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Recurrent respiratory papillomatosis is an infrequent benign neoplasm that commonly affects the upper airway with a predilection for the larynx. Isolated tracheobronchial involvement is very rare. Diagnosis and treatment of this disease is a challenge due to its non-specific clinical manifestation and its recurrent nature. We present a 6-year-old male with a diagnosis of asthma refractory to treatment, without history or evidence of laryngeal papillomatosis. The endoscopic examination revealed extensive tracheobronchial papillomatosis and the computed tomography, pulmonary involvement. He received adjuvant therapy with intravenous Bevacizumab with very good response. We alert pediatricians to consider this rare tracheobronchial neoplasm in all children with atypical asthma symptoms or in those who do not improve with conventional medical treatment., (Sociedad Argentina de Pediatría.)

Introduction: Bronchial neuroendocrine tumors (NETs) are rare tumors representing approximately 20%-30% of all neuroendocrine tumors and 2%-3% of all adult lung cancers. Here, they present a large case series of well-differentiated bronchial NETs with the aim of investigating the behavior of these tumors and long-term outcomes., Methods: A retrospective review was performed of 105 patients with bronchial NETs managed in a tertiary referral center in the period between January 1998 and January 2012., Results: Bronchial NETs are commoner in females and the commonest presenting symptoms were cough (13.9%) and dyspnoea (11.6%). Octreoscan TM and Gallium-68 DOTATATE PET were found to have similar diagnostic sensitivity and FDG PET was more sensitive for higher-grade tumors. Over a median follow-up period of 35.5 months mortality rate was 5.7%. The 5-year survival was 76% and the 10-year survival was 62%. Female patients survived longer but this difference was not statistically significant (P = .59). Older age greater than 50 years (P = .027), higher levels of Chromogranin A (CgA) (P = .034), first-line treatment with surgery (P = .005), ki67 over 10% (P = .037), and tumor stage (P = .036) but not tumor grade (P = .22), were significantly associated with survival., Discussion: Several factors have been identified which are independently associated with survival including CgA levels greater than 100 pmol/L, tumor stage, age greater than 50, ki67 over 10% and having surgery as first-line treatment. There was no difference in survival between typical and atypical carcinoids., (© 2016 John Wiley & Sons Ltd.)

Adenocarcinoma (AC) is the most common type of primary pulmonary malignancy. Lung carcinoid, however, is a rare neuroendocrine tumor. Their coexistence is extremely uncommon. We report the unique case of synchronous advanced lung AC of the right upper lobe (stage IIIB) and typical endobronchial carcinoid tumor in the contralateral lower lobe in a 49-year-old white female who had never smoked. PET-computed tomography scan revealed a fluorine-18-fluorodeoxyglucose-avid AC lesion, whereas the carcinoid tumor was fluorine-18-fluorodeoxyglucose occult. After two lines of platinum-based combination chemotherapies and radiotherapy, the AC progressed, and oral tyrosine kinase inhibitor therapy with erlotinib was initiated in third line. On erlotinib, the AC remained stable for 50 months until disease progression, whereas the carcinoid completely regressed. Molecular testing of the rebronchoscopied AC revealed an exon 19 deletion mutation in the epidermal growth factor receptor (EGFR) gene, whereas the carcinoid was retrospectively EGFR mutation negative. The patient eventually succumbed to ileus caused by intra-abdominal spread of disease, surviving a remarkable 80 months with good performance status throughout most of the follow-up period. To the best of our knowledge, this is the first reported case of synchronous primary lung cancers with different EGFR mutation status, describing an unexpected response of an EGFR-wild-type carcinoid to third-line erlotinib.

A 59-year-old man was admitted to our hospital with dyspnea and cough. A large polypoid tumor was observed in the lower trachea and bronchoscopic polypectomy was performed using a snare to relieve symptoms. The tumor was diagnosed as a high grade mucoepidermoid carcinoma mainly by the histology of piecemeal specimens obtained by bronchoscopic resection. The primary lesion involved the trachea and the main bronchus, and there were multiple metastases in the lung. The patient was treated with the combination of carboplatin and paclitaxel. After four cycles of chemotherapy, the tumors were significantly reduced. He remains well without evidence of tumor progression for 25 months. This case suggests that the combination chemotherapy of carboplatin and paclitaxel can be an option for treatment of pulmonary mucoepidermoid carcinoma.

