Neurotrophic tropomyosin receptor kinase (NTRK) and nerve growth factor (NGF) are not expressed in Caucasian patients with biliary tract cancers: pooled data from three independent cohorts.

BACKGROUND: Neuronal signaling has been implicated in the pathophysiology of multiple malignancies. In biliary tract cancers (BTCs), tumor cell expression of nerve growth factor (NGF) and its receptor neurotrophic tropomyosin receptor kinase (NTRK) has been reported in Asian patients and linked to inferior clinical outcome. Furthermore, NTRK fusions have emerged as a promising target in various cancers. Expression patterns of these markers in Caucasian patients remain unknown. METHODS: In this study, 106 patients with BTCs were included. Immunohistochemistry for pan-NTRK and NGF-beta was performed on > 90 samples of this cohort. Additionally, samples from two independent cohorts, incorporating 254 cases, were used to confirm the findings of the original cohort. RESULTS: While expression of pan-NTRK and NGF-beta was readily detectable in peri-tumoral nerves, these markers were not detectable in malignant epithelial cells in our cohort. CONCLUSIONS: In a large cohort of Caucasian patients with BTC, NTRK and NGF-beta were not detectable, underscoring potential differences between Caucasian and Asian patient populations.

Acoustic radiation force impulse (ARFI) and high-frequency ultrasound of the liver surface for the diagnosis of compensated liver cirrhosis.

PURPOSE: To evaluate the diagnostic value of acoustic radiation force impulse (ARFI) and high-frequency ultrasound of the liver surface, using histology as a gold standard for the diagnosis of compensated liver cirrhosis. MATERIALS AND METHODS: 73 patients without ascites undergoing liver biopsy were included in the study. The left and right liver lobes were examined with ARFI and high-frequency ultrasound. Liver surface irregularity was quantified using image analysis software to calculate the difference between the real surface and the approximated physiological surface through a 20 mm standardized line. RESULTS: There is a significant difference between cirrhotic and non-cirrhotic patients for both quantified liver surface (QLS) and ARFI (p < 0.001). The mean values for QLS of the left lobe were 0.71 ± 0.24 mm and 1.17 ±â€Š0.80 mm, of the right lobe 0.56 ±â€Š0.26 mm and 0.87 ±â€Š0.26 mm for non-cirrhotic and cirrhotic patients, respectively. The mean values of ARFI measurements of the left lobe were 2.04 ±â€Š0.76 m/s and 2.85 ±â€Š0.81 m/s, of the right lobe 1.65 ±â€Š0.61 m/s and 3.02 ±â€Š0.77 m/s for non-cirrhotic and cirrhotic patients, respectively. Diagnostic accuracy (AUROC) was 0.78/0.80 for QLS and 0.77/0.91 for ARFI of the left/right lobe, respectively. ARFI of the right lobe is significantly better than ARFI of the left (p = 0.023) or QLS of the left (p = 0.025)/right (p = 0.046) lobe of the liver. CONCLUSION: Assessment of liver surface irregularity by high-frequency ultrasound (QLS) is a useful diagnostic test for the assessment of compensated liver cirrhosis. ARFI of the right liver lobe is significantly better than high-frequency ultrasound (QLS of the left/right lobe of the liver) and ARFI of the left lobe of the liver.

[Diagnosis of tumours of the liver and the biliary tract: new tissue and serum markers]. / Diagnose von Tumoren der Leber und Gallenwege: Neue Gewebe- und Serummarker.

Hepatocellular carcinomas (HCC) and bile duct carcinomas (BDC) have a poor prognosis since they are often detected at advanced stages and respond poorly to adjuvant therapy. Serum markers (e.g. AFP, CA19-9, etc.) can be used for early detection of these tumours but have only moderate sensitivity and specificity. The Golgi-associated protein GOLPH2 was found in the tissue and serum of patients with HCC and CCC and might be used to detect these tumours in time. The biopsy still remains the gold standard in the diagnosis of HCC and CCC. When biopsies are taken from these tumours they are often fragmented and contain reactive changes. Therefore immunohistochemical markers can aid in excluding or ascertaining malignancy. Studies have shown that the oncofetal protein "IGF-II mRNA-binding protein 3" (IMP3), the cell adhesion molecules P-cadherin and CD24, the cancer testis antigen MAGE-C2/CT-10 as well as the protein periostin can be used as tissue markers in the diagnosis of HCC and CCC.

Intraepithelial CD8-positive T lymphocytes predict survival for patients with serous stage III ovarian carcinomas: relevance of clonal selection of T lymphocytes.

