Optimal communication associated with lower risk of acute traumatic stress after lung cancer diagnosis.

PURPOSE: The aim of this study was to assess the role of the patient's background and perceived healthcare-related factors in symptoms of acute stress after lung cancer diagnosis. METHODS: The study population consisted of 89 individuals referred for diagnostic work-up at Landspitali National University Hospital in Iceland and subsequently diagnosed with lung cancer. Before diagnosis, the patients completed questionnaires on sociodemographic characteristics, pre-diagnostic distress (Hospital Anxiety and Depression Scale), social support, and resilience. At a median of 16 days after diagnosis, the patients reported symptoms of acute stress on the Impact of Event Scale-Revised (IES-R) and experience of communication and support from healthcare professionals and family during the diagnostic period. RESULTS: Patients were on average 68 years and 52% reported high levels of post-diagnostic acute stress (IES-R > 23) while 24% reported symptoms suggestive of clinical significance (IES-R > 32). Prior history of cancer (ß = 6.7, 95% CI: 0.1 to 13.3) and pre-diagnostic distress were associated with higher levels of post-diagnostic acute stress (ß = 8.8, 95% CI: 2.7 to 14.9), while high educational level (ß = - 7.9, 95% CI: - 14.8 to - 1.1) was associated with lower levels. Controlling for the abovementioned factors, the patients' perception of optimal doctor-patient (ß = - 9.1, 95% CI: - 14.9 to - 3.3) and family communication (ß = - 8.6, 95% CI: - 14.3 to - 2.9) was inversely associated with levels of post-diagnostic acute stress after lung cancer diagnosis. CONCLUSIONS: A high proportion of patients with newly diagnosed lung cancer experience high levels of acute traumatic stress of potential clinical significance. Efforts to improve doctor-patient and family communication may mitigate the risk of these adverse symptoms.

[Advances in lung cancer diagnosis and treatment - a review].

Lung cancer is the second and third most common cancer in Iceland for females and males, respectively. Although the incidence is declining, lung cancer still has the highest mortality of all cancers in Iceland. Symptoms of lung cancer can be specific and localized to the lungs, but more commonly they are unspecific and result in significant diagnostic delay. Therefore, majority of lung cancer patients are diagnosed with non-localized disease. In recent years, major developments have been made in the diagnosis and treatment of lung cancer. Positive emission scanning (PET) and both transbroncial (EBUS) or transesophageal ultrasound (EUS) biopsy techniques have resulted in improved mediastinal staging of the disease and minimal invasive video-assisted thoracic surgery (VATS) has lowered postoperative complications and shortened hospital stay. Technical developments in radiotherapy have benefitted those patients who are not candidates for curative surgery. Finally, and most importantly, recent advances in targeted chemotherapeutics and development of immunomodulating agents have made individual tailoring of treatment possible. Recent screening-trials with low-dose computed tomography show promising results in lowering mortality. This evidence-based review focuses on the most important developments in the diagnosis and treatment of lung cancer, and includes Icelandic studies in the field.

Achieving Thoracic Oncology data collection in Europe: a precursor study in 35 Countries.

BACKGROUND: A minority of European countries have participated in international comparisons with high level data on lung cancer. However, the nature and extent of data collection across the continent is simply unknown, and without accurate data collection it is not possible to compare practice and set benchmarks to which lung cancer services can aspire. METHODS: Using an established network of lung cancer specialists in 37 European countries, a survey was distributed in December 2014. The results relate to current practice in each country at the time, early 2015. The results were compiled and then verified with co-authors over the following months. RESULTS: Thirty-five completed surveys were received which describe a range of current practice for lung cancer data collection. Thirty countries have data collection at the national level, but this is not so in Albania, Bosnia-Herzegovina, Italy, Spain and Switzerland. Data collection varied from paper records with no survival analysis, to well-established electronic databases with links to census data and survival analyses. CONCLUSION: Using a network of committed clinicians, we have gathered validated comparative data reporting an observed difference in data collection mechanisms across Europe. We have identified the need to develop a well-designed dataset, whilst acknowledging what is feasible within each country, and aspiring to collect high quality data for clinical research.

