"Bone in the penis" or fasciitis ossificans of the penis - a first time description of a pseudo-tumor at an extraordinary site.

BACKGROUND: Fasciitis ossificans is a rare subtype of nodular fasciitis, a benign soft tissue tumor with reactive characteristics. Due to its rapid growth, it is often misdiagnosed as a malignant tumor. While fasciitis ossificans commonly originates from the subcutaneous tissue and can appear throughout the body, it may also arise from extraordinary sites. CASE PRESENTATION: We report the first-ever documented case of fasciitis ossificans arising from the penis in a male patient who presented with a tumor on the glans penis. The tumor was surgically resected due to suspicion of penile cancer. Initial histopathological analysis led to a misdiagnosis of squamous cell carcinoma. However, pathological consultation ultimately confirmed the diagnosis of fasciitis ossificans of the penis originating from the glans penis by demonstrating ossification. CONCLUSION: This case underscores the importance of considering fasciitis ossificans in the differential diagnosis of soft tissue tumors, even in unusual locations such as penile soft tissue.

PSMA Expression in 122 Treatment Naive Glioma Patients Related to Tumor Metabolism in 11C-Methionine PET and Survival.

Apart from its expression in benign and malignant prostate tissue, prostate specific membrane antigen (PSMA) was shown to be expressed specifically in the neovasculature of solid tumors. For gliomas only little information exists. Therefore, we aimed to correlate PSMA expression in gliomas to tumor metabolism by L-[S-methyl-11C]methionine (MET) PET and survival. Therefore, immunohistochemical staining (IHC) for isocitrate dehydrogenase 1-R132H (IDH1-R132H) mutation and PSMA expression was performed on the paraffin embedded tissue samples of 122 treatment-naive glioma patients. The IHC results were then related to the pre-therapeutic semiquantitative MET PET data and patients' survival. Vascular PSMA expression was observed in 26 of 122 samples and was rather specific for high-grade gliomas ([HGG] 81% of glioblastoma multiforme, 10% of WHO grade III and just 2% of grade II gliomas). Significantly higher amounts of gliomas without verifiable IDH1-R132H mutation showed vascular PSMA expression. Significantly shorter median survival times were seen for patients with vascular PSMA staining in all tumors as well as HGG only. Additionally, significantly higher numbers of PSMA staining vessels were found in tumors with high amino acid metabolic rates. Vascular PSMA expression in gliomas was seen as a high-grade specific feature associated with elevated amino acid metabolism and short survival.

Neuroendocrine liver metastasis from the small intestine: Is surgery beneficial for survival?

BACKGROUND: Neuroendocrine neoplasia of the small intestine (siNEN) are frequently diagnosed with liver metastases. The impact of the presence of liver metastases on overall survival and the necessity of surgery for liver metastasis is discussed controversially. The aim of this study is to evaluate and compare the overall long-term survival of patients with siNENs with and without liver metastasis at initial diagnosis and the possible benefit of surgical treatment as compared to active surveillance of metastases. 123 consecutive patients with siNENs were treated between 1965 and 2016. All clinical and histological records were reevaluated including analysis of the proliferation rates in all specimens. The 1-, 5-, 10- and 20-year overall survival was estimated by Kaplan-Meier analysis for patients with and without liver metastasis and according to the type of treatment (surgical vs. surveillance) of liver metastases if present. RESULTS: The 1-, 5-, 10- and 20-year overall survival rate was 89.0%, 68.4%, 52.8% and 31.0% in patients without and 89.5%, 69.5%, 33.2% and 3.6% in those with liver metastases. No statistically significant differences were observed comparing the two groups. Within the group of patients with liver metastases, the type of treatment (surgical vs. surveillance) was in favor of patients undergoing surgery. Multivariate analysis showed that the presence of liver metastases upon diagnosis was an individual risk factor associated with worse survival. CONCLUSION: The presence of liver metastasis at initial diagnosis does not have a statistically significant influence on survival. Surgery for hepatic metastasis seems to show a benefit for overall survival and may be indicated especially in patients symptomatic due to high tumor burden and serotonin hypersecretion to reduce hormone activity.

The Immune Phenotype of Isolated Lymphoid Structures in Non-Tumorous Colon Mucosa Encrypts the Information on Pathobiology of Metastatic Colorectal Cancer.

