Urothelial Carcinoma Of Renal Pelvis Research Articles

P1-6-6 - A Renal Pelvic Urothelial Carcinoma with an Inferior Vena Cava Tumor Thrombus Treated with Gemcitabine Plus Cisplatin

Background: The occurrence of a renal pelvic urothelial carcinoma (UC) with an inferior vena cava (IVC) tumor thrombus is very rare. Chemotherapy with gemcitabine plus cisplatin (GC) is globally established as standard treatment for patients with unresectable metastatic UC. Although standard treatment for local advanced renal pelvic UC has not been established, we report a case of renal pelvic UC with IVC tumor thrombus treated with GC.Case: A 74-year-old woman was admitted to our hospital with progressive upper abdominal pain and increasing fever in the preceding week. Computed tomography scan revealed a large right renal tumor with IVC tumor thrombus extending from the hepatic portal region to both sides of the iliac branch. Urine cytology of the right ureter showed UC cells. The patient was eventually diagnosed with advanced renal pelvic UC and IVC tumor thrombus and was treated with GC for 4 cycles. A partial response to chemotherapy was observed; however, we had to cease chemotherapy owing to hematological toxicity. We planned a right nephroureterectomy and thrombectomy that could not be performed because the tumor directly invaded the duodenum and pancreas. Pathological findings of the abnormal nodes showed metastatic UC.Conclusion: A renal pelvic UC with an IVC tumor thrombus presented with a different tumor extension compared to a renal cell carcinoma with an IVC tumor thrombus. Although continual GC may improve the prognosis of a renal pelvic UC with an IVC tumor thrombus, its use should be further investigated in a large number of patients.

Reassessment of Prognostic Heterogeneity of pT3 Renal Pelvic Urothelial Carcinoma: Analysis in Terms of Proposed pT3 Subclassification Systems

We determined whether the 3 pT3 subclassification systems reported by the Asan, Cornell and Nagoya groups provide an accurate estimation of patient prognosis. We also determined which subclassification is most predictive of the heterogeneous oncological outcomes of pT3 renal pelvic urothelial carcinoma. Using a Korea-Japan multi-institutional, retrospective database 250 pT3 renal pelvic urothelial carcinomas treated with radical nephroureterectomy were assigned to the 3 pT3 subcategories by tumor location and depth of parenchymal invasion after pathological reevaluation. Recurrence-free and cancer specific survival was assessed according to the 3 pT3 subclassifications. Predictive accuracy for survival in 4 models (baseline and each of the 3 pT3 subclassifications) was quantified and predictive accuracy increments for each model were compared. In the baseline multivariate Cox regression model nodal metastasis and high grade were significant for survival. On multivariate analysis including the pT3 subclassifications the 3 subclassifications remained significantly associated with survival rates. Of the 3 pT3 subclassification systems the Cornell subclassification had the highest predictive accuracy for discriminating the heterogeneous prognosis of pT3 renal pelvic urothelial carcinoma, followed by the Nagoya subclassification. Compared with the baseline model adding the Cornell subclassification significantly increased predictive accuracy for recurrence-free survival from 0.687 to 0.742 (p = 0.029) and for cancer specific survival from 0.713 to 0.758 (p = 0.047). The criteria of microscopic vs macroscopic parenchymal invasion and/or peripelvic fat invasion provide the most accurate differential classification of the prognostic heterogeneity of pT3 renal pelvic urothelial carcinoma. Further studies should be performed to determine the need to modify the current pT3 renal pelvic urothelial carcinoma staging system.

The value of serum CYFRA21-1 examination in the detection of urothelial carcinoma

