Small Cell Carcinoma Patients Research Articles

Surgery and Stereotactic Radiotherapy for Stage I Small-Cell Lung Carcinoma: A 25-Year Experience

ObjectivesSmall-cell lung carcinoma (SCLC) is usually a wide-spread, highly-lethal malignancy but occasionally presents as localized, limited stage cancer amenable to local treatment. We reviewed our experience using surgery or stereotactic body radiotherapy (SBRT) to assess safety, survival rates and treatment toxicity in clinical stage I SCLC patients. Materials and MethodsElectronic medical records of patients with clinical stage I lymph node-negative SCLC who underwent surgical resection or SBRT between 1996 and 2021 were retrospectively reviewed. A multivariable Cox Proportional Hazards model was constructed. ResultsOf 96 patients meeting inclusion criteria, 77 underwent resection and 19 underwent SBRT. Surgical patients were younger (mean 68.4 ± 9.2 years surgery versus 74.3 ± 6.6 years SBRT, P = .005) and had better pulmonary function (81.5 ± 19.6 FEV1% of predicted surgery versus 44.0 ± 20.9% SBRT, P < .001). SBRT patients had significantly more comorbidities. For both cohorts, 59 tumors were pure SCLC and 37 were mixed SCLC/NSCLC histology. Median survivals were 21 months versus 31 months for SBRT and surgery patients respectively (P = .07). There were no treatment-related mortalities. Mean length of hospital stay for surgical patients was 5.4 ± 5.7 days. Survival was longer in lymph node-negative surgery patients (median 48 months node-negative versus 19 months node-positive, P = .04). For node-negative-surgery patients, the estimated 2- and 5-year survival rates are 60% and 48%. ConclusionsOur single-institutional experience over 25 years demonstrates that local treatment with surgery or SBRT for clinical stage I SCLC is safe and effective, with survivals lower than similar stage non–small-cell carcinoma patients. However, our results compare favorably with prior small-cell surgical series and far better than reported results of chemoradiotherapy for similar stage patients, thereby validating current recommendations for employing surgery or SBRT for stage I SCLC.

COMPUTED TOMOGRAPHY IN DIFFERENTIATION BETWEEN SMALL CELL AND NON SMALL CELL CARCINOMA LUNG

Background :- Lung carcinoma is common in the developed world as well as developing world with high morbidity and mortality. It is broadly classified into two categories as small cell and non small cell carcinoma, in which radiological imaging plays a critical role in diagnosing and staging of cancer. Multi Detector computed tomography (MDCT) is the investigation of choice for evaluation of lung carcinomas. - The objectives of our study is radiologi Objectives: cal assessment of difference in size and location of primary and metastatic spread at presentation in histologically proven cases of small cell vs non small cell carcinoma of lung. This study comprised of patients who Material And Methods: presented to the department of radiodiagnosis Shri Ram Murti Smarak Institute Of Medical Science a tertiary care center of west Uttar Pradesh, for CT scan of thorax, with clinical symptomsand / or radiographic suspicion of lung cancer and cytohistopathological diagnosis of lung cancer over the period of two years. : In the present Observations And Results study a total of 84 patients were included. The non small cell carcinoma patients were 66(78.5%) which included Squamous cell carcinoma(40%) and adenocarcinoma (38%) and 18(21.4%) patients were of small cell carcinoma. On CT imaging non small cell carcinoma had larger size at presentation as compared to small cell carcinoma. Small cell carcinoma was more frequently associated with distant metastasis (77% cases) and mediastinal lymphadenopathy (100% cases) as compared to non small cell carcinoma

Evaluation the impact of IL-17 level in pulmonary carcinoma patients

The cancer burden continues to grow globally, exerting tremendous physical, emotional and financial strain on individuals, families, communities and health systems, immune dysfunction is an important cause of tumor development. A case -control study aimed to assess the role of IL-17 serum level in pathophysiology of lung cancer patients.150 patients attending to Middle Euphrates Cancer Center in AL-Najaf province from September till December 2021 that included 6(4%) small cell carcinoma patients and 144 (94 %) non small carcinoma patients from which squamous cell carcinoma patients represent 72(48%), Adenocarcenoma 48(16 %) and large –cell lung carcinoma 24(16%). as well as 30 apparently healthy subjects as control group . Two ml of vien blood were collected from all subjects put in gel tube to separate serum that used to estimate the IL-17 level by ELISA. The results showed a significant increase (P&lt;0.05) in serum concentration of IL-17 in lung cancer patients compare to healthy subjects. According to stage of lung cancer the concentration of IL-17 increased with severity of disease and this considar as biomarker for prograssve of state.