The gut-associated lymphoid tissue represents an integral part of the immune system. Among the powerful players of the mucosa-associated lymphoid tissue are isolated lymphoid structures (ILSs), which as information centers, drive the local (and systemic) adaptive immune responses. Germinal center reactions, taking place within ILSs, involve the coordinated action of various immune cell types with a central role given to B cells. In the current study, we aimed at dissecting the impact of ILSs within non-tumorous colon tissue (NT) on the pathobiology of colorectal cancer (CRC) with metastasis in the liver (CRCLM). In particular, we focused on the immune phenotypes of ILSs and ectopic lymphoid structures (ELSs), built up at matching primary and metastatic tumor sites. We implemented an integrative analysis strategy on the basis of tissue image cytometry and clonality assessment to explore the immune phenotype of ILS/ELS at three tissue entities: NT, CRC, and CRCLM (69 specimens in total). Applying a panel of lineage markers used for immunostaining, we characterized and compared the anatomical features, the cellular composition, the activation, and proliferation status of ILSs and ELSs, and assessed the clinical relevance of staining-derived data sets. Our major discovery was that ILS characteristics at the NT site predefine the immune phenotype of ELSs at CRC and CRCLM. Thereby, B-cell-enriched (CD20) and highly proliferative (Ki67) ILSs and ELSs were found to be associated with improved clinical outcome in terms of survival and enabled patient stratification into risk groups. Moreover, the data revealed a linkage between B-cell clonality at the NT site and the metastatic characteristics of the tumor in the distant liver tissue. Consolidation of immunostaining-based findings with the results of compendium-wide transcriptomic analysis furthermore proposed CD27 as a novel marker of T follicular helper cells within lymphoid structures. Overall, the study nominates the ILS immune phenotype as a novel prognostic marker for patients with metastatic CRC.

Positive central lymph-nodes are underdiagnosed in patients with Bethesda V cytology in an endemic goiter region.

BACKGROUND: Fine needle aspiration (FNA) is a significant diagnostic procedure for detecting malignancy in patients with nodular thyroid disease. A high proportion of patients with cytological diagnosed follicular neoplasia (Bethesda IV and V) ultimately have thyroid cancer. The aim of this study was to evaluate the incidence of preoperatively undiagnosed central lymph node metastasis in patients with multinodular goiter (MNG). METHODS: Patients who underwent FNA and were classified as Bethesda IV/V were included. Applying a radical approach, all patients underwent (hemi)thyroidectomy and prophylactic unilateral central neck dissection. RESULTS: During our study period 2009-2013, 60 patients (19.7%) were classified as Bethesda IV and 21 (6.9%) Bethesda V. Final histopathological results revealed malignancy in 35 (43.2%) of 81 Bethesda IV/V nodules. Of the nodules classified as Bethesda IV, 20 (33.3%) showed malignancy in the final histology. Ten patients (16.7%) had papillary micro-carcinoma (mPTC, <10 mm), 4 (6.6%) PTC and 6 (10%) follicular thyroid cancer. Fifteen of 21 (71.4%) Bethesda V nodules were revealed as PTC of whom seven (33.3%) patients also had lymph-node metastases. CONCLUSIONS: While 33.3% of the patients with PTC, preoperatively classified as Bethesda V, had previously undetected positive lymph-nodes, only one patient with Bethesda IV had lymph-node metastasis.

Early Diagnosis of Medullary Thyroid Cancer: Are Calcitonin Stimulation Tests Still Indicated in the Era of Highly Sensitive Calcitonin Immunoassays?

