Primitive pituitary perivascascular epithelioid cell tumor: A challenging diagnosis of melanocytic pituitary lesion.

BACKGROUND: Perivascular Epithelioid cell tumors (PEComa) are rare mesenchymal tumors. They generally occur in the gynecologic or digestive tract. The diagnosis of Central Nervous System PEComa is exceptional and challenging. CASE DESCRIPTION: We report the case of a 46-year-old woman, with no particular medical history, who presented a secondary amenorrhea and a slight hyperprolactinemia. She was diagnosed on MRI with a pituitary tumor showing spontaneous hypersignal in T1-weighted images. After failure of medical treatment with cabergoline, surgical resection was required due to progressive tumor growth. Macroscopic aspect and initial immunohistochemical features were in favor of a primitive hypophyseal melanocytoma. However, molecular and transcriptional study through targeted exome- and RNA-sequencing led to the exceptional diagnosis of pituitary Perivascular Epithelioid Cell Tumor (PEComa). Three-years of postoperative radio-clinical follow-up showed an asymptomatic non-evolutive small remnant. CONCLUSION: PEComa is an exceptional diagnosis among pituitary tumors. It should be evoked as a potential differential diagnosis in case of primitive melanocytic lesion of the pituitary gland. Specific molecular analysis is mandatory to confirm the diagnosis and exclude differential diagnosis.

Serious tumor seeding after brainstem biopsy and its treatment-a case report and review of the literature.

Stereotactic brain biopsies for histopathological diagnosis are a common technique in case of intracranial lesions, particularly in those not amenable for resection. Tumor seeding alongside the surgical trajectory after fine-needle aspiration is a known problem in several visceral tumors. Whereas in these cases a complete resection of the biopsy trajectory may later be performed, this strategy is not feasible in stereotactic brain biopsy. We report a case of tumor seeding along the entire biopsy tract after stereotactic biopsy of a brainstem metastasis. A 68-year-old male patient with a concomitantly diagnosed kidney lesion presented with a singular lesion in the brainstem. After confirmation of metastasis by stereotactic biopsy, stereotactic radiosurgery (SRS) was applied. The primary tumor was treated by laparoscopic nephrectomy. Three months after SRS, the patient presented with a secondary clinical deterioration for only a few weeks. The MRI scan showed tumor seeding along the entire biopsy tract. Salvage treatment including hypofractionated stereotactical irradiation and seven cycles of bevacizumab was administered to obtain symptom control. Massive seeding of tumor after stereotactic biopsy accordingly rare, taking into account that stereotactic biopsy is a very common neurosurgical intervention. Nonetheless, we think that the potential risk has to be kept in mind, as it might be neglected.

[Incidental finding of a cardiac paraganglioma]. / Zufallsbefund eines kardialen Paraganglioms.

Cardiac paragangliomas are extremely rare neoplasms with an incidence of 1% of all cardiac tumors and can be completely asymptomatic, therefore, diagnosis is difficult. This article reports the case of an 18-year-old man with a heart murmur detected during a routine physical examination. Echocardiography revealed a heart tumor measuring 7 cm in size in the right atrium. Due to the tumor size and the threat of tricuspid valve insufficiency, tumor resection was performed. The histopathological examination revealed a cardiac paraganglioma with positive reactions of the tumor cells for chromogranin A, synaptophysin and CD56. Differentiating a primary cardiac paraganglioma from other more common cardiac tumors and particularly from metastases of neuroendocrine neoplasms from other locations is essential not only for the further clinical treatment but also for the prognosis of the patient.

Levels of histamine and other biogenic amines in high-quality red wines.