Diagnostic value of adenosine deaminase in bronchoalveolar lavage fluid for patients with lung cancer.

Lung cancer is both the most common seen malignity and cause of cancer-related deaths worldwide. Adenosine deaminase (ADA) is a hydrolytic enzyme that catalyses the conversion of adenosine to inosine in the purine metabolism pathway. Studies examining ADA levels in bronchoalveolar lavage (BAL) fluids of patients with lung malignancy are very limited in the literature. Our aim examine the clinical significance of ADA levels in BAL fluids of patients with lung malignancy. A total of 89 patients undergoing fiberoptic bronchoscopy (FOB) with different indications from December 2017 to December 2018 were included in this study. The patients were divided into two groups as malignancy and non-malignancy groups. Demographic, laboratory data and ADA levels in bronchoalveolar lavage (BAL) were compared between the two groups. In addition, ADA levels in BAL were compared among the histopathological subtypes of patients in the malignant group. The mean age of the patients was 58.2±14.5years with 86% of male gender. ADA enzyme levels were statistically higher in the malignant patient group compared with the non-malignant group (37.2 [17.6-71] vs 17.1 [9-35.3], P<.001). When the patients in the malignant group were compared in terms of ADA levels according to their histopathological types, a statistically significant difference was obtained in small cell carcinoma patients (49 [12.5-75.3], P=.005). ADA levels in BAL may be a diagnostic biomarker in lung malignancies. In patients where a biopsy cannot be taken or histopathological typing cannot be performed because of tissue insufficiency, ADA levels in BAL can be an auxiliary parameter in making malignancy / histopathological diagnosis accompanied by radiological and clinical findings.

Current trend of worsening prognosis of prostate small cell carcinoma: A population-based study.

ObjectiveTo determine the accurate age‐adjusted incidence of prostate small cell carcinoma (SCC), update the clinical and pathological characteristics, as well as survival data of prostate SCC from Surveillance, Epidemiology, and End Results (SEER) datasets.MethodsA total of 260 patients with prostate SCC were selected from the SEER database of the National Cancer Institute between 2004 and 2015. Age‐adjusted incidence (AAI) rates, the observed and relative survival rates were evaluated over time by the SEER*Stat Software version 8.3.5. Overall survival (OS) rates that stratified by summary stage and treatment effects were evaluated by Kaplan‐Meier method. The significant differences were assessed in a log‐rank test. Univariate and multivariate cox hazard regression analysis were performed to determine independent predictors of OS.ResultsThe incidence of prostate SCC has increased over time. The average age of prostate SCC patients was 70.25 years. More than 90% of tumors were poorly differentiated or undifferentiated. The majority of prostate SCC (77.7%) was at stage IV. 49% of patients had lymph node metastases and 68% of patients presented distant metastases (Compared with 60.5% of patients with distant metastases between 1973‐2003). Interestingly only 23.5% patients had high level PSA (>10 ng/mL). 58.8% of patients underwent chemotherapy, 25.4% of patients were treated by surgery, and 31.9% of patients were treated by radiotherapy. The observed survival rates of 1‐year, 2‐year, and 5‐year were 42.1%, 22.1%, and 12.5%, respectively (Compared with 47.9%, 27.5%, and 14.3%, respectively, between 1973 and 2003). Chemotherapy prolonged the OS of patients with regional (distant) metastases from 3 months (2 months) to 12 months (9 months). Multivariate cox regression analysis showed age, race, and stage were independent prognostic factors for prostate SCC patients.ConclusionProstate SCC is a highly malignant cancer and our analysis of recent data has shown its incidence is increasing. Incidence rate of metastatic prostate SCC has increased and the survival rates have worsened in recent years. However, chemotherapy shows some survival benefit for prostate SCC patients with regional and distant metastasis over other treatment methods. Further work is needed to understand the reason prognosis of this type prostate cancer is worsening.

Abstract 3156: NGS-based screening for TP53 mutations in circulating cell-free DNA: A first step towards early detection of lung cancers

