Franz Sellner

2-18fluoro-deoxy-D-glucose Positron Emission Tomography Is a Reliable Predictor for Viable Tumor in Postchemotherapy Seminoma: An Update of the Prospective Multicentric SEMPET Trial

PURPOSE To define the clinical value of 2-18fluoro-deoxy-D-glucose positron emission tomography (FDG PET) as a predictor for viable residual tumor in postchemotherapy seminoma residuals in a prospective multicentric trial. PATIENTS AND METHODS FDG PET studies in patients with metastatic pure seminoma who had radiographically defined postchemotherapy residual masses were correlated with either the histology of the resected lesion or the clinical outcome documented by computer tomography (CT), tumor markers, and/or physical examination during follow-up. The size of the residual lesions on CT, either >3 cm or < or =3 cm, was correlated with the presence or absence of viable residual tumor. RESULTS Fifty-six FDG PET scans of 51 patients were assessable. All 19 cases with residual lesions >3 cm and 35 (95%) of 37 with residual lesions < or =3 cm were correctly predicted by FDG PET. The specificity, sensitivity, positive predictive value, and negative predictive value of FDG PET were 100% (95% CI, 92% to 100%), 80% (95% CI, 44% to 95%), 100%, and 96%, respectively, versus 74% (95% CI, 58% to 85%), 70% (95% CI, 34% to 90%), 37%, and 92%, respectively, for CT discrimination of the residual tumor by size (>3 cm/< or =3 cm). CONCLUSION This investigation confirms that FDG PET is the best predictor of viable residual tumor in postchemotherapy seminoma residuals and should be used as a standard tool for clinical decision making in this patient group.

Solitary and multiple isolated metastases of clear cell renal carcinoma to the pancreas : An indication for pancreatic surgery

BackgroundIsolated pancreatic metastases (isPMs) of clear cell renal carcinoma are rare. Most of them are solitary; some are multiple. The reported rates and the clinical implications of multiple isPMs from clear cell renal cancer vary. Therefore, the available literature was analyzed to shed light on the clinical significance of these extremely rare metastatic lesions.MethodsA literature search brought to light 236 cases of isPMs (both solitary and multiple) from renal cell carcinoma. These were analyzed.ResultsA total of 12% of the metastases were synchronous with the primary tumor, and 88% were metachronous, occurring 10.0 ± 6.5 years (mean ± SD) after nephrectomy. A predilection for a specific part of the pancreas was not identifiable. The localization of the renal cell cancer (left or right kidney) did not have any effect on the site of the metastases. Seventy-four (39%) of the metastases to the pancreas were multiple (3.2 ± 1.5). Their epidemiology did not differ from that of solitary metastatic lesions. Actuarial 3- and 5-year survival rates after radical resection were 78% and 78%, respectively, for multiple versus 75% and 64% for solitary metastases.ConclusionsThe epidemiological data do not support a direct local lymphogenous or venous spread from the primary tumor to the pancreas. They rather suggest a systemic spread. Because of the positive outcome, radical removal of both solitary and multiple metastases should be attempted in eligible patients.

Altered expression of organic anion transporter polypeptide (OATP) genes in human breast carcinoma

Organic anion transporter polypeptides (OATPs) mediate the transmembrane uptake of endogenous compounds and clinically important drugs in various tissues thereby effecting drug disposition and tissue penetration. OATPs have also been identified in gastric, pancreatic, and colon carcinomas but little is known about their expression in breast carcinoma. We therefore analyzed the expression pattern of all 11 known OATPs in three breast cancer cell lines (MCF-7, ZR-75-1, MDA-MB-231) and one immortalized breast epithelial cell line (MCF-10A) using quantitative real-time RT-PCR. Transcripts of 7/11 OATP genes with heterogeneity in their expression profile were detected in control and/or cancer cell lines. Of these seven OATPs, five were also expressed in breast tumor and adjacent non-tumorous specimens from 13 patients. OATP2B1, not found in the analyzed cell lines, was verified in the tissue samples. Interestingly, mRNA expression of OATP2B1, OPATP3A1, and OATP4A1 was significantly higher (p

The analysis of organic anion transporting polypeptide (OATP) mRNA and protein patterns in primary and metastatic liver cancer.

Organic anion transporting polypeptides (OATP, SLCO genes) mediate the uptake of endobiotics and drugs. Thus, their expression levels and pattern could be of relevance for cancer therapy. This prompted us to investigate the expression of poorly characterized OATPs, namely OATP2A1, OATP3A1, OATP4A1 and OATP5A1 in hepatic cancer of different origin. First, mRNA levels of all eleven OATPs were determined in paired (cancerous and adjacent non-cancerous) specimens from 43 patients with primary liver cancer (hepatocellular carcinoma, HCC; cholangiocellular carcinoma, CCC) and liver metastases from colon tumors (MLT). Real-time RT-PCR analysis revealed that all OATPs, except OATP1C1 and OATP6A1, are extensively expressed in nearly all samples. In contrast to downregulated OATP1B1, OATP1B3, OATP1A2 and OATP2B1 in cancerous vs. non-cancerous samples, an increase in OATP2A1, OATP3A1, OATP4A1 and OATP5A1 mRNA levels was seen in tumors (up to 40-fold for OATP5A1 in the MLT group). Therefore, OATP2A1, OATP3A1, OATP4A1 and OATP5A1 were further investigated by immunofluorescence microscopy on paraffin-embedded cancerous and non-cancerous sections (seven per group). OATP-derived immunoreactivity was observed in plasma membranes and cytosol of hepatic tumor cells, and additionally, in various cytokeratin 19 positive bile ducts. An increased percentage of immunoreactive cells and a higher staining intensity in cancerous vs. non-cancerous paraffin sections paralleled higher mRNA levels of OATP2A1, OATP3A1, OATP4A1 and OATP5A1 in cancerous tissues of HCC, CCC and MLT patients. The extensive expression of OATP2A1, OATP3A1, OATP4A1 and OATP5A1 in hepatic tumors of different origin suggests that these transporters might be further exploited for the discovery of novel anticancer agents.

