Adrenal cancer: relevance of different grading systems and subtypes

Purpose The subclassification of adrenal cancers according to the WHO classification in ordinary, myxoid, oncocytic, and sarcomatoid as well as pediatric types is well established, but the criteria for each subtype are not sufficiently determined and the relative frequency of the different types of adrenal cancers has not been studied in large cohorts. Therefore, our large collection of surgically removed adrenal cancers should be reviewed o establish the criteria for the subtypes and to find out the frequency of the various types. Methods In our series of 521 adrenal cancers the scoring systems of Weiss et al., Hough et al., van Slooten et al. and the new Helsinki score system were used for the ordinary type of cancer (97% of our series) and the myxoid type (0.8%). For oncocytic carcinomas (2%), the scoring system of Bisceglia et al. was applied. Results Discrepancies between benign and malignant diagnoses from the first thee classical scoring systems are not rare (22% in our series) and could be resolved by the Helsinki score especially by Ki-67 index (more than 8% unequivocally malignant). Since all our cancer cases are positive in the Helsinki score, this system can replace the three elder systems. For identification of sarcomatoid cancer as rarest type in our series (0.2%), the scoring systems are not practical but additional immunostainings used for soft tissue tumors and in special cases molecular pathology are necessary to differentiate these cancers from adrenal sarcomas. According to the relative frequencies of the different subtypes of adrenal cancers the main type is the far most frequent (97%) followed by the oncocytic type (2%), the myxoid type (0.8%) and the very rare sarcomatoid type (0.2%). Conclusions The Helsinki score is the best for differentiating adrenal carcinomas of the main, the oncocytic, and the myxoid type in routine work (AU)

Adrenal cancer: relevance of different grading systems and subtypes.

PURPOSE: The subclassification of adrenal cancers according to the WHO classification in ordinary, myxoid, oncocytic, and sarcomatoid as well as pediatric types is well established, but the criteria for each subtype are not sufficiently determined and the relative frequency of the different types of adrenal cancers has not been studied in large cohorts. Therefore, our large collection of surgically removed adrenal cancers should be reviewed o establish the criteria for the subtypes and to find out the frequency of the various types. METHODS: In our series of 521 adrenal cancers the scoring systems of Weiss et al., Hough et al., van Slooten et al. and the new Helsinki score system were used for the ordinary type of cancer (97% of our series) and the myxoid type (0.8%). For oncocytic carcinomas (2%), the scoring system of Bisceglia et al. was applied. RESULTS: Discrepancies between benign and malignant diagnoses from the first thee classical scoring systems are not rare (22% in our series) and could be resolved by the Helsinki score especially by Ki-67 index (more than 8% unequivocally malignant). Since all our cancer cases are positive in the Helsinki score, this system can replace the three elder systems. For identification of sarcomatoid cancer as rarest type in our series (0.2%), the scoring systems are not practical but additional immunostainings used for soft tissue tumors and in special cases molecular pathology are necessary to differentiate these cancers from adrenal sarcomas. According to the relative frequencies of the different subtypes of adrenal cancers the main type is the far most frequent (97%) followed by the oncocytic type (2%), the myxoid type (0.8%) and the very rare sarcomatoid type (0.2%). CONCLUSIONS: The Helsinki score is the best for differentiating adrenal carcinomas of the main, the oncocytic, and the myxoid type in routine work. Additional scoring systems for these carcinomas are generally not any longer necessary. Signs of proliferation (mitoses and Ki-67 index) and necroses are the most important criteria for diagnosis of malignancy.

Commentary on "Detection and oncological effect of circulating tumor cells in patients with variant urothelial carcinoma histology treated with radical cystectomy."

OBJECTIVES: To investigate for the presence of circulating tumor cells (CTC) in patients with variant urothelial carcinoma of the bladder (UCB) histology treated with radical cystectomy (RC), and to determine their impact on oncological outcomes. PATIENTS AND METHODS: We, prospectively, collected data of 188 patients with UCB treated with RC without neoadjuvant chemotherapy. Pathological specimens were meticulously reviewed for pure and variant UCB histology. Preoperatively collected blood samples (7.5ml) were analyzed for CTC using the CellSearch system (Janssen, Raritan, NJ). RESULTS: Variant UCB histology was found in 47 patients (25.0%), most frequently of squamous cell differentiation (16.5%). CTC were present in 30 patients (21.3%) and 12 patients (25.5%) with pure and variant UCB histology, respectively. At a median follow-up of 25 months, the presence of CTC and nonsquamous cell differentiation were associated with reduced recurrence-free survival (RFS) and cancer-specific survival (pairwise P ≤ 0.016). Patients without CTC had better RFS, independent of UCB histology, than patients with CTC with any UCB histology (pairwise P<0.05). In multivariable analyses, the presence of CTC, but not variant UCB histology, was an independent predictor for disease recurrence (hazard ratio = 3.45, P<0.001) and cancer-specific mortality (hazard ratio = 2.62, P = 0.002). CONCLUSION: CTC are detectable in about a quarter of patients with pure or variant UCB histology before RC, and represent an independent predictor for outcomes, when adjusting for histological subtype. In addition, our prospective data confirm the unfavorable influence of nonsquamous cell-differentiated UCB on outcomes.