Biogenic amines in wine may impair sensory wine quality and cause adverse health effects in susceptible individuals. In this study, histamine and other biogenic amines were determined by HPLC after amine derivatisation to dansyl chloride conjugates in 100 selected high-quality red wines made from seven different cultivars. Amine levels varied considerably between different wines. The most abundant amines were putrescine (median = 19.4 mg l(-1), range = 2.9-122), histamine (7.2 mg l(-1), 0.5-26.9), and tyramine (3.5 mg l(-1), 1.1-10.7), whereas lower levels were found for isoamylamine (median = 0.25 mg l(-1)), phenylethylamine (0.16 mg l(-1)), cadaverine (0.58 mg l(-1)), spermidine (1.8 mg l(-1)) and tryptamine (0.06 mg l(-1)). Positive correlations were observed between isoamylamine and phenylethylamine, and between histamine, putrescine and tyramine levels. Amine concentrations were similar in all wine cultivars except Pinot noir and St. Laurent wines, which showed significantly higher tryptamine and cadaverine levels. The results indicate that levels of histamine and other biogenic amines may vary considerably between red wines independent of grape variety and that high amounts can also be found in high-rated wines. Adopting a legal histamine threshold level of 10 mg l(-1) in the European Union, as formerly introduced in other countries, would have excluded 34% of the investigated wines from the market.

Evaluation of aortic cannula jet lesions in a porcine cardiopulmonary bypass (CPB) model.

In cardiosurgery patients atherosclerotic debris displaced from the cannulation site but also from the opposite aortic wall by the "sandblast-like" effect of the high-pressure jet emanating from the cannula is a potential source of intraoperative arterial embolization and consequently postoperative neurologic dysfunction. The present study examined the extent to which shear stress exerted on the intact aortic intima by an aortic cannula jet stream can cause endothelial lesions that promote thrombogenesis and consequently thrombembolism. A single-stream, straight-tip aortic cannula was used in a porcine cardiopulmonary bypass (CPB) model. Following a 120-minute CPB pump run, a 60-minute stabilization period was allowed before sacrificing the pigs (N.=40) for histological evaluation of the ascending aorta and the brain. Opposite the cannulation site endothelial lesions (diameter: 3.81±1.3 mm; depth: 0.017±0.003 mm) were present in 22.5% (9/40) of aortic specimens. Cerebral thrombembolic lesions were not found. The present study showed that single-stream, straight-tip aortic cannulas caused jet lesions of the formerly intact aortic endothelium opposite the cannulation site in 22.5% of cases in a porcine CPB model.

TROP2 expression as prognostic marker for gastric carcinoma.

BACKGROUND: In gastric cancer the recurrence rate is unacceptably high, even after R0 resection and (neo)adjuvant chemotherapy. Therefore, there is an urgent need for identification of predictive and/or prognostic biomarkers to select high-risk patients who might benefit from additional therapies. Expression of TROP2 has been shown to be associated with tumour aggressiveness and poor prognosis in patients with various epithelial cancers. AIMS: To investigate TROP2 expression in gastric cancer and its correlation with clinicopathological features and disease outcome. METHODS: Expression of TROP2 was investigated by immunohistochemistry of tumour specimens from 104 patients who underwent resection for gastric cancer. Parameters found to be of prognostic significance in univariate analysis were verified in a multivariate Cox regression model. RESULTS: TROP2 was found to be overexpressed in 58 (56%) tumour samples. Significantly higher expression of TROP2 could be detected in intestinal-type carcinomas (p = 0.03). In intestinal-type gastric cancer, TROP2 overexpression was significantly correlated with shorter disease-free survival (DFS) (p = 0.03). Among the total group, TROP2 overexpression was predictive for poor disease-free (p<0.01) and overall (p = 0.03) survival in lymph node positive patients. Multivariate Cox regression analysis revealed TROP2 overexpression to be an independent prognostic marker for poor DFS in the subgroup of patients with intestinal-type gastric cancer irrespective of lymph node involvement. CONCLUSION: Results show that TROP2 is an independent prognostic marker for disease recurrence in intestinal type gastric cancer. Due to its wide distribution TROP2 may become an attractive therapeutic target in a subgroup of patients with gastric cancer.

