Multidrug-Resistant Profiles in Non-Small Cell Lung Carcinoma Patient-Derived Cells: Implications for Personalized Approaches with Tyrosine Kinase Inhibitors.

The impact of tyrosine kinase inhibitors (TKIs) on multidrug resistance (MDR) in non-small cell lung carcinoma (NSCLC) is a critical aspect of cancer therapy. While TKIs effectively target specific signaling pathways of cancer cells, they can also act as substrates for ABC transporters, potentially triggering MDR. The aim of our study was to evaluate the response of 17 patient-derived NSCLC cultures to 10 commonly prescribed TKIs and to correlate these responses with patient mutational profiles. Using an ex vivo immunofluorescence assay, we analyzed the expression of the MDR markers ABCB1, ABCC1, and ABCG2, and correlated these data with the genetic profiles of patients for a functional diagnostic approach. NSCLC cultures responded differently to TKIs, with erlotinib showing good efficacy regardless of mutation burden or EGFR status. However, the modulation of MDR mechanisms by erlotinib, such as increased ABCG2 expression, highlights the challenges associated with erlotinib treatment. Other TKIs showed limited efficacy, highlighting the variability of response in NSCLC. Genetic alterations in signaling pathways associated with drug resistance and sensitivity, including TP53 mutations, likely contributed to the variable responses to TKIs. The relationships between ABC transporter expression, gene alterations, and response to TKIs did not show consistent patterns. Our results suggest that in addition to mutational status, performing functional sensitivity screening is critical for identifying appropriate treatment strategies with TKIs. These results underscore the importance of considering drug sensitivity, off-target effects, MDR risks, and patient-specific genetic profiles when optimizing NSCLC treatment and highlight the potential for personalized approaches, especially in early stages.

Twenty four-month follow-up after bullectomy, unilateral and bilateral lung volume reduction surgery: a single-center retrospective analysis of consecutive cases.

PURPOSE: While pharmacologic therapy remains the cornerstone of lung emphysema treatment, surgery is an additional therapeutic option in selected patient groups with advanced emphysema. The aim of lung volume reduction surgery (LVRS) is to improve lung function, exercise capacity, quality of life and survival. We sought to determine the therapeutic value of surgical resection in specific patients with lung emphysema. PATIENTS AND METHODS: A retrospective study was performed consisting of 58 patients with lung emphysema who underwent surgical intervention over a 10-year period and were followed for 2 years postoperatively. The clinical characteristics recorded were FEV1 (forced expiratory volume in 1 s), the 6-min walk test (6-MWT), the Modified Medical Research Council (mMRC), body mass index (BMI) and quality of life prior to and 6, 12 and 24 months after surgical intervention. Moreover, all peri- and post-operative complications were noted. RESULTS: Out of 58 emphysema patients (72% male, FEV1 (L) 2.21 ± 0.17, RV (L) 3.39 ± 0.55), 19 underwent surgical bullectomy, 31 unilateral LVRS and 8 sequential bilateral LVRS. Six months after surgery, there was a statistically significant improvement in FEV1, RV, TLC, 6-MWT and mMRC. Over a period of 12 to 24 months postoperatively, clinical benefit gradually declines most likely due to COPD progression but patients still experienced a significant improvement in FEV1. The most common postoperative complications were persistent air leakage (> 7 days), arrhythmia and subcutaneous emphysema in 60%, 51.6% and 22.4%, respectively. No deaths were observed after surgical intervention. CONCLUSION: In a selected patient population, surgery led to significant improvement of lung function parameters, exercise capacity and quality of life. Over a period of 12 to 24 months postoperatively, clinical benefit gradually decreased most likely due to COPD progression.

Correlation between Radiological Characteristics, PET-CT and Histological Subtypes of Primary Lung Adenocarcinoma-A 102 Case Series Analysis.

