Boosting Innovation for the Development of Smart-Service Factories of the Future: The Cases of the Federal State of Vorarlberg and its Neighbouring Regions

Factory of the Future is an initiative of the European Commission. It is highly narrative and describes the transformation of “ordinary” manufacturing operations and structures to fully-integrated cyber-physical manufacturing systems. Basing on case study research performed in the greater area of Vorarlberg, this article aims to explore how Small and Medium Enterprises (SMEs) in the field of manufacturing can evolve to smart-service Factories of the Future. It takes a mixed-methods approach with quantitative research (questionnaire) and qualitative case study interviews and provides findings about three main topics in service system engineering: “transformation of an operational need into a description of system performance parameters”, “integration of related technical parameters and assurance of compatibility of all physical, functional and program interfaces” and “integration of reliability, maintainability, safety, survivability, human and other such factors”. As it turns out, increased servitization measures, service management, service performance and service quality by development of service-oriented architectures (SOA) are key to evolve to a smart-service Factory of the Future

Klinische Bedeutung der aktivierten Thrombelastographie mit einem neuen Point-of-care-Analysegerät bei Routine-Herz-Operationen

Zur frühzeitigen gezielten Therapie perioperativer Blutungen bei herzchirurgischen Eingriffen ist eine point-of-care-Methode erforderlich, die Gerinnungsstörungen rasch erkennen und differenzieren lässt. In dieser Studie wurde der klinische Nutzen eines neuen Thrombelastographie-Systems zur perioperativen Gerinnungsüberwachung bei 42 konsekutiven herzchirurgischen Patienten zu fünf Messzeitpunkten evaluiert. Insbesondere interessierte die mögliche Vorhersagbarkeit und Differenzierung des postoperativen Blutverlustes. Das Thrombelastogramm (TEG) zeigte zuverlässig den bekannten charakteristischen Verlauf der operationsbedingten Gerinnungsbeeinträchtigung. Signifikante Korrelationen des Blutverlustes mit den erfassten Parametern fanden sich jedoch nicht. Trotz geringem Blutverlust war das TEG in 9 Fällen pathologisch. Ob Koagulopathien bei postoperativen Blutungen mit dieser Methode adäquat zu differenzieren sind, ließ sich aufgrund des geringen Blutverlustes nicht klären

Cut-resistant protective gloves in pathology—effective and cost-effective

Cutting injuries and needle-stitch injuries constitute a potentially fatal danger to both pathologists and autopsy personnel. We evaluated such injuries in a large German institute of pathology from 2002 to 2007 and analysed the effect of the introduction of cut-resistant gloves on the incidence of these injuries. In the observation period, 64 injuries (48 cutting injuries and 16 needle-stitch injuries) were noted in the injury report books. Most injuries were located at the non-dominant hand, preferentially at the index finger and the thumb. Around one fifths of the injuries were at the side of handedness. The average number of injuries per month was 1.22 for the 50months prior to the introduction of cut-resistant gloves, more than seven times higher than after their introduction (0.158; 19months; p < 0.001). Considering the medical and administrational costs of such injuries, cut-resistant protective gloves are an effective and cost-effective completion of personal occupational safety measures in surgical pathology and autopsy. We strongly recommend the use of such gloves, especially for autopsy personne

KPNA2 protein expression in invasive breast carcinoma and matched peritumoral ductal carcinoma in situ

The aim of this study was to evaluate protein expression of Karyopherin alpha 2 (KPNA2) in invasive breast cancer and matched ductal carcinoma in situ (DCIS) and to correlate it with clinicopathological data, including patient survival. KPNA2 protein expression was assessed by immunohistochemistry in breast tissue samples, containing invasive carcinomas, DCIS, and adjacent histologically benign breast tissues. A polyclonal goat KPNA2 antibody was used for immunostaining of 83 clinicopathologically characterized cases. For statistical analysis, staining of at least 10% of nuclei was considered KPNA2 positive. Immunohistochemical detection of KPNA2 in invasive carcinoma showed a significant correlation with higher tumor stage, positive lymph node status, higher tumor grade, and negative ER status. Concordantly, KPNA2-positive tumors (31.3%) showed significantly shorter disease-free survival times (69months vs 118months; p = 0.007). KPNA2 protein expression was also detected in DCIS (21.3%) adjacent to invasive tumor and correlated with nuclear grade (p = 0.013). Expression of KPNA2 in invasive breast cancer correlates with conventional prognostic parameters and shorter disease-free survival. Additionally, KPNA2 is overexpressed in DCIS, particularly high grade lesions, which emphasizes its potential role in carcinogenesis of invasive breast carcinoma

