5 protein-based signature for resectable lung squamous cell carcinoma improves the prognostic performance of the TNM staging.

INTRODUCTION: Prognostic biomarkers have been very elusive in the lung squamous cell carcinoma (SCC) and none is currently being used in the clinical setting. We aimed to identify and validate the clinical utility of a protein-based prognostic signature to stratify patients with early lung SCC according to their risk of recurrence or death. METHODS: Patients were staged following the new International Association for the Study of Lung Cancer (IASLC) staging criteria (eighth edition, 2018). Three independent retrospective cohorts of 117, 96 and 105 patients with lung SCC were analysed to develop and validate a prognostic signature based on immunohistochemistry for five proteins. RESULTS: We identified a five protein-based signature whose prognostic index (PI) was an independent and significant predictor of disease-free survival (DFS) (p<0.001; HR=4.06, 95% CI 2.18 to 7.56) and overall survival (OS) (p=0.004; HR=2.38, 95% CI 1.32 to 4.31). The prognostic capability of PI was confirmed in an external multi-institutional cohort for DFS (p=0.042; HR=2.01, 95% CI 1.03 to 3.94) and for OS (p=0.031; HR=2.29, 95% CI 1.08 to 4.86). Moreover, PI added complementary information to the newly established IASLC TNM 8th edition staging system. A combined prognostic model including both molecular and anatomical (TNM) criteria improved the risk stratification in both cohorts (p<0.05). CONCLUSION: We have identified and validated a clinically feasible protein-based prognostic model that complements the updated TNM system allowing more accurate risk stratification. This signature may be used as an advantageous tool to improve the clinical management of the patients, allowing the reduction of lung SCC mortality through a more accurate knowledge of the patient's potential outcome.

Perforator Flaps Covering Alloplastic Materials in Full-Thickness Chest Wall Defects Reconstruction: A Safe Option?

Large full-thickness chest wall reconstruction requires an alloplastic material to ensure chest wall stability, as well as a flap that provides good soft-tissue coverage. The choice not to use perforator flaps over any mesh or inert material is often based on the concern that the vascularization would be inadequate. However, perforator flaps have shown good results in several reconstructive fields, minimizing donor-site morbidity and offering versatility when local tissues are unavailable or affected by radiotherapy. In this study, we present 4 cases of patients with full-thickness chest wall defects that were repaired with a double Marlex mesh, acrylic cement (n = 2) or a double patch of Goretex (n = 2) in combination with perforator flaps (3 deep inferior epigastric artery perforators and 1 lumbar artery perforator flap). The results we obtained are encouraging, and we believe the use of perforator flaps in combination with alloplastic materials should be considered as a reliable option for full-thickness chest wall defect reconstruction.

Assessment of indeterminate pulmonary nodules detected in lung cancer screening: Diagnostic accuracy of FDG PET/CT.

BACKGROUND: A major drawback of lung cancer screening programs is the high frequency of false-positive findings on computed tomography (CT). We investigated the accuracy of selective 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (FDG) Positron Emission Tomography/Computed Tomography (PET/CT) scan in assessing radiologically indeterminate lung nodules detected in lung cancer screening. METHODS: FDG PET/CT was performed to characterize 64 baseline lung nodules >10mm and 36 incidence nodules detected on low-dose CT screening in asymptomatic current or former smokers (83 men, age range 40-83 years) at high risk for lung cancer. CT images were acquired without intravenous contrast. Nodules were analyzed by size, density, and metabolic activity and visual scored on a 5-point scale for FDG uptake. Nodules were classified as negative for malignancy when no FDG uptake was observed, or positive when focal uptake was observed in the visual analysis, and the maximum standardized uptake value (SUVmax) was measured. Final diagnosis was based on histopathological evaluation or at least 24 months of follow-up. RESULTS: A total of 100 nodules were included. The prevalence of lung cancer was 1%. The sensitivity, specificity, NPV and PPV of visual analysis to detect malignancy were 84%, 95%, 91%, and 91%, respectively, with an accuracy of 91% (AUC 0.893). FDG PET/CT accurately detected 31 malignant tumors (diameters 9-42mm, SUVmax range 0.6-14.2) and was falsely negative in 6 patients. With SUVmax thresholds for malignancy of 1.5, 2, and 2.5, specificity was 97% but sensitivity decreased to 65%, 49%, and 46% respectively, and accuracy decreased to 85%, 79%, and 78% respectively (AUC 0.872). CONCLUSIONS: The visual analysis of FDG PET/CT scan is highly accurate in characterizing indeterminate pulmonary nodules detected in lung cancer screening with low-dose CT. Semi-quantitative analysis does not improve the accuracy of FDG PET/CT over that obtained with a qualitative method for lung nodule characterization.