Background and Objectives: Lung cancer is the second most common form of cancer in the world for both men and women as well as the most common cause of cancer-related deaths worldwide. The aim of this study is to summarize the radiological characteristics between primary lung adenocarcinoma subtypes and to correlate them with FDG uptake on PET-CT. Materials and Methods: This retrospective study included 102 patients with pathohistologically confirmed lung adenocarcinoma. A PET-CT examination was performed on some of the patients and the values of SUVmax were also correlated with the histological and morphological characteristics of the masses in the lungs. Results: The results of this analysis showed that the mean size of AIS-MIA (adenocarcinoma in situ and minimally invasive adenocarcinoma) cancer was significantly lower than for all other cancer types, while the mean size of the acinar cancer was smaller than in the solid type of cancer. Metastases were significantly more frequent in solid adenocarcinoma than in acinar, lepidic, and AIS-MIA cancer subtypes. The maximum standardized FDG uptake was significantly lower in AIS-MIA than in all other cancer types and in the acinar predominant subtype compared to solid cancer. Papillary predominant adenocarcinoma had higher odds of developing contralateral lymph node involvement compared to other types. Solid adenocarcinoma was associated with higher odds of having metastases and with higher SUVmax. AIS-MIA was associated with lower odds of one unit increase in tumor size and ipsilateral lymph node involvement. Conclusions: The correlation between histopathological and radiological findings is crucial for accurate diagnosis and staging. By integrating both sets of data, clinicians can enhance diagnostic accuracy and determine the optimal treatment plan.

Immunofluorescence-Based Assay for High-Throughput Analysis of Multidrug Resistance Markers in Non-Small Cell Lung Carcinoma Patient-Derived Cells.

Lung cancer remains the leading cause of cancer death globally, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Multidrug resistance (MDR), often caused by ATP-binding cassette (ABC) transporters, represents a significant obstacle in the treatment of NSCLC. While genetic profiling has an important role in personalized therapy, functional assays that measure cellular responses to drugs are gaining in importance. We developed an automated microplate-based immunofluorescence assay for the evaluation of MDR markers ABCB1, ABCC1, and ABCG2 in cells obtained from NSCLC patients through high-content imaging and image analysis, as part of a functional diagnostic approach. This assay effectively discriminated cancer from non-cancer cells within mixed cultures, which is vital for accurate assessment of changes in MDR marker expression in different cell populations in response to anticancer drugs. Validation was performed using established drug-sensitive (NCI-H460) and drug-resistant (NCI-H460/R) NSCLC cell lines, demonstrating the assay's capacity to distinguish and evaluate different MDR profiles. The obtained results revealed wide-ranging effects of various chemotherapeutic agents on MDR marker expression in different patient-derived NSCLC cultures, emphasizing the need for MDR diagnostics in NSCLC. In addition to being a valuable tool for assessing drug effects on MDR markers in different cell populations, the assay can complement genetic profiling to optimize treatment. Further assay adaptations may extend its application to other cancer types, improving treatment efficacy while minimizing the development of resistance.

The role of the diaphragm in prediction of respiratory function in the immediate postoperative period in lung cancer patients using a machine learning model.

BACKGROUND: The prediction of postoperative respiratory function is necessary in identifying patients that are at greater risk of complications. There are not enough studies on the effect of the diaphragm on postoperative respiratory function prediction in lung cancer surgical patients. The objective of this study is to estimate the precision of machine learning methods in the prediction of respiratory function in the immediate postoperative period and how diaphragm function contributes to that prediction. MATERIALS AND METHODS: Our prospective study included 79 patients who underwent lung cancer surgery. Diaphragm function was estimated by its mobility measured both ultrasonographically and radiographically and by noninvasive muscle strength tests. We present a new machine learning multilayer regression metamodel, which predicts FEV1 for each patient based on preoperative measurements. RESULTS: The proposed regression models are specifically trained to predict FEV1 in the immediate postoperative period and were proved to be highly accurate (mean absolute error in the range from 8 to 11%). Predictive models based on resected segments give two to three times less precise results. Measured FEV1 was 44.68% ± 14.07%, 50.95% ± 15.80%, and 58.0%1 ± 14.78%, and predicted postoperative (ppo) FEV1 was 43.85% ± 8.80%, 50.62% ± 9.28%, and 57.85% ± 10.58% on the first, fourth, and seventh day, respectively. By interpreting the obtained model, the diaphragm contributes to ppoFEV1 13.62% on the first day, 10.52% on the fourth, and 9.06% on the seventh day. CONCLUSION: The machine learning metamodel gives more accurate predictions of postoperative lung function than traditional calculations. The diaphragm plays a notable role in the postoperative FEV1 prediction.

Cosmetic and Medical Tattooing: Procedural Planning from A to Z and the Informed Consent.