Cystic lung metastases are a rare presentation in non-small cell lung cancer and occurs mainly in squamous cell carcinoma. We present the case of a 57-year-old woman with a lung squamous cell carcinoma and cystic lung metastases, who developed bilateral metachronous pneumothorax while being administered erlotinib in third-line treatment. The apparition of a pneumothorax under chemotherapy is most often the result of tumor necrosis and formation of bronchopleural fistula. However, very few cases have been reported under targeted therapies, and to our knowledge this is the first case under erlotinib. This complication is potentially life-threatening, especially due to the possibility of pneumothorax bilateralization.

Introduction: In terms of well-differentiated neuroendocrine tumors (NETs), the lung is the second most common site of occurrence, after the gastro-entero-pancreatic axis, and comprises ∼ 25% of all NETs which may occur in various parts of the body. Pulmonary NETs are classified into four groups including typical carcinoid tumors, atypical carcinoid tumors, small cell lung carcinoma and large cell neuroendocrine carcinomas. Among pulmonary NETs, typical and atypical carcinoid tumors of the lung are generally indolent, but do have a (albeit low) potential to metastasize., Areas Covered: The molecular biology and novel molecular pathways and drug targets in bronchial carcinoids are reviewed in this paper. A full data search is performed through PubMed over the years 2000 - 2010 with key words 'neuroendocrine tumors of the lung, bronchial carcinoid, lung carcinoid, foregut carcinoid, pulmonary carcinoid, pulmonary NETs, lung NETs, molecular biology, autoradiography, nuclear medicine, treatment'; all relevant publications are included, together with selected publications prior to that date., Expert Opinion: Although lying at the benign end of the spectrum of pulmonary NETs, bronchial carcinoids can metastasize, and the pathogenesis of these tumors is poorly understood. Several intracellular signaling pathways are under investigation to define new targets for the successful treatment of these tumors. In terms of treatment, further research should additionally focus on the already known but promising drug options.

Background/aim: Bronchus-associated lymphoid tissue (BALT) lymphoma is a rare subtype of low grade marginal zone B cell lymphoma representing 10% of all MALT lymphomas. The purpose of this study was to analyze the outcome of this group of patients comparing prognostic parameters and therapy modalities., Methods: A total of eight patients with BALT lymphoma had diagnosed between January 1998-April 2008 at the Institute of Hematology, Clinical Center of Serbia, Belgrade, and they were included in this retrospective analysis., Results: Male/female ratio was 2/6, the median age was 64 years (range 37-67 years). Six patients had nonspecific respiratory symptoms and all of them had B symptoms. The patients were seronegative for HIV, HCV and HBsAg. Three patients had Sjogren's syndrome, rheumatoid arthritis and pulmonary tuberculosis, respectively. Seven patients were diagnosed by transbronchial biopsy and an open lung biopsy was done in one patient. Patohistological findings revealed lymphoma of marginal zone B cell lymphoma: CD20+/CD10-/CD5-/CyclinD1/CD23-/IgM- with Ki-67+< 20% of all cells. According to the Ferraro staging system, five patients had localized disease (CS I-IIE) and three had stage IVE; bulky tumor mass had 3 patients. All patients had Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. Five patients received monochemotherapy with chlorambucil and 3 were treated with CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone). A complete response (CR) was achieved in 5 patients and a partial response (PR) in 3 of them, treated with chlorambucil monotherapy and CHOP regimen. All patients were alive during a median follow-up period of 49 months (range 6-110 months). Three patients relapsed after monochemotherapy into the other extranodal localization. They were treated with CHOP regimen and remained in stable PR. CONCLUSION. BALT lymphoma tends to be localised disease at the time of diagnosis, responds well to monochemotherapy with chlorambucil and has a favourable prognosis.

The goal of this study was to characterize and classify pulmonary neuroendocrine tumors based on array comparative genomic hybridization (aCGH). Using aCGH, we performed karyotype analysis of 33 small cell lung cancer (SCLC) tumors, 13 SCLC cell lines, 19 bronchial carcinoids, and 9 gastrointestinal carcinoids. In contrast to the relatively conserved karyotypes of carcinoid tumors, the karyotypes of SCLC tumors and cell lines were highly aberrant. High copy number (CN) gains were detected in SCLC tumors and cell lines in cytogenetic bands encoding JAK2, FGFR1, and MYC family members. In some of those samples, the CN of these genes exceeded 100, suggesting that they could represent driver alterations and potential drug targets in subgroups of SCLC patients. In SCLC tumors, as well as bronchial carcinoids and carcinoids of gastrointestinal origin, recurrent CN alterations were observed in 203 genes, including the RB1 gene and 59 microRNAs of which 51 locate in the DLK1-DIO3 domain. These findings suggest the existence of partially shared CN alterations in these tumor types. In contrast, CN alterations of the TP53 gene and the MYC family members were predominantly observed in SCLC. Furthermore, we demonstrated that the aCGH profile of SCLC cell lines highly resembles that of clinical SCLC specimens. Finally, by analyzing potential drug targets, we provide a genomics-based rationale for targeting the AKT-mTOR and apoptosis pathways in SCLC.