Cribado de cáncer de pulmón: catorce años de experiencia del Programa Internacional de Detección Precoz de Cáncer de Pulmón con TBDR de Pamplona (P-IELCAP) / Lung Cancer Screening: Fourteen Year Experience of the Pamplona Early Detection Program (P-IELCAP)

Introducción y objetivos: La experiencia europea en relación con el cribado de cáncer de pulmón con tomografía de baja dosis de radiación (TBDR) es amplia. Sin embargo, la evidencia sobre la experiencia en España es limitada. Nuestro objetivo es presentar los resultados del programa de cribado de cáncer de pulmón más largo de España. Métodos: El Programa Internacional de Detección Precoz de Cáncer de Pulmón con TBDR de Pamplona (P-IELCAP) viene reclutando individuos de manera activa desde el año 2000 siguiendo el protocolo IELCAP. Se incluyen individuos ≥ 40 años de edad, fumadores o ex fumadores (consumo acumulado ≥ 10 paquetes-año). Los resultados se comparan con los de otros estudios europeos. Resultados: Un total de 2.989 participantes fueron reclutados hasta marzo de 2014 (73% varones), realizando una mediana de 2 (IQR 1-3) rondas de cribado por individuo. Se detectaron 60 cánceres de pulmón en 53 participantes (73% en estadio i). Adenocarcinoma fue el tipo histológico más frecuente. La proporción de prevalencia e incidencia de cáncer de pulmón fue del 1,0 y del 1,4%, respectivamente, con una tasa de detección anual de 0,41. La tasa de supervivencia a 10 años de los pacientes con cáncer de pulmón fue del 70%. La enfermedad pulmonar obstructiva crónica y el enfisema son importantes factores de riesgo para desarrollar cáncer de pulmón. Conclusiones: La experiencia del programa de cribado de cáncer de pulmón más largo de España es comparable con lo descrito en el resto de Europa y confirma la viabilidad y la eficacia del cribado mediante TBDR

Introduction and objectives: European experience regarding lung cancer screening using low-dose chest CT (LDCT) is available. However, there is limited data on the Spanish experience in this matter. Our aim is to present the results from the longest ongoing screening program in Spain. Methodology: The Pamplona International Early Lung Cancer Detection Program (P-IELCAP) is actively screening participants for lung cancer using LDCT since year 2000 following the IELCAP protocol, including spirometric assessments. Men and women, ≥ 40 years of age, current or former smokers with a tobacco history of ≥ 10 pack-years are included. Results are compared to those from other European trials. Results: A total of 2989 participants were screened until March 2014 (73% male). A median of 2 (IQR 1-3) annual screening rounds were performed. Sixty lung cancers were detected in 53 participants (73% in Stage I). Adenocarcinoma was the most frequent. The lung cancer prevalence and incidence proportion was 1.0% and 1.4%, respectively, with an annual detection rate of 0.41. The estimated 10-year survival rate among individuals with lung cancer was 70%. Chronic obstructive pulmonary disease and emphysema are important lung cancer predictors. Conclusions: The experience in Spain’s longest lung cancer screening program is comparable to what has been described in the rest of Europe, and confirms the feasibility and efficacy of lung cancer screening using LDCT

Lung cancer screening: fourteen year experience of the Pamplona early detection program (P-IELCAP).