Objective To evaluate the value of CYFRA21-1 examination in the detection of urothelial carcinoma (UC).Methods Serum concentrations of CYFRA21-1 were examined by electrochemiluminescence technique in 65 cases with UC,61 cases of non-UC patients (including 21 cases of renal carcinoma,20 cases of benign prostatic hyperplasia,10 cases of prostatic carcinoma,10 cases of urolithiasis) and 43 hea]thy individuals.Sixty-five UC cases including 9 renal pelvis UC cases,4 ureter UC cases,52 bladder UC cases,61 non-UC cases including 21 renal carcinoma cases,20 benign prostatic hyperplasia cases,10 prostatic carcinoma cases,10 urolithasis cases.Results The serum CYFRA21-1 concentration in UC patients (7.57± 12.76) μg/L was significantly higher than the healthy controls (2.58±0.97) μg/L and also the non-UC patients (2.75± 1.34) μg/L (P＜0.01).The difference between the healthy individuals and the nonUC patients was not significant (P＞0.05).According to the manual in the reagent kit,the positive value of serum CYFRA21-1 was defined as greater than 3.3 μg/L.The false positive rate in healthy controls and the non-UC patients was 10％-30％.The positive percentage of serum CYFRA21-1 of the 65 UC patients was 67.7％ (44/65).In low,middle and high grade UC cases,the positive rates were 50.0％ (10/20),62.5％ (5/8) and 78.3％ (29/37) respectively.The difference of the positive rates between the high grade group and middle,low grade groups was significant (x2 =4.55,P＜0.05).The positive rates in non-muscle invasive (Ta-Ti) UC and in healthy controls were 40.9％ (9/22) and 23.2％ (10/43) respectively,and the difference between the two groups was not significant (x2=2.19,P＞0.05).The positive rate in muscle invasive (T2-T3) UC was 78.6％ (22/28) and the difference compared with healthy controls was significant (x2=20.96,P＜0.01).The positive rate in local advanced and metastatic UC (＞T3) was 86.7％ (13/15).The positive rates were not significantly deferent between the T2-T3 group and the ＞ T3 group (x2 =1.97,P＞0.05).Conclusions The serum CYFRA21-1 positive rate is 67.7％ in UC patients,which was higher than non-UC patients and healthy controls,and associated positively with the pathologic grade and the clinical stage of UC.Monitoring the serum CYFRA21-1 is effective in assessing the outcomes and prognosis of UC,if the serum CYFRA21-1 was positive.The serum CYFRA21-1 test has some significance in distinguishing UC from renal carcinoma and prostatic carcinoma. Key words: Urothelium; Carcinoma; Tumor markers; Keratins

Synchronous Triple Distinct Urological Tumors in a Patient: Urothelial Carcinoma of Bladder, Unilateral Renal Oncocytoma and Papillary Adenoma

Synchronous multiple primary tumors of the urinary tract are quite rare. The medical literature refers to a small percentage (around 4%) of the incidence of oncocytomas synchronous with other kidney tumors as renal cell carcinoma, pelvic urothelial carcinoma, angiomyolipoma etc. Papillary adenoma is one of those tumors that may rarely coexist with oncocytoma. In this study, we present a case of 69-year-old male patient with synchronous occurrence of concomittant unilateral renal oncocytoma and papillary adenoma, and urothelial carcinoma in bladder. To the best of our knowledge, this is the first case report combining those urinary tumors in the medical literature.

Utility of MRI Features in Differentiation of Central Renal Cell Carcinoma and Renal Pelvic Urothelial Carcinoma

The purpose of this article is to evaluate the utility of various morphologic and quantitative MRI features in differentiating central renal cell carcinoma (RCC) from renal pelvic urothelial carcinoma. Sixty patients (39 men and 21 women; mean [± SD] age, 65 ± 14 years; 48 with central RCC and 12 with renal pelvic urothelial carcinoma) who underwent MRI, including diffusion-weighted imaging (b values, 0, 400, and 800 s/mm(2)) and dynamic contrast-enhanced imaging, before histopathologic confirmation were included. Tumor T2 signal intensity and apparent diffusion coefficients (ADCs) were measured and normalized to muscle and CSF (hereafter referred to as normalized T2 signal and normalized ADC, respectively) and then were compared using receiver operating characteristic analysis. Also, two blinded radiologists independently assessed all tumors for various qualitative features, which were compared with the Fisher exact test and unpaired Student t test. Urothelial carcinoma exhibited significantly lower normalized ADC than did RCC (p = 0.008), but no significant difference was seen in ADC or normalized T2 signal intensity (p = 0.247-0.773). Normalized ADC had the highest area under the curve (0.757); normalized ADC below an optimal threshold of 0.451 was associated with sensitivity of 83% and specificity of 71% for diagnosing urothelial carcinoma. Features that were significantly more prevalent in urothelial carcinoma included global impression of urothelial carcinoma, location centered within the collecting system, collecting system defect, extension to the ureteropelvic junction, preserved renal shape, absence of cystic or necrotic areas, absence of hemorrhage, homogeneous enhancement, and hypovascularity (all p < 0.033). Increased T1 signal intensity suggestive of hemorrhage was significantly more prevalent in RCC (p = 0.02). Interreader agreement for the subjective features ranged from 61.7% to 98.3%. In addition to various qualitative MRI parameters, normalized ADC has utility in differentiating central RCC from renal pelvic urothelial carcinoma. Such differentiation may assist decisions regarding possible biopsy and treatment planning.

