Alessandro Marra

• MD, PhD
• Head of Department at Rems-Murr-Klinikum

Surgical staplers play an important role in the contemporary minimally invasive thoracic surgery including resection of lung tissue. However, staple line failure resulting in postoperative air leaks is a common complication after lung surgery, that if persist more than five days are defined as prolonged air leaks (PALs). PALs are associated with in...

Simple Summary Lung cancer is the leading cause of cancer related deaths and non-small cell lung cancer (NSCLC) is its most relevant subtype. Here, we present data on p53 co-playing 5′-Nucleotidase Domain-Containing Protein 2 (NT5DC2) protein- and gene-expression and its clinical implication and prognostic value. NT5DC2 overexpression was associate...

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide underlining the urgent need for new biomarkers and therapeutic targets for this disease. Long noncoding RNAs are critical players in NSCLC but the role of small RNA species is not well understood. In the present study, we investigated the role of H/ACA box small nucle...

Background: T cell infiltration in non-small cell lung cancer (NSCLC) is essential for the immunological response to malignant tissue, especially in the era of immune-checkpoint inhibition. To investigate the prognostic impact of CD4+ T helper cells (Th), CD8+ cytotoxic (Tc) and FOXP3+ regulatory T (Treg) cells in NSCLC, we performed this analysis...

Background: Epithelial-to-mesenchymal transition (EMT) is a crucial step in lung cancer pathogenesis. Among others, cancer-associated fibroblasts (CAFs) are reported to regulate this process. Objectives: To investigate the prognostic and clinical impact, we analyzed CD34+ and SMA+ CAFs in non-small cell lung cancer (NSCLC). Methods: Retrospect...

While targeted nonsmall cell lung cancer (NSCLC) therapies have improved the outcome of defined disease subtypes, prognosis for most patients remains poor. We found the AAA+ ATPase Reptin to be highly expressed in the vast majority of 278 NSCLC tumour samples. Thus, the objective of the study was to assess the role of Reptin in NSCLC. Survival anal...

Objectives PSMA (prostate-specific membrane antigen) is overexpressed in prostate cancer cells and is reported to be a promising target for antibody-based radioligand therapy in patients with metastasized prostate cancer. Since PSMA expression is not restricted to prostate cancer, the underlying study investigates PSMA expression in non-small cell...

Correlation of clinicopathological variables with PSMA expression in NSCLC patients depending on tumor histology and grading. (DOCX)

[This corrects the article DOI: 10.1371/journal.pone.0177146.].

Background Aminopeptidase N (CD13) is a zinc-binding protease that has functional effects on both cancerogenesis and tumor angiogenesis. Since CD13 is an antigen suitable for molecular targeted therapies (e.g. tTF-NGR induced tumor vascular infarction), we evaluated its impact in NSCLC patients, and tested the effects of the CD13-targeted fusion pr...

Mouse trial: A549 Xenotransplants (tTF-NGR vs. PBS; raw data). (PDF)

Representative example for CD31 expression in NSCLC microvessels. (EPS)

The prognostic impact of CD13 in lung cancer with regard to univariate analyses. (PDF)

FACS analysis (A 549; raw data). (PDF)

NSCLC study collective (CD13 expression; raw data). (PDF)

Einleitung: Zunehmend gewinnt die Immuntherapie an Bedeutung in der Behandlung des Lungenkarzinoms. Erste klinische Studien bekraftigen bereits den therapeutischen Nutzen einer gezielten Beeinflussung von PD-1 („programmed cell death receptor“) und seinem Liganden PD-L1. Der diagnostische, prognostische sowie pradiktive Nutzen beider Faktoren ist j...

Objectives: Several blood group-related carbohydrate antigens are prognosis-relevant markers of tumor tissues. A type 3 (repetitive A) is a blood group antigen specific for A1 erythrocytes. Its potential expression in tumor tissues has so far not been examined. Material and methods: We have evaluated its expression in normal lung and in lung can...

A lung abscess is an infectious pulmonary disease characterised by the presence of a pus-filled cavity within the lung parenchyma. The content of an abscess often drains into the airways spontaneously, leading to an air-fluid level visible on chest X-rays and CT scans. Primary lung abscesses occur in patients who are prone to aspiration or in other...

Introduction: To improve the prognosis of lung cancer patients, immunotherapy is expected to become a powerful therapeutic option. Several clinical studies demonstrate a positive prognostic effect of a targeted therapy against the programmed cell death receptor PD1 and its ligand PDL1 in solid tumors. For non-small lung cancer (NSCLC) however, the...

Background: Immunotherapy can become a crucial therapeutic option to improve prognosis for lung cancer patients. First clinical trials with therapies targeting the programmed cell death receptor PD-1 and its ligand PD-L1 have shown promising results in several solid tumors. However, in lung cancer the diagnostic, prognostic and predictive value of...

