Assessment and Optimisation of Lung Cancer Patients for Treatment with Curative Intent.

Over the past decade the field of lung cancer management has seen many developments. Coupled with an ageing population and increasing rates of comorbid illness, the work-up for treatments with curative intent has become more complex and detailed. As well as improvements in imaging and staging techniques, developments in both surgery and radiotherapy may now allow patients who would previously have been considered unfit or not appropriate for treatment with curative intent to undergo radical therapies. This overview will highlight published studies relating to investigation and staging techniques, together with assessments of fitness, with the aim of helping clinicians to determine the most appropriate treatments for each patient. We also highlight areas where further research may be required.

Synchronous pleuro - renal solitary fibrous tumors: a new clinical-pathological finding.

Solitary fibrous tumors of the pleura (SFTP) are rare mesenchymal neoplasms usually originating from the visceral pleura, but sometimes found in other sites like the orbit, dura, paranasal sinus, upper respiratory tract, thyroid, sublingual gland, lung, periosteum, cauda equina, ovary, scrotum and testicular tunica vaginalis. Solitary fibrous tumor of the kidney is extremely rare with fewer than 15 reported cases in modern English literature. To the best of our knowledge, this report describes the first known case of synchronous SFTP in the left parietal pleura and left kidney. The SFTP of the pleura, widely compressing and displacing the left lower lung lobe, was resected via left thoracotomy, whereas the renal SFTP, diagnosed by echo-guided histological biopsy, was closely monitored by computed tomography scan and ultrasound. After a one-year follow-up no recurrence was detected in the left hemithorax and the renal lesion remained stable.

Pneumocephalus after Pancoast's tumor surgery: to be or not to be conservative?

We report a case of a 62-year-old man affected by Pancoast's tumor who developed pneumocephalus 17 days after right upper lobectomy with en bloc resection of the first three ribs and C8-D1 branches of the brachial plexus. The patient complained of aphasia, disorientation and sphincterial release. A chest and brain-CT scan showed a right apical pneumothorax associated with a massive pneumocephalus of the ventricles and of the subarachnoidal spaces. A pneumoperitoneum was also seen. The patient was treated using pleural drainages, Trendelenburg's position and antibiotic therapy. Clinical and radiological remission was achieved after 12 days of additional hospital stay.

A safe and effective method for an immediate bronchopleural fistula repair.

Bronchopleural fistula (BPF) is a well recognized and potentially fatal complication of major thoracic surgery and several strategies regarding its prevention and subsequent management have been described. An immediate BPF occurring intraoperatively after bronchial closure is a rare event and is usually treated by bronchial stump reamputation and/or hand-suture reinforcement by mattress suture, or myoplasty. We report a simple and successful technique, using azygous vein flaps, to repair an intraoperative BPF associated to a small bronchial dehiscence occurred after a right pneumonectomy in a 70-year-old diabetic man receiving induction chemotherapy treatment.

[Technique, results and impact of induction chemotherapy in sleeve lobectomy for lung cancer]. / Tecnica, risultati e ruolo della chemioterapia di induzione nella lobectomia con resezione/anastomosi bronchiale (sleeve).

AIM: The aim of this study was to evaluate the safety of continuous nonabsorbable (3/0 polypropylene) sutures for sleeve lobectomy, and the influence of induction chemotherapy on postoperative outcome in patients with lung malignancies. METHODS: A review of a prospective database of a single surgeon identified 41 consecutive patients who underwent sleeve lobectomy from May 1998 to July 2003. Bronchial reconstruction was done placing two 3/0 polypropylene sutures at the far side of the cartilaginous wall and subsequently fixed. Afterwards, two running sutures were performed in order to obtain a telescopic anastomosis. RESULTS: Twenty-four patients (59%) underwent induction chemotherapy. There were 31 right upper, 3 left lower ''reverse'', and 7 left upper sleeve lobectomies with radical lymph node dissection. Eight patients underwent reconstruction of the pulmonary artery. There were 34 non-small cell lung cancers, 3 limited small cell lung cancers, 1 neuroendocrine large cell carcinoma, and 3 bronchial carcinoid tumors. N2, N1, and N0 diseases were found in 13, 12 and 16 patients, respectively. Post-operative morbidity and mortality were 14.5% (n=6) and 4.8% (n=2) (1 patient, 4%, after induction chemotherapy). The rate of postoperative anastomotic complications was 2.4% (n=1). Late bronchial stenosis developed in 3 cases, but all were successfully medically treated. Twenty-nine patients are still alive, 27 without evidence of disease. The overall 2-year probability of survival (Kaplan-Meier) was 59%. Induction chemotherapy did not influence postoperative morbidity/mortality (chi2 test: P=0.64/P=0.56). CONCLUSIONS: Continuous nonabsorbable suture for sleeve lobectomy is quick and technical easy to perform, with low postoperative morbidity/mortality; induction chemotherapy does not influence postoperative outcome in these patients.

