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1.
Updates Surg ; 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38691329

ABSTRACT

This is a case involving a 3-year-old child who presented with an iatrogenic left subclavian/innominate vein lesion, leading to severe bleeding and intravascular catheter rupture during its removal. We successfully performed a very challenging and minimally invasive repair of the vein, along with the removal of the catheter entrapped in the innominate vein.

2.
Updates Surg ; 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38421567

ABSTRACT

The replacement of the superior vena cava and thoracic outlet vessels for thoracic malignancies often becomes necessary for radical oncological surgery. The pulmonary artery can be directly infiltrated by the tumor or affected by metastatic hilar lymph nodes. In some cases, it must be resected and reconstructed to achieve oncological radicality and/or avoid pneumonectomy. This study reflects a single-surgeon, retrospective experience spanning 6 years (2017-2023). We reviewed data from patients undergoing early anticoagulant therapy after superior vena cava or thoracic outlet vessels bypass and from patients undergoing early antiaggregation therapy following pulmonary artery reconstruction or resection. This series comprises 41 patients treated by a single surgeon. Fourteen patients underwent superior vena cava and thoracic outlet vessel procedures. Among these, eight patients received superior vena cava replacement (six for thymic malignancies and two for lung cancer), and six patients underwent jugular and subclavian artery/vein resection or replacement (all six had sarcomas). There was one death due to respiratory failure, not associated with bleeding or bypass closure. Additionally, there was one graft closure in a patient with severe coagulopathy and three instances of hemothorax (two patients had undiagnosed complex coagulopathies not evident in pre-operative routine blood tests). Following bleeding incidents, anticoagulation was initiated the next day in one case and based on hematological indications in the two coagulopathic patients. In the pulmonary artery series, 27 patients were involved: 20 underwent direct suture after tangential resection, and 7 received pericardial patch reconstruction. Only one case experienced bleeding necessitating redo-surgery. All these patients received early and chronic antiaggregation therapy after pulmonary artery reconstruction. We conclude that major thoracic oncological vascular surgery is safe and feasible with appropriate technical skills. However, achieving optimal results requires integration with correct early anticoagulant therapy or antiaggregation to maintain the patency of bypasses/grafts and prevent life-threatening risks associated with closure of the "new vessels."

3.
Updates Surg ; 76(2): 641-646, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38007402

ABSTRACT

Reducing morbidity, length of hospital stay, and readmission rate are of paramount importance to improve patients' care. In the present paper, we aim to describe our experience in managing major oncologic thoracic surgery in clinical practice. This is a retrospective experience over the last 7 years. Data from 215 consecutive patients (performed by a single-team of two surgeon) undergoing thoracic surgery were reviewed and evaluated. The total hospital mean stay was 3,3 days. Complications were represented by 4 hemothorax, 1 pleural empyema without fistula, 3 arrhythmias (atrial fibrillation), 2 pnuemonias and 1 chylotorax. No 30-day severe surgery-related complication occurred, no mortality. In 169 Vats procedures, no convertion was necessary. We conclude that a united team work represented by two close-knit surgeons, with similar clinical background, propensity to share problems, no competitive behavior, allow to do faster surgery, to standardize the procedure improving the post-operative outcomes of cancer patients.


Subject(s)
Empyema, Pleural , Fistula , Surgeons , Humans , Retrospective Studies , Thoracic Surgery, Video-Assisted/adverse effects , Thoracic Surgery, Video-Assisted/methods , Empyema, Pleural/etiology , Empyema, Pleural/surgery , Length of Stay , Treatment Outcome
4.
Updates Surg ; 75(5): 1093-1102, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37402065

ABSTRACT

The extension of chest wall resection for the treatment of primary and secondary tumours is still widely debated. The reconstructive strategy after extensive surgery is challenging as well as chest wall demolition itself. Reconstructive surgery aims to avoid respiratory failure and to guarantee intra-thoracic organs protection. The purpose of this review is to analyse the literature on this issue focusing on the planning strategy for chest wall reconstruction. This is a narrative review, reporting data from the most interesting studies on chest wall demolition and reconstruction. Representative surgical series on chest wall thoracic surgery were selected and described. We focused to identify the best reconstructive strategies analyzing employed materials, techniques of reconstruction, morbidity and mortality. Nowadays the new "bio-mimetic" materials in "rigid" and "non-rigid" chest wall systems reconstructive represent new horizons for the treatment of challenging thoracic diseases. Further prospective studies are warranted to identify new materials enhancing thoracic function after major thoracic excisions.