BACKGROUND: The aim of this study was to investigate the prognostic effect of tumour-infiltrating lymphocytes (TILs) in serous stage III ovarian carcinoma to determine TIL clonality and to correlate this to Her2/neu expression. METHODS: Formalin-fixed and paraffin-embedded ovarian carcinomas were examined for CD20-, CD3-, CD4- and CD8-positive lymphocytes (n=100), and for Her2/neu-positive tumour cells (n=55/100) by immunohistochemistry. Clonality analysis was carried out by T-cell receptor gamma (TCRgamma) gene rearrangements (n=93/100). Statistical analyses included experimental and clinico-pathological variables, as well as disease-free (DFS) and overall (OS) survival. RESULTS: CD20-positive B lymphocytes were present in 57.7% (stromal)/33.0% (intraepithelial) and CD3-positive T lymphocytes in 99.0% (stromal)/90.2% (intraepithelial) of ovarian carcinomas. Intraepithelial CD3-positive T lymphocytes were correlated with improved DFS in optimally debulked patients (P=0.0402). Intraepithelial CD8-positive T lymphocytes were correlated with improved OS in all optimally debulked patients (P=0.0201) and in those undergoing paclitaxel/carboplatin therapy (P=0.0092). Finally, rarified and clonal TCRgamma gene rearrangements were detected in 37 out of 93 (39.8%) and 15 out of 93 (16.1%) cases, respectively. This was marginally associated with improved DFS (P=0.0873). Despite a significant correlation of HER2/neu status and intraepithelial CD8-positive lymphocytes (P=0.0264), this was non-directional (R=-0.257; P=0.0626). CONCLUSION: Improved survival of ovarian cancer patients is related to the infiltration, clonal selection and intraepithelial persistence of T lymphocytes.

Craniomaxillofacial fibrous dysplasia: a 10-year database 1996-2006.

Fibrous dysplasia is a rare bone disease caused by an abnormal proliferation of fibrous tissue in bone. We retrospectively evaluated eight patients (female to male ratio 3:1, mean age 22.5 years, range 10-32) with a monostotic form who were treated between 1996 and 2006. Two each were affected in the lower jaw, the upper jaw, the midface, and the frontoparietal region. Most patients were referred because of a painless swelling. Biopsy specimens from two patients were examined, six patients had modelling osteotomies, two of whom had further operations because of progressive enlargement. There was no visual impairment or malignant transformation. Fibrous dysplasia should be treated as conservatively as possible, but in cases of functional disturbance that results from malignant transformation, or from the involvement of the optic foramen or the foramen magnum, an immediate operation is needed. Disfigurement can be another reason for operation. When there is a risk of malignant transformation, follow-up of patients is recommended.

Jaw osteonecrosis related to bisphosphonate therapy: a severe secondary disorder.

Bisphosphonate-related osteonecrosis of the jaws (BON), first described in 2003, is gaining importance due to the increasing indication spectrum of bisphosphonate therapy [S. Takeyama, M. Ito, H. Shinoda, A novel bisphosphonate, TRK-530, for periodontitis, Bone 38 (2006) 31-31; M. Tagil, A. W-Dahl, J. Astrand, D. Little, S. Toksvig-Larsen, Decreasing the catabolic response by a single bisphosphonate infusion shortens the healing time in hemicallotasis operations, Bone 38 (2006) 84-85; E. Rodriguez, M.C. Duran, L.M. Rodriguez, R. Ros, M.R. Aleman, M. Rodriguez-Gaspar, A.M. Lopez, E. Garcia-Valdecasas, F. Santolaria, Intravenous (IV) bisphosphonates for osteopenic cancer survivor women: an alternative treatment, Bone 38 (2006) 72-73; D.G. Little, K. Ward, P. Kiely, M.C. Bellemore, J. Briody, C.T. Cowell, Bisphosphonate rescue in distraction osteogenesis: a case series, Bone 38 (2006) 80-80; R. Marx, Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic, J. Oral Maxillofac. Surg. 61 (2003) 1115-1118]. BON patients suffering from varying bony defects and symptoms are extremely restricted in their quality of life. Due to a limited knowledge of the aetiology of BON efficient evidence-based treatment strategies are lacking. Until now 23 patients with bisphosphonate-related osteonecrosis have been admitted to the Department of Cranio-Maxillofacial Surgery of the University of Zurich. A complete history has been recorded. All patients underwent clinical and radiographic examination. CT scans and MRI have been performed in selected cases. All patients had in common that, before signs of BON were observed, a local traumatic incidence had occurred. All patients showed signs of infection which could be remarkably reduced by antibacterial treatment. Furthermore, the period of bisphosphonate treatment was found to be one of the significant factors causing bisphosphonate-related osteonecrosis of the jaws. The aetiology of BON appears to depend on multiple factors: period and type of bisphosphonate therapy and trauma paving the way for an invasion of pathogens. Because evidence based therapy protocols for complete remodelling of bone defect are still missing, prevention in bisphosphonate-treated patients seems to be of utmost importance. A close interdisciplinary collaboration is required.