INTRODUCTION AND OBJECTIVES: European experience regarding lung cancer screening using low-dose chest CT (LDCT) is available. However, there is limited data on the Spanish experience in this matter. Our aim is to present the results from the longest ongoing screening program in Spain. METHODOLOGY: The Pamplona International Early Lung Cancer Detection Program (P-IELCAP) is actively screening participants for lung cancer using LDCT since year 2000 following the IELCAP protocol, including spirometric assessments. Men and women, ≥40 years of age, current or former smokers with a tobacco history of ≥10 pack-years are included. Results are compared to those from other European trials. RESULTS: A total of 2989 participants were screened until March 2014 (73% male). A median of 2 (IQR 1-3) annual screening rounds were performed. Sixty lung cancers were detected in 53 participants (73% in StageI). Adenocarcinoma was the most frequent. The lung cancer prevalence and incidence proportion was 1.0% and 1.4%, respectively, with an annual detection rate of 0.41. The estimated 10-year survival rate among individuals with lung cancer was 70%. Chronic obstructive pulmonary disease and emphysema are important lung cancer predictors. CONCLUSIONS: The experience in Spain's longest lung cancer screening program is comparable to what has been described in the rest of Europe, and confirms the feasibility and efficacy of lung cancer screening using LDCT.

A prognostic DNA methylation signature for stage I non-small-cell lung cancer.

PURPOSE: Non-small-cell lung cancer (NSCLC) is a tumor in which only small improvements in clinical outcome have been achieved. The issue is critical for stage I patients for whom there are no available biomarkers that indicate which high-risk patients should receive adjuvant chemotherapy. We aimed to find DNA methylation markers that could be helpful in this regard. PATIENTS AND METHODS: A DNA methylation microarray that analyzes 450,000 CpG sites was used to study tumoral DNA obtained from 444 patients with NSCLC that included 237 stage I tumors. The prognostic DNA methylation markers were validated by a single-methylation pyrosequencing assay in an independent cohort of 143 patients with stage I NSCLC. RESULTS: Unsupervised clustering of the 10,000 most variable DNA methylation sites in the discovery cohort identified patients with high-risk stage I NSCLC who had shorter relapse-free survival (RFS; hazard ratio [HR], 2.35; 95% CI, 1.29 to 4.28; P = .004). The study in the validation cohort of the significant methylated sites from the discovery cohort found that hypermethylation of five genes was significantly associated with shorter RFS in stage I NSCLC: HIST1H4F, PCDHGB6, NPBWR1, ALX1, and HOXA9. A signature based on the number of hypermethylated events distinguished patients with high- and low-risk stage I NSCLC (HR, 3.24; 95% CI, 1.61 to 6.54; P = .001). CONCLUSION: The DNA methylation signature of NSCLC affects the outcome of stage I patients, and it can be practically determined by user-friendly polymerase chain reaction assays. The analysis of the best DNA methylation biomarkers improved prognostic accuracy beyond standard staging.

Investigation of complement activation product c4d as a diagnostic and prognostic biomarker for lung cancer.

BACKGROUND: There is a medical need for diagnostic biomarkers in lung cancer. We evaluated the diagnostic performance of complement activation fragments. METHODS: We assessed complement activation in four bronchial epithelial and seven lung cancer cell lines. C4d, a degradation product of complement activation, was determined in 90 primary lung tumors; bronchoalveolar lavage supernatants from patients with lung cancer (n = 50) and nonmalignant respiratory diseases (n = 22); and plasma samples from advanced (n = 50) and early lung cancer patients (n = 84) subjects with inflammatory lung diseases (n = 133), and asymptomatic individuals enrolled in a lung cancer computed tomography screening program (n = 190). Two-sided P values were calculated by Mann-Whitney U test. RESULTS: Lung cancer cells activated the classical complement pathway mediated by C1q binding that was inhibited by phosphomonoesters. Survival was decreased in patients with high C4d deposition in tumors (hazard ratio [HR] = 3.06; 95% confidence interval [CI] = 1.18 to 7.91). C4d levels were increased in bronchoalveolar lavage fluid from lung cancer patients compared with patients with nonmalignant respiratory diseases (0.61 ± 0.87 vs 0.16 ± 0.11 µg/mL; P < .001). C4d levels in plasma samples from lung cancer patients at both advanced and early stages were also increased compared with control subjects (4.13 ± 2.02 vs 1.86 ± 0.95 µg/mL, P < 0.001; 3.18 ± 3.20 vs 1.13 ± 0.69 µg/mL, P < .001, respectively). C4d plasma levels were associated with shorter survival in patients at advanced (HR = 1.59; 95% CI = 0.97 to 2.60) and early stages (HR = 5.57; 95% CI = 1.60 to 19.39). Plasma C4d levels were reduced after surgical removal of lung tumors (P < .001) and were associated with increased lung cancer risk in asymptomatic individuals with (n = 32) or without lung cancer (n = 158) (odds ratio = 4.38; 95% CI = 1.61 to 11.93). CONCLUSIONS: Complement fragment C4d may serve as a biomarker for early diagnosis and prognosis of lung cancer.