Epigenomic changes are an important feature of malignant tumors. How tumor aggressiveness is affected by DNA methylation of specific loci is largely unexplored. In genome wide DNA methylation analyses we identified the KCa 3.1 channel gene (KCNN4) promoter to be hypomethylated in an aggressive non-small cell lung carcinoma (NSCLC) cell line and in...

Pneumothorax is defined as an accumulation of air between the parietal and visceral pleura followed by lung collapse. Whereas primary pneumothorax occurs without an appa- rent cause and in the absence of significant lung disease, secondary pneumothorax is associated with underlying lung disease (for example COPD, lung fibrosis or malignent tumor)....

Background Sleeve lobectomy (SL) is considered a valid therapeutic option in untreated, centrally located non-small cell lung cancer (NSCLC) even in patients “fit” for pneumonectomy (PN). Nevertheless, SL feasibility and long-term results after induction therapy (IT) have been only rarely investigated. We herein report the results of a multicenter...

Introduction: Apoptosis is a crucial pathway in tumor growth and metastatic development. Apoptotic proteins regulate the underlying molecular cascades and are thought to modulate the tumor response to chemotherapy and radiation. However, the prognostic value of the expression of apoptosis regulators in localized non-small-cell lung cancer (NSCLC)...

e18511 Background: Neoadjuvant platinum-based chemotherapy in stage III NSCLC offers the chance to eradicate occult metastases and decrease tumor volume, thus improving curative surgical resection rates. A remission after induction therapy is correlated with prolonged survival. However, only 40-50% of patients respond to therapy since there is stil...

Alterations of Eph receptor tyrosine kinases are frequent events in human cancers. Genetic variations of EPHB6 have been described but the functional outcome of these alterations is unknown. The current study was conducted to screen for the occurrence and to identify functional consequences of EPHB6 mutations in non-small cell lung cancer. Here, we...

The treatment of locally advanced non-small-cell lung cancer at present consists of definitive combined chemoradiotherapy using full-dose cisplatin. An irradiation dose of 60–66 Gy is considered optimal and trials concerning dose escalation have not provided any additional benefit up to now. A modified fractionation, however, can influence survival...

The aim of this study was to evaluate the safety and efficacy of an original technique of single-port video-assisted thoracoscopy (S-VATS) for the minimally invasive treatment of pleural empyema in fibrinopurulent stage. Single-port video-assisted thoracoscopy was performed under general anesthesia and single-lung ventilation using a 2-cm incision...

Zielsetzung: Ziel der vorliegenden Studie war die Evaluierung der Durchfuhrbarkeit, des Risikoprofils sowie der Effektivitat der Single-Port videoassistierten Thorakoskopie (S-VATS) zur minimal-invasiven Behandlung des Pleuraempyems im Stadium I-II. Methode: Es handelt sich um eine retrospektive Analyse der Daten 61 konsekutiver, einer S-VATS unter...

Objective: To investigate the prognostic significance of location and extent of lymph node metastasis in resected non-small cell lung cancer (NSCLC), and to weigh up the influence of treatment modalities on survival. Patients and method: On exploratory analysis, patients were grouped according to location and time of diagnosis of nodal metastasis:...

The functions of large noncoding RNAs (ncRNAs) have remained elusive in many cases. Metastasis-Associated-in-Lung-Adenocarcinoma-Transcript-1 (MALAT-1) is an ncRNA that is highly expressed in several tumor types. Overexpression and RNA interference (RNAi) approaches were used for the analysis of the biological functions of MALAT-1 RNA. Tumor growth...

Loss of EPHB6 receptor tyrosine kinase expression in early-stage non-small cell lung carcinoma (NSCLC) is associated with the subsequent development of distant metastasis. Here, we analyzed the regulation and function of EPHB6 in lung cancer metastasis. The expression levels of EPHB6 were compared among normal lung tissue (n = 9), NSCLC without met...

S100 proteins are implicated in metastasis development in several cancers. In this study, we analyzed the prognostic role of mRNA levels of all S100 proteins in early stage non-small cell lung cancer (NSCLC) patients as well as the pathogenetic of S100A2 in the development of metastasis in NSCLC. Microarray data from a large NSCLC patient cohort wa...

The aim of the present study was to evaluate the feasibility and diagnostic value of repeat mediastinoscopy as part of the response-evaluation protocol of 2 phase II multimodality studies for either stage IIIA/B non-small cell lung cancer or small cell lung cancer. From January 1991 through December 1998, 104 patients (79 men and 25 women) with sta...

The traditional treatment of Pancoast tumour with local approaches (surgery, radiotherapy or a combination of both) leads to a poor outcome due to the high rate of incomplete resection and the lack of systemic control. The aim of the present prospective feasibility study was to determine whether a trimodality approach improves local control and sur...