Background: Measurements of both basal (b) calcitonin (CT) and calcium (Ca)-stimulated CT (Ca-sCT) levels are performed to identify medullary thyroid cancer (MTC) at an early stage when used as part of the diagnostic workup of thyroid nodules (CT screening). Novel immunochemiluminometric assays, which are highly sensitive and specific for monomeric CT and avoid cross-reactivity, have been introduced over the past decade. No prospectively generated data have so far become available to answer the frequently raised question as to whether Ca-sCT in contrast to bCT alone is helpful and, therefore, still indicated for the early detection of MTC. Methods: Ca-stimulation tests were performed in 149 consecutive patients with thyroid nodules and elevated bCT. Regardless of Ca-sCT levels, all patients had an operation applying a uniform surgical protocol, including thyroidectomy and systematic lymph node dissection. Recently published sex-specific cutoff levels for the differentiation of MTC and other C-cell pathologies (C-cell hyperplasia [CCH]) were used to compare the diagnostic performance of bCT or Ca-sCT alone and in combination using receiver-operating characteristic (ROC) analysis. In addition, CT cutoff levels to predict lateral lymph node metastasis were evaluated for bCT compared with Ca-sCT. Follow-up for all patients was documented and correlated with initial CT levels. Results: MTC was identified in 76 (50.1%) patients, in 21/76 (27.6%) with lymph node and in 4 (5.3%) with distant metastasis. Using predefined cutoff levels, patients could effectively be subdivided into a group above the cutoff level with definitive diagnosis of MTC (100%) and below (gray zone) with a significant overlap of CCH and MTC (all classified as pT1a; males: 19/58 [37.5%], females: 7/41 [17.1%]). The areas under the ROC curve (AUC) were excellent for the diagnosis of MTC in all tests. Determination of bCT proved to be superior for both diagnosing MTC in males (AUC for bCT: 0.894; AUC for Ca-sCT: 0.849) and females (bCT: 0.935; Ca-sCT: 0.868) and also for diagnosing lymph node metastasis in the lateral compartment (males: bCT: 0.925; Ca-sCT: 0.810; females: bCT: 0.797; Ca-sCT: 0.674). Combining both tests did not improve diagnostic accuracy. Using a cutoff level of >85 pg/mL for females and >100 pg/mL for males, the sensitivity for diagnosing lateral neck lymph node metastasis was 100%. Below these cutoff levels, no patient showed persistent or recurrent disease (median follow-up: 46 [ ± 27] months). Conclusions: Predefined sex-specific bCT cutoff levels are helpful for the early detection of MTC and for predicting lateral neck lymph node metastasis. Ca-sCT did not improve preoperative diagnostics. bCT levels >43 and >100 pg/mL for males and of >23 and >85 pg/mL for females are relevant for advising patients and planning the extent of surgery.

A Nomogram to Predict the Outcome of Fine Needle Aspiration Cytology in Head and Neck Masses.

Fine needle aspiration cytology (FNAC) is an important diagnostic tool for tumors of the head and neck. However, non-diagnostic or inconclusive results may occur and lead to delay in treatment. The aim of this study was to evaluate the factors that predict a successful FNAC. A retrospective search was performed to identify all patients who received an FNAC at the Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna. The variables were patients' age and sex, localization and size of the punctured structure, previous radiotherapy, experience of the head and neck surgeon, experience of the pathologist and the FNAC result. Based on these parameters, a nomogram was subsequently created to predict the probability of accurate diagnosis. After performing 1221 FNACs, the size of the punctured lesion (p = 0.0010), the experience of the surgeon and the pathologist (p = 0.00003) were important factors for a successfully procedure and reliable result. FNACs performed in nodes smaller than 20 mm had a significantly worse diagnostic outcome compared to larger nodes (p = 0.0004). In conclusion, the key factors for a successful FNAC are nodal size and the experience of the head and neck surgeon and the pathologist.

Intertumor heterogeneity in 60 pancreatic neuroendocrine tumors associated with multiple endocrine neoplasia type 1.

BACKGROUND: Patients with multiple endocrine neoplasia type 1 (MEN-1) develop multiple pancreatic neuroendocrine neoplasias (PNENs). Size at diagnosis and growth during follow-up are crucial parameters. According to the WHO 2017, grading is another important parameter. The impact of grading compared to size (WHO 2000) on the clinical course needs to be evaluated. METHODS: Sixty PNENs of six patients with MEN-1 were retrospectively evaluated. RESULTS: Fifty-one tumors with a diameter of < 20 mm were graded as G1. Two of 9 tumors with diameters of ≥20 mm were graded as G2. Tumor size of ≥20 mm correlated significantly with higher proliferation (p = 0.000617). Lymph node metastases were documented in two patients with a total of 19 tumors. In one patient, all 13 tumors (diameter: 0.4 to 100 mm) were classified as G1. However, metastases were documented in 9/29 lymph nodes. In the other patient, 5 tumors (3.5 to 20 mm) were classified as G1. The sixth tumor (30 mm) was classified as G2 (Ki-67: 8%). Metastases were revealed in 2/20 lymph nodes. CONCLUSIONS: Tumor size of ≥20 mm seems to correlate with more aggressive MEN-1 related pancreatic disease, regardless of individual proliferation. Tumors ≥20 mm and tumors graded as G2 should be treated surgically regardless of their size.