High expression of TROP2 correlates with poor prognosis in pancreatic cancer.

Pancreatic cancer is one of the most devastating human malignancies. Despite considerable research efforts, it remains resistant to almost all available treatment regimens. The human trophoblast cell-surface antigen, TROP2, was found to be strongly expressed in a variety of human epithelial cancers, correlating with aggressiveness and poor prognosis. TROP2 antigen expression was investigated retrospectively by immunohistochemistry in paraffin-embedded primary tumour tissue samples from a series (n=197) of consecutive patients with pancreatic adenocarcinoma. Survival was calculated using Kaplan-Meier curves. Parameters found to be of prognostic significance in univariate analysis were verified in a multivariate Cox regression model. TROP2 overexpression was observed in 109 (55%) of 197 pancreatic cancer patients and was significantly associated with decreased overall survival (P<0.01). By univariate analysis, TROP2 overexpression was found to correlate with the presence of lymph node metastasis (P=0.04) and tumour grade (P=0.01). Furthermore, in the subgroup of patients treated surgically with curative intent, TROP2 overexpression significantly correlated with poor progression-free survival (P<0.01). Multivariate analyses revealed TROP2 to be an independent prognosticator. These findings suggest for the first time that TROP2 could be a novel prognostic biomarker for pancreatic cancer. Targeting TROP2 might be a useful treatment approach for patients with pancreatic cancer overexpressing this cell-surface marker.

[Non-Hodgkin lymphoma of the lacrimal gland]. / Non-Hodgkin-Lymphom der Tränendrüse.

BACKGROUND: Non-Hodgkin lymphoma is a systemic disease and various organs can therefore be affected. Ocular manifestations of non-Hodgkin lymphomas are possible but involvement of the eyelids or lacrimal glands are uncommon. CASE REPORT: A 63-year-old female patient suffered from a painless upper eyelid swelling of the left eye for 3 weeks. The anterior and posterior parts of the eyes showed no pathologic signs and X-ray examination of both orbits revealed no pathologic findings. Magnetic resonance imaging and computer tomography of the head revealed a neoplasm of the left lacrimal gland and also of the left parotid gland. The histologic examination revealed a recurrent non-Hodgkin lymphoma. CONCLUSIONS: The causes of eyelid swellings can be multiple, however, painless swellings may also be caused by neoplasms. In the case described here it was interesting that behind a painless eyelid swelling even a systemic disorder was hidden, i.e. a recurrence of a non-Hodgkin lymphoma, which was localized in the lacrimal gland.

Lornoxicam characteristically modulates cerebral pain-processing in human volunteers: a functional magnetic resonance imaging study.

BACKGROUND: Lornoxicam like other non-steroidal anti-inflammatory drugs (NSAIDs) is widely used for postoperative pain therapy. Evaluation of the effect of lornoxicam on cerebral processing of surgical pain was thus the aim of the present functional magnetic resonance imaging (fMRI) study. METHODS: An fMRI-compatible pain model that mimics surgical pain was used to induce pain rated 4-5 on a visual analogue scale (VAS) at the anterior margin of the right tibia in volunteers (n=22) after i.v. administration of saline (n=11) or lornoxicam (0.1 mg kg(-1)) (n=11). RESULTS: Lornoxicam, which significantly reduced pain sensation [VAS: mean (sd) 4.6 (0.7) vs 1.2 (1.5)], completely suppressed pain-induced activation in the SII/operculum, anterior cingulate cortex, insula, parietal (inferior), prefrontal (inferior, medial), temporal (inferior, medial/superior) lobe, cerebellum, and contralateral (e.g. left-sided) postcentral gyrus (SI). Only the hippocampus and the contralateral superior parietal lobe (BA 7) were activated. CONCLUSIONS: As compared with saline, lornoxicam typically suppressed pain-induced brain activation in all regions except the hippocampus. Furthermore, de novo activation was found in the contralateral, superior parietal lobe (BA 7).

