Carcinoid Tumor Of Lung Research Articles

Robotic resection of Stage III lung cancer: an international retrospective study.

Minimally invasive surgery is accepted for early-stage lung cancer, but its role in locally advanced disease is controversial, especially using a robotic platform. The aim of this retrospective study was to assess the safety and effectiveness of robot-assisted resection in patients with Stage IIIA non-small-cell lung cancer (NSCLC) or carcinoid tumours in the series as a whole and in different subgroups according to adjuvant treatment. This was a retrospective multicentre study of consecutive patients with clinically evident or occult N2 disease (210 NSCLC and 13 carcinoid) who, in 2007-2016, underwent robot-assisted resection at 7 high-volume centres. Perioperative outcomes, recurrences and overall survival were assessed. N2 disease was diagnosed preoperatively in 72 (32%) patients and intraoperatively in 151 (68%) patients. Surgical margins were negative in 98.4% of cases with available data. Thirty-four (15.2%) patients received neoadjuvant treatment, 140 (63%) patients received postoperative treatment, and 49 (22%) patients underwent surgery only. There were 22 (9.9%) conversions to thoracotomy, 23 (10.3%) had serious (Grades III-IV) postoperative morbidity and the mean hospital stay was 5.3 days. Complications and outcomes did not differ significantly between treatment groups. Of the 34 patients who were given neoadjuvant chemotherapy, all had R0 resection, 5 (15%) patients required conversion but none required conversion because of bleeding and 4 (12%) patients had Grade III or IV postoperative complications. After a median of 18 (interquartile range 8-33) months, 3-year overall survival in NSCLC patients was 61.2% and 60.3% (P = 0.6) of patients in the subgroup were given induction treatment. However, overall survival was significantly better (P = 0.012) in NSCLC patients with ≤2 positive nodes (vs >2). Nineteen (8.5%) patients developed local recurrence. Robot-assisted lobectomy is safe and effective in patients with Stage III NSCLC or carcinoid tumours with low conversions and complications. Among patients with NSCLC, including those who were given induction chemotherapy, survival was similar to that reported for open surgery.

A RARE CASE OF MULTIPLE-PRIMARY CANCER IN A WOMAN WITH BRCA 1 GENE MUTATION: BRCA-ASSOCIATED OVARIAN CANCER AND LUNG CARCINOID TUMOR

Inherited mutations in the BRCA1 and BRCA2 genes more often provoke the development of metachronous tumors compared to the general population. Women who carry inherited BRCA1 mutations have an increased risk of developing not only breast and ovarian cancers, but they have also increased risks of developing other types of cancers, such as cervical cancer, endometrial (uterine), ovarian, pancreatic, prostate, and salivary gland cancers. Common views on the pathogenesis of hereditary cancers imply that the development of the tumor is always preceded by the loss of the remaining (normal) allele of the involved gene. Nevertheless, there is reliable information that some BRCA1-associated ovarian cancers demonstrate retention of the second BRCA1copy. We report a rare case of the development of neuroendocrine cell carcinoma- metachronous ovarian cancer and lung carcinoid tumor in the patient with the BRCA1 gene mutation. In addition, the tumor demonstrated loss of heterozygosity at the BRCA1 locus (loss of the wild-type allele).

A Rare Case of Metastasis of Lung Carcinoid to Breast

Metastases to the breast from non-mammary primary tumors are uncommon. We present a rare, but typical, case of metastasis to the breast from lung carcinoid tumor, 20 years after the primary cancer was treated.

Case Report: Transection of Radial Arterial Catheter Requiring Surgical Intervention

We report a case in which a radial arterial line was placed prior to induction of general anaesthesia in a 76 year old male with prostate cancer and multiple co-morbidities who presented for thoracoscopic resection of a right lower lobe carcinoid lung tumor. The patient's intra-operative course was complicated by acute blood loss requiring conversion to an open procedure. A subsequent injury to the superior vena cava resulted in the need for immediate re-exploration at the conclusion of surgery. While the arterial line was still indicated in this patient's postoperative course in the ICU, malfunction on post-operative day one resulted in removal of the catheter. The catheter was secured by stay sutures and during the attempt to cut these sutures, the arterial catheter was inadvertently severed and a fragment remained within the patient's radial artery. Surgical intervention was required to remove the retained catheter and the patient recovered without evidence of residual injury or deficit to the artery and extremity. Literature review reveals only one other case report of a retained catheter in a radial artery caused by accidental transection during removal. We review indications for arterial line placement, complications, as well as methods for securing arterial catheters.