Subject(s)
Plastic Surgery Procedures , Thoracic Surgical Procedures , Thoracic Wall , Humans , Thoracic Wall/surgery , Thoracic Wall/pathology
5.
Tumori ; 107(3): 261-266, 2021 Jun.
Article in English | MEDLINE | ID: mdl-32458749

ABSTRACT

BACKGROUND: Three-dimensional (3D) vision systems are available for video-assisted thoracic surgery (VATS). It is unclear whether 3D-VATS is superior to bidimensional (2D) VATS systems. METHODS: We analyzed patients who received 3D-VATS (n = 171) or 2D-VATS (n = 228) lobectomy in a single institutional retrospective comparative study of 399 patients with resectable lung cancer conducted from June 2012 to December 2017. The operative and perioperative data were compared between the 2 groups. RESULTS: Operative time, length of hospital stay, number of dissected lymph nodes, and rate of postoperative complications were similar in both groups. In the 3D group, there was no conversion to thoracotomy for intraoperative major vascular injuries, while conversion to an open procedure for uncontrolled bleeding was recorded in 4 (1.7%) patients in the 2D group. Reoperation for hemostasis and/or aerostasis occurred in 6 (2.6%) patients of the 2D group (p = 0.04). CONCLUSION: Nonrandomized comparison of different surgical approaches is challenging. In our experience, 3D-VATS was safe and effective and offered excellent operative perception and sensitivity, enabling safer dissection of hilar structures. The 3D-VATS system helped skilled surgeons beyond the boundaries of more oncologically aggressive surgery.


Subject(s)
Lung Neoplasms/diagnosis , Thoracic Surgery, Video-Assisted/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Imaging, Three-Dimensional/methods , Length of Stay , Lymph Node Excision/methods , Male , Middle Aged , Operative Time , Pneumonectomy/methods , Postoperative Complications/diagnosis , Reoperation/methods , Retrospective Studies , Thoracotomy/methods , Treatment Outcome
6.
J Thorac Dis ; 11(3): 1022-1030, 2019 Mar.
Article in English | MEDLINE | ID: mdl-31019792

ABSTRACT

The extra-pleural pneumonectomy (EPP) is a standardised surgical procedure born for pleural tuberculosis and later used in pleural cancer treatment, especially in malignant pleural mesothelioma (MPM). This systematic review aimed to focus on the actual overall EPP role in surgical oncology. The literature search was performed from January 1985 to January 2018 In PubMed, Embase, and Cochrane according to PRISMA protocol. The search was restricted to publications in English with the research words "extrapleural pneumonectomy", "malignant pleural mesothelioma", "pleural malignancies". The results were then filtered focusing only on papers with series of patients treated with EPP, for mesothelioma and non-mesothelioma malignancies. The search was restricted to publications in English. We found a 5-year overall survival (OS) ranging from 0 to 78%. The peri-operative mortality and morbidity ranged from 0 to 11.8% and 0 to 82.6%, respectively. The most represented and described post-operative complications reported were ARDS, pericardial tamponade, cardiac herniation, pulmonary embolism, respiratory infections, respiratory failure, atrial arrhythmia, myocardial infarction. In referral centres and selected patients, EPP is a cytoreductive or radical surgical treatment in extended pleural malignancies. Prospective studies are needed to standardise the timing of the procedure in a multimodality treatment program, according to the oncological and functional indications, to keep an acceptable complications rate and post-operative quality of life status.