Prevalence, molecular markers, and outcome of bronchial squamous carcinoma in situ in high-risk subjects.

Bronchial squamous carcinoma in situ (CIS) is a preinvasive lesion that is thought to precede invasive carcinoma. We conducted prospective autofluorescence and white light bronchoscopy trials between 1992 and 2016 to assess the prevalence, molecular markers, and outcome of individuals with CIS and other preneoplastic bronchial lesions. Biopsies were evaluated at multiple levels and selected biopsies were tested for aneuploidy and DNA sequenced for TP53 mutation. Thirty-one individuals with CIS were identified. Twenty-two cases of CIS occurred in association with concurrent invasive carcinomas. Seven of the invasive tumors were radiographically occult. In two cases, CIS spread from the focus of invasive carcinoma into contralateral lung lobes, forming secondary invasive tumors. In nine cases, CIS occurred as isolated lesions and one progressed to invasive squamous carcinoma at the same site 40 months after discovery. In a second case, CIS was a precursor of carcinoma at a separate site in a different lobe. In seven cases CIS regressed to a lower grade or disappeared. High level chromosomal aneusomy was often associated with TP53 mutation and with invasive carcinoma. CIS most often occurs in association with invasive squamous carcinoma and may extend along the airways into distant lobes. In rare cases, CIS may be observed to directly transform into invasive carcinoma. CIS may be indicative of invasive tumor at a separate distant site. Isolated CIS may regress. Molecular changes parallel histological changes in CIS and may be used to map clonal expansion in the airways.

Pulmonary carcinoid tumours: incidence, histology, and surgical outcome. A population-based study.

BACKGROUND: Pulmonary carcinoids (PCs) represent only a minority of all primary pulmonary malignancies but they are the most common type of pulmonary malignancy diagnosed in children and adolescents. In this nationwide study, we analyzed data on all PC tumours in the Icelandic population over a 60-year period and concentrated especially on incidence and patient outcomes. METHODS: We studied all cases of PCs diagnosed in Iceland in the period 1955‒2015. Histological specimens were re-evaluated and the tumours were staged according to the TNM system (seventh edition). Survival was estimated using the Kaplan-Meier method, with a mean follow-up of 15.7 years. RESULTS: Altogether, 88 patients (median age 51.0 years, 65.9% women) were diagnosed with PCs in the study period. The incidence increased from 0.19/100,000/year in the first decade (1955‒1964) to 0.58/100,000/year in the last decade (2005‒2015), with a mean increase of 29.0% per decade of the study period (p < 0.001). The rise in incidental detection was, however, not significant. The median tumour diameter was 2.2 cm (range 0.4‒7.0) and typical histology was seen in 74 patients (84.1%). The other 14 patients (15.9%) had atypical histology. In all, 90.9% of the patients underwent pulmonary resection, 81.2% of them with lobectomy, with all of them surviving at least 30 days postoperatively. Most patients (n = 52, 62.7%) were stage IA at diagnosis, 15 (18.1%) were stage IB, nine (10.8%) were stage IIA, and three were stage IIIA (3.6%). Four patients (4.8%) had distant metastases (stage IV), two of whom had typical histology. Five-year survival was 89.8% for all patients: 93.2% for patients with typical histology and 70.7% for those with atypical histology. CONCLUSION: The incidence of PCs in Iceland has increased significantly over the last six decades, which cannot be explained by a rise in incidental detection at chest imaging. Most patients have localized disease and a favourable histology, where the long-term outcome is excellent.

Chromosomal aneusomy in bronchial high-grade lesions is associated with invasive lung cancer.