P3.15-002 Molecular Profiling and Networks Relevant to Disease Mechanisms in Small Cell Lung Cancer and Lung Carcinoid Tumor

Small Cell lung cancer (SCLC), which belongs to neuroendocrine tumor (NT), is known for its highly aggressive clinical features and poor prognosis. The molecular underpinnings that may prognosticate survival and could increase our understanding of tumor development and progression are still poor understood in its highly aggressive malignancies. We aimed to describe the proteomic characteristics and biomarker profiling of high-grade NT, SCLC versus low-grade NT, carcinoid tumor (CT) by the state-of-the-art proteomics techniques utilizing clinical specimens.

Fine needle aspiration cytology of hepatic metastases of neuroendocrine tumors: A 20-year retrospective, single institutional study.

Fine needle aspiration (FNA) is considered an excellent technique for documenting metastatic neuroendocrine tumors (NETs). This study aims to evaluate the accuracy of FNA in diagnosing metastatic NETs to the liver and determining the grade and origin of these metastases. Our laboratory information system was searched from 1997 to 2016 to identify all cases of metastatic NETs to the liver that were sampled by FNA. The cytopathology and surgical pathology reports as well as the patients' electronic medical records were reviewed. The cytohistologic type and grade of the metastatic NETs, as well as the site of the patient's primary were recorded. High-grade NETs, including small cell and poorly differentiated neuroendocrine carcinomas, constituted 62% (167/271) of the cases, while low-grade NETs, including well differentiated NET (grade1 and grade 2), pheochromocytomas, paragangliomas, and carcinoid tumors of lung, constituted 38% (104/271) of cases. The most common diagnosis was metastatic small cell carcinoma accounting for 45% (122/271) of cases. The most common primary sites were lung (44%; 119/271) followed by pancreas (19%; 51/271). The FNA diagnosis was confirmed by histopathology in 121 cases that had a concurrent biopsies or resection specimens. FNA is an accurate method for diagnosing metastatic NETs to the liver. There were significantly more high-grade (62%) than low-grade (38%) metastatic NETs to the liver. In our practice, lung (44%) and pancreas (19%) were the most common primary sites of metastatic NETs involving the liver. In 16% of the cases, a primary site could not be established.

68Gallium DOTANOC-PET Imaging in Lung Carcinoids: Impact on Patients' Management

Background:⁶⁸Gallium DOTA-PET imaging is preferable to standard somatostatin receptor scintigraphy where available; however, its role in the management of lung carcinoid tumours (LC) remains unclear. Methods: All consecutive patients with histologically confirmed LC from two ENETS Centres of Excellence were identified retrospectively. The primary objective was to assess the impact of ⁶⁸Ga-DOTANOC-PET on clinical management in patients with LC. Results: Of 166 patients screened, 46 were eligible: 52% female, median age 57 years (range 21-86); type of LC: diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (4%), typical (44%), atypical (35%), not reported (17%); stage: localised (63%), locally advanced (13%), and metastatic (17%) (7% unknown). A total of 47 ⁶⁸Ga-DOTANOCs were performed with the following rationale: LC diagnosis confirmation (4; 9%), primary tumour identification (2; 4%), post-surgical assessment (19; 40%), staging (patients with known LC present at time of ⁶⁸Ga-DOTANOC) (19; 40%), and consideration of peptide receptor radionuclide therapy (3; 7%). Twenty-seven (57%) scans showed evidence of non-physiological uptake: median maximum standardised uptake value 7.2 (range 1.42-53). ⁶⁸Ga-DOTANOC provided additional information in 37% (95% CI 22-51) of patients and impacted on management in 26% (95% CI 12-41); 9 patients (21%) were identified to have occult sites of metastases. Out of the 19 patients with post-surgical ⁶⁸Ga-DOTANOC, 3 (16%) were identified to have distant metastases. There were no differences in the rate of practice changing ⁶⁸Ga-DOTANOC results by type of LC (p value 0.5). Conclusions: Our results support the role of ⁶⁸Ga-DOTANOC for optimising the management of patients with LC, including post-surgical re-staging due to the potential for identifying occult metastases.