Neuroendocrine Liver Metastasis-a Specific Set of Markers to Detect Primary Tumor Sites.

The diagnosis of neuroendocrine neoplasia (NEN) is often made at an advanced stage of disease, including hepatic metastasis. At this point, the primary may still be unknown and sometimes cannot even be detected by functional imaging, especially in very small tumors of the pancreas (pan) and small intestinal (si) entities. The site of the primary may be based on biopsy specimens of the liver applying a specific set of markers. Specimens of liver metastases from 87 patients with NENs were studied. In retrospect, 50 patients had si and 37 pan NENs. Tissue samples were evaluated by immunohistochemistry. The markers applied were insulin gene enhancer protein Islet-1 (ISL-1), homeobox protein CDX-2 (CDX2), thyroid transcription factor 1 (TTF-1), and serotonin. Positive stains for CDX2 were documented in 43 (86%) and for serotonin in 45 (90%) of 50 siNENs. Three panNENs were positive for CDX2 and one for serotonin, respectively. ISL-1 was negative throughout in siNENs and also negative in 8 of 50 panNENs (21.6%). TTF-1 was negative in more than 90% of the specimens of either entity. Immunohistochemical markers in liver metastasis can lead the way to the site of the primary NEN. They should always be used in combined clusters.

Calcium-stimulated calcitonin - The "new standard" in the diagnosis of thyroid C-cell disease - clinically relevant gender-specific cut-off levels for an "old test".

INTRODUCTION: Pentagastrin (Pg) stimulated calcitonin (sCT) was used to enhance accuracy in medullary thyroid cancer (MTC) diagnosis. As it is now unavailable, calcium (Ca) has been recommended as an alternative. The aim of this study was to define gender-specific cut-off values to predict MTC in patients with elevated basal CT (bCT) following Pg-sCT and Ca-sCT stimulation and to compare the time courses of CT release during stimulation. MATERIALS AND METHODS: The stimulation tests were applied in 62 consecutive patients with thyroid nodules. Basal calcitonin was measured by chemiluminescent immunometric assay. All patients underwent thyroidectomy and bilateral central neck dissection. C-cell pathology was confirmed by histological and immunohistochemical evaluation. RESULTS: In 39 (0.63) patients MTC was documented while isolated C-cell hyperplasia (CCH) was identified in 23 (0.37) patients. Medullary thyroid cancer was predicted in males with bCT values > 43 pg/mL or sCT concentrations > 470 pg/mL (Pg-sCT) or > 1500 pg/mL (Ca-sCT), and in females with bCT concentrations > 23 pg/mL or sCT concentrations > 200 pg/mL (Pg-sCT) or > 780 pg/mL (Ca-sCT), respectively. Pg-sCT correctly predicted MTC in 16 (0.66) compared to 13 (0.54) after Ca-sCT in males and in 12 (0.80) compared to 11 (0.73) in females; without statistical significance. In patients with CCH or low tumor burden, there was a tendency of faster CT release after Ca stimulation (CT peak after 3min in > 60%) compared to patients with advanced MTC (CT peak after 3min in < 10%). CONCLUSIONS: Using gender-specific cut-off values, Ca could replace Pg to predict MTC with similar diagnostic power.

Medullary Thyroid Carcinoma: Do Ultrasonography and F-DOPA-PET-CT Influence the Initial Surgical Strategy?