RATIONALE: The development of lung cancer (LC) is accompanied by field changes in the airway mucosa that may have prognostic importance. OBJECTIVES: To compare patients with prevalent LC to control subjects regarding their histologic dysplasia scores and chromosomal aneusomy as measured by fluorescence in situ hybridization (FISH). METHODS: The most advanced bronchial histology lesion was assessed from each of 44 LC cases and 90 cancer-free control subjects using a four-color FISH probe set encompassing the chromosome 6 centromere, 5p15.2, 7p12 (epidermal growth factor receptor), and 8q24 v-myc myelocytomatosis viral oncogene homolog (MYC) sequences. Histology grades were coded as dysplasia (moderate or severe) or carcinoma in situ (CIS). MEASUREMENTS AND MAIN RESULTS: CIS was the highest histologic grade for 32 subjects, and dysplasia was the highest grade for 102 subjects (54 moderate, 48 severe). Chromosomal aneusomy was seen in 64% of the LC cases, but in only 31% of the control subjects (odds ratio [OR], 4.68; 95% confidence interval [CI]. 1.97-11.04). Among those with any level of dysplasia, the OR for positive FISH and LC was 2.28 (95% CI, 0.75-6.86). Among those with CIS, the OR for positive FISH and LC was 5.84 (95% CI, 1.31-26.01). CONCLUSIONS: Chromosomal aneusomy is associated with LC. Prospective examination of aneusomy as a precursor lesion that predicts LC is needed.

Improved long-term survival following pulmonary resections for non-small cell lung cancer: results of a nationwide study from Iceland.

BACKGROUND: We studied the outcome of pulmonary resection with curative intent for non-small cell lung cancer (NSCLC) in a nationwide study covering a 24-year period, focusing on survival. METHODS: All patients who underwent pulmonary resection for NSCLC in Iceland in the period 1991-2014 were reviewed for demographics, TNM stage and survival. Median length of follow-up was 45 months. Three 8-year periods were compared, overall survival was estimated, and prognostic factors for survival were identified. RESULTS: Altogether, 652 surgical resections were performed on 644 individuals (52% females): 492 lobectomies (75%), 77 pneumonectomies (12%), and 83 sublobar resections (13%). Mean age increased from 65 to 68 yrs during the study period (P=0.002). The number of cases operated at stage IA increased substantially between the first and last periods (29% vs. 37%; P<0.001). Survival improved from 75% to 88% at 1 year and from 38% to 53% at 5 years (P<0.001). Independent prognostic factors for mortality were advanced TNM stage (HR =2.68 for stage IIIA vs. I), age (HR =1.04), ischaemic heart disease (HR =1.26), any minor complication (HR =1.26), and sublobar resection (HR =1.33), but surgical margins free from tumour growth (HR =0.59) and treatment during the latter two eight-year periods were predictors of lower mortality. The best survival was seen between 2007 and 2014 (HR =0.61, 95% CI: 0.48-0.78; P<0.001). CONCLUSIONS: Survival of patients who have undergone pulmonary resection for NSCLC has improved significantly in Iceland. This may be explained by the increased number of patients diagnosed at lower stages and improved preoperative staging, with fewer understaged patients.

Association of BRCA2 K3326* With Small Cell Lung Cancer and Squamous Cell Cancer of the Skin.

Background: Most pathogenic mutations in the BRCA2 gene carry a high risk of hereditary breast and ovarian cancer (HBOC). However, a stop-gain mutation, K3326* (rs11571833), confers risk of lung cancer and cancers of the upper-aero-digestive tract but only a modest risk of breast or ovarian cancer. The Icelandic population provides an opportunity for comprehensive characterization of the cancer risk profiles of K3326* and HBOC mutations because a single mutation, BRCA2 999del5, is responsible for almost all BRCA2-related HBOC in the population. Methods: Genotype information on 43 641 cancer patients and 370 971 control subjects from Iceland, the Netherlands, and the United States was used to assess the cancer risk profiles of K3326* and BRCA2 999del5. BRCA2 expression was assessed using RNAseq data from blood (n = 2233), as well as 52 tissues reported in the GTEx database. Results: The cancer risks associated with K3326* are fundamentally different from those associated with 999del5. We report for the first time an association between K3326* and small cell lung cancer (odds ratio [OR] = 2.06, 95% confidence interval [CI] = 1.35 to 3.16) and squamous cell carcinoma of the skin (OR = 1.69, 95% CI = 1.26 to 2.26). Individuals homozygous for K3326* reach old age and have children. Unlike BRCA2 999del5, the K3326* allele does not affect the level of BRCA2 transcripts, and the allele is expressed to the same extent as the wild-type allele. Conclusions: K3326* associates primarily with cancers that have strong environmental genotoxic risk factors. Expression of the K3326* allele suggests that a variant protein may be made that retains the DNA repair capabilities important to hormone-responsive tissues but may be less efficient in responding to genotoxic stress.

