Tomasz Grodzki

Imaging Requirements in the Practice of Pulmonary Metastasectomy

The primary imaging modality for the detection of pulmonary metastases is computed tomography (CT). Ideally, a helical CT scan with 3- to 5-mm reconstruction thickness or a volumetric thin section scanning should be performed within 4 weeks of pulmonary metastasectomy. A period of observation to see whether further metastases develop does not seem to allow better patient selection. If positron emission tomography is available, it may identify the extrathoracic metastatic sites in 10 to 15% of patients. Despite helical CT scan, palpation identifies the metastases not detected by imaging in 20 to 25% of patients and remains the standard. No data define the optimal interval for follow-up surveillance imaging.

Accelerated treatment of postpneumonectomy empyema : a binational long-term study

OBJECTIVE Postpneumonectomy empyema remains a clinical challenge. We proposed an accelerated therapy without an open chest window 5 years ago. This concept was evaluated on a larger scale in 2 centers in 2 different countries. METHODS Between July 1995 and October 2005, 75 consecutive patients with postpneumonectomy empyema were treated in Szczecin, Poland (n = 35), and Zurich, Switzerland (n = 40). The therapy consisted of repeated open surgical debridement of the pleural cavity after achievement of general anesthesia, a negative pressure wound therapy of the temporarily closed chest cavity filled with povidone-iodine-soaked towels, and continuous suction and systemic antimicrobial therapy. If present, bronchopleural fistulae were closed and reinforced either with a muscle flap or the omentum. Finally, the pleural space was filled with an antibiotic solution and definitively closed. RESULTS Of 75 patients (63 men; median age, 59 years; age range, 19-82 years), postpneumonectomy empyema was present on the right in 46 patients (32 with bronchopleural fistula) and in 29 patients (12 with bronchopleural fistula) on the left. Median time between pneumonectomy and postpneumonectomy empyema was 131 days (range, 7-7200 days). Bronchopleural fistulae have been closed and additionally reinforced by means of different methods (omentum, 18; muscle, 11; pericardial fat, 5; azygos vein, 1). The chest was definitively closed within 8 days in 94.6% of patients. The median hospitalization time was 18 days (range, 9-134 days). Postpneumonectomy empyema was successfully treated in 97.3% of patients, including 10 (13%) patients who needed a second treatment cycle. Three (4%) patients died within 90 days. The median follow-up time was 29.5 moths (range, 3-107 months). CONCLUSIONS Treatment of postpneumonectomy empyema with the accelerated treatment is effective and safe. Our results are superior compared with those in reported series using a (temporary) chest fenestration. Patients appreciate the physical integrity of the chest.

Constitutional CHEK2 mutations are associated with a decreased risk of lung and laryngeal cancers

Mutations in the CHEK2 gene have been associated with increased risks of breast, prostate and colon cancer. In contrast, a previous report suggests that individuals with the I157T missense variant of the CHEK2 gene might be at decreased risk of lung cancer and upper aero-digestive cancers. To confirm this hypothesis, we genotyped 895 cases of lung cancer, 430 cases of laryngeal cancer and 6391 controls from Poland for four founder alleles in the CHEK2 gene, each of which has been associated with an increased risk of cancer at several sites. The presence of a CHEK2 mutation was protective against both lung cancer [odds ratio (OR) = 0.3; 95% confidence interval (CI) 0.2-0.5; P = 3 x 10(-8)] and laryngeal cancer (OR = 0.6; 95% CI 0.3-0.99; P = 0.05). The basis of the protective effect is unknown, but may relate to the reduced viability of lung cancer cells with a CHEK2 mutation. Lung cancers frequently possess other defects in genes in the DNA damage response pathway (e.g. p53 mutations) and have a high level of genotoxic DNA damage induced by tobacco smoke. We speculate that lung cancer cells with impaired CHEK2 function undergo increased rates of cell death.

A Low Selenium Level Is Associated with Lung and Laryngeal Cancers

Purpose It has been suggested that selenium deficiency is a risk factor for several cancer types. We conducted a case-control study in Szczecin, a region of northwestern Poland, on 95 cases of lung cancer, 113 cases of laryngeal cancer and corresponding healthy controls. Methods We measured the serum level of selenium and established genotypes for four variants in four selenoprotein genes (GPX1, GPX4, TXNRD2 and SEP15). Selenium levels in the cases were measured after diagnosis but before treatment. We calculated the odds of being diagnosed with lung or laryngeal cancer, conditional on selenium level and genotype. Results Among lung cancer cases, the mean selenium level was 63.2 µg/l, compared to a mean level of 74.6 µg/l for their matched controls (p<0.0001). Among laryngeal cancer cases, the mean selenium level was 64.8 µg/l, compared to a mean level of 77.1 µg/l for their matched controls (p<0.0001). Compared to a serum selenium value below 60 µg/l, a selenium level above 80 µg/l was associated with an odds ratio of 0.10 (95% CI 0.03 to 0.34; p = 0.0002) for lung cancer and 0.23 (95% CI 0. 09 to 0.56; p = 0.001) for laryngeal cancer. In analysis of four selenoprotein genes we found a modest evidence of association of genetic variant in GPX1 with the risk of lung and laryngeal cancers. Conclusion A selenium level below 60 µg/l is associated with a high risk of both lung and laryngeal cancer.

