Pancreatic infiltrative malignancy masquerading as autoimmune pancreatitis: Case report, review of radiological criteria, and literature.

We report a case of a 44-year-old male patient, who presented to the University Hospital of Salzburg, Austria with abdominal pain, persistent jaundice, and lack of appetite. Radiological work-up (CT, MRI, PET/CT) indicated a suspicious mass of the uncinate process of the pancreatic head with adjacent infiltration and regional lymphadenopathy. The differential diagnosis was between primary pancreatic cancer and focal autoimmune pancreatitis. Further laparoscopic biopsies from multiple areas, showed only fibrous scarring processes, with no malignancy. Treatment with steroids didn't give any benefits. After multiple follow-up CTs and MRs within 6 months-additional biopsies were done, which eventually demonstrated adenocarcinoma. Evidently the cancer diagnosis was much delayed and the patient started receiving chemotherapy, but radical surgery was not possible. Multiple articles and case reports can be found in the literature, that are reviewing the fact that pancreatic inflammatory processes are mimicking pancreatic tumor, but not many articles or case reports are available in the literature, where neoplastic processes are misinterpreted as inflammatory and incorrectly proven with histological examination. One of the main reasons for improper diagnosis is the desmoplastic reaction around the pancreatic malignancy. Another important aspect is the acceptance of histological diagnosis as conclusive, where no opposing arguments are specified, based on radiological criteria.

HER2 copy number determination in breast cancer using the highly sensitive droplet digital PCR method.

Human epidermal growth factor receptor 2 (HER)-positive breast cancer (BC) is characterized by an aggressive clinical course. In the case of HER2 overexpression/amplification, patients benefit from HER2-targeting therapies. Standardized diagnostic HER2 assessment includes immunohistochemistry (IHC) and/or in situ hybridization (ISH). The aim of this study was to compare this "gold standard" with the Droplet Digital™ polymerase chain reaction (ddPCR), a method that allows sensitive and precise detection of copy number variations (CNV) in FFPE (formalin-fixed, paraffin-embedded) DNA samples. Partitioning of the PCR reaction into 20,000 droplets enables a precise quantitative "CN" discrimination also in heterogeneous samples. FFPE breast cancer samples (n = 170) with routinely assessed HER2 status by IHC/ISH were retrospectively analyzed using the ddPCR CNV ERBB2 assay. Comparison of HER2 status assessment by the two methods revealed concordant results in 92.9% (158/170) of the cases. Discrepant cases were verified and interpreted. For ddPCR, a cut off value of 3 HER2 copies was set to distinguish between HER2-negative and HER2-positive BC. Results obtained with the ddPCR CNV ERBB2 assay were consistent and reproducible, and serial dilutions demonstrated a high stability and sensitivity of the method. The ddPCR CNV ERBB2 assay may be a specific and convenient tool to quantify HER2 copy numbers in BC samples. In our study, this method showed high reproducibility in accuracy of HER2 assessment compared to IHC/ISH analysis.

Substrate Affinity Versus Catalytic Efficiency: Ancestral Sequence Reconstruction of tRNA Nucleotidyltransferases Solves an Enzyme Puzzle.

In tRNA maturation, CCA-addition by tRNA nucleotidyltransferase is a unique and highly accurate reaction. While the mechanism of nucleotide selection and polymerization is well understood, it remains a mystery why bacterial and eukaryotic enzymes exhibit an unexpected and surprisingly low tRNA substrate affinity while they efficiently catalyze the CCA-addition. To get insights into the evolution of this high-fidelity RNA synthesis, the reconstruction and characterization of ancestral enzymes is a versatile tool. Here, we investigate a reconstructed candidate of a 2 billion years old CCA-adding enzyme from Gammaproteobacteria and compare it to the corresponding modern enzyme of Escherichia coli. We show that the ancestral candidate catalyzes an error-free CCA-addition, but has a much higher tRNA affinity compared with the extant enzyme. The consequence of this increased substrate binding is an enhanced reverse reaction, where the enzyme removes the CCA end from the mature tRNA. As a result, the ancestral candidate exhibits a lower catalytic efficiency in vitro as well as in vivo. Furthermore, the efficient tRNA interaction leads to a processive polymerization, while the extant enzyme catalyzes nucleotide addition in a distributive way. Thus, the modern enzymes increased their polymerization efficiency by lowering the binding affinity to tRNA, so that CCA synthesis is efficiently promoted due to a reduced reverse reaction. Hence, the puzzling and at a first glance contradicting and detrimental weak substrate interaction represents a distinct activity enhancement in the evolution of CCA-adding enzymes.