Nephron-sparing surgery with autotransplantation for high-grade upper urinary tract urothelial carcinoma in a patient with solitary kidney

Instead of nephroureterectomy with bladder cuff excision, nephron-sparing surgery can be considered in selected patients with non-muscle invasive upper urinary tract urothelial carcinoma. The role of kidney-sparing surgery has been established for the management of low-grade urothelial carcinoma. We report a solitary kidney patient with high-grade renal pelvis urothelial carcinoma treated with nephron-sparing surgery by ex vivo tumor excision and autotransplantation. The results of the surgery were excellent.

Retroperitoneal laparoscopic radical nephrectomy and thrombectomy for renal tumor with renal vein and vena cava thrombus

Objective To evaluate the feasibility of retroperitoneal laparoscopic radical nephrectomy and thrombectomy for renal tumor with renal vein and vena cava thrombus.Methods Twelve cases of renal tumor with renal vein and vena cava thrombus were reported.Contrast-enhanced CT showed renal tumor extended to renal vein and vena cava in two cases,and filling defects were found in right or left renal vein in ten cases.All the patients received retroperitoneal laparoscopic radical nephrectomy and thrombectomy.Four trocars were placed during the procedure,early arterial division and milking of the thrombus away from the inferior vena cava may facilitate laparoscopic surgery,a laparoscopic clamp was used to occlude the vena cava partially containing the thrombus in two cases.Hem-o-lok was used to dissect the renal vein for left renal tumors.During the operation,inferior mesenteric artery,abdominal aorta and inferior vena cava were mobilized in order to expand the operating space.Results One patient was conver~d to open procedure.The two right tumor thrombi were 2.5 cm and 3.7 cm,respectively.The mean length of left tumor thrombi was 4.1 cm (2.0-7.5 cm).Post-operative pathology showed renal epithelioid angiomyolipoma in one patient,clear cell carcinoma in 9 cases (grade 1 in 2 cases,grade 1-2 in 2 cases,grade 2 in 5 cases),chromophobe carcinoma in 1 case and renal pelvic urothelial carcinoma in 1 case.Mean hospital stay was 7 d (4-11 d).Contralateral adrenal metastasis occurred in one case 14 months after surgery.No tumor recurrence or metastasis occurred with a mean follow-up of 20 months (5-42 months) for others.Conclusion Retroperitoneal laparoscopic radical nephrectomy and thrombectomy can be applied safely and effectively with adherence to proper techniques in carefully selected patients. Key words: Kidney neoplasms ; Thrombus ; Laparoscopic ; Nephrectomy ; Thrombectomy

Expression of carbonic anhydrase IX, PAX2 and PAX8 and their association with clinicopathologic characteristics in renal epithelial tumors