Cosmetic and medical tattooing are in rapid growth on all continents. The tattoos contribute to self-esteem and quality of life. Clients and patients have many different backgrounds and often highest aesthetic expectations, which the professionals shall meet. In this situation, correct, relevant, and personalized information on effectiveness, technique, procedures, and risks is highly important to reach a shared goal without misunderstanding and conflict. Information and agreement between provider and client are crystalized in the informed consent document. This article reviews the many aspects of pre-procedure client information explained in a book format providing information, which is of direct practical usefulness.

Tattooing of the Lips by Needle Technique: Artwork and Performance.

Lip tattooing for cosmetic or medical purposes is a difficult operation with indications and contraindications. Lips have a refined microanatomy and many functions ranging from aesthetics and mimics supporting facial expressions to entirely biological functions such as supporting oral functions and servicing sound expression as part of linguistic performance. The anatomy of the lip is explained and illustrated. In lip tattooing, the outlining and enhancement of contour particularly towards the philtrum is important along with keeping symmetry and shape right and as intended. The coloring of the vermilion and dosing of tattoo pigment is another challenge. The article reviews the technical and artistic aspects of lip tattooing down to detail and step by step procedures starting with client selection, strategy planning, and informed consent. Pitfalls and complications are described. When applied as a corrective operation as part of reconstructive plastic surgery, a close cooperation with medical specialists is needed. Lip tattooing appears underrated regarding medical usefulness. The review can be used as a tutorial in the training of newcomers in the field, having a cosmetic or a medical purpose, same technique.

The Sudden Rise of Cosmetic and Medical Tattoos on All Continents.

Cosmetic tattooing dedicated to beautifying the normal anatomy such as the eyebrows, the eyelines, or the lips is in a remarkable growth all over the world. Medical tattooing with reconstruction of the areola and the nipple after breast surgery, correction of the lost color of vitiligo and scars is a spin-off, which has made tattooing cross the barrier and become accepted and used in clinics and hospitals in service of the quality of life of patients. The last years have seen a major development of machinery, inks, techniques, experiences, and services. The overwhelming rise of the activity created by client pressure and business opportunity, however, also has its cons: amateur work and even malpractice. The development is driven by elite technicians, but competence is little transparent to clients, and there is no distinct authoritative recognition of practitioners based on a recognized educational curriculum. National regulations of the industry are highly variable and scattered. Some countries have no restriction and in others cosmetic tattoos shall be performed by medical doctors. The challenge of the coming decades is to parallel the success of the industry with quality assurance to better control practices and safeguard clients, and the patients.

Needle Configuration and Application in Cosmetic and Medical Tattooing.

Needles, machines, and techniques used for professional cosmetic and medical tattooing have reached a high level of sophistication. Best utensils are combined with operator's insight - the key to best results. Nowadays, a broad range of different tattoo needles serving different purposes are available. The chapter reviews round, flat, triangular, magnum, nano, polished, textured needles, etc. and their coding and preferred use in practice. The chapter is intended to be the vade mecum for practitioners in the field, the newcomer as well as the experienced, in private setting as well as in hospital.

Auxiliary Utensils in Cosmetic and Medical Tattoo Settings.

Cosmetic and medical tattooing is miniaturized tattooing of high precision and thus requires many dedicated utensils including advanced devices for marking and anatomical delineation. Symmetry is a special demand, as is aesthetic outcome, building on perfectionated detail. The artist shall master design and strategy along with advanced technical performance helped by having and using the right tools. This article reviews and illustrates the many special utensils involved in good-practice cosmetic and medical tattooing, exemplified by selected tools used for cleansing, disinfection, pre-operative measurement and marking, and special tattoo machines, cartridges, microblades and needles. Personal protective equipment used to prevent infections among technicians and customers are also illustrated. Educational tools, such as face phantoms and eyebrow mats, are displayed. Mastering cosmetic and medical tattooing is a challenge and involves mastering the many auxiliaries along with needle configurations, machines, inks and the whole setting of the activity. This review is an illustrated practical record and a guideline to good professional practice.

Sonographic Indicators for Treatment Choice and Follow-Up in Patients with Pleural Effusion.