Acute mesenteric ischemia and hepatic infarction after treatment of ectopic Cushing's syndrome.

SummaryPatients with Cushing’s syndrome and excess exogenous glucocorticoids have an increased risk for venous thromboembolism, as well as arterial thrombi. The patients are at high risk of thromboembolic events, especially during active disease and even in cases of remission and after surgery in Cushing’s syndrome and withdrawal state in glucocorticoid users. We present a case of Cushing’s syndrome caused by adrenocorticotropic hormone-secreting lung carcinoid tumor. Our patient developed acute mesenteric ischemia after video-assisted thoracoscopic surgery despite administration of sufficient glucocorticoid and thromboprophylaxis in the perioperative period. In addition, our patient developed hepatic infarction after surgical resection of the intestine. Then, the patient was supported by total parenteral nutrition. Our case report highlights the risk of microthrombi, which occurred in our patient after treatment of ectopic Cushing’s syndrome. Guidelines on thromboprophylaxis and/or antiplatelet therapy for Cushing’s syndrome are acutely needed.Learning points:The present case showed acute mesenteric thromboembolism and hepatic infarction after treatment of ectopic Cushing’s syndrome.Patients with Cushing’s syndrome are at increased risk for thromboembolic events and increased morbidity and mortality.An increase in thromboembolic risk has been observed during active disease, even in cases of remission and postoperatively in Cushing’s syndrome.Thromboprophylaxis and antiplatelet therapy should be considered in treatment of glucocorticoid excess or glucocorticoid withdrawal.

Tumeur carcinoïde ovarienne responsable d’une érythrose faciale permanente et de flushs au décours des coïts

IntroductionOvarian neuroendocrine tumors are extremely rare. In the ovary, the term of neuroendocrine tumor is usually related to carcinoid tumors although it may be sometimes applied to neuroendocrine carcinomas of non-small cells or small cells cancers usually occurring in the lungs. These carcinoid tumors may develop de novo or from other tumors including teratomas. Case reportWe report a patient who presented with an ovarian carcinoid tumor developed, near or from a dermoid cyst, which was original by its mode of discovery in the dermatology department. Indeed, the patient consulted because of permanent facial erythrosis, with flushes but also facial telangiectasias. During medical examination, classic symptoms of carcinoid syndrome including heart disease were obvious. The occurrence of flushes during coitus should evoke pelvic tumor location. ConclusionA carcinoid syndrome is naturally evoked in the presence of flushes but it must also be part of the differential diagnosis in a patient with facial erythrosis or telangiectasias, especially if they are associated with diarrhea or right heart failure. The prognosis of carcinoid heart disease is considerably better in case of ovarian location than when it is a primitive carcinoid tumor of lung or from gastrointestinal tract.

Clinicopathological characteristics and prognosis of resected cases of carcinoid tumors of the lung.

BackgroundLung carcinoid tumors are rare, low‐grade, malignant neoplasms with some unclear features. The aim of this study was to analyze clinicopathological features and long‐term survival in patients with primary lung carcinoid tumors.MethodsPatients who underwent surgery in our clinic and were diagnosed with carcinoid tumors, between August 1997 and July 2012, were included in the study. Patient characteristics and clinicopathological factors were retrospectively evaluated.ResultsBronchial carcinoids comprised only 1.0% of lung cancer cases treated by resection. They are classified into two distinct categories: typical carcinoid (TC) and atypical carcinoid (AC) tumors. AC tumors occurred more frequently in younger patients and in smokers, and had a poorer prognosis than TC tumors. Overall three and five‐year survival rates for TC and AC were 92.6% and 81.1%, respectively. Univariate analysis showed that tumor size (P = 0.012) and histological type (P = 0.013) are prognostic factors. Multivariate analysis revealed that only tumor size (P = 0.044) was an independent prognostic factor.ConclusionsThe prognosis for bronchial carcinoid tumors was better than other types of lung cancer and TC was significantly better than AC. Radical lymph node dissection was the best treatment, with complete removal of the tumor. Tumor size was an independent prognostic factor for bronchial carcinoid tumors.