Incidental detection by computed tomography is an independent prognostic factor for survival in patients operated for nonsmall cell lung carcinoma.

We studied the rate of incidental detection of lung carcinomas and its effect on long-term survival in a nationwide cohort of patients operated for nonsmall cell lung cancer (NSCLC). All patients operated for NSCLC in Iceland during 1991-2010 were included. Demographic and clinicopathological features were compared in patients diagnosed incidentally using chest radiography or computed tomography (CT), and in those with symptomatic presentation. Multivariate analysis was used to evaluate prognostic factors. Out of 508 patients, 174 (34%) were diagnosed incidentally; in 26% of cases by chest radiography and in 8% by CT. The CT-detected tumours were significantly smaller than symptomatic tumours, diagnosed at earlier TNM (tumour, node and metastasis) stages and more often of adenocarcinoma histology. 5-year cancer-specific survival for symptomatic versus incidentally diagnosed patients detected by chest radiography and CT was 41%, 57% and 68%, respectively (p=0.003). After adjusting for stage, the hazard ratio (HR) for NSCLC mortality was significantly lower for incidental diagnosis by CT (HR 0.55, 95% CI 0.31‒0.98; p=0.04) compared to incidental diagnosis by chest radiography (HR 0.95, 95% CI 0.70‒1.27; p=0.71) or symptomatic diagnosis (HR 1.0). One-third of surgically treated NSCLCs were detected incidentally, with an increasing rate of incidental CT diagnosis. NSCLC patients diagnosed incidentally by CT appear to have better survival than those diagnosed incidentally by chest radiography, and particularly those who present with symptoms.

[Fast diagnostic track for suspected lung cancer: A patient centered approach].

INTRODUCTION: The aim of this study is to describe the characteristics of patients who underwent a fast diagnostic track (FDT) due to suspected lung cancer at Landspitali University Hospital, Iceland. MATERIAL AND METHODS: Hospital records were reviewed on background characteristics, diagnosis, staging, waiting times and survival of all 550 patients (mean age 68.1 years, 57% female) that participated in the FDT from February 1, 2008 to January 31, 2015. Adjusting for clinical characteristics in a multivariate analysis, overall survival was compared for patients diagnosed with lung cancer within or outside the FDT in Iceland in 2014 (n=167, mean age 69.3 years, 61.7% female). RESULTS: Of the 550 FDT patients, 426 were diagnosed with lung cancer (77.5%); 346 of the non-small cell type (NSCLC) (81.2%). The proportion of patients receiving lung cancer diagnosis through the FDT increased from 23.3% in 2008 to 47.9% in 2014 (p<0.001). The waiting time from referral to diagnosis was 10 days median and 19 days from diagnosis to initiation of treatment. More patients with advanced disease were diagnosed outside the FDT (70.1% vs. 37.5%, p<0.05). When ad-- justed for age, sex, histology, stage at diagnosis and therapy, patients diagnosed with lung cancer outside the FDT had higher risk of all-cause mortality (HR 1.60; 95% CI: 0.95 - 2.71) although the difference was not statistically significant. CONCLUSION: An increasing proportion of lung cancer diagnosis in Iceland is made through a fast diagnostic track with potential benefits for patients. The waiting time from referral to diagnosis and treatment is in line with international guidelines. Key words: lung cancer, non-small cell lung cancer, diagnostic track, waiting times, survival. Correspondence: Hronn Hardardottir, hronnh@landspitali.is.

Resection rate and operability of elderly patients with non-small cell lung cancer: Nationwide study from 1991 to 2014.