8.
Tumori ; 100(3): 259-64, 2014.
Article in English | MEDLINE | ID: mdl-25076235

ABSTRACT

AIMS: This randomized trial evaluated the feasibility and safety of thulium 2010-nm laser to perform anatomic lung resections in patients with incomplete fissures, as compared to mechanical staplers with or without sealants. STUDY DESIGN: Seventy-two patients scheduled for segmentectomy or lobectomy were enrolled. After intraoperative confirmation of the extent of resection and incomplete fissures (Craig type 2, 3 or 4), they were randomized and allocated to one of the following arms: laser resection by thulium (group A) or standard resection with mechanical staplers with or without sealants (group B). The primary endpoints of the study included analysis of intraoperative and postoperative course, and costs. RESULTS: Thirty-eight patients were assigned to group A (32 lobectomies, 6 segmentectomies) and 34 to group B (31 lobectomies, 3 segmentectomies). No 30-day mortality was observed. Median operative times were 145.0 minutes (group A) and 142.5 minutes (group B, P = 0.83). The median time to drainage removal was 5 days (group A) and 4 days (group B), while the median length of hospital stay was the same (7 days). Prolonged air leaks >7 days were observed in 12 patients of group A (32%) and 10 patients of group B (29%, P = 0.46). Unpredictable late pneumothorax occurred in 3 patients of group A (2 readmissions, need for 1 repeat thoracotomy). Cost analysis demonstrated an intraoperative advantage for group A (mean 807 ± 212 euro) versus group B (mean 1,047+/-276 euro, P <0.0001), but the differences in total costs could be due to chance (P = 0.83). CONCLUSIONS: The use of laser to complete fissures can lead to late pneumothorax, even in the absence of postoperative air leaks. Moreover, the use of laser to complete fissures did not prove to reduce overall costs. Trial Registration Identification Number: 41/10 (IRB00001457 - FWA00001798 - IORG0001063).


Subject(s)
Laser Therapy/adverse effects , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Pneumonectomy/methods , Pneumothorax/etiology , Surgical Staplers , Thulium/therapeutic use , Aged , Aged, 80 and over , Drainage , Feasibility Studies , Female , Humans , Italy/epidemiology , Kaplan-Meier Estimate , Laser Therapy/economics , Lung Neoplasms/economics , Male , Middle Aged , Operative Time , Patient Safety , Pneumonectomy/economics , Pneumothorax/epidemiology , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Prospective Studies , Surgical Staplers/economics , Time Factors , Treatment Outcome
9.
Eur J Cardiothorac Surg ; 46(1): 137-9, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24179094

ABSTRACT

Many surgical procedures are used to restore the defect of the alimentary tract after cervical oesophagectomy. We present a case of a 69-year old woman, affected by a G2 squamous cell carcinoma of retro-cricodeal hypopharynx extend to the cervical oesopaghus. She underwent a direct reconstruction with a direct trans-oral anastomosis by a mechanical device and without any interposition. No postoperative complication was observed and there was a good functional result at 24 months after surgery. In a few selected cases, this technique can be usefully performed, avoiding gastric or intestinal resection and improving the quality of life.


Subject(s)
Anastomosis, Surgical/methods , Esophagectomy/methods , Esophagus/surgery , Tongue/surgery , Aged , Carcinoma, Squamous Cell/surgery , Esophageal Neoplasms/surgery , Female , Humans , Hypopharyngeal Neoplasms/surgery , Laryngectomy , Pharyngectomy , Suture Techniques
10.
Eur Respir J ; 40(1): 177-84, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22267755

ABSTRACT

Nonsmall cell lung cancer samples from the European Early Lung Cancer biobank were analysed to assess the prognostic significance of mutations in the TP53, KRAS and EGFR genes. The series included 11 never-smokers, 86 former smokers, 152 current smokers and one patient without informed smoking status. There were 110 squamous cell carcinomas (SCCs), 133 adenocarcinomas (ADCs) and seven large cell carcinomas or mixed histologies. Expression of p53 was analysed by immunohistochemistry. DNA was extracted from frozen tumour tissues. TP53 mutations were detected in 48.8% of cases and were more frequent among SCCs than ADCs (p<0.0001). TP53 mutation status was not associated with prognosis. G to T transversions, known to be associated with smoking, were marginally more common among patients who developed a second primary lung cancer or recurrence/metastasis (progressive disease). EGFR mutations were almost exclusively found in never-smoking females (p=0.0067). KRAS mutations were detected in 18.5% of cases, mainly ADC (p<0.0001), and showed a tendency toward association with progressive disease status. These results suggest that mutations are good markers of different aetiologies and histopathological forms of lung cancers but have little prognostic value, with the exception of KRAS mutation, which may have a prognostic value in ADC.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Genes, erbB-1/genetics , Lung Neoplasms/genetics , Mutation , Proto-Oncogene Proteins/genetics , Tumor Suppressor Protein p53/genetics , ras Proteins/genetics , Female , Follow-Up Studies , Genes, p53/physiology , Humans , Immunohistochemistry , Male , Prognosis , Proto-Oncogene Proteins p21(ras) , Smoking , Survival Analysis , Tumor Suppressor Protein p53/metabolism
11.
Tumori ; 97(5): 34e-5e, 2011.
Article in English | MEDLINE | ID: mdl-22158508

ABSTRACT

Giant cell tumor is an unusual neoplasm of the ribs. Herein is presented the case of a patient with an abdominal wall mass, which turned out to be a giant cell tumor of the 11th rib. This is a very uncommon site for a giant cell tumor, which also had a peculiar shape. No other similar case has been reported in the medical literature.