En bloc re-resection of high-risk NMIBC after en bloc resection: results of a multicenter observational study.

PURPOSE: To investigate the role of en bloc re-resection (EBRS) in patients who had undergone previous en bloc resection for high-risk non-muscle-invasive bladder cancer (NMIBC). METHODS: An international, multicenter, observational retrospective analysis of prospectively collected data. Patients with a high-risk NMIBC who had previously undergone en bloc resection were scheduled for EBRS of the resected area after 40 days. The primary outcome was the presence of residual tumor or recurrence-free survival. RESULTS: Overall, 78 patients underwent EBRS. Only five (6.41%) residual cancers were found: one patient had a pTa G3 (1.28%) cancer and four (5.13%) had a pTis. The detrusor muscle was preserved in all samples. Only one patient had a positive margin on EBRS. No procedure called for a conversion to traditional re-TURBT. No patient experienced bladder perforation or other intra-operative complications. The recurrence rate at the first follow-up cystoscopy (RRFF-C at 3 months) was 3.85% (three patients). The median follow-up period was 30.8 months (range 6.9-76.0 months). In univariate analysis, the only predictor of recurrence was grade. Overall we observed 11 recurrences. Only one tumor progressed to T2 MIBC. CONCLUSIONS: The low rates of residual tumor, recurrence, and progression seem to raise doubts about the efficacy of EBRS in patients who have previously undergone en bloc resection. EBRS appears to be a feasible and safe procedure with a low rate of complications. However, further data will be needed before EBRS can be used in clinical trials or recommended as a treatment modality.

Sporadic renal hemangioblastoma: A case report of a rare benign renal tumor.

In renal tumors, suspicious for renal cell carcinoma, where there is any doubt and discrepancy between morphology and immune profile, we recommend performing further immunohistochemical staining for pan-cytokeratin, S100, NSE, and inhibin-alpha. Thus, follow-up overtreatment can be avoided in cases of benign kidney tumors.

Non-ischemic laparoscopic partial nephrectomy using 1318-nm diode laser for small exophytic renal tumors.

PURPOSE: Warm ischemia (WI) and bleeding constitute the main challenges for surgeons during laparoscopic partial nephrectomy (LPN). Current literature on the use of lasers for cutting and coagulation remains scarce and with small cohorts. We present the largest case series to date of non-ischemic LPN using a diode laser for small exophytic renal tumors. METHODS: We retrospectively evaluated 29 patients with clinically localized exophytic renal tumors who underwent non-ischemic laser-assisted LPN with a 1318-nm wavelength diode laser. We started applying the laser 5 mm beyond the visible tumor margin, 5 mm away from the tissue in a non-contact fashion for coagulation and in direct contact with the parenchymal tissue for cutting. RESULTS: The renal vessels were not clamped, resulting in a WIT (warm ischaemic time) of 0 min, except for one case that required warm ischemia for 12 min and parenchymal sutures. No transfusion was needed, with a mean Hemoglobin drop of 1,4 mg/dl and no postoperative complications. The eGFR did not significantly change by 6 months. Histologically, the majority of lesions (n = 22/29) were renal-cell carcinoma stage pT1a. The majority of malignant lesions (n = 13/22) had a negative margin. However, margin interpretation was difficult in 9 cases due to charring of the tumor base. A mean follow-up of 1.8 years revealed no tumor recurrence. The mean tumor diameter was 19.4 mm. CONCLUSION: The 1318-nm diode laser has the advantages of excellent cutting and sealing properties when applied to small vessels in the renal parenchyma, reducing the need for parenchymal sutures. However, excessive smoke, charring of the surgical margin, and inability to seal large blood vessels are encountered with this technique.