Aim: The aim of this study was to evaluate the role of thoracic sonography in treatment of pleural effusions and to identify sonographic indicators for surgical intervention. Materials and Methods: This study included 378 patients with pleural effusions. US characteristics of effusions as the echo structure and pleural thickening were analyzed. Regarding the US finding, the diagnostic or therapeutic procedure was performed. Results: The study included 267 male and 111 female patients, an average of 56.7 years. Infection was the most frequent cause of effusion. Two hundred sixty-nine patients had loculated and 109 free pleural effusion. Most frequent echo structure of loculated effusion was complex septate, whereas free effusion was mostly anechoic. Successful obtaining of the pleural fluid without real-time guidance was in 88% and under real-time guidance in 99% patients (p < 0.012). There was no significant difference in success rate between free and loculated effusion and regarding the echo structure (p=0.710 and 0.126, respectively). Complete fluid removal after serial thoracentesis or drainage was achieved in 86% patients. Forty-five patients with significantly thicker pleural peel and impairment of the diaphragmatic function than remaining of the group (p < 0.001) underwent surgery. Open thoracotomy and decortication was more frequently performed in patients with completely fixed diaphragm and complex, dominantly septated effusions. There is no significant difference in US parameters comparing to patients underwent VATS, but the number of VATS is too small for valid conclusion. Conclusion: Thoracic sonography is a very useful tool in the evaluation of clinical course and treatment options in patients with pleural effusions of a different origin.

Comparison of mediastinal lymph node status and relapse pattern in clinical stage IIIA non-small cell lung cancer patients treated with neoadjuvant chemotherapy versus upfront surgery: A single center experience.

BACKGROUND: In spite of the progress made in neoadjuvant therapy for operable non small-cell lung cancer (NSCLC), many issues remain unsolved, especially in locally advanced stage IIIA. METHODS: Retrospective data of 163 patients diagnosed with stage IIIA NSCLC after surgery was analyzed. The patients were divided into two groups: a preoperative chemotherapy group including 59 patients who received platinum-etoposide doublet treatment before surgery, and an upfront surgery group including 104 patients for whom surgical resection was the first treatment step. Adjuvant chemotherapy or/and radiotherapy was administered to 139 patients (85.3%), while 24 patients (14.7%) were followed-up only. RESULTS: The rate of N2 disease was significantly higher in the upfront surgery group ( P < 0.001). The one-year relapse rate was 49.5% in the preoperative chemotherapy group compared to 65.4% in the upfront surgery group. There was a significant difference in relapse rate in relation to adjuvant chemotheraphy treatment ( P = 0.007). The probability of relapse was equal whether radiotherapy was applied or not ( P = 0.142). There was no statistically significant difference in two-year mortality ( P = 0.577). The median survival duration after two years of follow-up was 19.6 months in the preoperative chemotherapy group versus 18.8 months in the upfront surgery group ( P = 0.608 > 0.05). CONCLUSION: There was significant difference in preoperative chemotherapy group regarding relapse rate and treatment outcomes related to the lymph node status comparing to the upfront surgery group. Neoadjuvant/adjuvant chemo-therapy is a part of treatment for patients with stage IIIA NSCLC, but further investigation is required to determine optimal treatment.

Influence of Pulmonary Rehabilitation on Lung Function Changes After the Lung Resection for Primary Lung Cancer in Patients with Chronic Obstructive Pulmonary Disease.

Influence of physiotherapy on the outcome of the lung resection is still controversial. Study aim was to assess the influence of physiotherapy program on postoperative lung function and effort tolerance in lung cancer patients with chronic obstructive pulmonary disease (COPD) that are undergoing lobectomy or pneumonectomy. The prospective study included 56 COPD patients who underwent lung resection for primary non small-cell lung cancer after previous physiotherapy (Group A) and 47 COPD patients (Group B) without physiotherapy before lung cancer surgery. In Group A, lung function and effort tolerance on admission were compared with the same parameters after preoperative physiotherapy. Both groups were compared in relation to lung function, effort tolerance and symptoms change after resection. In patients with tumors requiring a lobectomy, after preoperative physiotherapy, a highly significant increase in FEV1, VC, FEF50 and FEF25 of 20%, 17%, 18% and 16% respectively was registered with respect to baseline values. After physiotherapy, a significant improvement in 6-minute walking distance was achieved. After lung resection, the significant loss of FEV1 and VC occurred, together with significant worsening of the small airways function, effort tolerance and symptomatic status. After the surgery, a clear tendency existed towards smaller FEV1 loss in patients with moderate to severe, when compared to patients with mild baseline lung function impairment. A better FEV1 improvement was associated with more significant loss in FEV1. Physiotherapy represents an important part of preoperative and postoperative treatment in COPD patients undergoing a lung resection for primary lung cancer.