To study the expression of carbonic anhydrase IX (CAIX), PAX2 and PAX8 in different types of renal epithelial tumor and their association with clinicopathologic characteristics. Immunohistochemical study by EnVision method was performed in order to assess the expression of CAIX, PAX2 and PAX8 in 155 cases of renal cell carcinoma and 4 cases of metastatic clear cell renal cell carcinoma (CCRCC). Ninety-six cases of non-neoplastic renal parenchymal tissue adjacent to CCRCC, 8 cases of clear cell hepatocellular carcinoma and 2 cases of clear cell hidradenoma were used as controls. CAIX was commonly expressed in CCRCC (94.0%, 63/67), of which 77.8% (49/63) showed strong positivity. CAIX was focally positive in papillary renal cell carcinoma, collecting duct carcinoma and urothelial carcinoma of renal pelvis. It was negative in chromophobe renal cell carcinoma, oncocytoma and adjacent non-neoplastic renal tissue. CAIX was also strongly expressed in the 4 cases of metastatic CCRCC. Focal expression of CAIX was demonstrated in the 8 cases of clear cell hepatocellular carcinoma and 2 cases of clear cell hidradenoma. The expression of CAIX in CCRCC did not correlate with tumor grading, clinical staging and presence of distal metastasis. On the other hand, PAX2 showed positive expression in different types of renal epithelial tumor, clear cell hepatocellular carcinoma and clear cell hidradenoma in various degrees. In contrast, PAX8 was commonly expressed in all types of renal epithelial tumor, with the exception of urothelial carcinoma of renal pelvis. PAX8 was not expressed in clear cell hepatocellular carcinoma and clear cell hidradenoma. Regarding diagnosis of CCRCC, CAIX demonstrated high sensitivity and specificity. PAX2 showed high specificity but low sensitivity. PAX8 was sensitive and specific in the diagnosis of renal epithelial tumor. CAIX is a useful immunohistochemical marker with high specificity and sensitivity in distinguishing CCRCC from other types of renal epithelial tumor and clear cell tumors of non-renal origin. PAX2 is a marker with high sensitivity and low specificity for diagnosis of renal epithelial tumors. PAX8 is typically expressed in renal epithelial tumors. The combined detection of CAIX, PAX2 and PAX8 is useful in the diagnosis and differential diagnosis of renal epithelial tumors.

Evaluation of renal urothelial carcinoma by contrast-enhanced ultrasonography

PurposeTo observe ultrasonographic features of urothelial carcinoma in renal pelvis and evaluate contrast-enhanced ultrasound (CEUS) in diagnosis. Materials and methodsFifty-two patients with urothelial carcinoma underwent preoperative conventional US, colour Doppler flow imaging (CDFI) and CEUS. ResultsOf 52 total lesions, 41 (78.8%) could be clearly identified by US, and 49 (94.2%) were enhanced by CEUS. Among US-imaged lesions, 39 (95.1%) were solid tumours, and two (4.9%) were mixed solid-cystic; 25 (61.0%) were isoechoic, 11 (26.8%) hypoechoic, and five (12.2%) hyperechoic. Analysis of tumour blood flow by CDFI characterised 17 avascular lesions (41.5% of total), 16 hypovascular (39.0%), and 8 hypervascular (19.5%). The resistance index ranged from 0.65 to 0.88 (mean of 0.71). Enhancement was seen in 49 lesions after injection of SonoVue. A slow enhancement pattern was observed in 36 lesions (73.5%) relative to renal cortex, and 13/49 (26.5%) showed simultaneous enhancement. At peak enhancement, 38 lesions (77.6%) were hypo-enhanced, six (12.2%) iso-enhanced, and five (10.2%) hyper-enhanced. There were 12 lesions with intertumoural necrosis or haemorrhage (24.5%) that were heterogeneously enhanced, and 37 (75.5%) were homogeneously enhanced. A fast washout pattern was observed in 46 lesions (93.9%), synchronous washout in two (4.08%), and slow washout in one (2.04%). ConclusionsSlow-in, fast-out, and hypo-enhancement properties are associated with renal urothelial carcinoma and may thus have diagnostic value. We found that CEUS is able to identify tumours that are ambiguous by conventional US, and it thus significantly improves the confidence of diagnosis.

Laparoscopic Nephroureterectomy in Renal Pelvic Urothelial Carcinoma With Situs Inversus Totalis: Preoperative Training Using a Patient-specific Simulator

To report the first case of preoperative training using a patient-specific laparoscopic simulator for a patient with situs inversus totalis (SIT). A 61-year-old man presented with gross hematuria and was diagnosed with right renal pelvic cancer T1N0M0. A whole-body computed tomography (CT) scan also revealed his organs showed a mirror image, with left-to-right reversal, and SIT was diagnosed. A laparoscopic right nephroureterectomy through a retroperitoneal approach was scheduled. Before the operation, we practiced the operation using a patient-specific laparoscopic surgical simulator that we have developed. The patient's CT data were used to reproduce the retroperitoneal space in the simulator, and the surgeon trained and became familiar with his SIT anatomy. The insufflation time was 182 minutes, and the estimated blood loss was 50 mL. The surgeon was able to complete the right retroperitoneoscopic nephroureterectomy safely, without any problems. To our knowledge, we report the first case of preoperative training using a patient-specific simulator for a patient with SIT. Preoperative training was useful, and retroperitoneoscopic nephroureterectomy was successfully performed in a patient with renal pelvic urothelial carcinoma and SIT.