The AR/NCOA1 axis regulates prostate cancer migration by involvement of PRKD1.

Due to the urgent need for new prostate cancer (PCa) therapies, the role of androgen receptor (AR)-interacting proteins should be investigated. In this study we aimed to address whether the AR coactivator nuclear receptor coactivator 1 (NCOA1) is involved in PCa progression. Therefore, we tested the effect of long-term NCOA1 knockdown on processes relevant to metastasis formation. [(3)H]-thymidine incorporation assays revealed a reduced proliferation rate in AR-positive MDA PCa 2b and LNCaP cells upon knockdown of NCOA1, whereas AR-negative PC3 cells were not affected. Furthermore, Boyden chamber assays showed a strong decrease in migration and invasion upon NCOA1 knockdown, independently of the cell line's AR status. In order to understand the mechanistic reasons for these changes, transcriptome analysis using cDNA microarrays was performed. Protein kinase D1 (PRKD1) was found to be prominently up-regulated by NCOA1 knockdown in MDA PCa 2b, but not in PC3 cells. Inhibition of PRKD1 reverted the reduced migratory potential caused by NCOA1 knockdown. Furthermore, PRKD1 was negatively regulated by AR. Immunohistochemical staining of PCa patient samples revealed a strong increase in NCOA1 expression in primary tumors compared with normal prostate tissue, while no final conclusion could be drawn for PRKD1 expression in tumor specimens. Thus, our findings directly associate the AR/NCOA1 complex with PRKD1 regulation and cellular migration and support the concept of therapeutic inhibition of NCOA1 in PCa.

Fluorescence Guided Targeted Pelvic Lymph Node Dissection for Intermediate and High Risk Prostate Cancer.

PURPOSE: We investigated whether visualization of the drainage system of the prostate by free indocyanine green would lead to identification of all or even more lymph node metastases detected by super-extended pelvic lymph node dissection in an intermediate and high risk patient population with prostate cancer. MATERIALS AND METHODS: A total of 38 consecutive men with intermediate or high risk prostate cancer according to the D'Amico criteria underwent fluorescence targeted pelvic lymph node dissection during laparoscopic radical prostatectomy. Super-extended pelvic lymph node dissection was added as the control. Patients with neoadjuvant hormonal therapy, macroscopic lymph node involvement or prior transurethral prostate resection were excluded from study. Statistical descriptive methods, and the chi-square test and independent t-test were used to analyze data. RESULTS: Mean patient age was 64.9 years (range 46 to 74) and mean preoperative prostate specific antigen was 13.8 ng/ml (range 0.3 to 44). A total of 23 (60.5%) and 15 cases (39.5%) were classified as intermediate and high risk, respectively. Fluorescence stained nodes were found on each side in all except 1 patient. A total of 700 lymph nodes (mean ± SD 18.4 ± 8.2 per patient) were removed, of which 531 (75% of all nodes) were fluorescence stained (mean 14 ± 8.07 per patient). Lymph node metastases were found in 15 patients (39.5%). Two patients (5.3%) had a solitary micrometastasis and 3 (7.9%) had nodes containing isolated tumor cells. Metastases were found outside the extended pelvic lymph node dissection template in 5 of 15 patients (33.3%). Three of those 5 patients attained a prostate specific antigen nadir of less than 0.1 ng/ml 6 weeks postoperatively. Fluorescence targeted pelvic lymph node dissection showed superior sensitivity and negative predictive value compared to extended and super-extended pelvic lymph node dissection to detect lymph node metastasis. CONCLUSIONS: Fluorescence targeted pelvic lymph node dissection allows for the lymphatic drainage of the prostate to be identified with great reliability. Since only the nodes draining the prostate are removed, the absolute number of removed nodes is decreased while diagnostic accuracy is increased.