A 60-year-old woman was diagnosed with pulmonary metastasis with endobronchial spread of sinonasal melanoma 9 years after the initial treatment. She had originally been diagnosed with sinonasal malignant melanoma and received chemotherapy combined with carbon ion radiotherapy. During routine follow-up, chest CT showed a nodular lesion on the left upper lung lobe. Bronchoscopic examination showed diffuse melanosis without intrinsic masses from the left main bronchus to the peripheral bronchial mucosa. Transbronchial biopsy was performed for both the pulmonary lesion and endobronchial melanosis lesions. Melanoma cells were histologically detected in both the mucosal and submucosal layers.

Situs inversus (SI), is left to right inversion of internal organs. It may remain unrecognized until discovery during emergency surgery or investigation of symptoms. There are three reports of lung cancer with SI in Medline. However search in PubMed by 15 December 2008, there isn't any report of superior vena cava syndrome (SVCS) with any benign or malignant disease in patients with SI. We present the case of a 59 year old man with small cell carcinoma in left main bronchus presented with SVCS. Chest radiography and contrast enhanced CT scan confirmed SI with compression left side located superior vena cava with left lung small cell carcinoma. To our knowledge, here, we present the first case of SVCS with SI.

Background: Survival rates for gastrointestinal (GI) and bronchopulmonary (BP) neuroendocrine tumors (NETs) have not significantly altered (overall 67%, 5-year survival) in 30 years (1973-2004), whereas the incidence has increased ( approximately 1000%) in the same time frame. No effective or specific antineoplastic agent is available for treatment, although somatostatin analogs inhibit tumor secretion. Given the coexistence of somatostatin and dopamine regulatory receptors on NET cells, the antiproliferative efficacy as well as the signaling and transcriptional targets of their ligands were evaluated., Methods: The cytotoxic effects of 12 somatostatin/dopamine compounds were evaluated in 3 NET cell lines, and real-time polymerase chain reaction and enzyme-linked immunoadsorbent assay studies were performed to delineate antiproliferative signaling pathways., Results: The atypical BP-NET, NCI-H720, was most sensitive to the sst(5) analog BIM23206 (half-maximal concentration, 2.4 pM) and demonstrated similar sensitivity to lanreotide and the sst(2) analog BIM23120. The typical BP-NET, NCI-H727, was most sensitive to BIM23120 (0.7 nM) and to the pan-somatostatin receptor analog (BIM23A779). The GI-NET, KRJ-I, was most sensitive to sst(2,5) analogs lanreotide (1 nM) and BIM23244 (7.4 nM). Lanreotide activated extracellular signal regulated kinase-1/2 phosphorylation and p21(WAF1/CIP1) transcription, but inhibited Ki-67 transcription. NCI-H720 was most sensitive to the sst(2,5)- and D(2)-selective compound BIM23A761 (4.2 nM), as was NCI-H727 (5.5 nM). KRJ-I did not respond to any chimeric analog. BIM23A761 activated c-Jun N-terminal kinase signaling and caused inhibition of Ki-67 transcription. P21(WAF1/CIP1) transcription was activated only in NCI-H727 cells., Conclusions: The different responses of each individual cell line suggested that NETs from different locations arising from different neuroendocrine cells may require cell-specific antiproliferative agents based on the unique receptor profile of individual lesions., (2008 American Cancer Society)

