Leonidas Sakkas

Extrapelvic endometriosis: a rare entity or an under diagnosed condition?

Endometriosis is a clinical entity characterized by the presence of normal endometrial mucosa abnormally implanted in locations other than the uterine cavity. Endometriosis can be either endopelvic or extrapelvicdepending on the location of endometrial tissue implantation. Despite the rarity of extrapelvic endometriosis, several cases of endometriosis of the gastrointestinal tract, the urinarytract, the upper and lower respiratory system, the diaphragm, the pleura and the pericardium, as well as abdominal scars loci have been reported in the literature. There are several theories about the pathogenesis and the pathophysiology of endometriosis. Depending on the place of endometrial tissue implantation, endometriosis can be expressed with a wide variety of symptoms. The diagnosis of this entity is neither easy nor routine. Many diagnostic methods clinical and laboratory have been used, but none of them is the golden standard. The multipotent localization of endometriosis in combination with the wide range of its clinical expression should raise the clinical suspicion in every woman with periodic symptoms of extrapelvic organs. Finally, the therapeutic approach of this clinical entity is also correlated with the bulk of endometriosis and the locum that it is found. It varies from simple observation, to surgical treatment and treatment with medication as well as a combination of those.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1968087883113362.

Solitary Papillomas of the Lower Airways: Epidemiological, Clinical, and Therapeutic Data during a 22-Year Period and Review of the Literature

Introduction: Solitary respiratory papillomas (SRPs) are considered uncommon yet benign neoplasms of the lower respiratory tract. Most of our understanding stems from single case reports or limited case series. Objective: To determine the incidence of solitary SRPs and more accurately describe the localization, distribution of subtypes of solitary SRPs, clinical features, and the risk of malignant transformation. This retrospective report is based on data collected in a busy single-center bronchoscopy practice during a 22-year period. Methods: Among 36,780 patients who underwent bronchoscopic procedures between 1986 and 2008, we identified 32 patients with SRPs. This patient group was compared with 69 patients with SRPs described in the English literature as case reports, case series, or diagnostic dilemmas. Results: Twenty-three patients were men (male/female ratio of 3:1), and 21 patients were former smokers (65.6%). The mean age of initial presentation in men and women was 56.9 ± 14.3 versus 53.3 ± 14.4 years, respectively. The presenting symptoms included cough in 18 patients (40.6%), hemoptysis in 11 (25%), dyspnea in seven (21.8%), and fever in five patients (15.7%). Two patients with papillomas in the subglottic region had wheezing and were on aerosolized bronchodilator therapy. In one patient, the papilloma was incidentally discovered on a chest computed tomography scan. The histologic analysis of lesions revealed squamous papillomas in 65.6%, a glandular subtype in 18.75%, and a mixed subtype in 15.6%. Malignant transformation was observed in five patients (15.7%). The malignancies consisted of squamous cell carcinoma in two patients, and single cases of small cell lung carcinoma, glandular carcinoma, and low-grade carcinoma. Conclusion: In our experience, the estimated incidence of SRPs is 3.95 cases/100,000 patients/yr. SRPs occur more commonly in men (ratio 3:1). Squamous papillomas occur commonly during the fifth decade of life, glandular papillomas predominate in the sixth decade, and the distribution of mixed type papillomas is from the third to the sixth decade of life. Malignant transformation was observed in a minority of patients.

Docetaxel-carboplatin in combination with erlotinib and/or bevacizumab in patients with non-small cell lung cancer