Coexpression of the melatonin receptor 1 and nestin in human breast cancer specimens

Abstract:  Activation of the G‐protein‐coupled receptor (GPCR) for melatonin (MT1) suppresses breast cancer cell growth in experimental models. To elucidate whether MT1 might play a role in cancer cells positive for the stem cell marker nestin, we assessed paired carcinomatous (Ca) and adjacent noncancerous (NCa) samples from 42 patients with primary breast cancer for MT1 and nestin by double immunofluorescence staining and quantitative image analysis with Tissue‐Quest® software. MT1 was located in luminal and myoepithelial cells in milk ducts and in tumor cells in 40/42 and 39/42 of NCa and Ca specimens, respectively, independent of hormone receptor and HER‐2 status. Nestin was located together with MT1 in myoepithelial cells in 38 NCa specimens (total n = 42) and in 18 Ca specimens with intact milk ducts. Quantitative evaluation of selected 16 NCa and Ca samples revealed that MT1 levels were higher in invasive Ca sections than in NCa specimens in eight and lower in six cases. Specimens from higher tumor stages (TII/III) with a higher risk of relapse were associated with MT1/nestin co‐staining in more than 10% of tumor cells, whereas a lack of co‐staining correlated with lower tumor stages. Abundant expression of MT1 and, particularly, coexpression of MT1 with nestin in invading tumor cells in more advanced tumors suggest an important role for this GPCR in the pathogenesis of breast cancer.

TNM stage and grade in predicting the prognosis of operated, non-functioning neuroendocrine carcinoma of the pancreas - A single-institution experience

To evaluate the prognostic significance of TNM and grading categories in curatively resected non‐functioning neuroendocrine pancreatic carcinoma (nfnepC).

Intermittent hepatic portal vein gas complicating diverticulitis - A case report and literature review

Case reportThis report describes a case of intermittent hepatic portal venous gas (HPVG) because of colonic diverticulitis in a 48-year-old man, who was successfully treated by surgery.ConclusionBased on an extensive literature search, which produced 21 observations, the etiology, symptoms, imaging features, clinical significance, treatment strategy, and outcome of HPVG because of colonic diverticulitis are evaluated: While observations with an underlying intramesocolic abscess carry a favorable prognosis, the prognosis of observations because of septic thrombophlebitis with gas forming germs is poor.

Exploring the surgical landscape of pancreatic neuroendocrine neoplasia in Austria: Results from the ASSO pNEN study group

INTRODUCTION Pancreatic neuroendocrine neoplasia (pNEN) show increasing incidence and management is complex due to biological heterogeneity. Most publications report isolated high-volume single-centre data. This Austrian multi-centre study on surgical management of pNENs provides a comprehensive real-life picture of quality indicators, recurrence-patterns, survival factors and systemic treatments. METHODS Retrospective, national cohort-study from 7 medium-/high-volume centres in Austria, coordinated under the auspices of the Austrian Society of Surgical Oncology (ASSO). RESULTS Two-hundred patients underwent resection for pNEN, 177 had non-functioning tumours and 31 showed stage 4 disease. Participating centres were responsible for 2/3 of pNEN resections in Austria within the last years. The mean rate of completeness of variables was 98.6%. Ninety-days mortality was 3.5%, overall rate of complications was 42.5%. Morbidity did not influence long-term survival. The 5-year overall-survival (OS) was 81.3%, 10-year-OS 52.5% and 5-year recurrence-free-survival (RFS) 69.8%. Recurrence was most common in the liver (68.1%). Four out of five patients with recurrence underwent further treatment, most commonly with medical therapy or chemotherapy. Multivariable analysis revealed grading (HR:2.7) and metastasis (HR:2.5) as significant factors for relapse. Tumours-size ≥2 cm (HR:5.9), age ≥60 years (HR:3.1), metastasis (HR:2.3) and grading (HR:2.0) were associated with OS. Tumours <2 cm showed 93.9% 10-year-OS, but 33% had G2/G3 grading, 12.5% positive lymph-nodes and 4.7% metastasis at diagnosis, each associated with significant worse survival. CONCLUSION Resection of pNENs in Austria is performed with internationally comparable safety. Analysed factors allow for risk-stratification in clinical treatment and future prospective trials. A watch-and-wait strategy purely based on tumour-size cannot be recommended.