Background: Currently, no consistently effective therapy is available to inhibit cell proliferation or metastasis of neuroendocrine tumor (NET) disease. The effects of 4 novel peptides were analyzed: a targeted cytotoxic analog of luteinizing hormone-releasing hormone (LH-RH) analog (AN-152), a targeted cytotoxic analog of somatostatin (AN-238), and 2 antagonists of growth hormone-releasing hormone (GH-RH) on 3 NET (carcinoid) cell lines that expressed respective peptide receptors., Methods: The effects of the compounds were evaluated on cell proliferation in vitro using MTT uptake and Ki67 expression, apoptosis (caspase 3 expression and activity), and cell cycle parameters (DNA distribution)., Results: Proliferation of the LH-RH receptor-expressing lung NET, NCI-H720 line, was inhibited 2-fold by AN-152 containing doxorubicin compared with the chemotherapy alone (IC50 of 9.1 nM vs 24 nM). This was associated with a reduction in Ki67 transcript and an increase in both caspase 3 mRNA levels and activity. Proliferation of the GH-RH receptor expressing lung NET, NCI-H727 line, was inhibited by both GH-RH antagonists, the effects being mediated through changes in Ki67 expression, but not in caspase 3-mediated apoptosis. The small intestinal NET, KRJ-I line, was 8x more sensitive to inhibition by AN-238 than to 2-pyrolino-doxorubicin, reflected by increased caspase 3 transcript as well as activity. AN-238-mediated growth inhibition culminated in complete G1 arrest., Conclusions: The data demonstrate GH-RH antagonists or peptide-linked antineoplastic agents such as AN-152 and AN-238 are effective inhibitors of NET proliferation in vitro. Because peptide receptors such as those for GH-RH, LH-RH, and SST subtypes are commonly expressed by NETs, the development of antineoplastic agents targeted to specific tumor receptors may provide a more efficacious strategy than systemic chemotherapeutic agents currently in use., (Copyright (c) 2008 American Cancer Society.)

The EGFR T790M mutation has been identified in tumors from lung cancer patients that eventually develop resistance to erlotinib. In this study, we generated a mouse model with doxycycline-inducible expression of a mutant EGFR containing both L858R, an erlotinib-sensitizing mutation, and the T790M resistance mutation (EGFR TL). Expression of EGFR TL led to development of peripheral adenocarcinomas with bronchioloalveolar features in alveoli as well as papillary adenocarcinomas in bronchioles. Treatment with an irreversible EGFR tyrosine kinase inhibitor (TKI), HKI-272, shrunk only peripheral tumors but not bronchial tumors. However, the combination of HKI-272 and rapamycin resulted in significant regression of both types of lung tumors. This combination therapy may potentially benefit lung cancer patients with the EGFR T790M mutation.

Tobacco carcinogens induce Akt activation and lung carcinogenesis. We previously demonstrated that deguelin, a natural plant product, specifically inhibits the proliferation of premalignant and malignant human bronchial epithelial cells by blocking Akt activation. To evaluate the ability of deguelin to block tobacco carcinogen-induced lung tumorigenesis, we evaluated the in vivo effects of deguelin on Akt activation and lung tumorigenesis in transgenic mice in which Akt expression was induced by tamoxifen and in 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK)/benzo(a)pyrene (BaP)-treated A/J mice. Deguelin suppressed Akt activation in vivo, as measured by immunohistochemistry and immunoblotting, and statistically significantly reduced NNK/BaP-induced lung tumor multiplicity, volume, and load in A/J mice, as monitored by microcomputed tomography image analysis, with no detectable toxicity. These results indicate that deguelin warrants consideration as a chemopreventive agent for early-stage lung carcinogenesis in a clinical lung cancer chemoprevention trial.

Background: An obstructing primary lung cancer is a challenging disease frequently requiring endobronchial interventional therapy. A variety of interventional modalities, including Nd:YAG laser, stenting, photodynamic therapy (PDT), and endoluminal brachytherapy, are utilized to relieve airway obstruction and bleeding. The aim of this study is to compare the effect on patient survival of bronchoscopic palliation for lung cancer utilizing one interventional modality compared to the use of combination of modalities to relieve the airway problem. METHODS. We reviewed our longitudinal experience with interventional bronchoscopy in 75 patients who underwent 176 procedures for the management of endobronchial lung cancer between 1994 and 2002. Indication for intervention was hemoptysis in 24 patients (32%) and airway obstruction in the remaining. Six patients died within 30 days from the first intervention and were excluded. Forty of the surviving 69 patients (58%) were treated with a single interventional modality (group A). In 29 patients (42%) a multimodality endoscopic treatment was utilized (group B). Single-modality treatment in group A included Nd-YAG laser in 60%, stent in 17%, brachytherapy in 20%, and PDT in 3%. A variety of combinations of the aforementioned modalities were used in group B to enhance airway patency. Patient data were compared with the Student's t-test and chi-square test. Survival analysis and the log rank test were used to compare difference in survival between the two groups. A p-value of 0.05 was considered significant., Results: There were 46 males and 23 females, with a mean age of 67 years. The tumor was located in the trachea 9%, in the carina in 7%, and primary bronchial in 84%. Two patients had complications due to stent malposition. There was no significant difference between the two groups in relation to age, gender, tumor location, histology, and type of previous cancer therapy. There was a significant improvement in survival for the multimodality group (p = 0.04). The 1- and 3-year cumulative survival rate for groups A and B was 51.3% versus 50% and 2.3% versus 22%, respectively., Conclusions: Improvement in survival can be seen with diligent airway surveillance after interventional bronchoscopy and liberal use of a variety of endobronchial treatment modalities for airway obstruction or bleeding. Physicians involved in the management of this difficult problem should be versed in the use of all available treatment modalities to enhance therapeutic outcome.

