[Show abstract][Hide abstract] ABSTRACT: The S3 guidelines for pancreatic cancer were revised in 2013. Besides the oncological and palliative therapy modalities and surgical therapy, the guidelines for pathologists in topic 3 were updated. The modifications essentially concern the histopathological assessment of surgical specimens and in particular the circumferential resection margin and the R classification. In addition, the current recommendations were amended by recommendations concerning the pathohistological records, which should include the lymph node ratio in the future.
[Show abstract][Hide abstract] ABSTRACT: Ductal adenocarcinoma of the pancreas is the fourth most common cause of death from cancer in men and women in Germany: about 15 000 persons die of this disease each year.
[Show abstract][Hide abstract] ABSTRACT: A 28-year-old man presented with loss of appetite, night sweats, eczema, and axillary and inguinal lymph node swelling. The tentative diagnosis of malignant lymphoma was made. To confirm the diagnosis, extirpation of a lymph node and a skin biopsy were performed. Systemic treatment with methylprednisolone resulted in an improvement of eczema and lymph node swelling. Because of the histological findings and clinical course, we diagnosed dermatopathic lymphadenopathy, also known as Pautrier-Woringer syndrome.
[Show abstract][Hide abstract] ABSTRACT: Malignant peripheral nerve sheath tumors (MPNST) account for up to 10% of all malignant soft tissue tumors in adults. Insufficient data are available on diagnosis, differential diagnosis and treatment modalities as well as prognosis.
Examining our sarcoma database from 1991 to 2004, we evaluated 65 patients with histologically-proven MPNST in terms of clinical, histopathological as well as prognostic factors.
The median age was 54 years, the gender ratio was equal, the follow-up 36 months. Extremities were involved in 75% of cases, the trunk in 15% and the head in 9% respectively. A total of 9% of our patients presented with disease-positive lymph nodes, in 28%, distant metastases (primarily lung) occurred. A primary closure was performed in 60%; in 22%, a tendon transfer and flap coverage was necessary. In 11% of cases, the final treatment was amputation. The initial diagnoses which had to be revised during re-evaluation was 32.3%. The 5-year disease-free survival rate was 49%. Overall, 27% of patients first operated on at our Institution experienced local recurrence. The only significant negative prognostic factor for survival was occurrence of metastases.
Our data indicate, that MPNST are tumor entities with a high rate of initial diagnoses that subsequently need to be adjusted (32%). Therefore, reference pathology should be requested. Tumor localization close to major nerves often results in functional restrictions after tumor resection. Because of the low mean life expectancy, early functional reconstructions by tendon transfer should be performed instead of nerve repair. Despite less radical tumor excision with often marginal resections, the survival rate is comparable to that of the literature where patients were treated with more radical procedures.
Anticancer research 02/2014; 34(2):777-83. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Targeting the centromers of chromosomes 3, 7, 17 (CEP3, 7, 17) and the 9p21-locus (LSI9p21) for diagnosing bladder cancer (BC) is time- and cost-intensive and requires a manual investigation of the sample by a well-trained investigator thus overall limiting its use in clinical diagnostics and large-scaled epidemiological studies. Here we introduce a new computer-assisted FISH-spot analysis tool enabling an automated, objective and quantitative assessment of FISH patterns in the urinary sediment. Utilizing a controllable microscope workstation, the microscope software Scan^R was programmed to allow automatic batch-scanning of up to 32 samples and identifying quadruple FISH signals in DAPI-scanned nuclei of urinary sediments. The assay allowed a time- and cost-efficient, automated and objective assessment of CEP3, 7 and 17 FISH signals and facilitated the quantification of nuclei harboring specific FISH patterns in all cells of the urinary sediment. To explore the diagnostic capability of the developed tool, we analyzed the abundance of 51 different FISH patterns in a pilot set of urine specimens from 14 patients with BC and 21 population controls (PC). Herein, the results of the fully automated approach yielded a high degree of conformity when compared to those obtained by an expert-guided re-evaluation of archived scans. The best cancer-identifying pattern was characterized by a concurrent gain of CEP3, 7 and 17. Overall, our automated analysis refines current FISH protocols and encourages its use to establish reliable diagnostic cutoffs in future large-scale studies with well-characterized specimens-collectives.