A suspected malignancy in osteolytic bone tumour of the thumb.

A 75-year-old male patient was referred to our institution owing to a painful and gradually developing lesion of the thumb with suspicious malignancy. The patient was suffering from a swollen, red, tender left thumb for 3 months. An old scar at the finger pulp could be traced from an old minor trauma. The x-ray revealed an osteolytic lesion in the terminal phalanx of the non-dominant hand that raised concerns of malignancy. Additional investigations such as ultrasound, CT-scan and MRI have been performed to get better insight to the lesion. After performing a biopsy, no malignant cells were found. Owing to the local destroying effect of the lesion and the clinical signs of the patient, the lesion was excised in total. The histopathological evaluation confirmed the tumour as a rare intraosseous epidermoid cyst. A bone graft after resection was not needed. The postoperative follow-up of the patient was uneventful.

Laparoscopic treatment of intrinsic endometriosis of the urinary tract and proposal of a treatment scheme for ureteral endometriosis.

OBJECTIVE: To discuss the contemporary management of urinary tract endometriosis and report our experience concerning laparoscopic treatment of intrinsic urinary tract endometriosis. METHODS: We performed a retrospective, multicenter study of data collected from March 2006 to March 2011. Ten women were referred from gynecology, seven with ureteral involvement and hydronephrosis and three with bladder involvement, for urologic management. Of the 7 women with hydronephrosis, 5 were symptomatic, with recurrent urinary tract infections or pain. All 3 women with bladder endometriosis had hematuria. All patients had previously undergone unsuccessful hormonal therapy. Ureteral endometriosis was extensively investigated and treated by laparoscopic excision of endometriotic plaques and excision of intrinsic endometriosis of the ureter. Bladder endometriosis was treated by partial cystectomy. Some patients also had endometriosis in other organs and underwent, for example, wedge resection of sigmoid colon and oophorectomy. RESULTS: The median age of the patients was 30 years (range 25-44). Seven patients with intrinsic endometriosis of the ureter all had hydronephrosis and proximal hydroureter and underwent laparoscopic ureteral segment excision and either end-to-end, spatulated uretroureterostomy or ureteral reimplatation with psoas hitch. Three patients had hematuria, and cystoscopic biopsy of the bladder lesions confirmed intrinsic endometriosis. They were treated with laparoscopic partial cystectomy. One patient with bowel symptoms also underwent laparoscopic wedge resection of the sigmoid colon and another underwent oophorectomy for a chocolate cyst. Most patients also had peritoneal endometriotic plaques excised. We did not perform simple ureterolysis. No complications were encountered. The median follow-up was 26.5 months (range 4-53), with no return of symptoms or recurrence. The annual follow-up examinations included urinalysis and ultrasonography of the urinary tract. CONCLUSION: Intrinsic endometriosis can be successfully managed with minimally invasive techniques to provide relief of symptoms, protect renal function, and prevent recurrence. We describe a classification of ureteral endometriosis determined from staging investigations.

pS6 Expression in normal renal parenchyma, primary renal cell carcinomas and their metastases.