OBJECTIVES: An increasing number of elderly patients are diagnosed with non-small cell lung cancer (NSCLC). We compared the surgical resection rate, operability and survival in this age group (≥75 years) to younger patients using centralized databases in Iceland. METHODS: The study population comprised all patients diagnosed with NSCLC in Iceland from 1991 to 2014. A total of 140 elderly patients (≥75 years) with NSCLC underwent pulmonary resection and were compared with 550 surgically resected patients less than 75 years, with respect to resection rate, short and long-term survival and complications of surgery. Reasons for exclusion from surgery were registered for elderly surgical candidates (stages IA-IIB). RESULTS: Surgical resection rate in the elderly group was 18% compared to 32% in the younger age group ( P < 0.001). The most frequent reasons for not operating on elderly patients in stages IA-IIB were poor pulmonary function (58%), heart disease (17%) or multiple comorbidities (17%). The rate of major complications following surgery was comparable in the elderly versus the younger age group, 13 vs 11%, respectively ( P = 0.578). The same was true for 30 day mortality (2 vs 1%, P = 0.397). Five-year overall survival was 40% vs 44% ( P = 0.019) and cancer-specific survival 51% vs 50% ( P = 0.802). CONCLUSIONS: Elderly patients with resectable NSCLC according to stage are frequently excluded from surgery due to comorbid conditions. Although the operated patients may represent a selected group, their favourable 30-day and long-term survival indicate that more elderly patients with NSCLC could be operated on.

Primary adenocarcinoma of the lung--histological subtypes and outcome after surgery, using the IASLC/ATS/ERS classification of lung adenocarcinoma.

Adenocarcinoma is the most common histological type of lung carcinoma. Recently the histologic classification of adenocarcinomas in the lung was modified to better reflect biologic properties and prognosis. We reviewed the histology of all primary lung adenocarcinomas operated on in Iceland during a 20-year period and assessed the impact of histology on survival. This nationwide study included 285 patients (mean age 67 years, 57% female), who underwent resection in Iceland from 1991 to 2010. Tumors were reclassified according to the current IASLC/ATS/ERS classification system. Overall survival was estimated by the Kaplan-Meier method and Cox regression analysis used to evaluate prognostic factors of overall mortality. Acinar predominant adenocarcinoma was the most common histological subtype (46%) followed by solid-predominant (SPA) with mucin production comprised (23%). Non-invasive carcinomas were rare. A difference in survival between the histological adenocarcinoma subtypes was not seen (p = 0.32) and multivariate analysis showed that advanced stage and age predicted worse outcome, but histologic subtyping of adenocarcinoma did not. In this nation-wide study there was not a statistical difference in survival according to adenocarcinoma subtypes and the histological subtype did not predict mortality. Preinvasive and minimally invasive adenocarcinomas were rare.

[Outcome of surgical treatment for Pancoast lung carcinoma in Iceland]. / Árangur skurdmedfedar vid Pancoast-lungnakrabbameini á Íslandi.

OBJECTIVE: Pancoast tumors are lung carcinomas that invade the apical chest wall and surrounding structures. Treatment is complex and often involves surgery together with radio- and chemotherapy. We studied the outcome of surgical resection for Pancoast tumors in Iceland. MATERIALS AND METHODS: A retrospective study including all patients that underwent resection of a Pancoast tumor with curative intent in Iceland in the years 1991-2010. Data on symptoms, complications, TNM-stage, relapse and survival were analyzed. RESULTS: Twelve patients were operated on; 7 on the right lung. Shoulder pain (n=5) and/or chest pain (n=3), cough (n=6) and weight loss (n=5) were the most common presenting symptoms. Adenocarcinoma (n=5) and squamous cell carcinoma (n=4) were the most frequent histological types. Average tumor size was 5,9 cm (range: 2,8-15). Five cases were stage IIB and 7 stage IIIA according to operative staging. In 10 cases (83%) the surgical margins were free of tumor. All patients survived surgery and only one patient suffered a major operative complication, an intraoperative bleeding. In one case induction chemo-radiation prior to surgery was administrated, and 8 patients received postoperative radiotherapy. Recurrent disease was diagnosed in 9 patients; four had local or regional recurrence, four had distant metastases and one patient was diagnosed with both local and distant recurrences simultaneously. Survival at 5 years was 33% and median survival was 27,5 months (range: 4-181). CONCLUSIONS: Operative and short-term outcomes for patients with Pancoast tumors in Iceland are excellent. However, long-term outcomes are not as favorable and recurrence rate is high compared to other studies, possibly due to incomplete preoperative staging and less use of chemo-radiation therapy prior to surgery among these patients.