Subject(s)
Bone Neoplasms/diagnosis , Giant Cell Tumor of Bone/diagnosis , Ribs/pathology , Bone Neoplasms/pathology , Bone Neoplasms/surgery , Giant Cell Tumor of Bone/pathology , Giant Cell Tumor of Bone/surgery , Humans , Male , Middle Aged , Ribs/surgery
12.
Ann Thorac Surg ; 92(4): 1208-15; discussion 1215-6, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21958766

ABSTRACT

BACKGROUND: Sternal tumors represent a rare subgroup of chest wall neoplasms in which indication, surgical issues, and long-term results are rarely reported. Thus, in this study we reevaluated our experience in sternal replacement from a series of 101 consecutive cases during the last 30 years. METHODS: Clinical records of patients who underwent sternal resection between January 1980 and December 2008 were reviewed. The technique of reconstruction after sternectomy varied over time, including mesh replacement in 52 patients (group A), rigid prosthesis in 27 patients (group B), and the "rib-like" technique, a semi-rigid tridimensional prosthesis reproducing the shape of native ribs, in 22 patients (group C). Postoperative outcomes and long-term survival were analyzed. RESULTS: Of 101 patients, 42 underwent resection for primary chest wall tumors, 30 for breast cancer, 15 for locally advanced tumors, 11 for metastatic disease, and 3 for benign disease. One patient died postoperatively. The overall major complications rate was similar between groups. Local infection required prosthetic removal in 7 patients of groups A and B (9%). No infection occurred in group C (p = 0.02). Median survival exceeded 60 months for primary sternal tumors and 22 months for other cancer (p = 0.01). The worst survival was recorded in radioinduced sarcoma (17 months) and in patients who underwent previous resection before salvage sternectomy (18 months). CONCLUSIONS: Results from this study showed that an adequate sternal resection should be done at the first operation and that improving prosthetic integration with surrounding tissues may reduce the local complication rate.


Subject(s)
Bone Neoplasms/surgery , Plastic Surgery Procedures/methods , Prosthesis Implantation/methods , Sarcoma/surgery , Sternotomy/methods , Sternum/surgery , Bone Neoplasms/diagnosis , Bone Neoplasms/mortality , Disease-Free Survival , Female , Follow-Up Studies , Humans , Italy/epidemiology , Male , Middle Aged , Prosthesis Design , Retrospective Studies , Ribs , Sarcoma/diagnosis , Sarcoma/mortality , Survival Rate/trends , Treatment Outcome
13.
Ann Thorac Surg ; 90(6): 2065-7, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21095375

ABSTRACT

Diaphragmatic plication is usually obtained by suturing the entire dome, which can be laborious when an anterior approach is used. The same result can be obtained by anchoring the redundant diaphragm to the anterior costal arch maneuver, which resembles the action of reefing the mainsail on the boom of a sailboat. Radiologic results have been analyzed from a series of 10 consecutive patients who underwent mediastinal surgery with phrenic nerve section. One week after surgery, no patient had an eventrated diaphragm on lateral chest roentgenogram. No lower lobe atelectasis was recorded in the series until discharge. This technique represents an alternative to classic diaphragmatic plication with three main advantages: (1) it does not require suturing of the posterior part of the dome, which can be difficult to reach when an anterior approach (sternotomy or hemi-clamshell) is used; (2) the presence of three sequential steps, which progressively increases diaphragmatic stretching and permits adjusting the tension of the dome; and (3) the possibility of standard plication is not precluded.