Diagnostic Utility of Orthopedia Homeobox (OTP) in Pulmonary Carcinoid Tumors.

Recently, Orthopedia Homeobox (OTP) was described as a prognostic marker for pulmonary carcinoid tumors; however, little is known about the function and distribution pattern of this transcription factor in normal organs/tissues and in tumors. Consequently, OTP expression was investigated in a variety of tumors, with special interest in pulmonary and nonpulmonary neuroendocrine tumors (NETs) and high-grade neuroendocrine carcinomas. OTP immunohistochemical analysis was performed on a total of 162 pulmonary carcinoid tumors, 31 pulmonary neuroendocrine hyperplasias, 104 pulmonary high-grade neuroendocrine carcinomas (large cell neuroendocrine and small cell neuroendocrine), 102 nonpulmonary NETs (G1/G2 NETs, small cell and large cell neuroendocrine carcinomas, and Merkel cell carcinomas), 150 endocrine tumors (thyroid, parathyroid, adrenocortical, and pheochromocytomas/paragangliomas), 279 adenocarcinomas, and 88 squamous cell carcinomas of various organs, including those of the lungs and others. In addition, normal tissues from various organs were studied. OTP nuclear expression was seen in 80% of lung carcinoid tumors. Among other tumors, 4 small-cell carcinomas showed focal expression (2 pulmonary and 2 bladder), but all other tumors were completely negative. Overall, the sensitivity and specificity of OTP were 80.2% and 99.4%, respectively. All TTF1-positive lung carcinoid tumors were diffusely positive for OTP, but none of the OTP-negative carcinoid tumors was positive for TTF1. OTP expression was not seen in any normal tissues/organs. OTP was also negative in neuroendocrine cells of the normal bronchus/bronchiole. However, OTP was strongly expressed in neuroendocrine hyperplasia, including reactive and preneoplastic hyperplasia. Our results suggest that OTP may serve as a useful diagnostic marker for lung carcinoid tumors.

Giant cell arteritis and polymyalgia rheumatica as first manifestation of typical pulmonary carcinoid tumor

Giant cell arteritis (GCA), a systemic vasculitis of unknown origin, may appear rarely as a paraneoplastic syndrome. Cases secondary to pulmonary neuroendocrine tumors have not been reported. A 75-year-old female developed prednisone-responsive GCA/polymyalgia rheumatica (PMR) shortly followed by syndrome of inappropriate antidiuretic hormone secretion. An 8 mm carcinoid lung tumor with positron emission tomography normal uptake was found. After a thoracoscopic tumor resection the patient experienced complete clinical and laboratory remission. This is the first report of GCA with PMR in the context of carcinoid lung tumor. It emphasizes the role of paraneoplastic vasculitis as a possible cause of GCA.

Primary lung tumors in children: 24 years of experience at a referral center.

Primary lung tumors are rare during childhood and encompass a wide variety of histological types. Each has a different biology and a different therapeutic approach. The aim of this article is to review the experience of a pediatric referral center with this kind of tumors during the last 24 years. A retrospective chart review was performed for patients with diagnosis of primary lung tumor between the years 1990-2014. The variables analyzed were age, sex, course of the disease, symptoms, localization, surgery, histology and outcome. Between 1990 and 2014, 38 patients with primary lung tumors were treated at our institution. Age at presentation was 6.6 ± 5.2 years (r 0.91-16.58) and the female:male relationship was 1.37. Inflammatory myofibroblastic lung tumor (n = 13), carcinoid tumor (n = 6) and pleuropulmonary blastoma (n = 6) were the most frequent histological types. Persistent radiographic abnormality was the most frequent presenting sign (34 %). Global mortality was 15.8 % varying according to histology. Although the diagnosis of primary lung tumor is rare, the persistence of a radiographic abnormality in spite of adequate treatment for inflammatory processes forces us to evaluate further. The age of the patient is an important factor in the decision of the diagnostic work-up.