Biochemical and Biophysical Research Communications 01/2014; · 2.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background & Aims
Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in combination with cytopathology is the optimal method for diagnosis and staging of pancreatic ductal adenocarcinoma (PDAC) and other pancreatic lesions. Its clinical utility, however, can be limited by high rates of indeterminate or false negative results. We aimed to develop and validate a microRNA (miRNA)-based test to improve preoperative detection of PDAC.
Levels of miRNAs were analyzed in a central clinical laboratory by relative quantitative PCR in 95 formalin-fixed, paraffin-embedded (FFPE) specimens and 228 samples collected by EUS-FNA during routine evaluations of patients with solid pancreatic masses at 4 institutions in the United States, 1 in Canada, and 1 in Poland.
We developed a 5-miRNA expression classifier, consisting of MIR24, MIR130B, MIR135B, MIR148A, and MIR196, that could identify PDAC in well-characterized FFPE specimens. Detection of PDAC in EUS-FNA samples increased from 78.8% by cytology analysis alone (95% confidence interval [CI], 72.2%–84.5%) to 90.8% when combined with miRNA analysis (95% CI, 85.6%–94.5%). The miRNA classifier correctly identified 22 additional true PDAC cases among 39 samples initially classified as benign, indeterminate, or non-diagnostic by cytology. Cytology and miRNA test results were each significantly associated with PDAC (P<.001), with positive predictive values >99% (95% CI, 96%–100%).
We developed and validated a 5 miRNA classifier that can accurately predict which preoperative pancreatic EUS-FNA specimens contain PDAC. This test might aid in the diagnosis of pancreatic cancer by reducing the number of FNAs without a definitive adenocarcinoma diagnosis, thereby reducing the number of repeat EUS-FNA procedures.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 01/2014; · 5.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Osteosarcomas of the craniomaxillofacial region in adults are rare malignant tumors with many sites of origin. The purpose of this study was to analyze the outcome of adult patients suffering from osteosarcomas and investigate whether neoadjuvant chemotherapy would be beneficial to overall outcome.
The medical records of 36 patients treated during 2002-2012 were reviewed. All patients suffered from primary osteosarcomas of the craniomaxillofacial region.
The mean survival of patients was 64.49 ± 23.52 months. The 2- and 5-year overall survival rates in the neoadjuvant treatment group were 100 and 66.7 %; in the surgery only group, the overall survival rates were 66.7 and 41.7 %, respectively. The neoadjuvant treatment (p = 0.017), tumor size (p = 0.004), tumor location (p = 0.02), and age (p < 0.0001) were significant parameters influencing survival, whereas other tumor-related or demographic factors had no significant influence on survival.
Early identification of osteosarcoma of the craniomaxillofacial region and combined treatment by neoadjuvant chemotherapy with radical surgery are the most important strategies in dealing with these sarcomas. If possible, this treatment option should be followed unless contraindicated by other factors.
Journal of Cancer Research and Clinical Oncology 11/2013; · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The interdisciplinary guidelines at the S3 level on the diagnosis of and therapy for hepatocellular carcinoma (HCC) constitute an evidence- and consensus-based instrument that is aimed at improving the diagnosis of and therapy for HCC since these are very challenging tasks. The purpose of the guidelines is to offer the patient (with suspected or confirmed HCC) adequate, scientifically based and up-to-date procedures in diagnosis, therapy and rehabilitation. This holds not only for locally limited or focally advanced disease but also for the existence of recurrences or distant metastases. Besides making a contribution to an appropriate health-care service, the guidelines should also provide the foundation for an individually adapted, high-quality therapy. The explanatory background texts should also enable non-specialist but responsible colleagues to give sound advice to their patients concerning specialist procedures, side effects and results. In the medium and long-term this should reduce the morbidity and mortality of patients with HCC and improve their quality of life.