D-JNKi, a peptide inhibitor of c-Jun N-terminal kinase, promotes functional recovery after transient focal cerebral ischemia in rats.

The c-Jun-N-terminal kinase (JNK) pathway has been shown to play an important role in excitotoxic neuronal death and several studies have demonstrated a neuroprotective effect of D-JNKi, a peptide inhibitor of JNK, in various models of cerebral ischemia. We have now investigated the effect of D-JNKi in a model of transient focal cerebral ischemia (90 min) induced by middle cerebral artery occlusion (MCAo) in adult male rats. D-JNKi (0.1 mg/kg), significantly decreased the volume of infarct, 3 days after cerebral ischemia. Sensorimotor and cognitive deficits were then evaluated over a period of 6 or 10 days after ischemia and infarct volumes were measured after behavioral testing. In behavioral studies, D-JNKi improved the general state of the animals as demonstrated by the attenuation of body weight loss and improvement in neurological score, as compared with animals receiving the vehicle. Moreover, D-JNKi decreased sensorimotor deficits in the adhesive removal test and improved cognitive function in the object recognition test. In contrast, D-JNKi did not significantly affect the infarct volume at day 6 and at day 10. This study shows that D-JNKi can improve functional recovery after transient focal cerebral ischemia in the rat and therefore supports the use of this molecule as a potential therapy for stroke.

The antiapoptotic effect of IL-6 autocrine loop in a cellular model of advanced prostate cancer is mediated by Mcl-1.

Levels of the proinflammatory cytokine interleukin-6 (IL-6) are increased in therapy-resistant prostate cancer. IL-6 has been considered a positive growth factor in late-stage prostate cancer cells and a potential target for therapeutic interference. Effects of inhibition of IL-6 on cell survival were studied in LNCaP-IL6+ cells, a model system for advanced prostate cancer, which produce IL-6. We show that the autocrine IL-6 loop is responsible for resistance to apoptosis and increased cellular levels of myeloid cell leukemia-1 (Mcl-1) protein, an antiapoptotic member of the Bcl-2 family. Treatment of cells with a chimeric anti-IL-6 antibody (CNTO 328) led to the induction of apoptosis and downregulation of Mcl-1 protein levels. Specific knockdown of Mcl-1 gene expression by small interfering RNA also yielded an increase in apoptosis of LNCaP-IL-6+ cells. Vice versa, inactivation of IL-6 autocrine loop had no influence on apoptosis levels in the absence of Mcl-1, thus suggesting this molecule as a mediator of the survival action of IL-6. Mcl-1 protein regulation by the endogenous cytokine directly involved the extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase pathway. Our data support the concept of anti-IL-6 targeted therapy in therapy-resistant prostate cancer.

[Evaluation of a cadaver workshop for education in regional anesthesia]. / Bewertung eines Anatomieworkshops für die Regionalanästhesieausbildung.

BACKGROUND: The aim of the present investigation was to survey former participants (n=869) of a cadaver workshop using a mail questionnaire to assess the demographic data and the impact of these courses on daily practice. METHODS: The deadline for acceptance of return mail was 60 days. Descriptive statistics were employed for analysis of results. RESULTS: The response rate was 36.7% and the course was judged to be recommendable by 98.2%. The average course attendant was board certified and had spent a mean time of 9+/-6 years in anesthesiology. The highest quality and degree of subsequent practicability in daily routine was attributed to peripheral nerve block training on cadavers. Of the course participants two-thirds performed regional anesthesia procedures more often following attendance. The majority of course attendants had to defray at least a part of the course fee themselves, and one-third was required to invest leisure time to attend. CONCLUSION: Attendance of a cadaver workshop increased knowledge of clinical anatomy and enhanced performance of regional anesthesia procedures. Courses of this format constitute a currently underestimated adjunct to contemporary regional anesthesia education.

Neurohormonal risk stratification for sudden death and death owing to progressive heart failure in chronic heart failure.