The multimodal management of locally advanced N2 non-small cell lung cancer: is there a role for surgical resection? A single institution's experience.

BACKGROUND: The management of operable locally advanced N2 non-small cell lung cancer (NSCLC) is a controversial topic. Concurrent chemoradiation (CT-RT) is considered the standard of care for inoperable or unresectable patients, but the role of trimodality treatment remains controversial. We present our institution's experience with the management of stage III (N2) NSCLC patients, analyzing whether the addition of surgery improves survival when compared with definitive CT-RT alone. METHODS: From 1996 to 2006, 72 N2 NSCLC patients were treated. Thirty-four patients received cisplatin-based induction chemotherapy, followed by paclitaxel-cisplatin CT-RT, and 38 patients underwent surgery preceded by induction and/or followed by adjuvant therapy. Survival curves were estimated by Kaplan-Meier analysis, and the differences were assessed with the log-rank test. RESULTS: Most of the patients (87 %) were men. The median age was 59 years. A statistically significant association between T3-T4c and definitive CT-RT as well as between T1-T2c and surgery was noted (p < 0.0001). After a median follow-up period of 35 months, the median overall survival (OS) was 42 months for the surgery group versus 41 months for the CT-RT patients (p = 0.590). The median progression-free survival (PFS) was 14 months after surgery and 25 months after CT-RT (p = 0.933). Responders to radical CT-RT had a better OS than non-responders (43 vs. 17 months, respectively, p = 0.011). No significant differences were found in the OS or PFS between the pN0 [14 (37.8 %) patients] and non-pN0 patients at thoracotomy. Three treatment-related deaths (7.8 %) were observed in the surgical cohort and none in the CT-RT group. CONCLUSIONS: The addition of surgery did not render a median OS or PFS benefit when compared with CT-RT alone in our series of stage III-N2 NSCLC patients, in accordance with previously published data. However, responses to CT-RT had a greater impact in terms of OS and PFS. Although the patients selected for management including surgery showed a favorable T clinical staging in comparison to patients exclusively treated with definitive CT-RT, similar survival outcomes were found.

Expression of tumor-derived vascular endothelial growth factor and its receptors is associated with outcome in early squamous cell carcinoma of the lung.

PURPOSE: Antiangiogenic therapies targeting the vascular endothelial growth factor (VEGF) pathway have yielded more modest clinical benefit to patients with non-small-cell lung cancer (NSCLC) than initially expected. Clinical data suggest a distinct biologic role of the VEGF pathway in the different histologic subtypes of lung cancer. To clarify the influence of histologic differentiation in the prognostic relevance of VEGF-mediated signaling in NSCLC, we performed a concomitant analysis of the expression of three key elements of the VEGF pathway in the earliest stages of the following two principal histologic subtypes: squamous cell carcinoma (SCC) and adenocarcinoma (ADC). PATIENTS AND METHODS: We evaluated tumor cell expression of VEGF, VEGF receptor (VEGFR) 1, and VEGFR2 using automatic immunostaining in a series of 298 patients with early-stage NSCLC recruited as part of the multicenter European Early Lung Cancer Detection Group project. A score measuring the VEGF signaling pathway was calculated by adding the tumor cell expression value of VEGF and its two receptors. The results were validated in two additional independent cohorts of patients with NSCLC. RESULTS: The combination of high VEGF, VEGFR1, and VEGFR2 protein expression was associated with lower risk of disease progression in early SCC (univariate analysis, P = .008; multivariate analysis, hazard ratio, 0.62; 95% CI, 0.42 to 0.92; P = .02). The results were validated in two independent patient cohorts, confirming the favorable prognostic value of high VEGF signaling score in early lung SCC. CONCLUSION: Our results clearly indicate that the combination of high expression of the three key elements in the VEGF pathway is associated with a good prognosis in patients with early SCC but not in patients with ADC.

The oncoprotein SF2/ASF promotes non-small cell lung cancer survival by enhancing survivin expression.