Abstract Background The US National Lung Cancer Screening Trial (NLST) demonstrated in 2011 that screening with computed tomography (CT) scans could reduce lung cancer mortality by 20%, but with important financial costs and high number of false positives. The identification of novel biomarkers is a need to obtain the maximum benefit from CT screening. Given its economical and minimally invasive nature, screening for somatic mutations in circulating tumor DNA (ctDNA) using next-generation sequencing may complement existing screening tools. However, for application in early detection, variant detection must also be done agnostically, i.e. without prior knowledge from tumour tissue of the mutations expected and unfortunately, most currently available variant callers are not adapted for this task. Methods We performed multiplex PCR on circulating free DNA (cfDNA) extracted from the plasma of 35 lung squamous cell carcinoma (SCC) and 64 small-cell carcinoma (SCLC) patients. We additionally included 133 hospital controls to evaluate the specificity of ctDNA. We applied (&amp;gt;10,000X) Ion torrent targeted sequencing on the full-coding region of TP53 since this gene is known to be mutated in more than 70% and 90% of SCC and SCLC, respectively. Each amplification, library preparation, and sequencing was performed in duplicate to control for amplification and sequencing errors. Detecting mutations on ctDNA raises important statistical and bioinformatics challenges as it represents only a small fraction of cfDNA. We therefore developed and applied a method based on the idea that a data-derived model of sequencing errors has the potential to improve our ability to detect low-allelic fraction (AF) somatic variants. Results We detected TP53 non-synonymous coding mutations with AFs between 0.04% and 85% (median 1.7%) in 8 (23%) SCC patients, 28 (44%) SCLC patients, and 8 (6%) controls. We estimated odds ratios of 4.6 (p = 0.006) for SCC and 12.0 (p = 6.7×10-10) for SCLC. Observations in controls are surprising, but in this instance there was no information regarding a subsequent cancer diagnosis. Conclusion We show that it is possible to detect ctDNA in the cfDNA of lung cancer patients. Since only patients with early stage (I-IIA) SCC tumours were included, these results support the potential utility of the approach for early detection. Nevertheless, if such mutations are found prior to diagnosis has not been explored in a prospective study design with pre-diagnostic plasma samples and individuals without a cancer diagnosis through a follow-up period. Citation Format: Patrice H. Avogbe, Tiffany Delhomme, Noémie Leblay, Florence Le Calvez-Kelm, Priscilia Chopard, Valérie Gaborieau, Ghislaine Scelo, Behnoush Abedi-Ardekani, David Zaridze, Anush Mukeria, Graham Byrnes, Paul Brennan, Lynnette Fernandez-Cuesta, Matthieu Foll, James D. McKay. NGS-based screening for TP53 mutations in circulating cell-free DNA: A first step towards early detection of lung cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3156.

O2–003 - Lung Cancer in Patients with Combined Pulmonary Fibrosis and Emphysema

Background: Combined Pulmonary Fibrosis and Emphysema (CPFE) is a new category of interatital lung diseases named in 2005 by Cottin et al. The syndrome is strongly relateg with smoking history and frequently combined by lung cancer. However, the clinical course of those patients has not comprehensively described. Method: A review of all patients of lung cancer treated by chemotherapy or chemo-radiotherapy from January 2009 to December 2012 was conducted. Diagnosis of CPFE was based on CT finding, and patients with connective tissue disease and with a diagnosis of other interstitial lung disease was excluded. Result: CPFE were identified in 48 patients. There were 12 CPFE patients in 104 adenocarcinoma patients, 13 in 59 squamous cell carcinoma, 5 in 30 non-small cell carcinoma, and 18 in 119 small cell carcinoma. Nine patients underwent chemo-radiotherapy, and radiation pneumonitis was observed in 6 patients (G2 = 5, G3 = 1). Chemotherapy was given to 39 patients and drug-induced lung injury occurred in 1 patient. Overall survival was 9.7 months in non-small cell carcinoma patients, and 11.4 months in small cell carcinoma patients. Conclusions: In this study, the incidence rate of treatment-related lung injury was not so high as reported in previous study about chemotherapy for lung cancer patients with interstitial pneumonitis. Since the pathogenesis and the deference between CPFE and other interstitial pneumonitis is still unclear, more investigation about this syndrome is needed and the indication for treatment to combining lung cancer should be considered.

Tumor Histology Predicts Patterns of Failure and Survival in Patients With Brain Metastases From Lung Cancer Treated With Gamma Knife Radiosurgery