BACKGROUND: At the time of diagnosis, one-third of medullary thyroid carcinoma (MTC) patients show lymph node (LN) or distant metastasis. A metastasized MTC requires different surgical strategies. OBJECTIVE: This study aimed to determine the value of ultrasound and [18F]fluoro-dihydroxyphenylalanine positron emission tomography with computed tomography (F-DOPA-PET-CT) in localizing MTC, as well as LN and distant metastasis. METHODS: The study included 50 patients (24 males/26 females) with preoperative ultrasound, F-DOPA-PET-CT, and histologically proven MTC. Imaging results were correlated with both preoperative basal calcitonin (bCt) levels and final histology. RESULTS: Tumors were classified as pT1a:17 (diameter, mean ± standard deviation: 5.8 ± 3.0 mm), pT1b:15 (15.0 ± 3.2 mm), pT2:9 (27.3 ± 7.0 mm), and pT3:9 (38.3 ± 24.2 mm). The median bCt level was 202 pg/mL (lower/upper quartile: 82/1074 pg/mL). Ultrasound was positive for tumor in 45/50 (92%) patients (20.0 ± 16.0 mm) and negative in 5 patients (3.2 ± 2.2 mm). Overall, 43/50 (86%) patients had positive F-DOPA local scans (20.0 ± 16.4 mm), while 7 (14%) patients were negative (7.7 ± 8.1 mm). Lastly, 21/50 (42%) patients had LN metastasis; 8/21 (38%) patients had positive LNs suspected with ultrasound, and 12/21 (57%) patients had positive LNs suspected with F-DOPA. Tumor and LN sensitivity of ultrasound was 92% and 43%, respectively, and 86% and 57% of F-DOPA-PET-CT, respectively. In 3/50 (6%) patients and 3/50 (6%) patients, mediastinal LN metastasis and distant metastasis, respectively, were diagnosed only by F-DOPA-PET-CT. CONCLUSION: Ultrasound and F-DOPA-PET-CT are sensitive for the localization of MTC but not for the presence and location of LN metastasis (limitations: size/number). Only F-DOPA ensures the diagnosis of distant metastasis and influences the extent of LN surgery. Surgical strategy cannot be predicted based on neither ultrasound nor F-DOPA-PET-CT.

Analysis of 10 Adrenocortical Carcinoma Patients in the Cohort of the Precision Medicine Platform MONDTI.

OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare disease with a dismal prognosis. We aimed to evaluate if a personalized medicine approach may be useful for matching patients with ACC to targeted therapies. METHODS: This is an analysis of 10 molecularly profiled ACCs that were progressing under standard of care treatment. The profile consisted of a 50-gene next-generation sequencing panel, immunohistochemistry (IHC), and fluorescence in situ hybridization for several proteins or chromosomal aberrations. RESULTS: In 6 (60%) tumor samples, no somatic mutation was detected, while in 3 (30%) tumors 1 mutation was detected and in 1 (10%) tumor 2 mutations were detected. These mutations were CTNNB1 (2 samples), TP53 (1 sample), RB1 (1 sample) and APC (1 sample). Expression of phospho-mTOR and of EGFR was commonly detected by IHC (87.5 and 62.5%). In 4 (50%) samples, IHC revealed a weak expression of progesterone receptor. Less frequent alterations were expression of PDGFR-α, c-KIT, and estrogen receptor, each in 1 case. CONCLUSIONS: Based on the molecular profile, no recommendation for targeted therapy was made by the multi-disciplinary team. Currently, ACC might not be suitable for a precision medicine approach according to our tests.

Colon cancer cell-derived 12(S)-HETE induces the retraction of cancer-associated fibroblast via MLC2, RHO/ROCK and Ca2+ signalling.

Retraction of mesenchymal stromal cells supports the invasion of colorectal cancer cells (CRC) into the adjacent compartment. CRC-secreted 12(S)-HETE enhances the retraction of cancer-associated fibroblasts (CAFs) and therefore, 12(S)-HETE may enforce invasivity of CRC. Understanding the mechanisms of metastatic CRC is crucial for successful intervention. Therefore, we studied pro-invasive contributions of stromal cells in physiologically relevant three-dimensional in vitro assays consisting of CRC spheroids, CAFs, extracellular matrix and endothelial cells, as well as in reductionist models. In order to elucidate how CAFs support CRC invasion, tumour spheroid-induced CAF retraction and free intracellular Ca2+ levels were measured and pharmacological- or siRNA-based inhibition of selected signalling cascades was performed. CRC spheroids caused the retraction of CAFs, generating entry gates in the adjacent surrogate stroma. The responsible trigger factor 12(S)-HETE provoked a signal, which was transduced by PLC, IP3, free intracellular Ca2+, Ca2+-calmodulin-kinase-II, RHO/ROCK and MYLK which led to the activation of myosin light chain 2, and subsequent CAF mobility. RHO activity was observed downstream as well as upstream of Ca2+ release. Thus, Ca2+ signalling served as central signal amplifier. Treatment with the FDA-approved drugs carbamazepine, cinnarizine, nifedipine and bepridil HCl, which reportedly interfere with cellular calcium availability, inhibited CAF-retraction. The elucidation of signalling pathways and identification of approved inhibitory drugs warrant development of intervention strategies targeting tumour-stroma interaction.

Expression of somatostatin receptor 2A in medullary thyroid carcinoma is associated with lymph node metastasis.

