Water safety plans for water supply utilities in China, Cuba, France, Morocco and Spain: costs, benefits, and enabling environment elements.

Water Safety Plans (WSPs) are a management tool to identify and prioritize risks and implement appropriate control measures throughout the water supply chain, from catchment to consumer. WSPs have been implemented in over 90 countries; yet, costs, benefits and the enabling environment elements necessary for WSP implementation are under-studied. To better understand these factors, we conducted interviews with WSP implementation management teams from 20 private urban water utilities in China, Cuba, France, Morocco and Spain in 2014. Collectively, these utilities serve 10.6 million consumers and supply over 2.2 million m3/day of water to consumers. Time for WSP implementation to achieve certification averaged 13 months. The main startup cost was staff time, averaging 16.2 full-time equivalent person-months. Additional costs, averaging €16,777, were for training staff, hiring consultants, purchasing equipment, and certifying WSPs. Benefits commonly reported included improved hazard control, treatment practices, record keeping, and client and health agency confidence.

[Non-small cell lung cancer. New biomarkers for diagnostics and therapy]. / Nicht-kleinzelliges Lungenkarzinom. Neue Biomarker für Diagnostik und Therapie.

Although advances in targeted therapies have recently been achieved, lung cancer remains a major health burden worldwide. It is therefore pivotal to investigate the biology of lung cancers in order to design new therapeutic strategies. To address this a multi-antibody assay has been developed for the classification of non-small cell lung cancer (NSCLC). Using this assay the pathologist is able to reliably subtype NSCLC into adenocarcinoma, squamous cell carcinoma, large cell neuroendocrine carcinoma (LCNEC) and NSCLC not otherwise specified (NOS) large cell carcinoma, as required by the new World Health Organization (WHO) classification of 2015, on a single glass slide. In our cohort this classification algorithm showed significant differences in overall survival of the therapeutically important subgroups, which reflects the accuracy of the assay. To investigate the biology of NSCLC subtypes further, several proteins involved in carbohydrate metabolism were analyzed. In a hierarchical cluster analysis it could be shown that adenocarcinoma and squamous cell carcinoma harbor different metabolic shifts and, furthermore, that two distinct groups of squamous cell carcinoma seem to exist, a hypoxia and a transporter type. These results could be verified by analysis of mRNA data obtained from the TCGA database. As a close association between tumor metabolism and anti-tumor immune response has been reported, the lymphocytic infiltrates were characterized with respect to T-cells and their location within the tumor. Besides a negative correlation of lymphocyte density and expression of lactate dehydrogenase, it could be shown that depending on the location and type a high lymphocyte density indicates a significantly better overall survival of NSCLC patients. Investigating the expression of PD-L1 in NSCLC cells, a significant correlation with lymphocyte density was detected. In conclusion, the multi-antibody assay is a new and economically attractive tool for a reliable subclassification of NSCLC. This subtyping results in a better biological stratification of NSCLC and is the basis not only for palliative treatment options but also for further investigations on NSCLC biology. It was discovered that metabolic changes during malignant transformation are different in adenocarcinoma and squamous cell carcinoma. The latter group can be further divided into a hypoxia and a transporter type. Anti-tumor immune responses are influenced by the metabolic shift in NSCLC and lymphocyte density with respect to the location within the tumor is of prognostic significance in NSCLC. Therefore, the results contribute to a better biological understanding of NSCLC and may lead to new treatment options by targeting metabolic enzymes or triggering anti-tumor responses.

Downregulation of MTSS1 expression is an independent prognosticator in squamous cell carcinoma of the lung.

BACKGROUND: The metastasis suppressor 1 (MTSS1) is a newly discovered protein putatively involved in tumour progression and metastasis. MATERIAL AND METHODS: Immunohistochemical expression of MTSS1 was analysed in 264 non-small-cell lung carcinomas (NSCLCs). RESULTS: The metastasis suppressor 1 was significantly overexpressed in NSCLC compared with normal lung (P=0.01). Within NSCLC, MTSS1 expression was inversely correlated with pT-stage (P=0.019) and histological grading (P<0.001). NSCLC with MTSS1 downregulation (<20%) showed a significantly worse outcome (P=0.007). This proved to be an independent prognostic factor in squamous cell carcinomas (SCCs; P=0.041), especially in early cancer stages (P=0.006). CONCLUSION: The metastasis suppressor 1 downregulation could thus serve as a stratifying marker for adjuvant therapy in early-stage SCC of the lung.

Cancer cell invasion and EMT marker expression: a three-dimensional study of the human cancer-host interface.