We review our experience with lung cancer patients with newly diagnosed brain metastases treated with Gamma Knife radiosurgery (GKRS). To determine whether tumor histology predicts patient outcomes. Between July 1, 2000, and December 31, 2010, 271 patients with brain metastases from primary lung cancer were treated with GKRS at our institution. Included in our study were 44 squamous cell carcinoma (SCC), 31 small cell carcinoma (SCLC), and 138 adenocarcinoma (ACA) patients; 47 patients with insufficient pathology to determine subtype were excluded. No non-small cell lung cancer (NSCLC) patients received whole-brain radiation therapy (WBRT) before their GKRS, and SCLC patients were allowed to have prophylactic cranial irradiation, but no previously known brain metastases. A median of 2 lesions were treated per patient with median marginal dose of 20 Gy. Median survival was 10.2 months for ACA, 5.9 months for SCLC, and 5.3 months for SCC patients (P = .008). The 1-year local control rates were 86%, 86%, and 54% for ACA, SCC, and SCLC, respectively (P = .027). The 1-year distant failure rates were 35%, 63%, and 65% for ACA, SCC, and SCLC, respectively (P = .057). The likelihood of dying of neurological death was 29%, 36%, and 55% for ACA, SCC, and SCLC, respectively (P = .027). The median time to WBRT was 11 months for SCC and 24 months for ACA patients (P = .04). Multivariate analysis confirmed SCLC histology as a significant predictor of worsened local control (hazard ratio [HR]: 6.46, P = .025) and distant failure (HR: 3.32, P = .0027). For NSCLC histologies, SCC predicted for earlier time to salvage WBRT (HR: 2.552, P = .01) and worsened overall survival (HR: 1.77, P < .0121). Histological subtype of lung cancer appears to predict outcomes. Future trials and prognostic indices should take these histology-specific patterns into account.

Primary small cell carcinoma of the esophagus: Retrospective analysis of the Veterans Affairs Cancer Registry.

e14641 Background: Small cell carcinoma (SCC) of the esophagus is a rare aggressive and rapidly fatal neoplasm, often diagnosed in late stages. Hence no prospective studies evaluating the most effective treatment strategies have been done. We aim to describe the clinicopathological features and treatment outcomes of this rare entity. Methods: Retrospective analysis of 49 patients diagnosed with SCC of the esophagus from 1995 to 2009 was done via the Veteran's Affairs Central Cancer Registry. Demographics, staging, treatment, and outcomes data was recorded. Staging was classified as limited (no distant metastasis) or extensive stage (metastatic disease). Results: Out of 10,540 patients with esophageal cancer, 49 were diagnosed with SCC (0.005%) and were mainly located in the middle and lower thirds of the esophagus (84%). Median age of diagnosis was 64.1 yrs (range: 26-90). 19 patients had limited disease, 26 patients had extensive disease and four patients who were not staged adequately were excluded. Patients received a variety of treatments (Table) with different survival outcomes. Limited stage SCC patients had a median survival of 6.3 mos with patients who received combined modality therapy showing a trend towards improved outcomes. Extensive stage patients who received no therapy had very poor outcomes compared to patients who received any therapy. Conclusions: SCC of esophagus should be considered a systemic disease and like pulmonary SCC, it is an aggressive tumor associated with a poor prognosis. Patient numbers are too low to draw definitive conclusions regarding choice of therapy. Extensive disease patients benefit from chemotherapy and combined modality therapy should be considered in limited stage disease. [Table: see text]

Primary small cell carcinoma of the esophagus: Retropective analysis of the Veterans Affairs Cancer Registry.

32 Background: Small cell carcinoma (SCC) of the esophagus is a rare aggressive and rapidly fatal neoplasm, often diagnosed in late stages. Hence no prospective studies evaluating the most effective treatment strategies have been done. We aim to describe the clinicopathological features and treatment outcomes of this rare entity. Methods: Retrospective analysis of 49 patients diagnosed with SCC of the esophagus from 1995 to 2009 was done via the Veteran's Affairs Central Cancer Registry. Demographics, staging, treatment, and outcomes data was recorded. Staging was classified as limited (no distant metastasis) or extensive stage (metastatic disease). Results: Out of 10,540 patients with esophageal cancer, 49 were diagnosed with SCC (0.005%) and were mainly located in the middle and lower thirds of the esophagus (84%). Median age of diagnosis was 64.1 yrs (range: 26-90). 19 patients had limited disease, 26 patients had extensive disease and four patients who were not staged adequately were excluded. Patients received a variety of treatments (Table) with different survival outcomes. Limited stage SCC patients had a median survival of 6.3 mos with patients who received combined modality therapy showing a trend towards improved outcomes. Extensive stage patients who received no therapy had very poor outcomes compared to patients who received any therapy. Conclusions: SCC of esophagus should be considered a systemic disease and like pulmonary SCC, it is an aggressive tumor associated with a poor prognosis. Patient numbers are too low to draw definitive conclusions regarding choice of therapy. Extensive disease patients benefit from chemotherapy and combined modality therapy should be considered in limited stage disease. [Table: see text]

Differential Expression of Glut1 in Pulmonary Neuroendocrine Tumors: Correlation with Histological Grade