Familial risk of lung carcinoma in the Icelandic population.

CONTEXT: The dominant role of tobacco smoke as a causative factor in lung carcinoma is well established; however, an inherited predisposition may also be an important factor in the susceptibility to lung carcinoma. OBJECTIVE: To investigate the contribution of genetic factors to the risk of developing lung carcinoma in the Icelandic population. DESIGN, SETTING, AND PARTICIPANTS: Risk ratios (RRs) of lung carcinoma for first-, second-, and third-degree relatives of patients with lung carcinoma were estimated by linking records from the Icelandic Cancer Registry (ICR) of all 2756 patients diagnosed with lung carcinoma within the Icelandic population from January 1, 1955, to February 28, 2002, with an extensive genealogical database containing all living Icelanders and most of their ancestors since the settlement of Iceland. The RR for smoking was similarly estimated using a random population-based cohort of 10,541 smokers from the Reykjavik Heart Study who had smoked for more than 10 years. Of these smokers, 562 developed lung cancer based on the patients with lung cancer list from the ICR. MAIN OUTCOME MEASURES: Estimation of RRs of close and distant relatives of patients with lung carcinoma and comparison with RRs for close and distant relatives of smokers. RESULTS: A familial factor for lung carcinoma was shown to extend beyond the nuclear family, as evidenced by significantly increased RR for first-degree relatives (for parents: RR, 2.69; 95% confidence interval [CI], 2.20-3.23; for siblings: RR, 2.02; 95% CI, 1.77-2.23; and for children: RR, 1.96; 95% CI, 1.53-2.39), second-degree relatives (for uncles/aunts: RR, 1.34; 95% CI, 1.15-1.49; and for nephews/nieces: RR, 1.28; 95% CI, 1.10-1.43), and third-degree relatives (for cousins: RR, 1.14; 95% CI, 1.05-1.22) of patients with lung carcinoma. This effect was stronger for relatives of patients with early-onset disease (age at onset < or =60 years) (for parents: RR, 3.48; 95% CI, 1.83-8.21; for siblings: RR, 3.30; 95% CI, 2.19-4.58; and for children: RR, 2.84; 95% CI, 1.34-7.21). The hypothesis that this increased risk is solely due to the effects of smoking was rejected for all relationships, except cousins and spouses, with a single-sided test of the RRs for lung carcinoma vs RRs for smoking. CONCLUSIONS: These results underscore the importance of genetic predisposition in the development of lung carcinoma, with its strongest effect in patients with early-onset disease. However, tobacco smoke plays a dominant role in the pathogenesis of this disease, even among those individuals who are genetically predisposed to lung carcinoma.

[Pulmonary alveolar proteinosis - a case report]. / Próteinútfellingar í lungnablöðrum meðhöndlaðar með lungnaskoli.

Pulmonary alveolar proteinosis (PAP) is a rare lung disease of unknown origin, where an amorphous lipoprotein material accumulates in the alveoli of the lungs. We describe a young male with a four month history of progressive dyspnea, low grade fever, hypoxemia and weight loss. Chest X-ray showed diffuse interstitial and alveolar infiltrates in both lungs. The diagnosis of PAP was confirmed with trans-bronchial lung biopsy. Because of a deteriorating clinical course a whole lung lavage was performed. Under general anesthesia, both lungs were lavaged with warm saline in two different sessions with good results. Two years later the patient is almost free of symptoms and lung function has markedly improved.

[Intensive care unit admissions following lobectomy or sublobar resections for non-small cell lung cancer]. / Innlagnir a gjorgaeslu aftir bladnam og fleygskurdi vid lungnakrabbameini.