PURPOSE: SF2/ASF is a splicing factor recently described as an oncoprotein. In the present work, we examined the role of SF2/ASF in human non-small cell lung cancer (NSCLC) and analyzed the molecular mechanisms involved in SF2/ASF-related carcinogenesis. EXPERIMENTAL DESIGN: SF2/ASF protein levels were analyzed in 81 NSCLC patients by immunohistochemistry. SF2/ASF downregulation cellular models were generated using small interfering RNAs, and the effects on proliferation and apoptosis were evaluated. Survivin and SF2/ASF expression in lung tumors was analyzed by Western blot and immunohistochemistry. Survival curves and log-rank test were used to identify the association between the expression of the proteins and time to progression. RESULTS: Overexpression of SF2/ASF was found in most human primary NSCLC tumors. In vitro downregulation of SF2/ASF induced apoptosis in NSCLC cell lines. This effect was associated with a reduction in the expression of survivin, an antiapoptotic protein widely upregulated in cancer. In fact, SF2/ASF specifically bound survivin mRNA and enhanced its translation, via a mammalian target of rapamycin complex 1 (mTORC1) pathway-dependent mechanism, through the phosphorylation and inactivation of the translational repressor 4E-BP1. Moreover, SF2/ASF promoted the stability of survivin mRNA. A strong correlation was observed between the expression of SF2/ASF and survivin in tumor biopsies from NSCLC patients, supporting the concept that survivin expression levels are controlled by SF2/ASF. Furthermore, combined expression of these proteins was associated with prognosis. CONCLUSION: This study provides novel data on the mTORC1- and survivin-dependent mechanisms of SF2/ASF-related carcinogenic potential, and shows that SF2/ASF and survivin expression is involved in NSCLC progression.

Long-term results after resection for bone sarcoma pulmonary metastases.

BACKGROUND: Pulmonary metastases from bone sarcomas occur in approximately 40% of the cases. The combination of both chemotherapy and surgical resection is currently the standard treatment options for these patients. We aim to study the influence of different prognostic factors on long-term survival. METHODS: We reviewed the prognostic factors and survival rate in 52 consecutive patients with pulmonary metastases from bone sarcomas. All of them were previously treated with chemotherapy and submitted to metastasectomy at our institution from 1996 to 2006. Clinical and demographic variables, related to the primary tumour as well as to the pulmonary metastases, and treatment procedures were registered. Univariate (log-rank) and multivariate (Cox regression) analysis were carried out to identify significant prognostic factors related to overall survival. Five-year survival rates were estimated using Kaplan-Meier methods. RESULTS: Median follow-up was 28 months. Follow-up duration ranged 7-148 months; the median survival was 27 months. As many as 31% of the patients were alive without disease, 3% were alive with disease, 64% died of disease while 2% died from other causes. Complete resection was achieved in 49 cases (94%). The overall 3- and 5-year survival rates were 43% and 31%, respectively. Univariate analysis showed (1) disease-free interval between treatment of the primary bone tumour and first lung metastasectomy (DFI) and (2) disease-free interval between first and second lung surgery (DFI2) as prognostic factors. Gender, primary site, histology of primary tumour, surgical approach, number of lung nodules, type of lung resection and re-do lung surgery did not have a significant impact on survival. CONCLUSION: The long-term survival after bone sarcoma lung metastasectomy is encouraging. In our series, DFI and DFI2 were identified as the only prognostic factors.

Primary mixed squamous carcinoma and osteosarcoma (carcinosarcomas) of the lung have a CGH mapping similar to primitive squamous carcinomas and osteosarcomas.