In cancer therapy novel concepts focus on phosphoinositide-3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) inhibitors. In this context, phosphorylated S6 protein of the 40S ribosomal subunit (pS6) overexpression was previously shown to be associated with sensitivity to inhibitors of mTOR. The present study therefore evaluated pS6 expression in normal renal parenchyma (NRP), primary renal cell carcinomas (PRCC) and their metastases. pS6 and pmTOR expression was immunohistochemically analyzed in a tissue microarray (TMA) from localized primary renal cell carcinoma (lPRCC) (n = 35), metastasized primary renal cell carcinoma (mPRCC) (n = 45), their metastases (n = 45), and NRP (n = 45). pS6 expression was stronger in mPRCCs and metastases than in NRP and lPRCCs (p < 0.05). In mPRCCs high-grade and high-stage tumors showed higher pS6 levels. pS6 overexpression was more frequently found in metastases (40/45; 88.9%) than in mPRCC (24/45; 53.3%) (p < 0.05). Overexpression of pS6 in metastases without concomitant overexpression in their primary tumors was found in 16/45 (35.56%) cases. Patients with pS6 overexpression in mPRCCs but also in metastases showed a tendency to shorter overall survival. pS6 score and pmTOR score correlated positively in NRP and in tumorous tissue (mPRCC and metastases). In conclusion, the present study showed stronger pS6 expression and more frequent overexpression in metastases than in corresponding PRCCs. In approximately one-third of the cases pS6 overexpression was found exclusively in metastases, which is interesting with regard to the association between high pS6 expression and sensitivity to mTOR inhibitor therapy.

PTEN, pAKT, and pmTOR expression and subcellular distribution in primary renal cell carcinomas and their metastases.

The present study evaluated pAKT, pmTOR, and PTEN expression in a tissue microarray of primary renal cell carcinomas (PRCCs), their metastases, and normal renal parenchyma (NRP) (N = 45) by means of immunohistochemistry. Metastases in most subcellular compartments showed comparable and stronger expression for pAKT, pmTOR, and PTEN than PRCC and NRP, which was even more pronounced in patients with high-risk Memorial Sloan-Kettering Cancer Center (MSKCC) score. Furthermore, most subcellular compartments showed no differences between lymphogenous, haematogenous, synchronous, and metachronous metastases, which is interesting with regard to sensitivity to mTOR inhibitor therapy in metastasized RCCs with alterations in the PI3K/AKT pathway.

Surgical vein occlusion--comparison of four different methods in a rat model.

BACKGROUND: Among many aspects, wound healing depends on early restoration of venous blood flow across wound margins. The type of surgical occlusion of vein stumps during operations was assumed to have an influence on the early postoperative reunion of vein stumps and thereby on wound healing. Currently, there are different methods of vein stump occlusion available: ligation (e.g., Vicryl), closure using metal clips (e.g., LigaClip), coagulation using manually controlled bipolar forceps, and the use of a computer-controlled bipolar system (e.g., BiClamp). The aim of this study was to surgically and histologically compare the healing process, including new vessel formation after vein occlusion using one of the methods listed. METHODS: In a rat model (n = 50), both jugular and femoral veins were prepared, occluded twice with one of the methods mentioned above (i.e., 400 occlusions), and finally cut in-between. Groups of 10 animals were reoperated and evaluated surgically and histologically after 5 days, 10 days, 15 days, 30 days, and 90 days. RESULTS: Occlusion methods using Vicryl, LigaClip, or bipolar forceps allow highly reliable vessel occlusion. Surgical evaluation showed higher occurrence of vessels in between the vein stumps after usage of Vicryl and LigaClip when compared with electrothermic occlusion methods (p = 0.017). Histologic examination showed different courses of the inflammatory reaction and varying capillary counts. Bipolar occlusion methods do cause less vessel occurrence, less inflammatory reaction, and less histologic capillary formation. CONCLUSION: If a reconnection of the venous flow is desirable, the use of Vicryl and LigaClip might be superior to using electrothermic occlusion methods. In contrast, electrothermic methods cause less new vessel formation as well as less inflammatory reaction.

p-AKT overexpression in primary renal cell carcinomas and their metastases.