Postoperative complications do not influence the pattern of early lung function recovery after lung resection for lung cancer in patients at risk.

BACKGROUND: The pattern and factors influencing the lung function recovery in the first postoperative days are still not fully elucidated, especially in patients at increased risk. METHODS: Prospective study on 60 patients at increased risk, who underwent a lung resection for primary lung cancer. INCLUSION CRITERIA: complete resection and one or more known risk factors in form of COPD, cardiovascular disorders, advanced age or other comorbidities. Previous myocardial infarction, myocardial revascularization or stenting, cardiac rhythm disorders, arterial hypertension and myocardiopathy determined the increased cardiac risk. The severity of COPD was graded according to GOLD criteria. The trend of the postoperative lung function recovery was assessed by performing spirometry with a portable spirometer. RESULTS: Cardiac comorbidity existed in 55%, mild and moderate COPD in 20% and 35% of patients respectively. Measured values of FVC% and FEV1% on postoperative days one, three and seven, showed continuous improvement, with significant difference between the days of measurement, especially between days three and seven. There was no difference in the trend of the lung function recovery between patients with and without postoperative complications. Whilst pO2 was decreasing during the first three days in a roughly parallel fashion in patients with respiratory, surgical complications and in patients without complications, a slight hypercapnia registered on the first postoperative day was gradually abolished in all groups except in patients with cardiac complications. CONCLUSION: Extent of the lung resection and postoperative complications do not significantly influence the trend of the lung function recovery after lung resection for lung cancer.

Clinical and radiological manifestations of primary tracheobronchial tumours: a single centre experience.

INTRODUCTION: Tracheobronchial tumours usually cause an airway obstruction and secondary pulmonary infections. Although rare, they are an important differential diagnosis as they may mimic other conditions and diseases. This paper aims to analyse clinical, radiological and histological characteristics of the patients with tracheobronchial tumours diagnosed for a period of 7 years. MATERIALS AND METHODS: In this retrospective, observational study, we carefully reviewed 65 patients who were diagnosed with tracheal and endobronchial tumours, and performed statistical analysis on the results. RESULTS: Among these 65 patients (36 men and 29 women) with a mean age of 48.8 years (range, 15 to 75), 50 had malignant tumours while 15 had benign ones. The most common symptoms were cough, chest pain and haemoptysis. Cough was a more frequent symptom in patients with benign tumours (P <0.0014). Only 2 patients were asymptomatic. Tumours were predominantly localised in the large airways (46 in large bronchi and 2 in trachea). The most common radiological manifestation of malignant tumours was tumour mass (46%) followed by atelectasis. One third benign tumour caused atelectasis, while tumour mass and consolidation were found in 3 patients each. Computerised tomography revealed endoluminal tumour mass in 29.2% of the cases, which was more frequently found in benign than malignant tumours (47% vs 24%, respectively). On bronchoscopy, tumours were visible in 73% and 70% benign and malignant cases respectively. CONCLUSION: Tracheobronchial tumours should be ruled as a possible diagnosis in patients with cough, haemoptysis, dyspnoea and chest pain. The imaging techniques and histological examination of the tissue would subsequently lead to correct diagnosis and proper treatment can be administered.

Relapse in resected lung cancer revisited: does intensified follow up really matter? A prospective study.

BACKGROUND: beside the well known predominance of distant vs. loco-regional relapse, several aspects of the relapse pattern still have not been fully elucidated. METHODS: prospective, controlled study on 88 patients operated for non-small cell lung cancer (NSCLC) in a 15 months period. Stage IIIA existed in 35(39.8%) patients, whilst stages IB, IIA and IIB existed in 10.2%, 4.5% and 45.5% patients respectively. INCLUSION CRITERIA: stage I-IIIA, complete resection, systematic lymphadenectomy with at least 6 lymph node groups examined, no neoadjuvant therapy, exact data of all aspects of relapse, exact data about the outcome of the treatment. RESULTS: postoperative lung cancer relapse occurred in 50(56.8%) patients. Locoregional, distant and both types of relapse occurred in 26%, 70% and 4% patients respectively. Postoperative cancer relapse occurred in 27/35(77.1%) pts. in the stage IIIA and in 21/40(52.55) pts in the stage IIB. In none of four pts. in the stage IIA cancer relapse occurred, unlike 22.22% pts. with relapse in the stage IB. The mean disease free interval in the analysed group was 34.38 +/- 3.26 months.The mean local relapse free and distant relapse free intervals were 55 +/- 3.32 and 41.62 +/- 3.47 months respectively Among 30 pts. with the relapse onset inside the first 12 month after the lung resection, in 20(66.6%) pts. either T3 tumours or N2 lesions existed. In patients with N0, N1 and N2 lesions, cancer relapse occurred in 30%, 55.6% and 70.8% patients respectively. Radiographic aspect T stage, N stage and extent of resection were found as significant in terms of survival. Related to the relapse occurrence, although radiographic aspect and extent of resection followed the same trend as in the survival analysis, only T stage and N stage were found as significant in the same sense as for survival. On multivariate, only T and N stage were found as significant in terms of survival.Specific oncological treatment of relapse was possible in 27/50(54%) patients. CONCLUSION: the intensified follow up did not increase either the proportion of patients detected with asymptomatic relapse or the number of patients with specific oncological treatment of relapse.

