBJECTIVE: To identify the combination of clinical data and high resolution computed tomography (HRCT) features that best identified biopsy verified usual interstitial pneumonia (UIP). METHODS: The study included 91 patients with a tentative diagnosis of interstitial lung disease. All underwent clinical investigation, surgical lung biopsy and HRCT. Two independent readers assessed the HRCT images for the extent and pattern of abnormality. On the basis of the biopsy result the patients were categorized in three groups: 1) Usual interstitial pneumonia, 2) Other idiopathic interstitial pneumonias (IIPs) and hypersensitivity pneumonitis and 3) Other interstitial lung diseases. The diagnostic value of HRCT was investigated using likelihood ratio to estimate the post-test probability of UIP. RESULTS: We found that UIP was associated with significantly higher scores for reticular pattern and for bronchiectasis than the remaining patients (p < 0.001). Moreover, these scores showed a steeper cranial-caudal increase in patients with histologically verified UIP than in the remaining patients (p < 0.001). UIP was associated with lower scores for ground glass opacities (p < 0.001). Using Bayes theorem and likelihood ratio estimation we found that UIP could be diagnosed with 90% certainty in patients 60 years or older and restrictive pattern in spirometry provided that HRCT demonstrated at least 15% reticular pattern and no ground glass opacities. CONCLUSION: In older patients with a restrictive spirometry in whom HRCT demonstrates a reticular pattern without ground glass opacities surgical lung biopsy is not warranted for the diagnosis of UIP.

Small cell lung cancer in Norway. Should more patients have been offered surgical therapy?

OBJECTIVE: The final outcome of patients with small cell lung cancer (SCLC) is poor with an overall 5-year survival rate of less than 10%. Therefore, the question of surgery in patients with a technically-operable solitary tumor has been raised. The purpose of this study was to identify the proportion of patients with operable SCLC and to assess the prognosis of different treatment strategies. For patients who were operated, we compared the resection specimens from patients with more than 5-year survival with those with shorter survival to see whether the specimens belonged to different subclasses of SCLC. METHODS: In Norway all clinical and pathologic departments submit reports on cancer patients to the Cancer Registry. The Registry also has a law-regulated authority to collect supplemental information regarding diagnosis, treatment and outcome for all cancer patients from the hospitals in charge. All reports on patients diagnosed as having SCLC in limited disease or unknown stage during the time interval 1993-1999 were reviewed. Patients with a T2-tumor, in whom a pneumonectomy would have to be performed, were classified as potentially operable. Five-year relative survival was calculated for patients diagnosed in 1993-1997. RESULTS: During the actual period 2442 individuals with SCLC were identified. The majority was treated with conventional chemotherapy or concurrent chemoradiotherapy while 38 underwent surgical therapy. Following reclassification of 697 patients reported to have limited disease or unknown stage 180 were judged to be in stage I. In addition to the 38 resected patients 14 were considered fit for surgery technically and medically while 97 were found to be potentially operable treatment modalities apart from surgery yielded a 5-year survival rate <7%. For stage I (N=96) the rate was 11.3% in conventionally treated patients compared to 44.9% for those who underwent surgical resection. By pathological review of surgical specimens a diagnosis of SCLC was confirmed in all patients treated by surgery in the groups with long and short survival. CONCLUSION: This investigation demonstrates that patients with SCLC having a peripherally located tumor should be referred to surgery, as long time survival is far better than for conventionally treated patients.

[Causes of postoperative mortality after lung cancer surgery]. / Arsaker til mortalitet etter reseksjon for lungekreft.

BACKGROUND: There is a relatively high postoperative mortality after lung cancer surgery. However, the alternative is almost 100% mortality within five years if surgery is not performed. MATERIAL AND METHODS: This study is based on data in the Cancer Registry of Norway and information from hospitals where the patients had been treated. From 1993 to 2000, 2528 patients with lung cancer were operated with lung resection. RESULTS: A total of 188 patients died within 60 days. In 54 of them the cause of death was respiratory failure or pneumonia. There were nine cases with serious intraoperative bleeding with seven deaths, six on the table. Further postoperative bleeding occurred in 27 cases, most often after pneumonectomy. Of these, 10 died because of the bleeding. For 15 patients the cause of death was bronchopleural fistula, of which 13 had been operated with pneumonectomy. Myocardial infarction or cardiac failure caused the death of 32 patients. An additional 70 patients died from other complications. INTERPRETATION: Postoperative fatal complications after lung resection for cancer are too high.