Pathological Processing Techniques and Final Diagnosis of Breast Cancer Sentinel Lymph Nodes

Background: Recommendations for intraoperative and postoperative breast sentinel lymph node (SLN) processing differ widely. Micrometastases and isolated tumor cells (ITC) have recently been proposed as prognostically and therapeutically relevant. We compared 3 SLN protocols with regard to intraoperative and postoperative diagnosis. Materials and Methods: SLN in cohort I (270 patients) were intraoperatively assessed by stereomicroscopy. Intraoperative frozen section (IFS) was used only in stereomicroscopically suspicious SLN. In cohort II (197 patients), all SLN were examined with only 1 IFS. Final SLN workup in cohorts I and II consisted of complete step sectioning with immunohistochemistry. In cohort III (268 patients) 2 or more IFS were performed followed by 3 step sections and immunohistochemistry. Results: pN1 stages were significantly higher in cohorts I and II (33.3% and 34.0% respectively) than in cohort III (24.6%). Intraoperative false negativity for the detection of metastases (pN1) ranged from 54.4% (cohort I) and 35.8% (cohort II) to 21.2% (cohort III). In contrast, ITC were detected significantly more frequently in cohort I (9.3%) and cohort II (14.7%) than in cohort III (1.9%). Conclusions: Higher rates of SLN metastases and ITC in cohort I/II compared to cohort III suggest that IFS may result in tissue loss thus increasing the risk of missing metastases. Sparse IFS but complete postoperative SLN workup with step sectioning and immunohistochemistry provides more accurate information regarding minimal disease in SLN, but often results in delayed axillary lymph node dissection. This is important for preoperative patient information and recommendations in SLN processing protocol

GOLPH2 expression may serve as diagnostic marker in seminomas

ABSTRACT: BACKGROUND: GOLPH2 (Golgi phosphoprotein 2) is a novel Golgi membrane protein. Despite its unknown physiologic function, however, it has been proposed as a biomarker for hepatocellular and prostate carcinoma due to its upregulation in those cancer entities. Whether the overexpression of GOLPH2 is tumour specific or a generic parameter of malignancy and whether this finding is true for additional carcinomas has not been determined. In this study, we aimed to evaluate the expression pattern of GOLPH2 in testicular seminomas, the most common histologic subtype of testicular neoplasm. METHODS: GOLPH2 protein expression was assessed by immunohistochemistry in 69 testicular seminomas and compared to the expression rates in matching normal testicular tissue and intratubular germ cell neoplasia of unclassified type (IGCNU). In addition, a subset of Leydig cell tumours was analyzed accordingly. RESULTS: GOLPH2 was consistently overexpressed (89.9%) in seminomas. Matching non-neoplastic tissue showed weak or negative staining. The observed differences between non-neoplastic and neoplastic tissue were statistically highly significant (p < 0.001). There were no significant associations with tumour status. Interestingly, GOLPH2 was also highly expressed in the intertubular Leydig cells as well as in Leydig cell tumours. CONCLUSIONS: GOLPH2 protein is highly expressed in seminomas and in Leydig cell tumours. This study fosters the association of GOLPH2 with malignant neoplastic processes. The staining pattern is easily assessable and consistent which is a favourable property especially in clinical settings. GOLPH2 could be a novel immunohistochemical marker for the assessment of testicular neoplasms, especially against the background that in analogy to hepatocellular carcinomas complementary GOLPH2 serum levels might be helpful in detecting metastases or recurrent tumour. Therefore serum studies and analyses of GOLPH2 expression in non-seminomatous germ cell tumours are strongly warranted

Down-regulation of the pro-apoptotic XIAP associated factor-1 (XAF1) during progression of clear-cell renal cancer