Long-term Survival of a Patient with Typical Lung Carcinoid Tumor and Supraclavicular Lymph Node Metastasis Treated by Surgical Resection

Long-term Survival of a Patient with Typical Lung Carcinoid Tumor and Supraclavicular Lymph Node Metastasis Treated by Surgical Resection

Analysis of an EGFR mutation by PNA clamping method in lung carcinoid tumors

Background Pulmonary carcinoid tumors consisting of typical carcinoid tumors (TC) and atypical carcinoid tumors (AC) are rare, accounting for 2–5% of all lung tumors. TC is considered a low-grade tumor with a rate of distant metastasis up to 12%. In contrast, ACs are more aggressive tumors, displaying a metastatic rate up to 70%. Surgery is the treatment of choice; however, the current treatment outcomes of metastatic lung carcinoids are discouraging. This study aimed to investigate the EGFR mutation using the PNA-mediated clamping method and to provide basic data for using EGFR-TK1 and its clinical implications. Materials and Methods A total of 14 cases that underwent surgery were diagnosed as carcinoid tumors and pathologically classified as TC and AC. The paraffin-embedded tissues were analyzed for EGFR mutations using the PNA-mediated PCR clamping technique. The mutant type was noted in the cases with a△Ct greater than 2.0. Result Of 14 cases, eight were AC and six cases were TC. No known EGFR mutation was detected with a△Ct less than 2.0. Conclusion The EGFR genotype determined using the PNA-mediated PCR clamping method was wild-type in all pulmonary carcinoid tumors. Therefore, the application of EGFR-TK1 is limited in pulmonary carcinoid tumors.

Usefulness of Ki-67, Mitoses, and Tumor Size for Predicting Metastasis in Carcinoid Tumors of the Lung: A Study of 48 Cases at a Tertiary Care Centre in Canada.

Background. Evaluation of Ki-67 index in lung carcinoid tumors (LCTs) has been of interest in order to identify high risk subsets. Our objectives are (1) to evaluate the usefulness of Ki-67 index, mitoses, and tumor size in predicting metastasis and (2) to compare the Manual Conventional Method (MCM) and the Computer Assisted Image Analysis Method (CIAM) for Ki-67 calculation. Methods. We studied 48 patients with LCTs from two academic centres in Canada. For Ki-67 calculation, digital images of 5000 cells were counted using an image processing software and 2000 cells by MCM. Mitoses/10 HPF was counted. Results. We had 37 typical carcinoids (TCs) and 11 atypical carcinoids (ACs). 7/48 patients developed metastasis. There was a positive relationship between metastasis and carcinoid type (P = 0.039) and metastasis and mitoses (≥2) (P = 0.017). Although not statistically significant, the mean Ki-67 index for ACs was higher than for TCs (0.95% versus 0.72%, CIAM, P = 0.299). Similarly, although not statistically significant, the mean Ki-67 index for metastatic group (MG) was higher than for nonmetastatic group (NMG) (1.01% versus 0.71% by CIAM, P = 0.281). However when Ki-67 index data was categorized at various levels, there is suggestion of a useful cutoff (≥0.50%) to predict metastasis (P = 0.106, CIAM). A significantly higher proportion of patients with mitosis ≥2 and Ki-67 index ≥0.50% had metastasis (P = 0.033) compared to other patients. Similarly patients with tumor size ≥3 cm and Ki-67 ≥0.50% had a greater percentage of metastases than others (P = 0.039). Although there was a strong correlation between two (MCM versus CIAM) counting methods (r = 0.929, P = 0.001), overall the calculated Ki-67 index was slightly higher by MCM (range 0 to 6.4, mean 1.5) compared to CIAM (range 0 to 2.9, mean 0.75). Conclusion. This study confirms that mitoses ≥2 is a powerful predictor of metastasis in LCTs. Although this is a small sample size, there is suggestion that analysis of Ki-67 index along with mitoses and tumor size may be a useful adjunct for predicting metastasis in LCTs.