Medullary carcinoma (MTC) is an aggressive tumour that derives from the thyroid parafollicular calcitonin-secreting cells (C cells). Lymph node metastasis may occur early in disease pathogenesis and is one of the most important negative prognostic parameters. Surgery is the only curative therapy while chemotherapeutic options are limited. Neuroendocrine differentiated C cells may express somatostatin receptors (SSTR), which have a wide range of biological actions including inhibitory effects on cell survival and angiogenesis and antiproliferative effects on cancer cell lines. Moreover, they are a potential target for various somatostatin analogues. Aim of this study was to analyse the protein expression of SSTR2A and 5 in MTCs with or without the presence of lymph node metastases in correlation with various clinicopathological parameters. This retrospective immunohistochemical analysis included 97 patients with medullary thyroid carcinomas. Protein expression was detected by immunohistochemistry for somatostatin receptors 2A and 5. Various clinicopathological parameters, such as Ki-67 proliferation index or presence of desmoplasia, were included for statistical analysis. SSTR2A protein expression significantly correlated with the presence of lymph node metastases (p = 0.009), locally advanced MTCs staged according to the TNM (p < 0.001) and degree of desmoplasia (p = 0.029). Although SSTR5 protein expression significantly correlated with advanced stages of MTCs (p = 0.023) and degree of desmoplasia (p = 0.020), no correlation was found with the presence of lymph node metastases. Our results provide additional information concerning the aggressiveness of MTCs and reveal that a high SSTR2A and SSTR5 expression might be a poor prognostic feature.

Multicenter Evaluation of a Novel Automated Rapid Detection System of BRAF Status in Formalin-Fixed, Paraffin-Embedded Tissues.

The mutated BRAF oncogene represents a therapeutic target in malignant melanoma. Because BRAF mutations are also involved in the pathogenesis of other human malignancies, the use of specific BRAF inhibitors might also be extended to other diseases in the future. A prerequisite for the clinical application of BRAF inhibitors is the reliable detection of activating BRAF mutations in routine histopathological samples. In a multicenter approach, we evaluated a novel and fully automated PCR-based system (Idylla) capable of detecting BRAF V600 mutations in formalin-fixed, paraffin-embedded tissue within 90 minutes with high sensitivity. We analyzed a total of 436 samples with the Idylla system. Valid results were obtained in 421 cases (96.56%). Its performance was compared with conventional methods (pyrosequencing or Sanger sequencing). Concordant results were obtained in 406 cases (96.90%). Reanalysis of eight discordant samples by next-generation sequencing and/or pyrosequencing with newly extracted DNA and the BRAF RGQ Kit confirmed the Idylla result in seven cases, resulting in an overall agreement of 98.57%. In conclusion, the Idylla system is a highly reliable and sensitive platform for detection of BRAF V600 mutations in formalin-fixed, paraffin-embedded material, providing an efficient alternative to conventional diagnostic methods, particularly for routine diagnostics laboratories with limited experience in molecular pathology.

Clinical presentation in insulinoma predicts histopathological tumour characteristics.

BACKGROUND: Insulinomas are rare neuroendocrine tumours (NETs) of the pancreas, characterized clinically by neuroglycopenic symptoms during periods of substrate deficiency. The gold standard test for diagnosing an insulinoma is a 72-h fast. However, the prognostic value of parameters in the standardized 72-h fast on histopathological tumour criteria and clinical presentation has not been examined. METHODS: In thirty-three patients diagnosed with an insulinoma records, and data were investigated retrospectively. Histopathological tumour characteristics, including staging, grading and size, were reviewed. Grading was performed using Ki-67 index. Cut-off values for classical grading (G(clas)) were set at G1(clas) ≤ 2%, G2(clas) 3-20% & G3(clas) >20% and for modified grading (G(mod)) at G1(mod) <5%, G2(mod) 5-20% & G3(mod) >20%. RESULTS: When G(mod) criteria were applied, the initial blood glucose was lower in GII/III(mod) patients compared to GI(mod) (2.8 ± 0.8 vs 3.8 ± 1.3 mmol/l; P = 0.046). Basal and end of fast levels of insulin (basal insulin 71 ± 61 vs 20 ± 16 mU/l; P < 0.001; end of fast insulin 77 ± 51 vs 21 ± 20 mU/l; P < 0.001) and c-peptide (basal c-peptide 5.4 ± 2.4 vs 2.7 ± 1.6 µg/l; P = 0.004; end of fast c-peptide 5.3 ± 2.4 vs 2.5 ± 1.4 µg/l; P = 0.001) were significantly higher in GII/III(mod) than in GI(mod). No differences between the groups were observed when G(clas) criteria were applied. Additionally, close correlations were observed between insulin concentration, Ki-67 index and tumour size. CONCLUSION: This study shows an impact of histopathological tumour characteristics in patients suffering from an insulinoma on clinical presentation during a standardized 72-h fast. Lower initial blood glucose levels and higher concentrations of insulin and c-peptide are associated with worse tumour grading and larger tumour size.