BACKGROUND: Decreased expression of the interferon-stimulated, putative tumour suppressor gene XAF1 has been shown to play a role during the onset, progression and treatment failure in various malignancies. However, little is yet known about its potential implication in the tumour biology of clear-cell renal cell cancer (ccRCC). METHODS: This study assessed the expression of XAF1 protein in tumour tissue obtained from 291 ccRCC patients and 68 normal renal tissue samples, utilizing immunohistochemistry on a tissue-micro-array. XAF1 expression was correlated to clinico-pathological tumour features and prognosis. RESULTS: Nuclear XAF1 expression was commonly detected in normal renal- (94.1%) and ccRCC (91.8%) samples, without significant differences of expression levels. Low XAF1 expression in ccRCC tissue, however, was associated with progression of tumour stage (p = 0.040) and grade (p < 0.001). Low XAF1 tumour levels were also prognostic of significantly shortened overall survival times in univariate analysis (p = 0.018), but did not provide independent prognostic information. CONCLUSION: These data suggest down-regulation of XAF1 expression to be implicated in ccRCC progression and implies that its re-induction may provide a therapeutic approach. Although the prognostic value of XAF1 in ccRCC appears to be limited, its predictive value remains to be determined, especially in patients with metastatic disease undergoing novel combination therapies of targeted agents with Interferon-alpha

Radiological and pathological findings of a metastatic composite paraganglioma with neuroblastoma in a man: a case report

INTRODUCTION: Composite tumors of the adrenal medulla or paraganglia are extremely rare and present a diagnostic dilemma. These tumors consist of a neuroendocrine component mixed with a neural component.We describe the imaging characteristics together with the corresponding pathological findings of a composite tumor. Apart from any component-specific imaging findings, the hallmark of this entity is the presence of histologically distinguishable components. CASE PRESENTATION: A 61-year-old Caucasian man was referred to our hospital due to a suspect lesion found on chest computed tomography carried out for unclear thoracic pain. An abdominal computed tomography scan and ultrasound examination detected a retroperitoneal tumor comprising two different tumor components. Twenty-four-hour urine revealed high levels of normetanephrine, characteristic of a neuroendocrine tumor. An octreoscan prior to surgical procedures revealed multiple osseous and intra-hepatic metastases. The final histopathological workup revealed a composite paraganglioma with neuroblastoma. Our patient died ten months after the initial diagnosis from tumor-associated complications. CONCLUSIONS: Composite paragangliomas with neuroblastoma are rare tumors of the retroperitoneum. Such tumors should be considered in the differential diagnosis of retroperitoneal masses

USP22 promotes HER2-driven mammary carcinoma aggressiveness by suppressing the unfolded protein response.

The Ubiquitin-Specific Protease 22 (USP22) is a deubiquitinating subunit of the mammalian SAGA transcriptional co-activating complex. USP22 was identified as a member of the so-called "death-from-cancer" signature predicting therapy failure in cancer patients. However, the importance and functional role of USP22 in different types and subtypes of cancer remain largely unknown. In the present study, we leveraged human cell lines and genetic mouse models to investigate the role of USP22 in HER2-driven breast cancer (HER2+-BC) and demonstrate for the first time that USP22 is required for the tumorigenic properties in murine and human HER2+-BC models. To get insight into the underlying mechanisms, we performed transcriptome-wide gene expression analyses and identified the Unfolded Protein Response (UPR) as a pathway deregulated upon USP22 loss. The UPR is normally induced upon extrinsic or intrinsic stresses that can promote cell survival and recovery if shortly activated or programmed cell death if activated for an extended period. Strikingly, we found that USP22 actively suppresses UPR induction in HER2+-BC cells by stabilizing the major endoplasmic reticulum (ER) chaperone HSPA5. Consistently, loss of USP22 renders tumor cells more sensitive to apoptosis and significantly increases the efficiency of therapies targeting the ER folding capacity. Together, our data suggest that therapeutic strategies targeting USP22 activity may sensitize tumor cells to UPR induction and could provide a novel, effective approach to treat HER2+-BC

Pulmonary Kaposi's sarcoma after heart transplantation: a case report

ABSTRACT: INTRODUCTION: Kaposi's sarcomas have been associated with different conditions of immunosuppression and are also known to be a typical complication of solid organ transplantations. CASE PRESENTATION: We report of a 65 year old man of Turkish origin with a history of heart transplantation 10 months ago who presented for clarification of his dyspnoea. The patient had a known history of chronic obstructive pulmonary disease and a smoking history of 40 pack years. Radiologically, three progressively growing intrapulmonary nodules were detected. The histology was diagnostic for a Kaposi's sarcoma. Visceral and especially primary intrapulmonary Kaposi's sarcomas are very rare and have been described to have a rather unfavourable prognosis. CONCLUSION: Even with a history suggestive for conventional lung cancer, Kaposi's sarcomas should be considered in patients after transplantation of solid organs. It should be noticed that in a minority of cases this tumour exists in the absence of the typical cutaneous lesions