A Case of Lung Carcinoid Tumor, Successfully Treated with Bronchoscopic Cryosurgery in Thailand

A lung carcinoid tumor is a rare malignant neoplasm. The clinical presentation depends on the characteristics of the tumor, its location and hormones secreted. The most common symptoms are cough, wheezing, chest pain, hemoptysis and dyspnea. Diagnosis can be established through radiographic images, biopsy of the tumor with tissue analysis supplemented by blood tests. In previous years, surgery has been the gold standard in treating carcinoid tumors. However, recently, there have been several studies conducted in the efficacy of the use of bronchoscopic methods such as cryosurgery in completely extracting and treating lung carcinoid tumors without metastases. This case report’s objective is to illustrate that cryosurgery should be considered as the new gold standard in treating lung carcinoid tumors.

NUT expression in primary lung tumours.

BackgroundNuclear protein in testis (NUT) midline carcinomas (NMC) are rare, highly aggressive epithelial neoplasms, characterised by protein expression of NUT-fusion proteins which reflects the genetic translocation between chromosome 15 and 19. NMC occurs mainly in midline structures, but there are reports regarding occurrence in structures outside the midline.We investigated specimens from 519 surgically resected lung carcinomas and carcinoid tumours for the presence of NUT protein using immunohistochemistry. Normal testis and two previously confirmed NMCs served as positive controls.FindingsAll 483 evaluable cases (278 adenocarcinomas, 140 squamous cell carcinomas, 30 large cell carcinomas, 7 small cell carcinomas, 10 undifferentiated carcinomas and 18 carcinoids) were completely negative for expression of NUT protein.ConclusionNUT gene rearrangement does not seem to be relevant in primary pulmonary carcinomas or carcinoid tumours of the lung.

The Post-Surgical Long-Term Behaviour of Lung Carcinoid Tumours

Here, we report a retrospective evaluation of long-term behaviour of lung carcinoids after surgery. A total of 23 patients (17 with typical pulmonary carcinoids and 6 with atypical pulmonary carcinoids) were enrolled in our hospital from April 1994 to July 2009. All patients underwent intervention at the Unit of Surgery and then were followed at the Unit of Oncology. The standard protocol for patient monitoring consisted of follow-up at 3months after surgery, 6months after first control and annually for 5years. The follow-up evaluations consisted in blood tests, imaging of chest and abdomen, bone scintigraphy, and brain computed tomography. In case of disease recurrence, patients underwent chemotherapy (etoposide, carboplatin) and radiotherapy. All patients were followed for a mean of follow-up period of 100months, ranging between 20 and 203months. In the group of typical carcinoid, the observed recurrence rate at 5years was zero, at 10years was 5.8%, whereas the observed mortality rate at 5 and 10years was zero. In the group of atypical carcinoid, both the recurrence rate and the mortality rate at 5 and 10years were 16.6%. A statistical significant difference (p = 0.002) in the recurrence rate between stage I and stage II was observed. The overall prognosis of pulmonary carcinoids was favourable, and the typical carcinoids presented a better prognosis than the atypical ones. The stage at time of diagnosis could be considered as a predictive prognostic factor.

Recent advances in histogenesis research of lung neuroendocrine cancers: Evidence obtained from functional analyses of primitive neural/neuroendocrine cell-specific transcription factors.

Small cell carcinoma (SmCC) and large cell neuroendocrine carcinoma (LENEC) are categorized as neuroendocrine cancers (NECs) of the lung and have extremely poor prognoses. The lack of an effective therapeutic strategy against SmCC and LCNEC is a serious issue. Because the regulation of the cellular phenotype is complicated by the actions of various transcription factors, investigations into the function of neural/neuroendocrine cell-specific transcription factors are important for elucidating the cellular characteristics and histogenesis of SmCC and LCNEC and for establishing innovative therapeutic strategies against them. In this review, the functions of ASCL1, NeuroD1, REST, TTF1, and class III/IV POU, that are specifically and highly expressed in lung NECs, are introduced. These transcription factors transactivate and/or transrepress various genes and are involved in neural progenitor phenotyping, neuroendocrine and stem cell marker expression, and epithelial-to-mesenchymal transition. Based on the evidence that certain carcinoids express ASCL1, NeuroD1, TTF1, and class III/IV POU and that lung NECs can develop from non-NE cells/non-NEC cells, the relationships among lung NECs, carcinoid tumors, and non-NECs are discussed. Finally, a model of the histogenesis of lung NECs in view of similarities in the expression of primitive neural/neuroendocrine cell-specific transcription factors is proposed.