BACKGROUND: This study tested various neurohormones for prediction of heart failure death (death owing to progressive deterioration of ventricular function; HFD). Moreover, B-type natriuretic peptide (BNP) as a predictor of sudden death (SD; as reported previously) and the best predictor of HFD were combined for a simple risk stratification model. DESIGN: BNP, the N-terminal fragment of BNP (N-BNP), and of the atrial natriuretic peptide (N-ANP) and big endothelin levels were obtained from 452 patients with a left ventricular ejection fraction 130 pg mL(-1) and N-ANP < 6300 fmol mL(-1) (Group B, n = 177; 18%; P = 0.0001) and patients with BNP > 130 pg mL(-1) and N-ANP > 6300 fmol mL(-1) (Group C, n = 50; 19%; P = 0.0001). Analyzing 293 survivors and 31 patients with HFD, fewer patients died in Group A (n = 109; 0%; P = 0.0001) and Group B (n = 153; 6%; P = 0.0001) as compared with patients of Group C (n = 62; 34%). CONCLUSION: Prognostic power of neurohormones depends on the mode of death. The combined determination of BNP and N-ANP identifies patients with minimal risk of death, elevated SD but low HFD risk as well as elevated SD and HFD risk.

CT findings of increased splanchnic circulation in a case of celiac sprue.

We report a diagnosis of celiac disease first suggested by the computed tomographic appearance, which included findings indicative of increased splanchnic circulation. Similar findings have been reported with angiography and ultrasound but, to our knowledge, have not been reported with computed tomography.

Testing of a new pneumatic device to cause pain in humans.

BACKGROUND: Surgical pain typically combines superficial and deep pain. We wished to generate pain that resembled surgical pain, reliably and reproducibly, in volunteers. METHODS: We constructed a computer-controlled pneumatic device to apply pressure to the anterior tibia. The reproducibility of the pain was tested by rating the pressure that caused pain rated 4-5 on a visual analogue scale (VAS) on days 0, 7, and 24 in 10 volunteers. The effect of remifentanil (0.025, 0.05, 0.075, and 0.1 microg kg-1 min-1) on pain tolerance in another set of volunteers (n=11) was used as an indirect measure of the reliability of pain production. RESULTS: The pressure needed (0.7 (0.3) to 0.9 (0.4) atm (mean (SD)) to induce pain rated 4-5 (VAS) did not vary, showing long-term reproducibility of the method. When pressure was applied to cause increasing pain in volunteers (n=11) 0.05 microg kg-1 min-1 remifentanil increased pain tolerance by 50%. An approximate doubling of the dose (0.1 microg kg-1 min-1) increased pain tolerance significantly more. The linear logarithmic dose-effect relationship shows that the device causes pain reliably, and this can be reduced with opioid treatment. CONCLUSION: This pneumatic device can apply pain reliably and reproducibly.

Epidermal growth factor receptor as a novel therapeutic target in anaplastic thyroid carcinomas.

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies, with a median survival of up to 6 months. Such a bad prognosis under the present treatment procedures suggests the need for novel approaches in the management of this disease. Since some epidermal growth factor receptor (EGFR) inhibitors are now in clinical trials and few data are available concerning EGFR expression in anaplastic thyroid carcinomas, we tried to estimate a possible overexpression of this receptor in a larger tumor series. Twenty-five ATCs, including 3 ATCs with poorly differentiated thyroid carcinoma (PDTC) parts, were immunohistochemically investigated with a mouse monoclonal antibody directed against EGFR (EGFR pharmDX kit). The tumors revealed primarily a distinct membranous staining pattern, and in several tumor cells an additional cytoplasmic reactivity could be observed. The anaplastic carcinomas presented with 5 of 25 (20%) without EGFR reaction, 10 of 25 (40%) with reactivity, and 10 of 25 (40%) with overexpression of the receptor. All ATCs with PDTC parts (100%) showed EGFR overexpression. Cytoplasmic reactivity was observed in 56% of all ATCs. A significant correlation was calculated for EGFR overexpression and cytoplasmic staining (P = 0.036). Concerning receptor overexpression, ATCs were significantly different from ATCs with PDTC parts (P = 0.023). For the first time, we present EGFR overexpression in ATC in a larger tumor series, demonstrating that EGFR overexpression is a common finding in ATC. For at least one-third of all anaplastic thyroid carcinomas, EGFR seems to be a promising agent for the targeted molecular therapy of these extraordinarily aggressive tumors.