11C-methionine PET/CT imaging of 99mTc-MIBI-SPECT/CT-negative patients with primary hyperparathyroidism and previous neck surgery.

CONTEXT: (99m)Tc-Methoxy-isobutyl-isonitrile (MIBI) scintigraphy is a standard preoperative localization imaging modality in patients with primary hyperparathyroidism (pHPT). Its accuracy in localizing a hyperactive parathyroid gland after previous cervical surgery is limited. Recently, (11)C-methionine has been introduced as a promising radiotracer for pHPT imaging. Yet, few data exist for this technique in patients with persisting or recurrent pHPT before reoperation. OBJECTIVES: We aimed to investigate the ability of (11)C-methionine positron emission tomography (PET)/computed tomography (CT) to localize a parathyroid disorder after cervical surgery and negative postsurgical (99m)Tc-MIBI single-photon emission CT (SPECT)/CT. DESIGN, SETTING, AND PARTICIPANTS: Fifteen patients (6 males, 9 females; age range, 36-85 years) with pHPT and negative (99m)Tc-MIBI SPECT/CT who had undergone earlier neck surgery because of pHPT and/or thyroid disorder were recruited. Twelve of the 15 patients had thyroidectomy for goiter or differentiated thyroid carcinoma. Ten patients had previous parathyroid surgery for pHPT, and 2 patients had a history of parathyroid carcinoma. Thirteen of 15 patients showed elevated levels of intact PTH at the time of PET/CT imaging, whereas all patients had elevated serum calcium values. MAIN OUTCOME MEASUREMENTS: Pathological results of contrast-enhanced (11)C-methionine PET/CT and surgical results were evaluated. RESULTS: In 6 of 15 patients (11)C-methionine PET/CT showed a hypermetabolic focus in the upper mediastinum in 2 patients, in the thoracic outlet in 1 patient, and in the cervical region in 3 patients. In 9 of the 15 patients, no hyperactive parathyroid gland could be visualized. Reoperation was performed in 5 of 6 patients without surgical complications. One patient refused surgery. In 2 of the 5 patients, a transsternal procedure was performed. Correlating with the (11)C-methionine PET/CT results, a single parathyroid adenoma was found in 4 patients and parathyroid carcinoma metastasis in 1 patient. CONCLUSION: (11)C-Methionine PET/CT is a useful complementary imaging technique to localize parathyroid adenoma or carcinoma in (99m)Tc-MIBI SPECT/CT-negative patients.

Phosphorylation of STAT3 correlates with HER2 status, but not with survival in pancreatic ductal adenocarcinoma.

Activation of signal-transcriptional factor signal transducer and activator of transcription 3 (STAT3) is associated with more aggressive behaviour in a variety of human malignancies. As selective STAT3 inhibitors exist, this protein might represent a novel therapeutic target. Although STAT3 seems to play an important role in progression of pancreatic ductal carcinoma (PDAC), only few data on this subject exist. The aim of our study was the investigation of STAT3 activation and its correlation with its possible regulator HER2. Expression of tyrosine-705 phosphorylated STAT3 (pSTAT3) was determined immunohistochemically in 79 PDACs. HER2 status assessed by immunohistochemistry and double colour silver in situ hybridization was available from a previous study. PSTAT3 expression was seen in 33 (41.8%) patients. Six patients were scored as HER2 positive having strong correlation with pSTAT3 expression (p = 0.004, Fisher's exact test). No association of pSTAT3 expression with patients' age, tumour staging and grading, perineural invasion of tumour cells or survival time was seen. pSTAT3 is frequently expressed in PDAC. Nevertheless, its immediate clinical relevance seems to be low. However, further research needs to determine whether STAT3 status in PDAC is predictive for the response to novel targeting therapies.