Carcinosarcomas are malignant tumors with a mixture of carcinomatous and differentiated sarcomatous elements. We investigate the morphology, immunohistochemistry, and comparative genomic hybridization analysis of 3 mixed squamous carcinoma and osteosarcoma of the lung. All patients were male and their ages were 72, 43, and 58 years. The sizes of the neoplasms were 7, 5, and 5 cm in maximum diameter, respectively. Two patients died of the disease 9 and 14 months after surgery; and one is alive 6 months later. By light microscopy, all cases had both squamous and osteosarcomatous structures. Immunohistochemistry was positive for AE3AE1, p63, 34 E12, CAM 5.2 (2/3 cases), CK-7 (2/3 cases), epithelial membrane antigen, E-cadherin, p53, and carcinogenic embryonic antigen in carcinomatous areas, and for vimentin and CD-68 in sarcomatous component. Areas of transition positive for both cytokeratins and vimentin were seen in all cases. A total of 55 copy number changes were detected with a median of 18 abnormalities per case: 48 gains, 6 losses, and 1 high-level amplification. Chromosome alterations in osteosarcomatous areas were similar to those found in lung metastatic osteosarcoma, comparable to those found in carcinomatous areas and to lung squamous carcinomas. Coincidences between carcinomatous areas and osteosarcomatous zones were found as gains in chromosomes 1q, 3q, 5p, 8q, and 12p. These findings provide arguments that favor a common origin for both types of cells, supported by the mixture of cells, the existence of undifferentiated cells positive to both cytokeratin and vimentin markers, and the CGH overlaps of chromosomal gains between carcinomatous and sarcomatous areas.

Molecular profiling of computed tomography screen-detected lung nodules shows multiple malignant features.

RATIONALE AND PURPOSE: Low-dose spiral computerized axial tomography (spiral CT) is effective for the detection of small early lung cancers. Although published data seem promising, there has been a significant degree of discussion concerning the potential of overdiagnosis in the context of spiral CT-based screening. The objective of the current study was to analyze the phenotypic and genetic alterations in the small pulmonary malignancies resected after detection in the University of Navarra/International Early Lung Cancer Action Project spiral CT screening trial and to determine whether their malignant molecular features are similar to those of resected lung tumors diagnosed conventionally. EXPERIMENTAL DESIGN: We analyzed 17 biomarkers of lung epithelial malignancy in a series of 11 tumors resected at our institution during the last 4 years (1,004 high-risk individuals screened), using immunohistochemistry and fluorescence in situ hybridization (FISH). A parallel series of 11 gender-, stage-, and histology-matched lung cancers diagnosed by other means except screening was used as control. RESULTS: The molecular alterations and the frequency of phenotypic or genetic aberrations were very similar when screen-detected and nonscreen-detected lung cancers were compared. Furthermore, most of the alterations found in the screen-detected cancers from this study were concordant with what has been described previously for stage I-II lung cancer. CONCLUSIONS: Small early-stage lung cancers resected after detection in a spiral CT-based screening trial reveal malignant molecular features similar to those found in conventionally diagnosed lung cancers, suggesting that the screen-detected cancers are not overdiagnosed.

Early lung cancer detection using spiral computed tomography and positron emission tomography.

RATIONALE: Lung cancer screening using computed tomography (CT) is effective in detecting lung cancer in early stages. Concerns regarding false-positive rates and unnecessary invasive procedures have been raised. OBJECTIVE: To study the efficiency of a lung cancer protocol using spiral CT and F-18-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: High-risk individuals underwent screening with annual spiral CTs. Follow-up CTs were done for noncalcified nodules of 5 mm or greater, and FDG-PET was done for nodules 10 mm or larger or smaller (> 7 mm), growing nodules. RESULTS: A total of 911 individuals completed a baseline CT study and 424 had at least one annual follow-up study. Of the former, 14% had noncalcified nodules of 5 mm or larger, and 3.6% had nodules of 10 mm or larger. Eleven non-small cell lung cancers (NSCLC) and one small cell lung cancer (SCLC) were diagnosed in the baseline study (prevalence rate, 1.32%), and two NSCLCs in the annual study (incidence rate, 0.47%). All NSCLCs (92% of prevalence cancers) were diagnosed in stage I (12 stage IA, 1 stage IB). FDG-PET was helpful for the correct diagnosis in 19 of 25 indeterminate nodules. The sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET for the diagnosis of malignancy were 69, 91, 90, and 71%, respectively. However, the sensitivity and negative predictive value of the screening algorithm, which included a 3-month follow-up CT for nodules with a negative FDG-PET, was 100%. CONCLUSION: A protocol for early lung cancer detection using spiral CT and FDG-PET is useful and may minimize unnecessary invasive procedures for benign lesions.

Chest wall reconstruction using iliac bone allografts and muscle flaps.