[Computed tomography in lung cancer--technique and quality]. / Computertomografi ved lungekreft--teknikk og kvalitet.

BACKGROUND: There are indications that more patients with lung cancer should be offered surgical treatment. The percentage of surgically treated patients varies from one region of Norway to the other. The Cancer Registry of Norway has received CT examinations from lung cancer patients who were not operated. Differences in examination technique and quality were evaluated. MATERIAL AND METHODS: Thoracic CT examinations from 42 patients (9 women) from 32 institutions were evaluated by three radiologists with regard to technique and quality. RESULTS: Twenty-seven examinations (63%) were considered acceptable for evaluation of operability, while 15 (37%) were not. The proportion of adequately performed examinations was higher with helical CT (22 out of 25 examinations, 88%) than with conventional, axial scanning (5 out of 17 examinations, 29%). There were substantial variations in scanning technique (area, collimation, contrast medium, algorithms, and photographic documentation). The majority (n = 40) of investigations were performed with intravenous contrast medium, two without. Contrast medium enhancement and vascular visualisation was judged as insufficient in seven examinations. INTERPRETATION: Many examinations were of suboptimal quality, inadequate for pre-operative tumour staging. Several different examination techniques were documented.

Endoscopic treatment of bronchial carcinoids in comparison to surgical resection: a retrospective study.

BACKGROUND: Surgery is the gold standard of lung carcinoid treatment. However, bronchoscopic treatment may provide a complete cure in selected patients. The aim of the study was to review the results of laser treatment of bronchial carcinoids and to compare the outcome after laser resection against the outcome after surgical resection. METHODS: Seventy-three patients, 29 men and 44 women, median age 53 years (range, 23 to 78 y), with bronchial carcinoids were treated by surgical resection (n=48) or endobronchial ablation (n=25). Bronchoscopic treatment was also performed in 5 of 48 surgical patients as a part of the surgical treatment strategy. RESULTS: Among 25 patients treated endoscopically, 16 were successfully treated with laser, whereas 9 were operated subsequently. One major complication was registered, as an inadvertent ventilation caused a nonfatal fire of the bronchoscope during Nd:YAG laser procedure. Forty-eight patients underwent surgical resection. Most of the patients underwent lobectomy and bilobectomy (30 and 5 patients, respectively). Four of the patients were dead by the end of the study, 1 was treated with laser, and 3 treated with surgical resection. The overall survival was 94.5% in the surgical group and 94.4% in the group treated with endoscopic ablation (P=0.9). None of the 69 survivors had any sign of recurrence on computed tomographic scans and bronchoscopy by the end of the study. CONCLUSIONS: This is a retrospective study and no randomization has been performed. However, the results add evidence to the view that transbronchial laser treatment may be offered as a safe, stand-alone procedure in the treatment of typical carcinoid tumor in the central airways.

Carcinoid lung tumors--incidence, treatment and outcomes: a population-based study.

OBJECTIVE: Few published reports have examined the incidence and outcomes for patients with carcinoid lung tumors. The aim of the current study was to explore incidence, type of surgical treatment given, and outcome for patients with typical (TC) and atypical (AC) lung carcinoids in a national cohort (Norway). METHODS: All lung-cancer patients diagnosed in the period 1993-2005 and who were reported to the Cancer Registry of Norway were identified. Biopsies or resection specimens were reviewed and reclassified according to the World Health Organization (WHO) 2004 classification. Surgically treated patients were staged according to the seventh edition of the pathological tumor-node-metastasis (pTNM) staging system. RESULTS: Of 26665 lung cancers registered during the period, 265 (1%) had carcinoid tumors, of which 11 were diagnosed coincidentally at autopsy. In the remaining 254 patients, TCs were found in 188 cases, and ACs were found in 59 cases; seven cases had unclassifiable carcinoids. Of the 217 resected tumors, 173 (80%) were TCs. General surgeons performed 94 resections, including 11 of 17 pneumonectomies. All six bronchial resections were performed by thoracic surgeons. Of the 33 operated patients who died during follow-up, 18 had metastatic carcinoid tumors, of which 10 (56%) were ACs. In 37 non-resected patients (15 with AC and seven with unclassifiable histology), metastatic or locally advanced disease (N=21, 12 of which were ACs) was the main cause of inoperability and death. Five-year survival for all patients was 92% for TC and 66% for AC; for resected patients, the survival rates were 96% and 79%, respectively. CONCLUSIONS: Carcinoids are rare malignant tumors and are, in most cases, resectable; the TC subgroup had better prognosis than the AC in univariate analyses. The main cause of death was metastasis/locally advanced tumor at presentation or recurrent disease following resection; both situations were three times more common in patients with AC.