Subject(s)
Diaphragm/surgery , Diaphragmatic Eventration/surgery , Suture Techniques , Thoracic Surgical Procedures/methods , Humans , Retrospective Studies , Treatment Outcome
14.
Eur J Cardiothorac Surg ; 37(4): 764-9, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19939694

ABSTRACT

BACKGROUND: After superior vena cava (SVC) resection, the need for reconstruction varies among tangential resection, pericardial patch repair and prosthetic replacement. Patients undergoing complete prosthetic replacement often require a different surgical approach, intra-operative SVC cross-clamping and anticoagulation when polytetrafluoroethylene (PTFE) prosthesis is used. This study tested the hypothesis that PTFE replacement may interfere with perioperative outcome. MATERIALS AND METHODS: Clinical records from a series of 72 consecutive SVC resections performed between 1998 and 2008 were reviewed. Complications were classed into five categories: surgical, respiratory, cardiac, SVC system thrombosis and nerve damage. Each category of postoperative complications was considered as an outcome variable in a univariate analysis testing 12 covariates as risk factors. Covariates considered clinically relevant or statistically significant were included in the multivariate model. RESULTS: During the considered period, 28 patients underwent total SVC resection with PTFE prosthetic replacement and 44 patients underwent SVC repair by the use of direct running suture (nine patients), stapling (30 patients) or autologous pericardial patch (five patients). Two patients died postoperatively (2.8%). Major complications were mainly due to respiratory failure, which occurred in nine cases (acute respiratory failure in five cases, recurrent atelectasis in three cases, acute respiratory distress syndrome (ARDS) in one case). In terms of overall mortality and morbidity, univariate analysis did not confirm a detrimental effect of SVC replacement as compared with SVC repair, as major postoperative complications occurred in similar proportion in both groups (respectively, 6/28, 21.4% vs 7/44, 15.9%, p=0.54). No other risk factor was identified by univariate analysis. CONCLUSIONS: Complete prosthetic replacement does not increase overall postoperative morbidity in patients undergoing SVC resection and can be safely performed when other reconstruction techniques preclude sufficient tumour-free resection margin or compromise adequate blood flow.


Subject(s)
Blood Vessel Prosthesis Implantation/adverse effects , Lung Neoplasms/surgery , Mediastinal Neoplasms/surgery , Vena Cava, Superior/surgery , Blood Vessel Prosthesis , Blood Vessel Prosthesis Implantation/methods , Epidemiologic Methods , Female , Humans , Lung Neoplasms/pathology , Male , Mediastinal Neoplasms/pathology , Middle Aged , Neoplasm Invasiveness , Patient Selection , Polytetrafluoroethylene , Postoperative Complications , Respiration Disorders/etiology , Surgical Stapling , Sutures , Treatment Outcome , Vena Cava, Superior/pathology
16.
Am J Respir Crit Care Med ; 179(5): 396-401, 2009 Mar 01.
Article in English | MEDLINE | ID: mdl-19096006

ABSTRACT

RATIONALE: Fragile histidine triad (FHIT) is a tumor suppressor gene involved in the pathogenesis of lung cancer. OBJECTIVES: The purpose of this study was to investigate the different molecular alterations leading to the inactivation of FHIT gene function and to validate their use as biomarkers of risk for progression of the disease in patients belonging to the multicentric European study for the Early detection of Lung Cancer (EUELC) who were resected for early-stage lung tumors. METHODS: FHIT immunostaining was performed on 305 tumor samples. The methylation status of FHIT promoter was assessed by nested methylation-specific polymerase chain reaction (MSP-PCR) in 232 tumor and 225 normal lung samples of which a subset of 187 patients had available normal/tumor DNA pairs. Loss of heterozygosity (LOH) at the FHIT locus was analyzed in 202 informative cases by D3S1300 and D3S1234 microsatellite markers. MEASUREMENTS AND MAIN RESULTS: Lost or reduced FHIT expression was found in 36.7 and 75.7% of the tumor samples, respectively. Methylation of the FHIT promoter was found in 36.7% of tumor and 32.7% of normal lung samples, whereas LOH was detected in 61.9% of the tumors. A strong association with complete loss of FHIT expression was present when methylation and LOH were analyzed together (P = 0.0064). Loss of FHIT protein expression was significantly more frequent in squamous cell carcinoma histotype (P < 0.0001) and in smokers (P = 0.008). FHIT methylation in normal lung was associated with an increased risk of progressive disease (OR, 2.27; P = 0.0415). CONCLUSIONS: Our results indicate that different molecular mechanisms interplay to inactivate FHIT expression and support the proposition that FHIT methylation in normal lung tissue could represent a prognostic marker for progressive disease.