Gender-specific outcomes of bladder cancer patients: a stage-specific analysis in a contemporary, homogenous radical cystectomy cohort.

INTRODUCTION: Controversial findings regarding gender-specific oncological outcomes of urothelial carcinoma of the bladder (UCB) have recently been reported. The aim of this study was to analyze gender-specific outcomes using a stage-adjusted approach in a homogenous, contemporary radical cystectomy (RC) cohort. MATERIAL AND METHODS: We prospectively collected data of 517 UCB patients treated with RC and pelvic lymphadenectomy without neoadjuvant chemotherapy at our institution between 1996 and 2010. Stage-adjusted uni- and multivariable Cox regression models analyzed the association of gender with disease recurrence, cancer-specific mortality and overall survival. RESULTS: In total, 398 (77%) patients were male and 119 (23%) were female. Compared to men, women were more likely to have advanced tumor stages (p = 0.017), nodal metastasis (p = 0.047) and received more frequently adjuvant chemotherapy (p = 0.009). At a median follow-up of 44 months, there was no statistical difference in disease recurrence, cancer-specific mortality and overall survival between both genders when analyzed as a group. In stage-adjusted analyses, only women with non-invasive UCB were more likely to die of UCB compared to the male counterparts (p = 0.013). In gender-specific multivariable analyses that adjusted for standard clinico-pathologic features, pathologic tumor stage was an independent predictor for disease recurrence (p-values ≤0.047) and cancer-specific mortality (p-values ≤0.049), respectively. CONCLUSION: Women present with more aggressive tumor biologic features at RC, however this did not translate into inferior outcomes compared to men in stage-specific analyses in our cohort. Tumor stage is the most important factor influencing the course of disease in both genders. Validation of our findings is warranted in a larger cohort.

UAP1 is overexpressed in prostate cancer and is protective against inhibitors of N-linked glycosylation.

Prostate cancer is the second most common cause of cancer-associated deaths in men, and signaling via a transcription factor called androgen receptor (AR) is an important driver of the disease. Consequently, AR target genes are prominent candidates to be specific for prostate cancer and also important for the survival of the cancer cells. Here we assess the levels of all hexosamine biosynthetic pathway (HBP) enzymes in 15 separate clinical gene expression data sets and identify the last enzyme in the pathway, UDP-N-acetylglucosamine pyrophosphorylase 1 (UAP1), to be highly overexpressed in prostate cancer. We analyzed 3261 prostate cancers on a tissue microarray and found that UAP1 staining correlates negatively with Gleason score (P=0.0039) and positively with high AR expression (P<0.0001). Cells with high UAP1 expression have 10-fold increased levels of the HBP end-product, UDP-N-acetylglucosamine (UDP-GlcNAc). UDP-GlcNAc is essential for N-linked glycosylation occurring in the endoplasmic reticulum (ER) and high UAP1 expression associates with resistance against inhibitors of N-linked glycosylation (tunicamycin and 2-deoxyglucose) but not with a general ER stress-inducing agent, the calcium ionophore A23187. Knockdown of UAP1 expression re-sensitized cells towards inhibitors of N-linked glycosylation, as measured by proliferation and activation of ER stress markers. Taken together, we have identified an enzyme, UAP1, which is highly overexpressed in prostate cancer and protects cancer cells from ER stress conferring a growth advantage.

High Nr-CAM expression is associated with favorable phenotype and late PSA recurrence in prostate cancer treated by prostatectomy.