Solitary fibrous pleural tumor associated with loss of consciousness due to hypoglycemia.

The patient suffered loss of consciousness, dysarthria and right sided hemiparesis. The CT scan and MRI scans were negative. These findings are more in keeping with a diagnosis of Transient Ischemic Attack (TIA) or mild CVA. Hypoglycemia per se does not usually cause hemiparesis. The blood glucose level was low but I am not sure if one can conclude that hypoglycemia caused the above noted neurological signs and symptoms. The authors do not present any data to prove that this patient had "hypoglycemic coma".

[Benign solitary fibrous pleural tumour and hypoglycaemia].

INTRODUCTION: Solitary fibrous tumours of the pleura are uncommon and discovered fortuitously or in patients with non-specific respiratory symptoms. When associated with hypoglycaemia, they are commonly referred to as Doege-Potter syndrome. CASE OUTLINE: A 68-year old woman presented with a large pleural mass. She had a long history of headache and decreased consciousness with one-year worsening dyspnoea and right-sided chest pain. The chest X-ray revealed an enormous opacity occupying almost the entire right hemithorax. Endocrine tests showed an extremely reduced glucose level and blood concentration of insulin, C-peptide, glucagon, growth hormone and catecholamines within normal range. After fine-needle aspiration, by histological and immunohistochemical analysis, a benign solitary fibrous pleural tumour was diagnosed. Although surgical resection of such a huge tumour with hypoglycaemia is usually curative, our patient declined surgery and opted for conservative treatment with intravenous glucose. CONCLUSION: Clinicians should be aware of this rare, but important cause of hypoglycaemia and exclude a fibrous pleural tumour in the assessment of their patients.

[The ectopic ACTH syndrome]. / Sindrom ektopicnog kortikotrofa.