BACKGROUNDIncreased glucose uptake, a process that is mediated by glucose transporter (Glut1) proteins, is an important metabolic feature in a variety of cancer cells. The overexpression of Glut1 in human cancers is known to be related to a variety of histopathological parameters, including histological grade, proliferation rate, and lymphatic invasion. The principal objective of this study was to evaluate Glut1 expression in the spectrum of pulmonary neuroendocrine (NE) tumors including typical carcinoid tumor (TC), atypical carcinoid tumor (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCC), and to characterize the relationship between Glut1 expression and the histologic grade of NE tumors.METHODS19 TC, 7 AC, 13 LCNEC, and 6 SCC patients were included in this study. The percentages of Glut1-positive tumor cells in these patients were determined. For statistical analysis, Glut1 expression was subdivided into a Glut1-low expression group (0-30%) and a Glut1-high expression group (31-90%).RESULTSIn our subgroup analyses, the histological grade of pulmonary neuroendocrine (NE) tumors was significantly correlated with Glut1 expression; TC (n=19, 3.6+/-4.2%), AC (n=7, 20.0+/-4.9%), LCNEC (n=13, 60.0+/-21.1%), and SCC (n=6, 74.2+/-16.9%). Glut1-high expression was significantly associated with high-grade NE tumors such as LCNEC and SCC (n=19, 62.6+/-21.0%) (p=0.000).CONCLUSIONSThe results of this study appear to indicate that Glut1 overexpression is a consistent feature of high-grade NE lung tumors.

Clinical analysis of 81 cases with primary small cell carcinoma of the esophagus

To evaluate the clinical characteristics, treatment and prognostic factors in patients with primary small cell carcinoma (SmCC) of the esophagus. Eighty-one esophageal SmCC patients were treated from 1999 to 2007 in our department, and their clinical data were retrospectively reviewed. Of the 81 patients, 52 (64.2%) were in limited stage (LS) and 23 (28.4%) in extensive stage (ES). The 1-, 3- and 5-year survival rates were 55.6%, 6.2% and 2.5%, respectively, with a median survival time of 13.5 months for the whole group; 69.2%, 7.3% and 3.6%, respectively, with a median survival time of 15 months for the LS group; while only 25.2%, 0 and 0, respectively, with a median survival time of 6 months for the ES group. Multivariate analysis showed that disease stage, performance status, multidisciplinary comprehensive therapy and mode of treatment were independent prognostic factors. Esophageal small cell carcinoma is a rare but highly aggressive malignant tumor. Disease stage and performance status are important prognostic factors. Appropriate treatment may play a key role in improving the survival of the patients.

Clinicopathologic features and histochemical analyses of proliferative activity and angiogenesis in small cell carcinoma of the esophagus

We investigated clinicopathologic features in patients with esophageal small cell carcinoma (SCEC), and its proliferative activity and angiogenesis. Ten patients with SCEC from 335 esophageal carcinoma patients were analyzed clinicopathologically. For analyses of cell proliferation, apoptosis, and angiogenesis of SCEC, Ki-67 immunostaining, the TUNEL method, and CD31 and CD68 immunostaining were used. Esophagectomy was performed in nine patients, while one with extensive SCEC was treated by repeated chemotherapy and radiotherapy. Four patients received chemotherapy both before and after surgery, one only before surgery, and four only after surgery. Cisplatin and etoposide were given to five patients, while irinotecan and cisplatin were given to three. Five survived more than 18 months, and two more than 36 months. One of these two had limited SCEC treated by surgery and chemotherapy, whereas the other had extended SCEC treated by repeated chemotherapy and radiotherapy. The microvessel count and the Ki-67 labeling index of SCEC were higher than those of squamous cell carcinoma (P = 0.0033 and P = 0.0005, respectively). Between SCEC with and without preoperative chemotherapy, the Ki-67 labeling index was lower (P = 0.027) and the apoptotic index was higher in the treated SCEC (P = 0.014). Between SCEC patients who survived more or less than 18 months, the microvessel count was lower in those who survived more than 18 months (P = 0.049). Esophagectomy may be indicated for limited SCEC combined with chemotherapy. SCEC has high proliferative activity and rich neovascularization, and its proliferative activity may be suppressed by chemotherapy.

Surgical treatment of neuroendocrine tumors of the lung.