Connecting community action and science to combat desertification: evaluation of a process.

Combating desertification requires the involvement of many people ranging from communities who experience the effects on a daily basis and scientists attempting to understand the biophysical and socio-economic causes and consequences of desertification, to developers and policy makers on all levels. In many instances, however, the understanding, approaches and actions of these different groups contradict rather than support one another. Over the period 2000 to 2002, a conference process undertaken in southern Africa brought together communities, scientists, and development workers to test the concept that they could connect and work together to combat desertification, given an appropriate framework. The conference was a success, and communities, scientists and developers did exchange experience, knowledge and information. Many lessons were learned, although some pitfalls were experienced. Time, funding, enhanced communication, and good will are the primary ingredients for ensuring that different sectors complement one another in their efforts to combat desertification.

Cytokine-regulated expression of collagenase-2 (MMP-8) is involved in the progression of ovarian cancer.

Matrix metalloproteinases (MMPs) have been implicated in ovarian cancer progression. Among them, MMP-8 that degrades type I collagen may play a crucial role. The aim of our study was to determine MMP-8 expression and regulation in ovarian cancer and its association with other MMPs and tissue inhibitors of metalloproteinases (TIMPs). Tissue microarrays (TMAs) containing tissue cylinders from 302 patients were used for immunohistochemical studies. In addition, MMP-8 expression in vitro was analysed by a specific immunoassay and PCR-analysis. MMP-7 (81%), MMP-8 (95%), MT3-MMP (100%), TIMP-2 (100%), and TIMP-3 (96%) were expressed in all the OVCAs, but the staining intensities varied. MMP-3 (6%), MMP-9 (57%) and TIMP-1 (43%) expressions were more rarely detected. Only MMP-8 expression levels correlated with tumour grade (P<0.01), tumour stage (P<0.01), and a poor prognosis (P<0.05). MMP-8 protein and gene expression in vitro was found to be significantly upregulated by interleukin-1beta (IL-1beta, P<0.01). The data indicate that MMP-8 overexpression in OVCAs is regulated by IL-1beta and that pro-inflammatory cytokines may promote the invasive potential of ovarian cancer.

Heparanase-1 gene expression in normal, hyperplastic and neoplastic prostatic tissue.

Heparanase-1 (Hpa-1) has been implicated in tumour invasion and metastasis. In the present study, we evaluated the clinicopathological significance of Hpa-1 mRNA expression in prostate cancer and non-cancerous prostatic tissue by one-step polymerase chain reaction (PCR) of laser microdissected prostatic gland cells. In addition, cell type-specific expression of Hpa-1 mRNA in prostatic tissue was analysed by in situ hybridisation. Hpa-1 mRNA expression was found in 50% of normal and 40% of hyperplastic prostatic tissue. In situ hybridisation showed that Hpa-1 mRNA was strongly expressed in prostate gland cells. Of the 26 prostate carcinomas tested, 42% were positive for Hpa-1 mRNA. However, in non-cancerous prostatic tissue, Hpa-1 mRNA was significantly more often expressed than in less differentiated or more invasive prostate cancers (P<0.05). In situ hybridisation revealed only focal Hpa-1 mRNA expression in the neoplastic gland cells. Hpa-1 mRNA expression in the tumours significantly correlated with tumour differentiation and tumour stage (P<0.05). Our data indicate that Hpa-1 gene expression may be lost during dedifferentiation of prostatic gland cells.