Extended redo sleeve resection for postoperative dehiscence after right upper bronchoplasty.

Complete anastomotic dehiscence after sleeve resection is a dramatic and often fatal event requiring an extremely aggressive and risky treatment; completion pneumonectomy represents the sole effective therapeutic option to rescue the patient, but postoperative mortality after this procedure is high. We report a case successfully treated by extended redo carinal sleeve resection after full bronchial dehiscence. This option should be taken into account in such a complication, mainly in patient with compromised respiratory function.

Fluorodeoxyglucose positron emission tomography improves preoperative staging of resectable lung metastasis.

OBJECTIVE: F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is now a procedure of proven clinical value in the staging of primary lung cancer. This study evaluated the role of PET in the preoperative assessment of resectable lung metastases. METHODS: Eighty-six patients with previously treated malignancy and proven or suspected lung metastases, deemed resectable at computed tomography scan, were investigated with 89 preoperative PET procedures. Primary tumor sites were: gastrointestinal in 32 cases, sarcoma in 13, urologic in 14, breast in 8, head and neck in 7, gynecologic in 5, thymus in 5, other in 5. Seventy lung resections were performed in 68 patients of whom only 54 proved to be lung metastasis, 7 were primary lung tumors, and 9 were benign lesions. RESULTS: In 19 cases (21%) lung surgery was excluded on the basis of PET scan results due to extrapulmonary metastases (11 cases), primary site recurrence (2), mediastinal adenopathy (2), or benign disease (4). All mediastinal node metastases (7 cases) were detected by PET with a sensitivity, accuracy, and negative predictive value for mediastinal staging of 100%, 96%, and 100%, respectively, versus 71%, 92%, and 95% of the computed tomography scan. In the group of patients who underwent lung resection, PET sensitivity for detection of lung metastasis was 87%. CONCLUSIONS: PET scan proved to be a valuable staging procedure in patients with clinically resectable lung metastasis and changed the therapeutic management in a high proportion of cases.

Postpneumonectomy-like syndrome after chemoradiation therapy for lymphoma.

Postpneumonectomy syndrome (PPS) is a rare complication of pneumonectomy due to an excessive mediastinal shift producing compression of the main bronchus or a lobe bronchus on the aorta or the spine. We report an exceptional case in which an extreme mediastinal shift was due to fibrosis and complete atelectasis of the left lung, as a complication of chemoradiation treatment for recurrent mediastinal Hodgkin's lymphoma. This condition, associated with a further recurrence of the disease, indicated a postpneumonectomy-like syndrome.

Fluoro-deoxi-glucose uptake and angiogenesis are independent biological features in lung metastases.

Neoangiogenesis and enhanced glucose metabolism in neoplasms are likely to be activated by the same biochemical stimulus; hypoxia. A correlation between these two parameters has been postulated. The objective of this study was to evaluate the relationship between Fluoro-desoxi-glucose uptake at positron emission tomography scan and angiogenesis in lung metastasis. Fluoro-desoxi-glucose activity, expressed as a standard uptake value, and microvessel intratumoural density, were retrospectively calculated in a series of 43 lung metastasis resected in 19 patients. Primary sites were colorectal cancer in 16 metastases, sarcoma in eight, gynaecological in four and other sites in 15. The correlation between the two parameters was tested by logistic regression and multivariate analysis. Positron emission tomography scan was positive in 17 patients (sensitivity 89%). No correlation was observed between standard uptake value and microvessel intratumoural density in this series of lung metastasis. Positron emission tomography negative and positive nodules presented comparable value of microvessel intratumoural density (12.9 vs 11.3). Standard uptake value was significantly correlated with nodules size and was higher in colon cancer metastasis than in sarcoma ones. Microvessel intratumoural density was independent from nodule size but significantly higher in sarcoma than in colon cancer metastasis. The lack of correlation was confirmed by multivariate analysis after adjustment for tumour type and nodules size. The present study demonstrated that positron emission tomography scan is positive in a high proportion of patients regardless of microvessel density. Glucose uptake and angiogenesis appear to be independent biological features in lung metastasis. This observation may have implications for future antiangiogenic therapies.

Low morbidity of bronchoplastic procedures after chemotherapy for lung cancer.