This report reviews the pattern of neuroendocrine (NE) differentiation, lymph-node involvement, extension of surgery, and survival in 125 NE lung tumor patients. Standard diagnostic workup included CT scan, bronchoscopy, bronchial biopsy or Fine Needle Aspiration Biopsy, (111)In-pentetreotide scan (OctreoScan) and mediastinoscopy in selected patients. NE differentiation was assessed based on the morphology and immunohistochemical reactivity for pan-neuroendocrine markers NSE, CGA, and Synaptophysin. For small cell carcinoma (SCC), only clinical stage I and II patients underwent surgery. Several different surgical procedures were utilized, from limited resections to lobectomy, pneumonectomy, and bronchoplastic procedures. Survival was assessed using Kaplan-Meyer method at 5 years. There were 79 typical carcinoid (TC), eight atypical carcinoid (AC), 18 large cell carcinoma (LCC) and 20 SCC patients. Mean age at diagnosis was 54.6+/-15.2 (ranges from 16 to 77 years) for TC, 68.5+/-9.1 (range 53-81) for AC, 68.7+/-4.6 (range 58-77) for LCC, 64.6+/-7.9 (range 48-82) for SCC. Male/female ratio was 1/1 for TC and AC, 2.6/1 for LCC and 9/1 for SCC. Lymph-node involvement was present in 14% of TC, 0% of AC, 31.5% of LCC, and 45% of SCC. Cancer specific survival was 96% for TC, 87.5% for AC, 37.5% for LCC, and 30% for SCC at 5 years from surgery. Presenting symptoms were invariably of respiratory-related. None had the carcinoid syndrome. History of tobacco abuse ranged from 46% for TC to 100% in SCC. Survival ranged from a minimum of 1 month for SCC to a maximum of 168 months with no evidence of disease for TC. Synchronous multicentric forms were found in 14% of TC. Twenty-one percent (4/19) of the patients with SCC treated by induction therapy and surgery, and in few cases by surgery and adjuvant chemotherapy are alive without the evidence of the disease for 5 years. Due to the high percentage of lymph-node involvement and multicentric forms found in our series lobectomy with radical lymph-node dissection appears, in our opinion, the most appropriate surgical treatment in well-differentiated forms, while more limited resection appears sub-optimal. Also, due to the finding of recurrences many years after surgery, the follow-up must be accurate and protracted in this subgroup. Only Small Cell Lung Carcinoma patients in clinical stage I and II underwent surgery with good long-term results.

HASH1 expression is closely correlated with endocrine phenotype and differentiation extent in pulmonary neuroendocrine tumors

The human homolog 1 of the Drosophila neurogenic achaete–scute genes, hASH1, is specifically expressed in fetal pulmonary neuroendocrine cells and in some neuroendocrine tumor cell lines. However, no data have been gathered regarding its in vivo expression in tumors. hASH1 mRNA expression was investigated by in situ hybridization in 238 surgically resected lung carcinomas, and the correlations between hASH1 expression status and immunostaining results of neuroendocrine markers chromogranin A, neural cell adhesion molecule, gastrin-releasing peptide and calcitonin, and clinical outcome were analyzed. hASH1 expression was detected in 2/20 (10%) adenocarcinomas, 4/30 (13.3%) typical carcinoids, 11/13 (84.6%) atypical carcinoids, 38/67 (56.7%) large-cell neuroendocrine carcinomas and 56/78 (71.8%) small-cell carcinomas, respectively, but not in any squamous cell carcinoma (0/21) or large-cell carcinoma (0/9). The 2 hASH1+ adenocarcinomas also expressed multiple neuroendocrine markers. Thus, hASH1 expression was restricted to lung cancers with neuroendocrine phenotypes. However, not all neuroendocrine tumors expressed hASH1. Within the entities of large-cell neuroendocrine carcinoma and small-cell carcinoma, hASH1 expression correlated very closely with chromogranin A, gastrin-releasing peptide and calcitonin expression (P<0.0001, r=0.852), but was not related to neural cell adhesion molecule expression (P=0.8892), suggesting that hASH1 expression, at least in lung cancer, is associated with endocrine phenotype expression other than ‘neuroendocrine differentiation’ in a broad sense. The fact that hASH1 was virtually absent in almost fully differentiated typical carcinoids, but was expressed in most, if not all, less differentiated atypical carcinoids as well as large-cell neuroendocrine carcinomas and small-cell carcinomas, suggests that hASH1 expression in lung cancer imitates its early and transient expression in fetal development, and that hASH1 is instrumental in the establishment, but not in the maintenance, of a cellular endocrine phenotype. Finally, hASH1 expression correlated with a significantly shortened survival in small-cell carcinoma patients (P=0.041).