Subject(s)
Acid Anhydride Hydrolases/genetics , Biomarkers, Tumor/genetics , Genes, Tumor Suppressor , Lung Neoplasms/genetics , Neoplasm Proteins/genetics , Acid Anhydride Hydrolases/biosynthesis , Aged , Biomarkers, Tumor/biosynthesis , Case-Control Studies , DNA Methylation , Disease Progression , Female , Gene Expression Regulation, Neoplastic , Gene Silencing , Humans , Loss of Heterozygosity , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Proteins/biosynthesis , Polymerase Chain Reaction , Promoter Regions, Genetic , Risk Assessment
17.
Ann Thorac Surg ; 80(6): 1994-2000, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16305831

ABSTRACT

BACKGROUND: We designed and assessed a new TNM staging system (herein called the INT [Istituto Nazionale Tumori] system) for thymic epithelial tumors in order to overcome the perceived drawbacks of Masaoka's system, which represents the current standard. METHODS: In all, 123 cases were evaluated. The histologic types according to the World Health Organization (WHO) classification were as follows: subtype A: 5 cases; AB: 40; B1: 16; B2: 29; B3: 16; and C: 17 cases. There were 45 Masaoka's stage I, 33 stage II, 26 stage III, and 19 stage IV cases. A total of 11 INT definitions were grouped into three stages: locally restricted disease (75 cases), which included Masaoka's stage I and selected stage II cases (no pleural invasion); locally advanced disease (37 cases), which included Masaoka's stage III cases plus those staged II owing to pleural invasion and those staged IV owing to intrathoracic nodal or limited pleuropericardial involvement; and systemic disease (11 cases), which included the remaining Masaoka's stage IV cases. RESULTS: Completeness of resection, WHO types, and both staging systems were significant prognostic factors (p < 0.0001) on univariate analysis. The 95-month progression-free survival rates according to Masaoka's system were stage I: 100%; II: 93.6%; III: 46.3%; and IV: 23.2%. The INT system corresponding figures were as follows: locally restricted disease: 98.6%; locally advanced disease: 46.9%; and systemic disease: 11.7%. The INT system was the prognostic factor with the greatest impact (p = 0.0218) on multivariate analysis (Masaoka's system: p = 0.2012; completeness of resection: p = 0.6855; histology: p = 0.9386). CONCLUSIONS: The INT system allows finer disease descriptions than Masaoka's system, resulting in a stage grouping with higher prognostic distinctiveness.


Subject(s)
Carcinoma/pathology , Neoplasm Staging/methods , Thymus Neoplasms/pathology , Carcinoma/mortality , Disease-Free Survival , Female , Humans , Male , Middle Aged , Prognosis , Survival Rate , Thymus Neoplasms/mortality
18.
Cancer Res ; 65(4): 1207-12, 2005 Feb 15.
Article in English | MEDLINE | ID: mdl-15735004

ABSTRACT

Chromosomal deletions are often observed in lung cancers suggesting that inactivation of tumor suppressor genes plays an important role in the development of this neoplasm. The region around chromosome 8p22 is a frequent and early target of these deletions and has therefore been investigated for the presence of candidate genes. The FEZ1/LZTS1 gene, located at 8p22, is inactivated in many cancers with 8p deletions, including prostate, esophageal, gastric, bladder, and breast cancer and the Fez1 protein has been shown to suppress growth of cancer cells and to regulate mitosis. To elucidate the role of FEZ1 in lung cancer, we have analyzed its expression by immunohistochemistry in 103 primary lung cancer specimens including 98 non-small cell lung cancers (57 adenocarcinomas, 32 squamous cell carcinomas, 7 large cell carcinomas, and 2 others) and five small cell carcinomas. Absence of Fez1 protein expression was observed in 27 cases (26%) and additional 43 cases (42%) showed strong reduction in immunoreactivity. There was a positive association between loss of FEZ1 expression and tumor grading (P = 0.0345) and a tendency toward a reduction in the mortality rate in subjects with strong FEZ1 expression. Overall, these data indicate an important role for FEZ1 in lung cancer and suggest the possibility that it may serve as a novel prognostic indicator.