Resected synchronous primary malignant lung tumors: a population-based study.

BACKGROUND: Synchronous lung tumors with a histology indicating primary lung carcinomas detected preoperatively or at surgery may represent intrapulmonary metastases from a primary tumor or two or more simultaneously occurring primary tumors. The situation is rare. This study was conducted to assess the characteristics and outcome for this patient group. METHODS: All clinical and pathology departments in Norway submit standardized reports on cancer patients to the Cancer Registry of Norway. The registry also has a law-regulated authority to collect supplemental information on diagnosis, treatment, and outcome for all cancer patients from hospitals. During the period 1993 to 2000, lung cancer was diagnosed in 15,308 patients, of whom 2528 underwent resection in 24 hospitals. This investigation included all patients with histology demonstrating primary lung carcinoma in more than one tumor in the resected specimen. RESULTS: Synchronous malignant tumors were found in 94 patients: 66 had two tumors and the remaining 28 had three or more. The tumors were of similar histology in 85 cases. The tumors were diagnosed preoperatively in 11 patients and peroperatively or in the resected specimen in the other 83. The 5-year relative survival rate was 31.4% for patients with squamous cell carcinomas, 23.2% for adenocarcinomas, and 42.7% for patients with tumors of other histology (two carcinoids). CONCLUSIONS: Survival in patients with synchronous lung tumors is good compared with historical reports on patients with distant metastases or other variants of T4 tumors; thus, they should be considered for surgery.

The solitary pulmonary nodule--is it malignant or benign? Diagnostic performance of Tc-depreotide SPECT.

BACKGROUND: The diagnosis of malignancy may be difficult to establish in solitary pulmonary nodules (SPNs). OBJECTIVES: It was the aim of this study to assess diagnostic performances of technetium-99m ((99m)Tc)-depreotide in differentiating benign from malignant SPNs and compare its diagnostic accuracy with fluor-18-fluoro-deoxyglucose positron emission tomography (FDG-PET) in a subgroup of patients. METHODS: One hundred and eighteen patients presenting with an SPN < or =3 cm suspected of malignancy on CT were included in a prospective, open-label, European multicentre trial. Single photon emission computed tomography (SPECT) images were acquired 1.1-4.5 h after injection of 459-770 MBq of (99m)Tc-depreotide. A subset of 29 patients also underwent FDG-PET imaging. Images were interpreted blindly and correlated with histopathology. RESULTS: (99m)Tc-depreotide was positive in 65 of 73 patients with a malignant lesion and negative in 30 of 45 patients with a benign lesion, resulting in a sensitivity, specificity and diagnostic accuracy of 89, 67 and 81%, respectively. In 40 patients with SPN < or =1.5 cm, diagnostic accuracy was 88, sensitivity 75 and specificity 96%. In the subset of 29 patients who underwent both (99m)Tc-depreotide SPECT and FDG-PET imaging, sensitivity, specificity and diagnostic accuracy were identical for both modalities, i.e. 90, 67 and 83%, respectively. CONCLUSIONS: The diagnostic accuracy of (99m)Tc-depreotide SPECT is good and comparable with FDG-PET imaging in SPN of indeterminate origin.

[Is the treatment of lung cancer in Norway adequate?]. / Er behandlingen av lungekreft i Norge god nok?

BACKGROUND: Almost 2,000 new cases of lung cancer are reported in Norway every year. Only 16-17% are operated upon with resection. MATERIAL AND METHODS: Over the 1995-98 period, 1,035 not resected cases with localized lung cancer were reported to the Cancer Registry of Norway; 166 cases were excluded for various reasons. Records from the Cancer Registry with additional information from clinicians were revised by the authors with regard to staging and operability. RESULTS: Of 869 evaluable patients, 386 were inoperable due to advanced disease, and in 86 the situation was not adequately clarified. Of the remaining 397, 270 were classified as being operable and 127 possibly operable. Of the operable patients, small cell lung cancer was considered as the sole contraindication to surgery in 61 patients despite being in stage 1. Poor lung function was noted as contraindication to surgery in 50 patients. However, most of them were inadequately investigated. In 124 patients one or more other risk factors were considered as contraindications, but the impact of some of them seemed to have been overestimated. INTERPRETATION: The study showed that the information about stage routinely submitted to the Cancer Registry was unsatisfactory. We believe that more patients with localized disease in the present series should have been operated on.