Background Bevacizumab and erlotinib have been demonstrated to prolong overall survival in patients with non-squamous non-small cell lung cancer (NSCLC). We designed a four-arm Phase III trial to evaluate the efficacy and toxicity of the combination of docetaxel, carboplatin, bevacizumab, and erlotinib in the first-line treatment of patients with NSCLC. Methods A total of 229 patients with stage IIIb/IV non-squamous NSCLC were treated with two cycles of carboplatin (area under the concentration-time curve 5.5) and docetaxel 100 mg/m2 as chemotherapy. After completion of two treatment cycles, patients were evaluated for response and divided into four groups: 61/229 continued with four more cycles of chemotherapy (control group), 52/229 received chemotherapy plus erlotinib 150 mg daily, 56/229 received chemotherapy plus bevacizumab 7.5 mg/kg, and 60/229 were treated with the combination of chemotherapy, erlotinib, and bevacizumab until disease progression. The primary endpoint was overall survival. Results Over 4 years of follow-up, there was no statistically significant difference in survival and time to progression between the four treatment groups. After two cycles of chemotherapy, responders and nonresponders were divided according to their response in order to examine the role of initial response as an independent factor in survival and response when a biological agent is combined with chemotherapy. Nonresponders, who received additional therapy with bevacizumab or combination therapy, had a survival benefit [657 days (95% confidence interval 349–970) and 681 days (95% confidence interval 315–912), respectively], which was statistically significant compared with continuation of cytotoxic chemotherapy (P < 0.001). The combination therapy had a safety profile comparable with that of bevacizumab and erlotinib taken individually. Conclusion Administration of bevacizumab and erlotinib in combination with first-line chemotherapy, followed by bevacizumab and erlotinib monotherapy as maintenance, showed promising results in patients with NSCLC, with reduced toxicity as compared with chemotherapy alone, but did not translate into longer overall survival.

Interleukin-7 and Interleukin-15 for Cancer

Interleukin 7 and 15 are considered powerful pro-inflammatory cytokines, they have the ability to destabilize chromosomes and induce tumorigenesis. Additionally, they can control malignancy proliferation by influencing the tumor microenvironment and immune system. Immunotherapy has been proposed as a treatment modality for malignancy for over a decade; the exact mechanisms of action and pathways are still under investigation. Interleukin 7 and 15 have been extensively investigated in hematological malignancies since their mode of action influences the stimulation of the immune system in a more direct way than other malignancies such as lung, melanoma, and breast, renal and colorectal cancer.

2-diethylaminoethyl-dextran methyl methacrylate copolymer nonviral vector: still a long way toward the safety of aerosol gene therapy

Revealing the lung tumor genome has directed the current treatment strategies toward targeted therapy. First line treatments targeting the genome of lung tumor cells have been approved and are on the market. However, they are limited by the small number of patients with the current investigated genetic mutations. Novel treatment administration modalities have been also investigated in an effort to increase the local drug deposition and disease control. In the current study, we investigated the safety of the new nonviral vector 2-diethylaminoethyl-dextran methyl methacrylate copolymer (DDMC; Ryujyu Science), which belongs to the 2-diethylaminoethyl-dextran family by aerosol administration. Thirty male BALBC mice, 2 month old, were included and divided into three groups. However, pathological findings indicated severe emphysema within three aerosol sessions. In addition, the CytoViva technique was applied for the first time to display the nonviral particles within the pulmonary tissue and emphysema lesions, and a spectral library of the nonviral vector was also established. Although our results in BALBC mice prevented us from further investigation of the DDMC nonviral vector as a vehicle for gene therapy, further investigation in animals with larger airways is warranted to properly evaluate the safety of the vector.

Enhancement of Aerosol Cisplatin Chemotherapy with Gene Therapy Expressing ABC10 protein in Respiratory System.

Inhaled therapy for lung cancer is a local form of treatment. Currently inhaled non-specific cytotoxic agents have been evaluated as a future treatment for local disease control and distant metastasis control. There are few information regarding the influence of local transporters and gene expression of the respiratory epithelium to the absorption of administered drugs. In the current work we used adenoviral-type 5(dE1/E3) (Cytomegalovirus promoter) with human ABCA10 transgene (Ad-h-ABCA10) purchased from Vector Labs® in order to investigate whether gene therapy can be used as a pre-treatment to enhance the efficiency of inhaled cisplatin. We included the following groups to our work: a) control, b) aerosol vector, c) aerosol vector plus cisplatin, d) aerosol cisplatin, e) intratumoral cisplatin administration, f) intratumoral vector plus cisplatin administration. The results indicate that the aerosol cisplatin group had a long term survival with the intratumoral cisplatin group following. The enhancement of the ABCA family locally to the respiratory system prior to the aerosol cisplatin administration can be used safely and efficiently. Future treatment design of local therapies should include the investigation of local transporters and genes.