A new method of treatment of pulmonary cancer using the introduction of cytostatic drugs and prednisolone into the tumor during bronchofibroscopy was suggested. This increases the effectiveness of treatment and reduces the side effects of drugs. Complete regression of tumor was observed in 9 (32.1%) patients of the main group, partial regression--in 12 (42.9%). In control group the regression was observed in 6 (20%) and in 10 (33.3%) patients, respectively.

A 69-year-old man had undergone low anterior resection and a right lobe resection of the liver for rectum cancer and metastatic liver tumor at the age of 66 years. He presented at our hospital because of an abnormal shadow on a CT chest scan, which indicated a tumor shadow 2.5 cm in size in the lingular lobe and enlarged hilar and mediastinal lymph nodes. A bronchoscopic tumor biopsy revealed pulmonary metastasis from the rectum cancer. Bronchoscopic examination also identified an endobronchial squamous cell lung cancer, which almost completely obstructed the orifice of B1 and B2. We concluded that the patient had squamous cell lung cancer with metastases in the mediastinal lymph nodes. He was initially treated with weekly chemotherapy with carboplatin (AUC 1.25) and paclitaxel (70 mg/m2). The endobronchial tumor was markedly reduced in size after 2 weeks of the chemotherapy. Furthermore, after 6 weeks of the chemotherapy, the tumor had disappeared completely, and 11 days later, lower division segmentectomy and hilar and mediastinal lymph node dissection were performed. Pathological examination revealed no metastases in the lymph nodes. The patient has continued to receive chemotherapy as an outpatient and has been well without recurrence of any metastases for over 16 months.

Background: Because lung cancer is the leading cause of cancer-related death, new approaches for preventing and controlling the disease are needed. Chemoprevention approaches are both feasible and effective. We evaluated the potential of deguelin, a natural plant product, as a lung cancer chemopreventive agent and investigated its mechanism of action., Methods: The effects of deguelin on proliferation and apoptosis of normal, premalignant, and malignant human bronchial epithelial (HBE) cells were assessed by using the MTT assay, a flow cytometry-based TUNEL assay, and western blot analyses. The effects of deguelin on the phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) pathways were assessed by western blot analyses and with adenoviral vectors that expressed constitutively active Akt., Results: Deguelin treatment in vitro at doses attainable in vivo inhibited the growth of and induced apoptosis of premalignant and malignant HBE cells but had minimal effects on normal HBE cells. Levels of phosphorylated Akt (pAkt) were higher in premalignant HBE cells than in normal HBE cells. In premalignant HBE cells, deguelin inhibited PI3K activity and reduced pAkt levels and activity but had mimimal effects on the MAPK pathway. Although overexpression of a constitutively active Akt in premalignant and malignant HBE cells had no effect on growth inhibition mediated by N-(4-hydroxyphenyl)retinamide (4-HPR), a novel chemopreventive retinoid, it blocked deguelin-induced growth arrest and apoptosis., Conclusions: The ability of deguelin to inhibit PI3K/Akt-mediated signaling pathways may contribute to the potency and specificity of this pro-apoptotic drug. Because both premalignant and malignant HBE cells are more sensitive to deguelin than normal HBE cells, deguelin may have potential as both a chemopreventive agent for early stages of lung carcinogenesis and a therapeutic agent against lung cancer.