OBJECTIVE: To evaluate if induction chemotherapy, with or without irradiation, represents an additional risk factor for early and late morbidity and perioperative mortality in bronchoplastic procedures for lung cancers. METHODS: From January 1998 to January 2001, 27 patients underwent a bronchial sleeve resection after induction treatment at the European Institute of Oncology in Milan. They represent 7% of lung cancer resections (387) and 27% of those performed after neoadjuvant treatment (100 cases). Histology was: 17 epidermoid carcinoma, 8 adenocarcinoma and 2 SCLC. Twenty-four patients (89%) received a preoperative cisplatin based polichemotherapy, and three cases (11%) a chemo-radiation therapy. A right sleeve lobectomy or bilobectomy was undertaken in 21 patients (78%) and a left lobectomy in 6 (22%). A resection of tracheal carina was associated in three cases and a vascular resection in 10 (five vena cava and five pulmonary artery). Twelve patients (44%) received adjuvant mediastinal irradiation. Perioperative morbidity of the study group (group 1) was compared with that of patients submitted to sleeve resection without neoadjuvant treatment (group 2), or standard pneumonectomy after induction treatment (group 3). RESULTS: There were no postoperative deaths. A major perioperative complication occurred in two patients (7%) of group 1, one patient of group 2 (3.5%), and four in group 3 (17%). Among patients of the study group, no anastomotic dehiscence or pleural empyema were observed. Only one late anastomotic stricture occurred after postoperative radiation treatment. No significant difference in early and late complication rate was found between the three groups of patients. High rate of complete resection was achieved (93%) in patients of the study group and extent of nodal dissection was similar between sleeve resections and pneumonectomy patients. CONCLUSIONS: Preoperative chemotherapy or combination of chemo-radio therapy is not associated with an additional risk of anastomotic complications in bronco and angioplastic procedures. Parenchyma sparing resection is a valid option for selected patients with locally advanced lung cancer after induction treatment. A longer follow up is necessary to evaluate efficacy of the procedure in term of survival and local control.

Double prosthetic replacement of pulmonary artery and superior vena cava and sleeve lobectomy for lung cancer.

We present a case of double prosthetic replacement of the right pulmonary artery and superior vena cava combined with upper sleeve bi-lobectomy for a limited pT4N1 adenocarcinoma occurring in a patient with poor pulmonary reserve, which, to the best of our knowledge, has never been reported before.

Life-threatening giant mediastinal goiter: a surgical challenge.

Mediastinal goiter is a well known benign disease, usually resectable through a cervical approach with minimal morbidity and mortality. Only occasionally a median sternotomy or a lateral thoracotomy may be required. The present case is worthy of presentation because of the exceptional dimension of the disease and the surgical challenge that it presented. In a 72-year-old woman a large intrathoracic goiter of the right thorax caused a severe dyspnoea due to an important contralateral mediastinal shift with compression of the lung, superior vena cava system and trachea. At surgical exploration, through a cervico-sternotomic approach, the mediastinal structures dislocation and the strong adherences between the anomalous neovascularized capsula of the mass and the surrounding structures, complicated the surgical dissection. An accidental lesion of the innominate artery required its reimplantation on the ascending aorta. An immense mass, was finally removed and pathological examination revealed a rare case of neovascularized, pseudosarcomatoid capsula among a benign hyperplastic proliferation. In spite of its benign nature, a giant goiter caused a life-threatening compression of the respiratory tract and lung parenchyma in this patient. The dimension of the lesions, the mediastinal anatomy alterations and the severe intraoperative haemorrhage represented major technical difficulties during surgical resection.

The bilobectomies for lung cancer.

BACKGROUND: The purpose of our retrospective study is to confirm that bilobectomy is a feasible operation with an oncological value. METHODS: From 1981 to 1998, 46 patients underwent bilobectomy for lung cancer. Eight upper and middle lobectomies (UML) and 38 middle and lower lobectomies (MLL) were performed. Intraoperative pneumoperitoneum was done in 11 MLL. We have considered operative mortality, postoperative complications, the persistence of drainage tubes and the length of hospital stay and the data were statistically compared with those relative to right lobectomies. Survival was estimated with the Kaplan-Meier method and the curves were compared with those of the right lobectomies and right pneumonectomies using the log-rank test. RESULTS: Overall morbidity was 43.4%. Mortality was 6.5%. Mean chest tube persistence was 7.8 days and mean hospital stay was 14 days. No statistical significance was found about these data comparing the UML and MLL separately and the bilobectomies with the right lobectomies. The pneumoperitoneum done in the MLL enabled a shorter hospital stay, statistically significant, in comparison with MLL without pneumoperitoneum. The overall 5-year survival rate was 38%. Considering the I and the II stages no statistical differences in survival were found considering the right lobectomies and right pneumonectomies. CONCLUSIONS: The bilobectomies can have a role in treatment of lung cancer that is equal to the other standard major resections.

Pulmonary epithelial-myoepithelial tumor of unproven malignant potential: report of a case and review of the literature.