Zeitschrift für Gastroenterologie 11/2013; 51(11):1269-326. · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chemotherapy for soft tissue sarcomas remains unsatisfactory due to their low chemosensitivity. Even the first line chemotherapeutic agent doxorubicin only yields a response rate of 18-29%. The antibiotic salinomycin, a potassium ionophore, has recently been shown to be a potent compound to deplete chemoresistant cells like cancer stem like cells (CSC) in adenocarcinomas. Here, we evaluated the effect of salinomycin on sarcoma cell lines, whereby salinomycin mono- and combination treatment with doxorubicin regimens were analyzed.
To evaluate the effect of salinomycin on fibrosarcoma, rhabdomyosarcoma and liposarcoma cell lines, cells were drug exposed in single and combined treatments, respectively. The effects of the corresponding treatments were monitored by cell viability assays, cell cycle analysis, caspase 3/7 and 9 activity assays. Further we analyzed NF-kappaB activity; p53, p21 and PUMA transcription levels, together with p53 expression and serine 15 phosphorylation.
The combination of salinomycin with doxorubicin enhanced caspase activation and increased the sub-G1 fraction. The combined treatment yielded higher NF-kappaB activity, and p53, p21 and PUMA transcription, whereas the salinomycin monotreatment did not cause any significant changes.
Salinomycin increases the chemosensitivity of sarcoma cell lines - even at sub-lethal concentrations - to the cytostatic drug doxorubicin. These findings support a strategy to decrease the doxorubicin concentration in combination with salinomycin in order to reduce toxic side effects.
BMC Cancer 10/2013; 13(1):490. · 3.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Octreotide is suggested to harden the pancreas, thus facilitating the construction of a pancreatic anastomosis and lowering the risk of postoperative fistula. We tested the hypothesis that intra-arterial application of octreotide in the gastroduodenal artery during pancreatectomy may increase pancreatic hardness.
A single-center, prospective, double-blinded, randomized controlled trial with parallel assignment was conducted. Patients planned for a pancreatoduodenectomy or a total pancreatectomy, who had a palpatory and durometer proven (<40 Shore units) soft pancreas, were assigned to receive intraoperatively either 5 mL 500µg octreotide or 5 mL 0.9% saline solution as a bolus injection in the gastroduodenal artery. Pancreatic hardness was measured before, early, and late after intervention. The investigator performing the durometer measurements and pathologist were masked to group assignment. The primary outcome was increased pancreatic hardness. Analysis was by intention to treat. This trial is registered at http://www.clinicaltrials.gov (ID NCT01400100).
A total of 12 patients received octreotide and 13 received saline solution. Pancreatic hardness marginally increased in the octreotide group: 0.67 ± 2.3 Shore units, whereas it decreased in the control group: -2.15 ± 2.7 Shore units. The difference was statistically significant, p = 0.029 (95% confidence interval = -4.87 to -0.77). Histology did not find any correlate for this clinically irrelevant hardening effect.
A single bolus application of octreotide did not deliver a clinically relevant increase in pancreatic hardness. Future studies on the hardening effect of octreotide should employ repeated or continuous preoperative administration of this drug.
Scandinavian journal of surgery: SJS: official organ for the Finnish Surgical Society and the Scandinavian Surgical Society 09/2013; 102(3):164-70. · 1.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The MRE11/RAD50/NIBRIN complex, a protein complex that repairs DNA double-strand breaks, could serve as an early marker for new lesions in pancreatic cancer. We determined the expression of MRE11, RAD50 and NIBRIN, and their possible prognostic value regarding survival. Forty-one patients with ductal adenocarcinoma of the pancreas were included. All underwent curative surgery. Immunohistochemistry was performed for MRE11, RAD50 and NIBRIN. Subsequent analyses were based on a modified immunoreactive score. Statistical analysis was conducted using the statistics program "R". The mean follow-up period was 509 days. The mean age of the patients was 67±8 years, male=56%, female=44%. Eighty-seven percent underwent a Kausch-Whipple procedure, whereas a left side resection was performed in 22% of patients. Positive lymph nodes were found in 80% of cases, and patients were staged UICC IIa (12%), IIb (56%) and IV (29%). Overall significant results were found for MRE11 (p=0.02) and NIBRIN (p=0.01) expression and postoperative survival. We found a significant relation between the expression of MRE11, NIBRIN and the postoperative survival of patients with ductal adenocarcinoma. The link between the expression of the MRN complex, ATM and pancreatic cancer can be used to develop new treatment options for pancreatic carcinoma.