The lung cancer epidemic is not expected to abate in the next two decades. Smoking cessation campaigns have not been successful in reducing the prevalence of smoking to < 25% of the adult population in the US. Among high school students, the prevalence of smoking is increasing (27.5% in 1991; 36.4% in 1997) (43). In addition, only 1 in 8 heavy smokers develop lung cancer and about 20% of patients with lung cancer have no history of active or passive smoking, thus indicating that genetic predisposing factors and other unidentified carcinogens play a crucial role in the etiology of this disease. The bronchial epithelium is like an internal skin where lung cancer originates after chronic exposure to airborne carcinogens in a predisposed host. Although the bronchial epithelium is not readily examinable, it is easily accessible to therapeutic intervention by using inhaled therapeutics. We hope to extend our findings using direct wild-type p53 gene replacement via intratracheal and aerosolized administrations in mice to NSCLC patients with p53 mutations. We also plan on utilizing aerosolized chemical agents to activate endogenous mechanisms of cytoprotection. If, in clinical trials, evidence of effective cytoprotection is observed in the absence of intolerable side effects, further exploration of this new strategy for the control and prevention of a neoplastic disease that accounts for a third of all cancer-related deaths will be fully justified.

Introduction: Bronchoplastic procedures have become established in the treatment of bronchial malignancies. We report our results on 108 operations performed between 1994 and 2001., Patients and Methods: Bronchial reconstruction techniques (wedge resection, end-to-end-anastomosis, y-sleeve), comorbidity (cardiovascular, respiratory, pulmonary, neoadjuvant chemotherapy, alcoholism), postoperative complications (septic/aseptic, light/severe), histology, tnm-stage and postoperative follow up (days) were recorded prospectively., Results: The bronchial tree was reconstructed with an end to end anastomosis in 75 cases (69.4%), a y-sleeve in 17 (15.7%) and a wedge resection in 16 (14.8%). In 11 patients (10.2%), an additional angioplasty of the pulmonary artery was performed. The comorbidity rate was 89.8%. A total of 52 patients (49.1%) presented with one or more cardiovascular risk factors and 84 patients (77.8%) with one or more respiratory risk factors. The overall postoperative morbidity was 26.8% and the mortality 5.5%. Aseptic complications were observed in 12 cases (11.1%) with a mortality of 25% while septic complications occurred in 17 patients (15.7%) with a mortality of 17%. Anastomotic fistulas occurred in three patients (2.8%) and pneumonia in 11 (10.2%). Stage I was found in 46 patients (42.6%), 29 (26.8%) had stage II, 21 (19.5%) stage IIIA, five (4.6%) stage IIIB and two had stage IV (1.8%). The follow up period ranged from 64 to 2,654 days (mean 756.42+/-643.46, median 575.0). Seven patients (6.5%) died with no evidence of disease. After 2 years, 65% of all patients were alive, after five years this had dropped to 50%., Conclusion: Bronchoplastic procedures are a safe method for the treatment of bronchial malignancies, even in cases with high comorbidity, and should be performed whenever possible.

A 51-year-old man was admitted because of complaints of cough and bloody sputa. A chest CT scan revealed a giant mass lesion in the right middle and lower lobes of the lung and mediastinal lymphadenopathy. Bronchoscopic findings showed a tumor which almost completely obstructed the intermediate bronchus. Histopathological examination of a biopsy specimen demonstrated malignant hemangiopericytoma. Two courses of chemotherapy that combined cisplatin, ifosfamide and gemcitabine were performed every 3 weeks. Both primary lesion and mediastinal lymph node metastases showed marked reduction and toxicity was manageable.

A 61-year-old male Caucasian smoker patient underwent chest radiography and CT scan for persistent non-inflammatory cough, which showed a left bronchial unresectable mass. Bronchoscopy showed an endobronchial mass; washing cytology was negative and histology findings suggested diagnosis of granular cell tumor (GCT), also called Abrikossoff's tumor. After 3 weeks a new washing cytology test revealed the presence of small cell lung cancer (SCLC). A CT-scan and chest radiography showed a 30% increase in the maximum diameter of the lesion, clinically defining the primary neoplasm as malignant. The patient was referred to our institution and started chemotherapy with cisplatin and etoposide. After 6 cycles of treatment, the CT scan showed complete, disappearance of the neoplasm and bronchoscopy examination showed no endobronchial lesion, defining the mucosal surface as normal. We have reviewed and summarized the international literature with regard to bronchial localization of malignant granular cell tumor and its association with SCLC, therefore concluding that our case is the first malignant endobronchial GCT linked to SCLC.