858 CLINICAL USE OF A PATIENT-SPECIFIC SIMULATOR FOR LAPAROSCOPIC RENAL SURGERY

You have accessJournal of UrologyTechnology & Instruments: Surgical Education & Skills Assessment/Ureteroscopy I1 Apr 2012858 CLINICAL USE OF A PATIENT-SPECIFIC SIMULATOR FOR LAPAROSCOPIC RENAL SURGERY Kazuhide Makiyama, Hiroyuki Yamanaka, Daiki Ueno, Yoshinobu Kubota, Kentarou Takanami, Manabu Nagasaka, and Masato Ogata Kazuhide MakiyamaKazuhide Makiyama Yokohama, Japan More articles by this author , Hiroyuki YamanakaHiroyuki Yamanaka Yokohama, Japan More articles by this author , Daiki UenoDaiki Ueno Yokohama, Japan More articles by this author , Yoshinobu KubotaYoshinobu Kubota Yokohama, Japan More articles by this author , Kentarou TakanamiKentarou Takanami Kamakura, Japan More articles by this author , Manabu NagasakaManabu Nagasaka Kamakura, Japan More articles by this author , and Masato OgataMasato Ogata Kamakura, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.951AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Training systems that simulate a surgical process are available on a commercial basis. They are useful for basic training, but do not correspond to the specific conditions of each patient. We, therefore, have developed a unique training system: a patient-specific type simulator for laparoscopic surgery. Using specific data of each individual patient, this system enables surgeons to exercise a “rehearsal” operation in virtual reality conditions. We performed preoperative simulations using this simulator for five patients who underwent renal surgery in Yokohama City University. METHODS Dynamic CT of each patient scheduled to undergo renal surgery was captured into the model data generation system. Each patient's specific volume data for the kidneys and organs around the kidney were extracted and entered into the simulator. In the simulator, the organs of each individual patient were reproduced. Two surgeons performed five preoperative simulations. Procedures included two nephroureterectomies, a pyeloplasty, a partial nephrectomy and a simple nephrectomy. The pyeloplasty was performed via transperitoneal approach and the other operations were via retroperitoneal approach. We evaluated whether anatomies reproduced in the simulator were correct or not compared with real operations and interviewed surgeons to determine whether it was useful or not as a preoperative training. RESULTS We were able to confirm that the anatomies were reproduced almost perfectly in the simulator compared with intraoperative findings. Three minor mistakes were identified. In the left pyeloplasty, a crossing vein (kidney→gonadal vein) was located on the back side of the UPJ in the simulator, but was actually just ventral of the UPJ in the operation. In the right partial nephrectomy, a right gonadal vein was connected to the renal vein in the simulator, but was actually connected to vena cava. In the same case, the simulator could not reproduce the lumber vein, which was able to be observed during the operation. In all five cases, surgeons could perform comfortable preoperative training, and stated their impressions that it was useful to make preoperative images. In particular, it was useful to make adequate preoperative images in the case of retroperitoneoscopic nephroureterectomy in renal pelvis urothelial carcinoma with situs inversus totalis. CONCLUSIONS The patient-specific simulator for laparoscopic renal surgery has been successfully developed. We confirmed that it reproduced organs correctly and surgeons feel it is useful as a preoperative training technique. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e350 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kazuhide Makiyama Yokohama, Japan More articles by this author Hiroyuki Yamanaka Yokohama, Japan More articles by this author Daiki Ueno Yokohama, Japan More articles by this author Yoshinobu Kubota Yokohama, Japan More articles by this author Kentarou Takanami Kamakura, Japan More articles by this author Manabu Nagasaka Kamakura, Japan More articles by this author Masato Ogata Kamakura, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Gigantic transitional cell carcinoma of the renal pelvis in the region of endemic nephropathy

To present the rare case of transitional cell carcinoma of the renal pelvic in the region of endemic nephropathy. A 64-year old man with gigantic urothelial carcinoma in renal pelvis and ureter. Patient underwent right nephrectomy. Hystopathological analysis after right nephrectomy revealed urothelial transitional cell carcinoma, grade III-IV with infiltration of right ureter. After one month, because of the hystopatological findings, patient underwent ureterectomy on the right side. Two years after surgery there are no signs of primary disease or metastasis and the cystoscopy findings are normal. Despite the poor prognosis, two years after surgery patient is without signs of primary disease or metastasis.