Pathology - Research and Practice 07/2013; · 1.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Spectral histopathology (SHP) is an emerging tool for label free annotation of tissue. While FTIR based SHP provides fast annotation of larger tissue sections, Raman based SHP is slower but achieves a 10 times higher spatial resolution as compared to FTIR. Usually NIR excitation is used for Raman measurements on biological samples. Here, for the first time 532 nm excitation is used to annotate colon tissue by Raman SHP. Excellent data quality is obtained, which resolves for example erythrocytes and lymphocytes. In addition to Raman scattering auto-fluorescence is observed. We found that this auto-fluorescence overlaps spatially with the fluorescence of antibodies against p53 used in routine immunohistochemistry in surgical pathology. This fluorescence indicates nuclei of cancer cells with mutated p53 and allows new label free assignment of cancer cells. These results open new avenues for optical diagnosis by Raman spectroscopy and autofluorescence.
[Show abstract][Hide abstract] ABSTRACT: We evaluated if preoperative serum apoptosis markers correlate with atrial histological remodeling and postoperative atrial fibrillation (POAF) after cardiac surgery.
A total of 33 patients with sinus rhythm (SR) and without history of atrial fibrillation (AF) undergoing cardiac surgery were prospectively enrolled. Serum concentrations of Fas (apoptosis-stimulating fragment ligand) and TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) were measured preoperatively. Right atrial appendage (RAA) tissue was obtained during surgery. Atrial apoptosis was assessed via TUNEL assay and degree of atrial fibrosis was categorized histologically by visual quantification. Continuous ECG-Monitoring was used to screen for POAF throughout 10 days after cardiac surgery. POAF occurred in 15 patients (45%). Atrial apoptosis was higher in patients with POAF as compared to those without (35.9 ± 9.8% vs 14.5 ± 7.5%; P < 0.0001) and correlated with the degree of atrial fibrosis (r = 0.69; P < 0.0001). In contrast to TRAIL (87.0 ± 8.2 pg/mL vs 83.3 ± 9.4 pg/mL; P = 0.77), preoperative Fas serum concentration was significantly higher in patients with POAF compared to patients in stable SR (91.3 ± 7.2 pg/mL vs 66.7 ± 3.0 pg/mL; P < 0.01). Serum Fas concentration correlated with the degree of atrial apoptosis (r = 0.63; P < 0.001) and the degree of atrial fibrosis (r = 0.39; P < 0.05).
Preoperative evaluation of serum apoptosis marker Fas is useful to identify patients at risk for POAF undergoing cardiac surgery. Fas but not TRAIL correlates with the documented degree of atrial apoptosis and atrial fibrosis in RAA tissue. Further studies need to identify the prospective role of Fas in predicting POAF events.
Journal of Cardiovascular Electrophysiology 05/2013; · 3.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Preneoplastic lesions of colorectal carcinoma can be divided in non-serrated and serrated lesions. Non-serrated lesions include conventional adenomas (tubular, tubulovillous and villous) and dysplasias associated with inflammatory bowel disease like flat intraepithelial neoplasia, dysplasia-associated lesions or masses (DALM) and adenoma-like masses (ALM). Conventional adenomas are mostly sporadic, but also found in hereditary adenomatous-polyposis syndromes. Hamartous polyposis syndromes are also associated with colorectal cancer. Serrated lesions include hyperplastic polyps, sessile serrated adenomas and traditional serrated adenomas. Based on these precancerous colorectal lesions different molecular subtypes were identified. Histological subtype, size and grade of dysplasia of polyps are essential for risk assessment of colorectal cancer.