The lack of tumor models that can reliably predict for response to anticancer agents remains a major deficiency in the field of experimental cancer therapy. Although heterotransplants of certain human solid tumors can be successfully grown in nude mice, they have never been appropriately explored for prediction of in vivo chemosensitivity to anticancer agents. We determined the tumor response rate and studied the influence of several biological and molecular tumor parameters on the in vivo sensitivity to paclitaxel in a series of heterotransplanted human non-small cell lung cancer (NSCLC) tumors. One hundred consecutive resected NSCLC tumors were heterotransplanted s.c. in nude mice. The in vivo sensitivity to i.v. paclitaxel (60 mg/kg every 3 weeks) was studied in 34 successfully grown heterotransplants. Treatment started when the tumors reached a size of 5 mm in diameter, and strict standard clinical criteria (>50% shrinkage in tumor weight or cross-sectional surface) were used to define tumor response. Baseline multidrug resistance protein (MRP), Her-2/neu, and epidermal growth factor receptor (EGFR) expression, and pre- and posttherapy bax and bcl-2 expression were determined by Western blot analysis. p53 status was determined by sequencing. The overall take rate was 46% (95% confidence interval, 36-56%) and was significantly higher (P < 0.05) for squamous carcinoma tumors (75%) than for adenocarcinoma tumors (30%) and bronchoalveolar tumors (23%). The heterotransplants were morphologically very similar to the original tumors. The response rate to paclitaxel was 21% (95% confidence interval, 9-38%). Baseline tumor parameters associated with response were no Her-2/neu expression (none of the responding tumors expressed Her-2/neu versus 48% of the nonresponding tumors, P = 0.05) and baseline bcl-2 expression (all responding tumors expressed bcl-2 versus only 43% of the nonresponding tumors, P = 0.02). There was a trend toward a higher response rate in bax-positive tumors, and MRP- and EGFR-negative tumors, but it was not statistically significant. The response was independent of baseline p53 status and baseline mitotic index. Responding tumors had a higher bax/bcl-2 ratio 24 h after therapy, but the difference was only marginally significant (2.8 for responding tumors versus 1.1 for nonresponding tumors, P = 0.07). The extent of mitotic arrest at 24 h after therapy was not associated with response. Human NSCLC heterotransplants are morphologically identical to the original tumors and have a response rate to paclitaxel that is equivalent to that reported in Phase II studies in patients with advanced NSCLC treated with single-agent paclitaxel. NSCLC heterotransplants deserve to be explored to evaluate new agents for lung cancer and to predict clinical response on an individual basis in selected groups of patients.

Photodynamic therapy (PDT) in early squamous cell carcinoma of the bronchus has been shown to result in complete response (CR) and cure. However, local recurrence after PDT develops frequently even after complete remission. Because the effect of PDT had been reported to depend on apoptosis, and apoptosis is inhibited by bcl-2 protein, the relationship between the expression of bcl-2 protein and local recurrence after PDT was examined immunohistochemically. From 1983 to 1997, 50 patients with 59 early squamous cell carcinoma of the bronchus received PDT, and a CR was obtained in 43 lesions (72.8%). As there was no recurrence among tumours that were disease-free for more than 2 years, in this study the tumours were defined as cured when recurrence did not occur 2 years subsequent to the receiving of PDT. Of these CR lesions, 31 carcinomas (53.4%) resulted in a cure. Bcl-2 immunoreactivity was detected in 23 tumours (46.9%) and p53 immunoreactivity was detected in 22 tumours (44.9%). When all tumours were divided into either a large tumour with a longitudinal tumour length of 10 mm or more, or a small tumour with a length of less than 10 mm, the large tumour expressed more bcl-2 protein than the small tumour (P = 0.0155). The degree of bcl-2 expression was significantly related with tumour size (P = 0.0155). The expression of bcl-2 and p53 protein was not associated with the cure rate due to PDT. Tumour length and T status in TNM staging were significantly related to the cure by univariate analysis. T status was the only predictor of the cure according to mutivariate analysis. Of 42 CR lesions, the expression of neither bcl-2 nor p53 protein was associated with local recurrence; only T status was significantly associated (P = 0.008). The relationship between the expression of oncoprotein and local recurrence after PDT was not documented in this study. The success of PDT may depend on the exact assessment of tumour size under optimized PDT illumination.

Effective adjuvant treatment for recurrent respiratory papillomatosis (RRP) is at present limited to alpha-interferon, which may have significant side effects including rebound growth of papillomata following its withdrawal, is given by injection and is expensive. High dose cimetidine is known to have immunomodulatory side effects and has been reported as a useful treatment for cutaneous warts. We report a case of very advanced RRP with tracheo-bronchial-pulmonary involvement treated with adjuvant cimetidine at a dose of 40 mg/kg for 4 months. The patient enjoyed a remarkable improvement in her clinical condition following treatment. The literature regarding cimetidine treatment for cutaneous warts is reviewed.