Subject(s)
Biomarkers, Tumor/biosynthesis , DNA-Binding Proteins/biosynthesis , Lung Neoplasms/metabolism , Tumor Suppressor Proteins/biosynthesis , Adaptor Proteins, Signal Transducing , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , DNA-Binding Proteins/genetics , Female , Genes, Tumor Suppressor , Humans , Immunohistochemistry , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Middle Aged , Nerve Tissue Proteins , Prognosis , Retrospective Studies , Tumor Suppressor Proteins/genetics
19.
Tumori ; 89(1): 16-9, 2003.
Article in English | MEDLINE | ID: mdl-12729355

ABSTRACT

AIMS AND BACKGROUND: Pathologic complete response in locally advanced non-small cell lung cancer is the main end point of combined therapies (chemotherapy and/or radiotherapy). Surgery after an induction treatment can improve local control, allowing the histologic assessment of treatment activity by means of resection or extensive biopsies. METHODS: Thirty patients surgically assessed without viable tumor after concurrent radiotherapy and continuous infusion of low-dose cisplatin, owing to an initially unresectable stage III non-small-cell lung cancer, were the object of evaluation to assess clinical implications, short- and long-term surgical results. RESULTS: The specificity rate of the preoperative restaging was 36.6%. The surgical procedures consisted of 22 resections and of extensive biopsies in 8 cases. The operative mortality was 4% (1/25) for procedures other than right pneumonectomy (3/5). No patient received postoperative chemotherapy. Eleven distant progressions, 4 local recurrences, and 4 new primary tumors were assessed as initial failures. The 8-year overall survival was 36%. CONCLUSIONS: Pathologic complete response after cisplatin-enhanced radiotherapy cannot be satisfactorily assessed by clinical means. Surgery is required to obtain a reliable evaluation; however, right pneumonectomy should be contraindicated because of prohibitive risk. Although an effective local treatment can cure patients with advanced stage III disease, the addition of chemotherapy seems advisable to improve tumor relapse control.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/radiotherapy , Cisplatin/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Radiation-Sensitizing Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Chemotherapy, Adjuvant , Disease-Free Survival , Female , Humans , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Middle Aged , Neoplasm Staging , Radiotherapy, Adjuvant , Survival Analysis , Treatment Outcome
20.
Clin Cancer Res ; 8(12): 3782-7, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12473590

ABSTRACT

PURPOSE: The p16(INK4A) tumor suppressor gene is inactivated in many solid tumors, including non-small cell lung cancers (NSCLCs), through promoter hypermethylation. Presence of p16(INK4A) hypermethylation in precursor lesions of NSCLC and in body fluids of individuals at risk makes it a potential candidate for early disease detection. However, the current low sensitivity of p16(INK4A) hypermethylation detection in plasma limits its consideration in a diagnostic grid. EXPERIMENTAL DESIGN: A fluorescent methylation-specific PCR assay (F-MSP) was established to evaluate p16(INK4A) promoter hypermethylation in 35 NSCLC and paired plasma samples and in 15 plasmas from healthy donors. F-MSP sensitivity was investigated in combination with microsatellite alterations on 3p (evaluated by fluorescent PCR), K-ras mutations (determined by a mutant-enriched PCR), and quantification of circulating DNA. Assay results were analyzed by two-sided chi(2) or Fisher's exact tests. RESULTS: p16(INK4A) promoter hypermethylation, detectable by F-MSP in 22 of 35 NSLCs (63%) and in 12 of 22 (55%) plasmas from patients with methylated tumors, was independent of microsatellite alterations (detectable in 57% of tumors and 50% of paired plasmas), K-ras mutations (detectable in 31% of tumors but in no paired plasma), or amount of circulating DNA. p16(INK4A) methylation in association with microsatellite alterations identified 62% (18 of 29) of plasma samples from patients presenting the same alteration in their tumors, and its sensitivity increased to 80% when combined with the amount of circulating DNA. CONCLUSIONS: The establishment of F-MSP remarkably improved p16(INK4A) promoter hypermethylation detection in plasmas from NSCLC patients. Microsatellite alterations, circulating DNA quantification, and p16(INK4A) hypermethylation might contribute to a diagnostic grid for NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Cyclin-Dependent Kinase Inhibitor p16/genetics , DNA Methylation , DNA, Neoplasm/blood , Lung Neoplasms/genetics , Promoter Regions, Genetic/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Chromosomes, Human, Pair 3/genetics , Cohort Studies , Female , Genes, ras/genetics , Humans , Lung Neoplasms/pathology , Male , Microsatellite Repeats , Middle Aged , Neoplasm Staging , Polymerase Chain Reaction , Prospective Studies , Survival Rate , Tumor Cells, Cultured
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