Smoking related cancers and loci at chromosomes 15q25, 5p15, 6p22.1 and 6p21.33 in the Polish population.

Genetic factors associated with the risk of smoking related cancers have until recently remained elusive. Since the publication of a genome-wide association study (GWAS) on lung cancer new genetic loci have been identified that appear to be associated with disease risk. In this replication study we genotyped 14 single nucleotide polymorphisms (SNPs) located at the 5p12.3-p15.33, 6p21.3-p22.1, 6q23-q27 and 15q25.1 loci in 874 lung, 450 bladder, 418 laryngeal cancer cases and cancer-free controls, matched by year of birth and sex to the cases. Our results revealed that loci in the chromosome region 15q25.1 (rs16969968[A], rs8034191[G]) and 5p15 (rs402710[T]) are associated with lung cancer risk in the Polish population (smoking status adjusted OR = 1.45, 1.35, 0.77; p≤0.0001, 0.0005, 0.002; 95%CI 1.23–1.72, 1.14–1.59, 0.66–0.91 respectively). None of the other regions analyzed herein were implicated in the risk of lung, bladder or laryngeal cancer. This study supports previous findings on lung cancer but fails to show association of SNPs located in 15q25.1 and 5p15 region with other smoking related cancers like bladder and laryngeal cancer.

Prevalence of the NOD2 3020insC mutation in aggregations of breast and lung cancer.

Both breast and lung cancers are common malignancies and within the context of known genetic predispositions to breast cancer, no association has been made in linking the two diseases together. This does not exclude the possibility that such associations may exist that lie outside the known high-risk breast cancer families. To examine the likelihood of common genetic factors that could influence the risk of disease, two sets of consecutively collected tumor groups were examined for the 3020insC mutation in the NOD2/CARD15 gene. A total of 4107 consecutively collected breast cancer patients were assessed for the prevalence of the 3020insC mutation and compared to a consecutively collected series of 389 lung cancer patients and 2068 control samples. The results revealed that a proportion of breast cancer patients who had a first or a second degree relative diagnosed with lung cancer were more likely to harbour a change in NOD2/CARD15 compared to patients who had no relatives affected by lung cancer. Furthermore, this difference appeared to be specific to the breast and lung cancer subgroup since there was no difference in the frequency of the 3020insC allele in the consecutively collected lung cancer patients. In conclusion, it appears that the 3020insC mutation of the NOD2/CARD15 gene may be a genetic predisposing factor for aggregations of breast and lung cancer.

Additional pulmonary resections after pneumonectomy: actual long-term survival and functional results

OBJECTIVE Pulmonary resections after pneumonectomy due to metastases or metachronous non-small cell lung cancer (NSCLC) are rare because of the high potential risk of the second procedure and uncertain long-term results. On the basis of our series (largest in Europe) we tried to assess the long-term survival of patients treated in stage IV NSCLC. METHODS Retrospective analysis was carried out on 18 patients treated at our department by pneumonectomy followed by additional resection in the years 1981-2002 (15 males and 3 females, 44-69 years, mean 57). Eleven pneumonectomies were performed on the right side and seven on the left. Twelve squamous cell carcinomas and six adenocarcinomas were diagnosed. All patients were staged postoperatively as IIB-IIIA (four were N2). Their WHO status ranged between 0 and 1. The second surgical procedure (16 wedge resections, 2 chest wall resections) was performed 4-106 months later (mean 26). The patients staged N2 were radiated postoperatively. RESULTS There were no early postoperative deaths. The morbidity rate after second surgery was comparable to that observed after ordinary wedge resection. Histology of the lesions removed during the second operation was the same as after pneumonectomy in all patients. The pulmonary function tests (PFT) results worsened significantly but still reached 56-63% of the predicted values. Sixteen resected tumors of the remaining lung were staged T1 (<3cm), 2 - T3 (<3cm but infiltration of the parietal pleura on an area of 2-4cm(2)). Three patients revealed N2 disease (they were all N0 after pneumonectomy). All patients were considered M1 after second surgery. WHO status after the second procedure remained the same in 8 patients (44%) and worsened in 10 patients (56%). The survival rates were as follows: 11 patients survived 2 years (61%) while 8 patients survived 5 years (44%). The majority of patients died due to lung cancer (70%) but all the rest (30%) due to circulatory or respiratory insufficiency. There was a significant difference (p<0.05) in 5-year survival for N0-N1 vs N2 status (63% vs 14% - 1 patient) and also regarding the time interval between surgeries: less than 12 months vs more than 12 months (0% vs 63%). CONCLUSIONS Pulmonary resections performed after pneumonectomy due to NSCLC are rare procedures but with an acceptable perioperative risk. The second procedure should be limited to wedge resection. The prognosis is poor for patients with N2 status and for those treated by second surgery earlier than 12 months after the first procedure.