BACKGROUND: Neuron-glia-related cell-adhesion molecule (Nr-CAM) is another potential membrane-bound target molecule for specific prostate cancer therapy. The role of Nr-CAM in normal and neoplastic prostate tissue has not been extensively studied. The aim of our study is to evaluate the prevalence of Nr-CAM expression in prostate cancer and to explore its association with phenotype and clinical disease course. METHODS: A preexisting tissue microarray including more than 3000 prostate cancers that underwent prostatectomy at our center with clinical follow-up data was used. The tissue microarray (TMA) was immunhistochemically stained for Nr-CAM. RESULTS: A total of 2883 (88.4%) of tumor samples were interpretable in our TMA analysis. Membranous Nr-CAM staining was seen in 1418 (49.2%) of 2883 analyzable cases. According to predefined criteria, staining was considered weak in 778 (27.0%), moderate in 412 (14.3%) and strong in 228 (7.9%) cancers. Significant associations were found with pathological tumor stage (P=0.0015), Gleason grade (P=0.0003), nodal stage (P=0.0061), preoperative PSA (P=0.0138) and prolonged PSA recurrence-free survival (P<0.0001). CONCLUSIONS: Nr-CAM expression is frequent in prostate cancer. High level of Nr-CAM expression is associated with favorable tumor phenotype and reduced risk of PSA recurrence. The abundant presence of Nr-CAM in prostate cancer epithelium makes Nr-CAM a potential target of therapy.

[Primary diffuse neurofibroma of the urinary bladder: a rare case report and review of the literature]. / Primäres diffuses Neurofibrom der Harnblase : Ein seltener Fallbericht und Literaturübersicht.

Diffuse neurofibromas are benign mesenchymal tumours with nerve sheath differentiation. Only a few cases have been reported in the urinary bladder. We present a well-documented case report of a 62-year-old man presenting with gross haematuria and histopathological confirmation of a diffuse neurofibroma. We further reviewed the current literature with regard to clinical features and treatment options.

[Tumors of the urinary system. Current and old problems]. / Tumoren des ableitenden Harntrakts. Aktuelle und alte Probleme.

Principally there are two different types of bladder cancer. Non-invasive papillary low grade tumors (pTa G1-G2) are genetically stable, recur frequently but show a low risk of progression. On the other hand there are high grade tumors (pT1-4, carcinoma in situ), which are genetically unstable, show biologically aggressive behaviour and progress. The distinction between non-invasive (pTa) and minimal-invasive (pT1) is one of the most challenging areas in bladder pathology. Due to the lack of appropriate auxiliary analysis the diagnosis is based entirely on histopathology. P53 immunohistochemistry can be helpful in the assessment of recurring high grade neoplasia. Targeted therapy in bladder cancer is particularly interesting, since a high number of oncogenes are activated and overexpressed (e.g. HER2 and EGFR).

[Randomized controlled trial on vessel sealing in thyroid surgery]. / Randomisierte kontrollierte Studie über die Gefässversiegelung in der Schilddrüsenchirurgie.

AIM: To compare conventional suture ligation with vessel sealing in thyroid surgery. METHODS: We investigated in a randomized controlled trial whether vessel sealing in thyroid surgery may shorten operative time compared to suture ligation. Included were all thyroid resections because of benign thyroid diseases. Primary endpoint was operative time and secondary endpoints were all postoperative complications. RESULTS: 150 patients were included into the study. 77 were randomized into the control group and 73 into the sealing group. Age, sex, BMI and extent of resection were not different between groups. Operative time was 10.2 min (CI - 1,3; 21,7) shorter in the sealing group. Sex, one- or two-sided resection, site of thyroid, and the experience of the surgeon had all a significant influence on operative time. Postoperative complications were not different between groups. CONCLUSION: Vessel sealing shortens operative time, especially if resection is performed by experienced surgeons, and did not increase postoperative complication rate.

[Long-term cosmetic results following thyroid resection]. / Kosmetische Spätergebnisse nach Schilddrüsenresektionen.

BACKGROUND: The long-term cosmetic results following thyroid resection may soon become more relevant because minimally invasive techniques are also being promoted. PATIENTS AND METHODS: Two hundred forty-four patients were prospectively enrolled for a questionnaire regarding long-term results following thyroid resection. Ninety of these patients were clinically examined. RESULTS: The cosmetic results were judged by more than 90% of the patients as excellent or good. Women were slightly more critical about their results (P=0.06). Some kind of wound infection was reported in 4.1%, hypertrophic scar in 4.1%, and mild dysphagia in 7%. The results were not associated with the kind or extent of resection. The length of the scars was 4 cm (range 3-7) and the width 2 mm (range 1-4). The surgeons also judged the scars as good or excellent in most cases but were more critical than the patients. CONCLUSION: Since the long-term results of conventional surgery are, in most cases, so good, it seems difficult to improve the results by new minimally invasive techniques.