Epithelial-myoepithelial tumors of the lung are rare neoplasms whose biological behavior and clinical course still remain to be defined. A case of epithelial-myoepithelial tumor of the lung arising from bronchial mucosa-submucosa and occurring as a polypoid lesion of the upper left bronchus in a 47-year-old man is reported. The tumor did not infiltrate the cartilaginous wall of the bronchus and showed a biphasic histological appearance with a double layering of epithelial and myoepithelial cells. Myoepithelial spindle cells with eosinophilic cytoplasm were also observed. Mitotic figures were very rare and necrosis absent. Immunohistochemical study for epithelial and muscular markers confirmed the presence of a double-cell component in the tumor, namely epithelial and myoepithelial. The patient is alive and well, with no evidence of recurrent or metastatic disease 6 months after surgery. On the basis of the present case and the six previously reported cases, we suggest using the noncommittal term pulmonary epithelial-myoepithelial tumor of unproven malignant potential (PEMTUMP) for this type of neoplasm. In addition, we first introduce p63 as a novel marker for highlighting the myoepithelial cells of the respiratory tract and speculate on the role of these cells in the development of this unusual tumor.

Unusually located hydatid cysts miming a pulmonary tumor invaliding the spine.

Hydatid disease is a worldwide encountered zoonosis but at present very rare in Europe, liver and lungs being the most frequently involved sites. Bone involvement is very uncommon and the vertebral spine is the most common site of skeletal involvement (less than 1% overall). We report a case of vertebral hydatid disease with secondary pleuro-pulmonary involvement successfully treated by emergency spinal decompression followed by lung resection en bloc with chest wall and partial vertebrectomy.

Cardiac dislocation after extended pneumonectomy with pericardioplasty.

Two cases of cardiac dislocation occurred after intrapericardial right pneumonectomy with extended pericardiectomy and radical nodal dissection in spite of proper reconstruction with a pericardial fat flap in one case and with a Gore-tex prosthesis in the other. In the case of major pericardial excision resulting in extensive mobilisation of the SVC a complete reconstruction of pericardium and mediastinal pleura is recommended in order to prevent cardiac dislocation.

Cisplatin and vinorelbine as second-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) resistant to taxol plus gemcitabine.

The aim of the study was to evaluate the activity of cisplatin (CDDP) plus vinorelbine (VNR) in patients with advanced non-small cell lung cancer (NSCLC) progressing after paclitaxel plus gemcitabine. Treatment consisted of CDDP 80 mg/m(2) administered on day 1 and VNR 25 mg/m(2) administered on day 1 and 8, repeated every 3 weeks. Nine patients who relapsed after partial response and eight patients refractory to prior CT received a minimum of two treatment cycles: three patients achieved a PR (18%; 95% CI: 4-43%), four had stable disease and 10 had disease progression. All responses were observed among the nine patients responsive to prior treatment. Median survival was 35 weeks. No patients required dose-reduction, treatment discontinuation or delay because of toxicity. Our results indicate a reasonable antitumor efficacy and no relevant toxicity of a second-line CDDP-based chemotherapy in patients with advanced NSCLC. We recommend the use of this regimen for patients not refractory to primary treatment.

GSTM1, P53 and K-ras molecular detection in resectable non-small cell lung cancer by denaturing gradient gel electrophoresis-bronchoalveolar lavage fluid analysis.

BACKGROUND: Understanding molecular abnormalities could potentially lead to novel investigational approaches in the molecular epidemiology of lung cancer. These might include the identification of patients at high risk for primary NSCLC and the surveillance of patients with known NSCLC who are being treated using lung-sparing surgical strategies. MATERIALS AND METHODS: The PCR-Denaturing Gradient Gel Electrophoresis (DGGE) strategy was used for primary tumors and corresponding bronchalveolare lavage (BAL) samples. RESULTS: We recruited 36 consecutive patients with NSCLC, 28 (77.7%) males and 8 females (22.3%). DGGE showed a good rate of accuracy in the genetic screening of K-ras and p53 mutations in BAL specimens. Specific mutations were more often detected in BAL fluid from patients with not peripheral tumors than parenchymal or peripheral tumors (p53: 85.7%, p=0.0004; K-ras: 75%, p=0.001). p53 mutations were more frequent in BAL fluid from squamous cell carcinomas (22%) than from adenocarcinomas (15%). A significant correlation was observed between null GST-Ml genotype and p53 overall mutations (p=0.0003), K-ras mutations (p=0.02), non peripheral tumors (p=0.04) and smoking habits (p=0.002). CONCLUSIONS: We observed that null GSTMl genotype is strongly related to p53 mutations. Individuals at high risk for primary NSCLC, such as heavy smokers or individuals exposed to occupational carcinogens, could be screened by BAL-analysis for cancer biomarkers of susceptibility like GSTM-1 in large scale molecular epidemiology studies.