Lung ossification: an orphan disease

Diffuse pulmonary ossification (DPO) is a rare entity which is characterized by metaplastic bone formation in the lung parenchyma. It is an uncommon condition without significant symptoms, which is usually diagnosed on autopsy. Diffuse pulmonary ossification can be easily misdiagnosed as one of interstitial lung diseases due to diffuse pulmonary lesions. Two types of diffuse ossification are described in medicine: dendriform and nodular. In this article, the authors present a patient with persistent pneumothorax who underwent investigation of the cause of his disease and a diagnosis of DPO was revealed.

“One-stop shop” spectral imaging for rapid on-site diagnosis of lung cancer: a future concept in nano-oncology

Background There are currently many techniques and devices available for the diagnosis of lung cancer. However, rapid on-site diagnosis is essential for early-stage lung cancer, and in the current work we investigated a new diagnostic illumination nanotechnology. Methods Tissue samples were obtained from lymph nodes, cancerous tissue, and abnormal intrapulmonary lesions at our interventional pulmonary suites. The following diagnostic techniques were used to obtain the samples: endobronchial ultrasound bronchoscopy; flexible bronchoscopy; and rigid bronchoscopy. Flexible and rigid forceps were used because several of the patients were intubated using a rigid bronchoscope. In total, 30 tissue specimens from 30 patients were prepared. CytoViva® illumination nanotechnology was subsequently applied to each of the biopsy tissue slides. Results A spectral library was created for adenocarcinoma, epidermal growth factor receptor mutation-positive adenocarcinoma, squamous cell carcinoma, usual interstitial pneumonitis, non-specific interstitial pneumonitis, typical carcinoid tumor, sarcoidosis, idiopathic pulmonary fibrosis, small cell neuroendocrine carcinoma, thymoma, epithelioid and sarcomatoid mesothelioma, cryptogenic organizing pneumonia, malt cell lymphoma, and Wegener’s granulomatosis. Conclusion The CytoViva software, once it had created a specific spectral library for each entity, was able to identify the same disease again in subsequent paired sets of slides of the same disease. Further evaluation of this technique could make this illumination nanotechnology an efficient rapid on-site diagnostic tool.

Epithelial-myoepithelial carcinoma of the trachea—a rare entity case report

Epithelial-myoepithelial tumors of the lung are rare neoplasms whose biological behavior and clinical course still remain to be defined. Epithelial-myoepithelial carcinoma (EMCa) is a low-grade malignant tumour. According to literature, most commonly occurs in salivary glands, particularly in parotic gland, but it can also occur in unusual locations such as breast, lachrymal gland, nose, paranasal sinus, lung, bronchus and, as in our case, trachea. There are no many documented case reports of a primary myoepithelial carcinoma in the trachea. We report a case of a 34-year-old man diagnosed with this unusual location of an epithelial-myoepithelial tumor. The tumour was removed by segmental tracheal resection and end-to-end anastomosis.

Physiology of the pleural space

The pleural cavity is created between the 4(th) and 7(th) week of embryologic development. These embryonic components of visceral and parietal pleurae develop different anatomic characteristics with regard to vascular, lymphatic, and nervous supply. There are two layers: a superficial mesothelial cell layer facing the pleural space and an underlying connective tissue layer. The pleura might present inflammatory response and maintenance of the pleural fluid is observed. The latter function is especially important in the mechanical coupling of the lung and chest wall. Fluid is filtered into the pleural space according to the net hydrostatic oncotic pressure gradient. It flows downward along a vertical pressure gradient, presumably determined by hydrostatic pressure and resistance to viscous flow. There also may be a net movement of fluid from the costal pleura to the mediastinal and interlobar regions. In these areas, pleural fluid is resorbed primarily through lymphatic stomata on the parietal pleural surface. In the current review we will present the physiology of the pleural space in a step by step manner.