In cancer therapy novel concepts focus on phosphoinositide 3-kinase (PI3K)/activated protein kinase B (p-AKT)/mammalian target of rapamycin (mTOR) inhibitors. In this context, p-AKT overexpression was previously shown to be associated with sensitivity to inhibitors of mTOR. The present study evaluated p-AKT expression in a tissue microarray of primary renal cell carcinomas (PRCCs) (n = 45), their metastases (primary onset n = 45, secondary onset n = 5), and normal renal parenchyma (n = 45) by means of immunohistochemistry. Total p-AKT overexpression was found in 24/45 (53.3%) PRCCs, in 32/45 (71.1%) primary and in 3/5 (60%) secondary onset metastases. Membranous p-AKT overexpression was seen more frequently in PRCCs, namely 11/45 (24.4%), than in primary onset metastases 1/45 (2.2%). Overexpression of total p-AKT solely in metastases without overexpression in PRCC was exclusively demonstrated in primary onset metastases, namely in 28.9%. Patients with total p-AKT overexpression in primary carcinomas showed a trend to longer, and those with total p-AKT overexpression in metastases a tendency to shorter survival. In conclusion, the present study shows total p-AKT overexpression to be more frequent in metastases than in PRCCs. Total p-AKT overexpression in metastases without concomitant overexpression in their primary tumors was found in approximately one-third of primary onset metastases, which is interesting with regard to the association between high p-AKT expression and sensitivity to mTOR inhibitor therapy.

Diagnostic accuracy of guided cervical biopsies: a prospective multicenter study comparing the histopathology of simultaneous biopsy and cone specimen.

OBJECTIVE: We sought to determine the validity of colposcopically directed cervical biopsies as a diagnostic test to define the degree of cervical intraepithelial neoplasia (CIN). STUDY DESIGN: In a prospective multicenter trial, patients undergoing excisional procedures of the transformation zone additionally had colposcopy and up to 3 guided cervical biopsies in a single procedure. Cervical biopsies were regarded as a diagnostic test to detect high-grade lesions (CIN 2,3), with the cone specimen as reference standard. RESULTS: In all, 488 biopsies were performed in 244 cases, with 2 biopsies done in 192 cases. Cervical biopsies underestimated the severity of lesions in 46.7% of cases. Sensitivity, specificity, and positive and negative predictive values were 66.2% (95% confidence interval [CI], 59.4-72.3), 95.0% (95% CI, 83.5-98.6), 98.5% (95% CI, 94.8-99.6), and 35.5% (95% CI, 27.1-44.9), respectively. CONCLUSION: Our data suggest that cytologically suspected high-grade lesions (CIN 2,3) can be confirmed by biopsy in many cases, but they cannot be excluded.

Nucleoporin 88 expression in normal and neoplastic squamous epithelia of the uterine cervix.

This study investigated the expression of nucleoporin 88 (Nup88) in formalin-fixed, paraffin-embedded archival tissues of cervical specimens consisting of normal ectocervical squamous epithelia (n = 34), low-grade squamous intraepithelial lesions corresponding to cervical intraepithelial neoplasia (CIN) 1 (n = 9), high-grade squamous intraepithelial lesions corresponding to CIN2 and CIN3 (n = 28), and invasive squamous cell carcinoma (ISCC; n = 30) to determine whether expression of this factor is involved in the progression of the morphological spectrum from normal cervical epithelia to CIN and cervical ISCC. A standard immunohistochemical technique was performed using a Ventana BenchMark XT immunostainer with a mouse antihuman monoclonal antibody to Nup88. Immunostaining was scored with regard to quantity and intensity of positively stained cells, with final immunoscores from 0 to 12 in each case. Nucleoporin 88 immunoscores increased significantly from normal ectocervical squamous epithelia to CIN1, CIN2/3, and ISCC (P < .0001, analysis of variance). Cervical intraepithelial neoplasia 2/3 as isolated lesions and adjacent to ISCC did not differ significantly. A significant correlation was noticed for immunoscores of CIN2/3 adjacent to ISCC and the corresponding ISCC (P = .0007). This study indicates that Nup88 is significantly overexpressed in high-grade CIN lesions and ISCC compared with normal ectocervical squamous epithelia and CIN1. However, Nup88 evaluation is of limited value as a diagnostic marker in individual cases.

Chromosomal imbalances, 11q21 rearrangement and MECT1-MAML2 fusion transcript in mucoepidermoid carcinomas of the salivary gland.