HASH1 expression is closely correlated with endocrine phenotype and differentiation extent in pulmonary neuroendocrine tumors

The human homolog 1 of the Drosophila neurogenic achaete–scute genes, hASH1, is specifically expressed in fetal pulmonary neuroendocrine cells and in some neuroendocrine tumor cell lines. However, no data have been gathered regarding its in vivo expression in tumors. hASH1 mRNA expression was investigated by in situ hybridization in 238 surgically resected lung carcinomas, and the correlations between hASH1 expression status and immunostaining results of neuroendocrine markers chromogranin A, neural cell adhesion molecule, gastrin-releasing peptide and calcitonin, and clinical outcome were analyzed. hASH1 expression was detected in 2/20 (10%) adenocarcinomas, 4/30 (13.3%) typical carcinoids, 11/13 (84.6%) atypical carcinoids, 38/67 (56.7%) large-cell neuroendocrine carcinomas and 56/78 (71.8%) small-cell carcinomas, respectively, but not in any squamous cell carcinoma (0/21) or large-cell carcinoma (0/9). The 2 hASH1+ adenocarcinomas also expressed multiple neuroendocrine markers. Thus, hASH1 expression was restricted to lung cancers with neuroendocrine phenotypes. However, not all neuroendocrine tumors expressed hASH1. Within the entities of large-cell neuroendocrine carcinoma and small-cell carcinoma, hASH1 expression correlated very closely with chromogranin A, gastrin-releasing peptide and calcitonin expression (P<0.0001, r=0.852), but was not related to neural cell adhesion molecule expression (P=0.8892), suggesting that hASH1 expression, at least in lung cancer, is associated with endocrine phenotype expression other than ‘neuroendocrine differentiation’ in a broad sense. The fact that hASH1 was virtually absent in almost fully differentiated typical carcinoids, but was expressed in most, if not all, less differentiated atypical carcinoids as well as large-cell neuroendocrine carcinomas and small-cell carcinomas, suggests that hASH1 expression in lung cancer imitates its early and transient expression in fetal development, and that hASH1 is instrumental in the establishment, but not in the maintenance, of a cellular endocrine phenotype. Finally, hASH1 expression correlated with a significantly shortened survival in small-cell carcinoma patients (P=0.041).

Risk of a new primary cancer among patients with lung cancer of different histological types

The risk of a new primary cancer (NPC) among 77 548 Finnish lung cancer patients from 1953 to 1995 was analysed by the histological type of the lung cancer. The relative risks were expressed as standardised incidence ratios (SIR, ratio of the observed and expected numbers of cases). During the follow-up, 1148 NPCs were observed among men and 152 among women. After exclusion of lung cancers, the risk of NPC was elevated in both males (SIR 1.07; 95% confidence interval (CI) 1.00–1.14) and females (SIR 1.21; 95% CI 1.02–1.42). The excess was larger among lung cancer patients with small-cell carcinoma and adenocarcinoma than those with squamous-cell carcinoma. In all major histological groups of lung cancer, significant excess risks were found for cancers of the larynx (SIRs 2.94–4.25), and bladder (SIRs 2.16–2.86). Significantly elevated SIRs were also found for cancers of the stomach (SIR 1.42; 95% CI 1.12–1.76) and kidney (SIR 2.18; 95% CI 1.56–2.97) in squamous-cell carcinoma; for brain tumours (SIR 3.26; 95% CI 1.20–7.09) in small-cell carcinoma; and for cancers of the prostate (SIR 1.68; 95% CI 1.21–2.27) and thyroid (SIR 3.79; 95% CI 1.23–8.85), and brain tumours (SIR 2.34; 95% CI 1.07–4.43) in adenocarcinoma. The risk of contracting NPC at sites where the majority of tumours are adenocarcinomas was elevated among patients with adenocarcinoma of the lung, but not among squamous-cell or small-cell carcinoma patients. In adenocarcinoma, the excess risks of several smoking-related cancers tended to be somewhat lower than those in the other two histological categories. The relative risk of a NPC among patients diagnosed with lung cancer in 1985–1995 was higher than that of patients from earlier periods in all comparable follow-up categories (up to 10 years), possibly suggesting that the increased use of cytostatic drugs had increased the risk of NPC.