Cancer cell invasion takes place at the cancer-host interface and is a prerequisite for distant metastasis. The relationships between current biological and clinical concepts such as cell migration modes, tumour budding and epithelial-mesenchymal transition (EMT) remains unclear in several aspects, especially for the 'real' situation in human cancer. We developed a novel method that provides exact three-dimensional (3D) information on both microscopic morphology and gene expression, over a virtually unlimited spatial range, by reconstruction from serial immunostained tissue slices. Quantitative 3D assessment of tumour budding at the cancer-host interface in human pancreatic, colorectal, lung and breast adenocarcinoma suggests collective cell migration as the mechanism of cancer cell invasion, while single cancer cell migration seems to be virtually absent. Budding tumour cells display a shift towards spindle-like as well as a rounded morphology. This is associated with decreased E-cadherin staining intensity and a shift from membranous to cytoplasmic staining, as well as increased nuclear ZEB1 expression.

[Granulomatous lung and systemic diseases]. / Granulomatöse Lungen- und Systemerkrankungen.

Granuloma formation occurs in the human body if there is a particle which persists in phagocytes and which the immune system cannot eliminate. The immune reaction of granuloma formation evolved in order to combat mycobacteria with the aim of localizing mycobacteria and to avoid spreading of mycobacteria throughout the body. Granulomatous lung diseases are often accompanied by severe, systemic inflammation. However, acute phase proteins may be only slightly elevated. The spectrum of granulomatous lung diseases is broad. Sarcoidosis is the most common granulomatous lung disease. To diagnose sarcoidosis, other infectious granulomatous lung diseases such as tuberculosis, atypical mycobacterial and fungal infection have to be ruled out. Pulmonary granuloma also evolve in the context of autoimmune diseases such as rheumatoid arthritis, granulomatosis with polyangiitis (GBA, Wegener's) and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). Furthermore, immunodeficiencies such as common variable immunodeficiency (CVID) and immune reconstitution syndrome in HIV can be associated with systemic granulomatous inflammation. Finally, occupational lung disease, particularly hypersensitivity pneumonitis, silicosis, hard metal lung, and chronic berylliosis are associated with pulmonary granuloma formation.

[Synchronous schwannoma of the vagus nerve and the cervical sympathetic chain]. / Synchrones Schwannom des N. vagus und des zervikalen sympathischen Grenzstrangs.

Schwannomas are rare neural sheath tumors which are generally benign. Up to 45% of all schwannomas originate in the head and neck region. In the parapharyngeal space (PPS) they may arise from any of the lower cranial nerves IX, X, XI and XII or from the cervical sympathetic chain. We report a unique case of a synchronous schwannoma of the vagal nerve and the cervical sympathetic chain in a patient without neurofibromatosis.

Relapsing high grade mucoepidermoid carcinoma. Long-lasting complete response following reirradiation and EGFR blockade.

BACKGROUND AND PURPOSE: The treatment strategy for inoperable recurrent mucoepidermoid carcinoma (MEC) is not well established. Here, we present a case of a relapsed high grade MEC of the salivary glands of the hard palate that was successfully treated with a reirradiation (re-RT) and cetuximab, an antibody against epidermal growth factor receptor (EGFR). CASE REPORT: Twelve years after resection and adjuvant radiotherapy for high grade MEC of the salivary glands, a patient presented with inoperable recurrent disease. She received another 59.4 Gy. In addition, 400 mg/m(2) cetuximab was administered in the first week, followed by six additional weekly courses at 250 mg/m(2). RESULTS: Treatment was well tolerated. The patient is doing well and continuous radiological complete response (CR) is documented for 25 months after completion of the combined treatment. CONCLUSION: Combined re-RT and targeted inhibition of EGFR with cetuximab may be a valuable therapeutic strategy in patients with recurrent localized high grade MEC who are not candidates for radical surgery.

[Large cystic tumor of the right neck]. / Große zystische Raumforderung zervikal rechts.

A 32-year-old patient presented to our department with a large cystic lesion in the right lateral neck (diameter 6 cm). After complete resection, the histopathological examination revealed a lymph node metastasis of a papillary thyroid carcinoma. We performed total thyroidectomy and bilateral selective neck dissection. There was a papillary microcarcinoma in the right lobe of the thyroid. The postoperative course was uneventful. Therapy with radioiodine was conducted. At 30 months after surgery the patient is free of disease.

[Chondrosarcoma of the larynx. Experience gained in Freiburg since 1999]. / Chondrosarkome des Larynx. Freiburger Erfahrungen seit 1999.

BACKGROUND: Chondrosarcomas are rare tumors of the head and neck. Nevertheless, they display the most common non-epithelial malignancy of the larynx. MATERIALS AND METHODS: Between 1999 and February 2010 we treated six patients with laryngeal chondrosarcoma. The group included two female and four male patients ranging in age from 54 to 82 years. RESULTS: An 82-year-old female patient died 3 months after diagnosis and tracheostomy due to other underlying diseases. An 82-year-old male patient underwent primary radiation therapy. In the other patients, we performed a modified hemilaryngektomy in three cases and a laryngectomy in one. In those four cases, there were no signs of recurrent disease 50, 85, 87 and 95 months after surgery, respectively. There were no local or distant metastases. CONCLUSIONS: Chondrosarcomas of the larynx are slow growing neoplasms. Metastases occur in less than 3% of cases. Complete resection is the therapy of choice. Function-preserving surgical approaches should be favoured.