INTRODUCTION: Endogenous Cushing's syndrome is a clinical state resulting from prolonged, inappropriate exposure to excessive endogenous secretion of cortisol and hence excess circulating free cortisol, characterized by loss of the normal feedback mechanisms of the hypothalamo-pituitary-adrenal axis and the normal circadian rhythm of cortisol secretion [2]. The etiology of Cushing's syndrome may be excessive ACTH secretion from the pituitary gland, ectopic ACTH secretion by nonpituitary tumor, or excessive autonomous secretion of cortisol from a hyperfunctioning adrenal adenoma or carcinoma. Other than this broad ACTH-dependent and ACTH-independent categories, the syndrome may be caused by ectopic CRH secretion, PPNAD, MAH, ectopic action of GIP or catecholamines, and other adrenel-dependent processes associated with adrenocortical hyperfunction. CASE REPORT: A 31 year-old men with 6-month history of hyperpigmentation, weight gain and proximal myopathy was refereed to Institute of Endocrinology for evaluation of hypercortisolism. At admission, patient had classic cushingold habit with plethoric face, dermal and muscle atrophy, abdominal strie rubrae and centripetal obesity. The standard laboratory data showed hyperglycaemia and hypokaliemia with high potassium excretion level. The circadian rhythm of cortisol secretion was blunted, with moderately elevated ACTH level, and without cortisol suppression after low-dose and high-dose dexamethason suppression test. Urinary SHIAA was elevated. Abdominal and sellar region magnetic resonance imaging was negative. CRH stimulation resulted in ACTH increase of 87% of basal, but without significant increase of cortisol level, only 7%. Thoracal CT scan revealed 14 mm mass in right apical pulmonary segment. A wedge resection of anterior segment of right upper lobe was performed. Microscopic evaluation showed tumor tissue consisting of solid areas of uniform, oval cells with eosinophilic cytoplasm and centrally located nuclei. Stromal tissue was scanty, and mitotic figures were infrequent. Tumor cells were immunoreactive for synaptophysin, neuron-specific enolase, and ACTH. The postoperative course was uneventful and the patient was discharged on glucocorticoid supplementation. Signs of Cushing's syndrome were in regression, and patient remained normotensive and normoglycaemic without therapy. DISCUSSION: A multitude of normal nonpituitary cells from different organs and tissues have been shown to express the POMC gene from which ACTH is derived. The tumors most commonly associated the ectopic ACTH syndrome arise from neuroendocrine tissues, APUD cells. POMC gene expression in non-pituitary cells differs from that in pituitary cells both qualitatively and quantitatively [8]. Aggressive tumors, like small cell cancer of the lung (SCCL) preferentially release intact POMC, whereas carcinoids rather overprocess the precursor, releasing ACTH and smaller peptides like CLIP. Some tumors associated with ectopic ACTH syndrome express other markers of neuroendocrine differentiation like two specific prohormone convertases (PCs). Assessment of vasopressin (V3) receptor gene expression in ACTH-producing nonpitultary tumors revealed bronchial carcinoid as a particular subset of tumors where both V3 receptor and POMC gene may be expressed in pattern indistinguishable from that in corticotroph adenoma [9]. In most, but not all, patients with ectopic ACTH syndrome, cortisol is unresponsive to high-dose dexamethason suppression test, what is used as diagnostic tool. It is not clear if the primary resistance resulted from structural abnormality of the native glucocorticoid receptor (GR), a low level of expression, or some intrinsic property of the cell line [9]. It appears that ectopic ACTH syndrome is made of two different entities. When it is because of highly differentiated tumors, with highest level of pituitary-like POMC mRNA, expressing PCs, high level of V3 receptors and GR, like bronchial carcinoids, it might be called ectopic corticotroph syndrome. In contrast, when it is caused by aggressive, poorly differentiated tumors, with much lower expression of V3 receptor, like SCCL, it might be called aberrant ACTH secretion syndrome. Carcinoid tumors have been reported in a wide range of organs but most commonly involve the lungs, bronchi, and gastrointestinal tract. They arise from neuroendocrine cells and are characterized by positive reactions to markers of neuroendocrine tissue, including neuron specific enolase, synaptophysin, and chromogranina [11]. Carcinoid tumors are typically found to contain numerous membrane-bound neurosecretory granules composed of variety of hormones and biogenic amines. One of the best characterized is serotonin, subsequently metabolized to 5-hydrohy-indolacetic acid (5-HIAA), which is excreted in the urine. In addition to serotonin, carcinoid tumors have been found to secrete ACTH, histamine, dopamine, substance P, neurotensin, prostaglandins and kallikrein. The release of serotonin and other vasoactive substances is thought to cause carcinoid syndrome, which manifestations are episodic flushing, weezing, diarrhea, and eventual right-sided valvular heart disease. These tumors have been classified as either well-differentiated or poorly differentiated neuroendocrine carcinomas. The term "pulmonary tumorlets" describes multiple microscopic nests of neuroendocrine cells in the lungs [12]. Pulmonary carcinoids make up approximately 2 percents of primary lung tumors. The majority of these tumors are perihilar in location, and patients often presents with recurrent pneumonia, cough, hemoptisis, or chest pain. The carcinoid syndrome occurs in less than 5 percent of cases. Ectopic secretion of ACTH from pulmonary carcinoid accounts for 1 percent of all cases of Cushing's syndrome. They are distinct clinical and pathologic entity, generally peripheral in location. Although they are usually typical by standard histologic criteria, they have mush greater metastatic potential than hormonally quiescent typical carcinoids [13]. Surgical treatment therefore should be one proposed for more aggressive malignant tumors. In all cases of ACTH-dependent Cushing's syndrome with regular pituitary MRI and bilateral inferior petrosal sinus sampling, thin-section and spiral CT scanning of the chest should be routine diagnostic procedure [14]. We present thirty-one year old patient with typical pulmonary carcinod with ACTH ectopic secretion consequently confirmed by histology.