Using semi-quantitative microarray technology, almost every one of the approximately 30 000 human genes can be analyzed simultaneously with a low rate of false-positives, a high specificity, and a high quantification accuracy. This is supported by data from comparative studies of microarrays and reverse-transcription PCR for established cancer gene...

Chlamydiales are familiar causes of acute and chronic infections in humans and animals. Human pulmonary emphysema is a component of chronic obstructive pulmonary disease (COPD) and a condition in which chronic inflammation manifested as bronchiolitis and intra-alveolar accumulation of macrophages is common. It is generally presumed to be of infecti...

Patients with N1 non-small cell lung cancer represent a heterogeneous population with varying long-term survivals. Prognosis and pattern of recurrence seem to be particularly affected by the level of lymph node involvement. From 1990 to 1995, a total of 1954 consecutive patients underwent surgical resection for non-small cell lung cancer: 549 (28%)...

An immunohistochemical comparative analysis of P-170 glycoprotein and p53 was performed in 37 breast cancer patients who underwent curative resection without preoperative chemotherapy. The antibodies utilized were C-219 and JSB-1 for P-gp and DO-7 for p53. Positive cytoplasmic and membrance positivity for P-gp was found in 22 (59.45%) of the 37 tum...

The locally advanced (T3 - 4) non-small cell lung cancer with pulmonary lymph node metastases (N1) is a mixture of different subgroups of disease with varying pattern of tumor extension and long-term survival rates. We retrospectively reviewed hospital records and follow-up data of 181 patients operated on between 1990 and 1995 with pathological st...

Hintergrund: Das lokal fortgeschrittene (T3 - 4) nicht-kleinzellige Bronchialkarzinom mit pulmonalen Lymphknotenmetastasen (N1) beinhaltet unterschiedliche Tumormanifestationen, die verschiedenen lymphatischen Metastasierungsmustern und möglicherweise Prognosen entsprechen. Patienten und Methode: Retrospektiv wurden die Krankenblätter und Verlaufsu...

Pulmonary tuberculosis has become a rare indication for surgical intervention in all industrial nations. Over a period of 10 years we overview 193 patients who were suffering this disease and underwent thoracotomy. Main indication (79.8 %) was pulmonary nodules, of unknown origin. In this cases wedge resection was performed. Expanded resectional te...

Operationen wegen einer Lungentuberkulose sind auch in thoraxchirurgischen Zentren zunehmend seltener. Im Verlauf eines 10-Jahres-Zeitraums wurden in unserer Klinik 193 Patienten operiert. Hauptindikation (79,8 %) ist heute der anders nicht auszuraumende Karzinomverdacht bei Rundherden und lokal begrenzten Infiltraten. Uberwiegend erfolgen hierbei...

Completion pneumonectomy is reported to be associated with high morbidity and mortality, especially when done in patients with benign disease. We review our 9 years of experience with this operation to evaluate the postoperative outcome and long-term results of various indications. Between January 1990 and December 1998, 66 consecutive patients und...

Whether mediastinoscopy is indicated in the preoperative staging of bronchogenic carcinoma is still a controversial issue. It may be performed routinely (to exclude locally inoperable patients from surgery), selectively, or it may be regarded as superfluous (in centers which prefer an extended lympho adenectomy at the time of thoracotomy). We regar...

Advances in early diagnosis of breast cancer have allowed most patients to come to treatment at an early stage (in the US in 1993, 75% of cases were stage I-II). In these cases, conservation surgery has played in the last two decades the role of first choice thearpy following randomized studies which definitely showed the same safety and effectiven...

To investigate the impact of age as a prognostic factor in older patients with breast cancer and to discuss the role of surgery in this category of patients. A retrospective study. A tertiary care university teaching hospital. One hundred ninety patients aged 70 years or older (mean age: 75 years) were treated for breast cancer from 1967 through 19...

The issue considered is whether surgery is affected by induction chemotherapy in stage II-III breast cancer. This aspect of breast cancer management has not until now been totally clarified and therefore has taken the attention of our study group, particularly with regard to peri-operative morbidity. Sixty patients with locally advanced/innammatory...

Preliminary results of concomitant radiation and chemotherapy in liver metastases from breast cancer are presented. The diagnosis approach before and after treatment, the related problems in imaging and the histological aspects, are discussed. Preliminary results seem to encourage further studies.

The treatment of inflammatory breast cancer is still controversial and the prognosis remains very poor. This retrospective study analyzes the role of surgery as part of a multimodal approach in 23 consecutive patients, treated at our institution from 1976 to 1986. Thirteen patients were treated with initial surgery followed by postoperative radioth...