Background: Vascular endothelial growth factor (VEGF) plays a crucial role in physiological and neoplastic angiogenesis. Moreover, VEGF has been found to be upregulated by conditions associated with the generation of free radicals and reactive oxygen intermediates. In patients with cancer, studies to evaluate VEGF as a measure of tumour activity were carried out. We tested the hypothesis that VEGF is additionally affected by oxidative stress due to anticancer therapy. Moreover, the suitability of epidermal growth factor (EGF) to estimate tumour activity was studied., Patients and Methods: 60 patients with non-small cell lung cancer (NSCLC) covering different therapy progress and modalities underwent bronchoalveolar lavage. VEGF-, EGF-, albumin- and total protein-concentrations in bronchoalveolar lavage fluid (BALF) and VEGF-levels in blood plasma were studied., Results: BALF VEGF-levels were increased in patients with advanced NSCLC before and in anticancer therapy. In patients who had received radiotherapy to the lung prior to chemotherapy, VEGF concentrations were noticeably higher than under sole chemotherapy. Pulmonary endothelial hyperpermeability was found in patients with recently diagnosed tumours and patients undergoing anti-cancer therapy. Evaluation of EGF-levels in BALF revealed no significant influence of tumour activity or cancer therapy on this parameter., Conclusion: BALF-levels of VEGF are affected by tumour activity and oxidative stress due to anticancer therapy.

Various new aminosterols were synthesized. The antiproliferative activity of these compounds (I-IV) was studied in vitro on a continuous human non small-cell bronchopulmonary carcinoma line (NSCLC-N6) at the cell cycle level. The histograms indicate cell blockage in Phase Gl (compound I-III) associated with a reduction in the number of cells phases S and G2M and appearance of cellular debris derived from cells in Phase G1.

Using an in vitro lung carcinogenesis model consisting of normal, premalignant, and malignant human bronchial epithelial (HBE) cells, we analyzed the growth inhibitory effects of 26 novel synthetic retinoic acid receptor (RAR)- and retinoid X receptor (RXR)-selective retinoids. RAR-selective retinoids such as CD271, CD437, CD2325, and SR11364 showed potent activity in inhibiting the growth of either normal or premalignant and malignant HBE cells (IC50s mostly <1 microM) and were much more potent than RXR-selective retinoids. Nonetheless, the combination of RAR- and RXR-selective retinoids exhibited additive effects in HBE cells. As the HBE cells became progressively more malignant, they exhibited decreased or lost sensitivity to many retinoids. The activity of the RAR-selective retinoids, with the exception of the most potent retinoid, CD437, could be suppressed by an RAR panantagonist. These results suggest that: (a) RAR/RXR heterodimers play an important role in mediating the growth inhibitory effects of most retinoids in HBE cells; (b) CD437 may act through an RAR-independent pathway; (c) some of the RAR-selective retinoids may have the potential to be used in the clinic as chemopreventive and chemotherapeutic agents for lung cancer; and (d) early stages of lung carcinogenesis may be responsive targets for chemoprevention by retinoids, as opposed to later stages.

A retrospective analysis by searching Medline to assess various criteria regarding the quality of publications in recent years in the treatment of bronchial cancer in France. Following some pre-defined principles for inclusion, 103 references corresponding to 90 papers were retained for this study. The data analysed had been the method of publication (45 abstracts and 58 articles), the origin of the study based on the place and the specialty of the first signatory to publication, the subject of the study (42 out of the 90 studies were on chemotherapy), the population of the patient studies (56 concerned non small cell cancer), the methodology of the study which most often used the rules for open phase II trials and only 13 times was it a phase III study, also the number of patients included was recorded. A tentative interpretation of the weak and strong points of French lung cancer research was carried out based on this analysis and has led to the proposition for the creation of a confederation of clinical research in this area.

A 58-year-old woman because of coughing and an abnormality on a chest renggenogram was referred to our hospital. A chest X-ray film and a computed tomogram revealed atelectasis of the right lower lobe and a round tumor in the left lower lobe. Fiberoptic bronchoscopy revealed an endobronchial polypoid tumor in the intermediate bronchus, which completely obstructed the orifice of the right lower-lobe bronchus. Microscopical examination revealed B-cell diffuse, large, non-Hodgkin's lymphoma. No extrapulmonary lesion was found, and therefore primary pulmonary non-Hodgkin's lymphoma was diagnosed. Chemotherapy resulted in rapid and complete regression of the tumor, which was confirmed endoscopically and histologically. The patient was still in complete remission 8 months after the end of chemotherapy. There have been no additional interventions.