Primary small cell carcinoma of the esophagus

BACKGROUND Few studies of patients with esophageal small cell carcinoma (SCC) have been conducted. Choice of treatment remains controversial. METHODS The authors analyzed data on 199 evaluable esophageal SCC patients, selected from among 230 patients found in the literature, and a data extraction form that recorded 11 features was completed. To allow for the evaluation of prognostic factors that influenced survival, the patients were grouped according to limited stage (LS), which was defined as disease confined to the esophagus, or extensive stage (ES), which was defined as disease that had spread beyond locoregional boundaries. Univariate and multivariate analyses were performed. Treatment was categorized as either local or local with systemic; for the ES cases, the categories were defined as treatment versus no treatment. RESULTS The tumor site was described in 178 cases (89%). Mean tumor size was 6.1. Pure SCC was found in 137 cases (68.8%), whereas 62 cases (31.2%) showed mixed SCC; 93 (46.7%) were LS, whereas 95 (47.7%) were ES. In 11 cases (5.5%), the stage was not determined. There was a significant difference in survival between patients with LS and those with ES (P < 0.0001). The median survival was 8 months for patients with LS and 3 months for those with ES. Univariate analysis of LS showed 3 significant prognostic factors: age (for patients age ≤60 years, the median survival was 11 months, whereas for those age >60 years, the median survival was 6 months), tumor size (for those with tumors ≤5 cm, the median survival was 12 months, whereas for those with tumors >5 cm, the median survival was 4 months), and type of treatment (with local plus systemic treatment, the median survival was 20 months, whereas with local it was 5 months). In multivariate analysis, tumor size (P = 0.007) and type of treatment (P < 0.001) were shown to be independent predictive variables. CONCLUSIONS Esophageal SCC is an aggressive type of tumor. This study shows that there are significant differences between LS and ES and that in LS, both tumor size and type of treatment are possible prognostic factors. Cancer 1997; 80:1366-72. © 1997 American Cancer Society.

Primary small cell carcinoma of the esophagus

Few studies of patients with esophageal small cell carcinoma (SCC) have been conducted. Choice of treatment remains controversial. The authors analyzed data on 199 evaluable esophageal SCC patients, selected from among 230 patients found in the literature, and a data extraction form that recorded 11 features was completed. To allow for the evaluation of prognostic factors that influenced survival, the patients were grouped according to limited stage (LS), which was defined as disease confined to the esophagus, or extensive stage (ES), which was defined as disease that had spread beyond locoregional boundaries. Univariate and multivariate analyses were performed. Treatment was categorized as either local or local with systemic; for the ES cases, the categories were defined as treatment versus no treatment. The tumor site was described in 178 cases (89%). Mean tumor size was 6.1. Pure SCC was found in 137 cases (68.8%), whereas 62 cases (31.2%) showed mixed SCC; 93 (46.7%) were LS, whereas 95 (47.7%) were ES. In 11 cases (5.5%), the stage was not determined. There was a significant difference in survival between patients with LS and those with ES (P < 0.0001). The median survival was 8 months for patients with LS and 3 months for those with ES. Univariate analysis of LS showed 3 significant prognostic factors: age (for patients age < or =60 years, the median survival was 11 months, whereas for those age >60 years, the median survival was 6 months), tumor size (for those with tumors < or =5 cm, the median survival was 12 months, whereas for those with tumors >5 cm, the median survival was 4 months), and type of treatment (with local plus systemic treatment, the median survival was 20 months, whereas with local it was 5 months). In multivariate analysis, tumor size (P = 0.007) and type of treatment (P < 0.001) were shown to be independent predictive variables. Esophageal SCC is an aggressive type of tumor. This study shows that there are significant differences between LS and ES and that in LS, both tumor size and type of treatment are possible prognostic factors.

Results of surgical treatment of stage I and II lung cancer: Shah R, Sabanathan S, Richardson J, Goulden C. Department of Thoracic Surgery, Bradford Royal Infirmary, Duckworth Lane, Bradford BD9 6RJ. J Cardiovasc Surg 1996; 37:169–172

Pulmonary resection remains the most appropriate treatment for localised bronchogenic carcinoma, since prognosis and outcome are currently dependent on surgical resectability. A retrospective analysis of our experience with three hundred and thirteen stage I (n=250) and stage II (n=63) patients treated surgically form the basis of this report. The initial pulmonary resection was lobectomy in 173 patients, bilobectomy in 38, sleeve lobectomy in 12, pneumonectomy in 59, wedge excision or segmentectomy in 31. The overall operative mortality was 3.2%; 4.03% for lobectomy and 1.6% for pneumonectomy. Morbidity was observed in 21 (6.7%) patients. Four out of sixteen small cell carcinoma patients had postoperative adjuvant chemotherapy. Survival in patients with stage I tumours was 71% at 5 years and 61% at 10 years compared with 41% at 5 years and 35% at 10 years for patients with stage II disease. The five year survival after pneumonectomy was significantly (p<0.05) better for both stage I and stage II lung cancer than after lobectomy. Five year survival in stage I carcinoma was not influenced by histological type, while there was statistically significant difference (p<0.05) in survival between adenocarcinoma (0%) and squamous cell carcinoma (46%) in stage II disease. We conclude that an aggressive surgical approach can provide an excellent prognosis for recovery and long term cure in most patients with early stage lung cancer.