INTRODUCTION: Following resection for non-small cell lung cancer (NSCLC), patients are usually admitted to the post-anesthesia care unit (PACU)for a few hours before admission to a general ward (GW). However, some patients need ICU-admission, either immediately post-surgery or from the PACU or GW. The aim of this study was to investigate the indications and risk factors for ICU-admission. MATERIAL AND METHODS: A retrospective study of 252 patients who underwent lobectomy, wedge resection or segmentectomy for NSCLC in Iceland during 2001-2010. Data was retrieved from medical records and patients admitted to the ICU compared to patients not admitted. RESULTS: Altogether 21 patients (8%) were admitted to the ICU, median length-of-stay being one day (range 1-68). In 11 cases (52%) the reasons for admission were intraoperative problems, usually hypotension or excessive bleeding. Ten patients were admitted from the GW (n=4) or PACU (n=6), due to hypotension (n=4), heart and/or respiratory failure (n=4) and reoperation for bleeding (n=2). There were three ICU-readmissions. Patients admitted to the ICU were six years older (p=0.004) and more often had chronic obstructive pulmonary disease and/or coronary artery disease. Tumor size, pTNM-stage, length of operation and the ratio of patients receiving TEA (thoracic epidural anaesthesia) were similar between groups. Over two-thirds of the ICU-patients had minor complications and around half had major complications, compared to 30% and 4%, respectively, for controls. CONCLUSION: ICU-admissions are infrequent following non-pneumonectomy lung resections for NSCLC, these patients being older with cardiopulmonary comorbidities. In half of the cases, admission to the ICU directly follows surgery and ICU-readmissions are few.

Resection rate and outcome of pulmonary resections for non-small-cell lung cancer: a nationwide study from Iceland.

BACKGROUND: The proportion of patients with non-small-cell lung cancer (NSCLC) who undergo surgery with curative intent is one measure of effectiveness in treating lung cancer. To the best of our knowledge, surgical resection rate (SRR) for a whole nation has never been reported before. We studied the SRR and surgical outcome of NSCLC patients in Iceland during a recent 15-year period. METHODS: This was a retrospective study of all pulmonary resections performed with curative intent for NSCLC in Iceland from 1994 to 2008. Information was retrieved from medical records and from the Icelandic Cancer Registry. Patient demographics, postoperative tumor, node, metastasis stage, overall survival, and complication rates were compared over three 5-year periods. RESULTS: Of 1530 confirmed cases of NSCLC, 404 were resected, giving an SRR of 26.4%, which did not change significantly during the study period. Minor and major complication rates were 37.4% and 8.7%, respectively. Operative mortality rates were 0.7% for lobectomy, 3.3% for pneumonectomy, and 0% for lesser resection. Five-year survival after all procedures was 40.7% and improved from the first to the last 5-year period (34.8% versus 43.8%, p = 0.04). Five-year survival for stages I and II together was 46.8%, with no significant change in stage distribution between periods. Five-year survival after pneumonectomy was 22.0%, which was significantly lower than for lobectomy (44.6%) and lesser resection (40.7%) (p < 0.005). Unoperated patients had a 5-year survival of 4.8%, as compared to 12.4% for all the NSCLC patients together. CONCLUSION: Compared with most other published studies, the SRR of NSCLC in Iceland is high. Short-term outcome is good, with a low rate of major complications and an operative mortality of only 1.0%. Five-year survival improved significantly over the study period.

[Sublobar resection for non-small cell lung cancer in Iceland]. / Arangur fleyg- og geiraskurda vid lungnakrabbbameini á Islandi.

INTRODUCTION: A sublobar resection is performed on patients with non-small cell lung cancer (NSCLC) who are not candidates for a lobectomy due to reduced pulmonary function or comorbid disease. The aim of this study was to investigate the outcomes of these operations in Iceland. MATERIAL AND METHODS: A retrospective study of all patients with NSCLC who underwent wedge resection or segmentectomy with curative intent during 1994-2008. Data on indication, pathological TNM-stage, complications and overall survival was analyzed. All histological samples were re-evaluated. RESULTS: Forty four patients underwent 42 wedge and 5 segmental resections (age 69.1 yrs, 55.3% female), with 38.3% of cases detected incidentally. The majority of patients (55.3%) had a history of coronary artery disease and 40.4% had chronic obstructive pulmonary disease. Mean operative time was 83 minutes (range 30-131), mean intraoperative bleeding was 260 ml (range 100-650) and median hospital stay was 9 days (range 4-24). Pneumonia (14.9%) and prolonged air leakage (12.8%) were the most common complications. Two patients had major complications and 36.2% stayed in the intensive care unit overnight. No deaths occurred within 30 days of surgery. Adenocarcinoma was the most common histological type (66.7%). Most cases were stage IA/IB (78.7%), 17.0% were stage IIA/IIB and 4.3% were stage IIIA. One and 5 year survival was 85.1% and 40.9% respectively. CONCLUSION: In Iceland, both survival and complication rate after sublobar resection for NSCLC are comparable to results published for lobectomies, even though a higher percentage of patients have underlying cardiopulmonary disease.