Serum p53 antibodies in small cell lung cancer: the lack of prognostic relevance

Prognostic relevance of serum p53 antibodies was assessed in 96 patients with microscopically proven small cell lung cancer (SCLC). The study group included 67 males and 29 females; mean age 58 years; range 35--86 years; 60 with limited disease (LD), and 36 with extensive disease (ED). The control group consisted of 41 patients with non-malignant diseases. The presence of p53 antibodies was assayed by the immunoenzymatic method (P53 ELISA kit, PharmaCell, France). Antibodies were present in 26 SCLC cases (27%); 15 (25%) in LD and 11 (31%) in ED. Antibodies were also found in one out of 41 control subjects (2%). There was no correlation between the level of antibodies and clinical characteristics of SCLC patients including age, gender and extent of disease. The median follow-up for the entire group was 30 months (range: 11--39 months). By the time of analysis, 78 patients (82%) had deceased. Median survival in SCLC patients with and without antibodies was 42 and 39 weeks, respectively (log rank, P=0.81). These results indicate the lack of clinical relevance of serum p53 antibodies in SCLC.

Non-intubated thoracic surgery-A survey from the European Society of Thoracic Surgeons.

BACKGROUND A survey amongst the European Society of Thoracic Surgeons (ESTS) members has been performed to investigate the currents trends, rates of adoption as well as potential for future expansion of non-intubated thoracic surgery (NITS) performed under spontaneous ventilation. METHODS A 14-question-based questionnaire has been e-mailed to ESTS members. To facilitate the completion of the questionnaire, questions entailed either quantitative or multiple-choice answers. Investigated issues included previous experience with NITS and number of procedures performed, preferred types of anesthesia protocols (i.e., thoracic epidural anesthesia, intercostal or paravertebral blocks, laryngeal mask, use of additional sedation), type of procedures, ideal candidates for NITS, main advantages and technical disadvantages. Non-univocal answer to multiple-choice questions was permitted. RESULTS Out of 105 responders, 62 reported an experience with NITS. The preferred types of anesthesia were intercostal blocks with (59%) or without (50%) sedation, followed by laryngeal mask with sedation (43%) and thoracic epidural anesthesia with sedation (20%). The most frequently performed procedures included thoracoscopic management of recurrent pleural effusion (98%), pleural decortication for empyema thoracis and lung biopsy for interstitial lung disease (26% each); pericardial window and mediastinal biopsy (20% each). More complex procedures such as lobectomy, lung volume reduction surgery and thymectomy have been performed by a minority of responders (2% each). Poor-risk patients due to co-morbidities (70%) and patients with poor pulmonary function (43%) were considered the ideal candidates. Main advantages included faster, recovery (67%), reduced morbidity (59%) and shorter hospital stay with decreased costs (43% each). Reported technical disadvantages included coughing (59%) and poor maneuverability due to diaphragmatic and lung movements (56%). Overall, 69% of responders indicated that NITS procedures will be likely to increase in the near future. CONCLUSIONS Results of this survey, suggest that NITS is already quite widely adopted by ESTS members to perform simple thoracoscopic procedures. A future expanded adoption of this strategy is also hypothesized.

Lung cancer in situs inversus totalis (SIT) - literature review

We present 21 studies of cases of lung cancer in patients with situs inversus totalis (SIT) published worldwide. The first case was described in 1952. Thirteen patients were from Japan, 4 from Eastern Europe, including 2 Polish cases from the authors` center (Department of Thoracic Surgery, Pomeranian Medical University in Szczecin, Poland), 2 from Western Asia, 1 from the U.S. and 1 from Australia. Male patients (20/21) as well as left-sided lung cancer cases (14/21) and squamous cell carcinoma cases (8/21) dominated in the entire group. Thirteen patients underwent surgical treatment. There were 10 left-sided and 3 right-sided surgical interventions with uneventful intra- and postoperative course. Explorative thoracotomy was performed in one case only on the right side. Upper lobectomy was performed in 5 cases, pneumonectomy in 3 cases, lower bilobectomy and middle lobectomy in one case and lower lobectomy in two cases. Surgery was performed through thoracotomy in 10 cases, VATS-assisted approach in two cases and sternotomy in one case. Descriptions of the surgical anatomy confirmed mirror image of the anatomy in all cases and were consistent with the preoperative CT images. Preoperative diagnosis was discussed including the role of 3-D reconstruction of CT for improving perioperative safety in this group of patients. In conclusion, lung cancer/SIT cases despite inversed but regular anatomy can be operated on radically as cases with normal anatomy with preservation of intraoperative security level.