The aim of this study was to determine genetic alterations in mucoepidermoid carcinomas of the salivary gland in association with clinical and histopathological parameters. Nineteen formalin-fixed, paraffin-embedded tumors were analysed by using comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH) on interphase nuclei and reverse transcriptase-polymerase chain reaction (RT-PCR) for detection of MECT1-MAML2 fusion transcript. The CGH analysis showed an overrepresentation of chromosome X and losses of entire chromosomes or regions on chromosome 1, 2, and 15 as the most frequent copy number changes. In 37% of the analysed tumors a MAML2-rearrangement by interphase FISH was detected, whereas 58% of the samples showed expression of MECT1-MAML2 fusion transcript. We conclude that the presence of MAML2-rearrangement as well as of MECT1-MAML2 fusion transcript may reflect a more favourable prognosis and may be a useful marker for clinical prediction of the biological behavior of these tumors as previously reported.

Increased activated Akt expression in renal cell carcinomas and prognosis.

Renal carcinogenesis is promoted by overexpression of the activated serine/ threonine kinase Akt (p-Akt) and supposedly a concomitant reduction in phosphatase and tensin homologue deleted on chromosome 10 tumour suppressor gene (PTEN), which normally inhibits the activation of Akt. Because promising anti-cancer therapies increasingly focus on pathways involving p-Akt and PTEN, the present study evaluated the expression of p-Akt in renal cell carcinomas and compared it with prognosis. P-Akt and PTEN expression were analysed in a tissue microarray (TMA) from renal cell carcinoma (n = 386) and adjacent uninvolved renal tissue (n = 32) specimens. Increased p-Akt was found more often in the nucleus than in the cytoplasm, and PTEN was concomitantly reduced in about 50% of cases. Neither tumour grade nor stage influenced p-Akt expression, whereas the clear cell and papillary subtypes showed increased p-Akt more often than did the chromophobe or sarcomatoid types. Increased cytoplasmic and nuclear p-Akt levels were independent prognostic factors for diminishing patient survival. The present study found significantly increased nuclear but also cytoplasmic p-Akt expression in renal cell carcinoma subtypes. Increased nuclear and cytoplasmic p-Akt was an independent prognostic factor for diminishing patient survival. The considerable number of high-grade and high-stage RCC showing increased p-Akt and reduced PTEN would justify further evaluation of therapeutic concepts based on inhibitors of the PI3K/p-Akt/mTOR pathway.

Association between atherosclerosis and urothelial tumors of the renal pelvis.

OBJECTIVES: An association between the prevalence of general and local atherosclerosis and various types of cancer has previously been reported. The present study therefore aimed to morphometrically compare atherosclerotic changes in kidneys with urothelial carcinomas of the renal pelvis and tumor-negative renal tissue. MATERIALS AND METHODS: The intima-to-media ratio (IMR), which is the most sensitive marker for the degree of atherosclerosis, was evaluated in arteries (n = 492) of non-invasive papillary urothelial carcinoma (n = 128), invasive urothelial carcinoma (n = 168) and tumor-negative renal specimens (n = 196). RESULTS: IMR was significantly higher and more often exceeded 1 in invasive and non-invasive urothelial carcinomas than in tumor-negative specimens. Furthermore, in invasive urothelial carcinomas IMR was significantly higher in immediately peritumorous arteries than in more distant arteries. Moreover, IMR correlated weakly with age and renal parenchymal inflammation but not with peritumorous inflammation, coronary heart disease (CHD) or gender. CONCLUSION: Local atherosclerosis was more pronounced in tumor-positive than in tumor-negative renal specimens. IMR > 1 was significantly associated with urothelial tumors and the overall odds of having a urothelial tumor were significantly greater for patients with an IMR > 1 than for patients with an IMR < or = 1, supporting the view that patients with local atherosclerotic lesions are at elevated risk for urothelial carcinoma of the renal pelvis.