[Lung volume reduction surgery for severe pulmonary emphysema in Iceland]. / Arangur lungnasmaekkunaradgerda vid langvinnri lungnathembu a Islandi.

INTRODUCTION: Lung volume reduction surgery (LVRS) can benefit patients with severe emphysema. The aim of this study was to evaluate the outcome of LVRS performed in Iceland. MATERIALS AND METHODS: A prospective study of 16 consecutive patients who underwent bilateral LVRS through median sternotomy between January 1996 and December 2008. All patients had disabling dyspnea, lung hyperinflation, and emphysema with upper lobe predominance. Preoperatively all patients underwent pulmonary rehabilitation. Spirometry, lung volumes, arterial blood gases and exercise capacity were measured before and after surgery. Mean follow-up time was 8.7 years. RESULTS: Mean age was 59.2 ± 5.9 years. All patients had a history of heavy smoking. There was no perioperative mortality and survival was 100%, 93%, and 63% at 1, 5, and 10 years, respectively. The forced expiratory volume in 1 second (FEV1) and the forced vital capacity (FVC) improved significantly after surgery by 35% (p<0.001) and 14% (p<0.05), respectively. The total lung capacity, residual volume and partial pressure of CO2 also showed statistically significant improvements but exercise capacity, O2 consumption and diffusing capacity of the lung for CO did not change. Prolonged air leak (≥ 7 days) was the most common complication (n=7). Five patients required reoperation, most commonly for sternal dehiscence (n=4). CONCLUSION: In this small prospective study, FEV1 and FVC increased and lung volumes and PaCO2 improved after LVRS. Long term survival was satisfactory although complications such as reoperations for sternal dehiscence were common and hospital stay therefore often prolonged.

Genome-wide significant association between a sequence variant at 15q15.2 and lung cancer risk.

Genome-wide association studies (GWAS) have identified 3 genomic regions, at 15q24-25.1, 5p15.33, and 6p21.33, which associate with the risk of lung cancer. Large meta-analyses of GWA data have failed to find additional associations of genome-wide significance. In this study, we sought to confirm 7 variants with suggestive association to lung cancer (P < 10(-5)) in a recently published meta-analysis. In a GWA dataset of 1,447 lung cancer cases and 36,256 controls in Iceland, 3 correlated variants on 15q15.2 (rs504417, rs11853991, and rs748404) showed a significant association with lung cancer, whereas rs4254535 on 2p14, rs1530057 on 3p24.1, rs6438347 on 3q13.31, and rs1926203 on 10q23.31 did not. The most significant variant, rs748404, was genotyped in an additional 1,299 lung cancer cases and 4,102 controls from the Netherlands, Spain, and the United States and the results combined with published GWAS data. In this analysis, the T allele of rs748404 reached genome-wide significance (OR = 1.15, P = 1.1 × 10(-9)). Another variant at the same locus, rs12050604, showed association with lung cancer (OR = 1.09, 3.6 × 10(-6)) and remained significant after adjustment for rs748404 and vice versa. rs748404 is located 140 kb centromeric of the TP53BP1 gene that has been implicated in lung cancer risk. Two fully correlated, nonsynonymous coding variants in TP53BP1, rs2602141 (Q1136K) and rs560191 (E353D) showed association with lung cancer in our sample set; however, this association did not remain significant after adjustment for rs748404. Our data show that 1 or more lung cancer risk variants of genome-wide significance and distinct from the coding variants in TP53BP1 are located at 15q15.2.