Technically we can divide full-thickness thoracic reconstruction into 2 parts: providing a rigid support and ensuring well-vascularized coverage. Since 1986, the authors' center has had ample experience with bone banks and the use of cryopreserved bone grafts, which led them to consider the possibility of using these grafts for full-thickness chest wall reconstruction. They describe 3 patients in whom resection of the tumor and reconstruction of the thorax were carried out using iliac bone allografts covered with muscle flaps (1 pectoralis major and 2 rectus abdominis). None of the patients experienced breathing difficulties, pain, or instability after 14 months, 18 months, and 11 years of follow-up. The result of the reconstruction was excellent in all 3 patients in terms of function and aesthetics. The advantage of allografts compared with synthetic materials is their potential integration; they can become part of the host patient's living tissue.

Altered patterns of expression of members of the heterogeneous nuclear ribonucleoprotein (hnRNP) family in lung cancer.

hnRNP A2/B1 has been suggested as a useful early detection marker for lung carcinoma. hnRNP A2/B1 is a member of a large family of heterogeneous nuclear ribonucleoproteins (hnRNP proteins) involved in a variety of functions, including regulation of transcription, mRNA metabolism, and translation. In lung cancer, we have evaluated the expression and cellular localization of several members of the hnRNP family, hnRNP A1, A2, B1, C1, C2 and K. 16 cell lines (SCLC and NSCLC) and biopsies from 32 lung cancer patients were analyzed. Our results suggest that, besides hnRNP A2/B1, the expression of other members of the hnRNP family is altered both in SCLC and NSCLC. In the biopsies, negative or low expression of the hnRNP proteins analyzed was observed in normal epithelial cells whereas lung cancer cells showed highly intense nuclear or cytoplasmic immunolocalization. In all the lung cancer cell lines, the mRNA for all the hnRNP proteins was detected. In general, higher levels of hnRNP mRNAs were found in SCLC as compared with NSCLC. Our results also suggest that the expression and processing of each hnRNP protein in lung cancer is independently regulated and is not exclusively related to proliferation status. In SCLC cell lines, hnRNP A1 protein expression correlated with that of Bcl-x(L). In the lung cancer cell lines, hnRNP K protein localization varied with the cellular confluence.

A randomized, double-blinded comparison of thoracic epidural ropivacaine, ropivacaine/fentanyl, or bupivacaine/fentanyl for postthoracotomy analgesia.

UNLABELLED: Epidural ropivacaine has not been compared with bupivacaine for postthoracotomy analgesia. Eighty patients undergoing elective lung surgery were randomized in a double-blinded manner to receive one of three solutions for high thoracic epidural analgesia. A continuous epidural infusion of 0.1 mL. kg(-1). h(-1) of either 0.2% ropivacaine, 0.15% ropivacaine/fentanyl 5 micro g/mL, or 0.1% bupivacaine/fentanyl 5 micro g/mL was started at admission to the intensive care unit. We assessed pain scores (rest and spirometry), IV morphine consumption, spirometry, hand grip strength, PaCO(2), heart rate, blood pressure, respiratory rate, and side effects (sedation, nausea, vomiting, and pruritus) for 48 h. Thoracic epidural ropivacaine/fentanyl provided adequate pain relief similar to bupivacaine/fentanyl during the first 2 postoperative days after posterolateral thoracotomy. The use of plain 0.2% ropivacaine was associated with worse pain control during spirometry, larger consumption of IV morphine, and increased incidence of postoperative nausea and vomiting. Morphine requirements were larger in the ropivacaine group, with no differences between bupivacaine/fentanyl and ropivacaine/fentanyl groups. Patients in the ropivacaine group experienced more pain and performed worse in spirometry than patients who received epidural fentanyl. There was no significant difference in motor block. We conclude that epidural ropivacaine/fentanyl offers no clinical advantage compared with bupivacaine/fentanyl for postthoracotomy analgesia. IMPLICATIONS: Thoracic epidural ropivacaine/fentanyl provided adequate pain relief and similar analgesia to bupivacaine/fentanyl during the first 2 postoperative days after posterolateral thoracotomy. Plain 0.2% ropivacaine was associated with worse pain control and an increased incidence of postoperative nausea and vomiting. We conclude that epidural ropivacaine/fentanyl offers no clinical advantage compared with bupivacaine/fentanyl for postthoracotomy analgesia.