Immunohistochemical Diagnosis of Renal Neoplasms

Histologic diagnosis of renal neoplasm is usually straightforward by routine light microscopy. However, immunomarkers may be essential in several contexts, including differentiating renal from nonrenal neoplasms, subtyping of renal cell carcinoma (RCC), and diagnosing rare types of renal neoplasms or metastatic RCC in small biopsy specimens. To provide a comprehensive review of the diagnostic utility of immunomarkers for renal neoplasms. This review is based on published literature and personal experience. The following markers may have diagnostic utility in various diagnostic contexts: cytokeratins, vimentin, α-methylacyl coenzyme A racemase, carbonic anhydrase IX, PAX2, PAX8, RCC marker, CD10, E-cadherin, kidney-specific cadherin, parvalbumin, claudin-7, claudin-8, S100A1, CD82, CD117, TFE3, thrombomodulin, uroplakin III, p63, and S100P. Cytokeratins are uniformly expressed by RCC, albeit in a somewhat limited amount in some subtypes, requiring broad-spectrum anti-CK antibodies, including both low- and high-molecular-weight cytokeratins. PAX2 and PAX8 are sensitive and relatively specific markers for renal neoplasm, regardless of subtype. CD10 and RCC marker are sensitive to renal cell neoplasms derived from proximal tubules, including clear cell and papillary RCCs. Kidney-specific cadherin, parvalbumin, claudin-7, and claudin-8 are sensitive markers for renal neoplasms from distal portions of the nephron, including chromophobe RCC and oncocytoma. CK7 and α-methylacyl coenzyme A racemase are sensitive markers for papillary RCC; TFE3 expression is essential in confirming the diagnosis of Xp11 translocation RCC. The potentially difficult differential diagnosis between chromophobe RCC and oncocytoma may be facilitated by S100A1 and CD82. Thrombomodulin, uroplakin III, p63, and S100P are useful markers for urothelial carcinoma. Together with high-molecular-weight cytokeratins, PAX2, and PAX8, they can help differentiate renal pelvic urothelial carcinoma from collecting duct RCC. A sensitive marker for sarcomatoid RCC is still not available. Immunomarkers are most often used for diagnosing metastatic RCC. Compared with primary RCC, expression of the above-mentioned markers is often less frequent and less diffuse in the metastatic setting. Recognizing the variable sensitivity and specificity of these markers, it is important to include at least CD10, RCC marker, PAX2, and PAX8 in the diagnostic panel.

Renal Urothelial Carcinoma with Extended Venous Thrombus

Vascular invasion is not uncommon histologically in patients with urothelial carcinoma (UC) arising from the renal pelvis or ureter, while tumor thrombus affecting the main renal vein or the inferior vena cava (IVC) is rare. Herein, we report a unique case of renal pelvic UC with extended IVC thrombus manifested as progressive swelling in the lower limbs.

PAX8 (+)/p63 (−) Immunostaining Pattern in Renal Collecting Duct Carcinoma (CDC)

Collecting duct carcinoma (CDC) is a relatively rare but aggressive type of renal malignancy with variable morphologic features. One of the World Health Organization diagnostic criteria for CDC is the exclusion of urothelial carcinoma of renal pelvis from the differential diagnosis. PAX8 is a novel lineage restricted transcription factor expressed in renal tubules. We investigated the expression pattern of PAX8 in CDC and its utility, in combination with p63, in resolving the differential diagnosis of CDC versus upper tract urothelial carcinoma (UUC). Archival tissues from 21 CDC and 34 UUC were retrieved from our institutional files. Immunohistochemistry for PAX8 and p63 were performed on routine and tissue microarray sections using standard immunohistochemistry protocol. Intensity of nuclear staining was evaluated for each marker and assigned an incremental 0, 1+, 2+, and 3+ score. Extent of staining was categorized as focal (<25%), nonfocal (25% to 75%), or diffuse (>75%). CDC: All 21 (100%) CDC were positive for PAX8. Intensity of expression was moderate to strong (2+/3+) in 19 cases (90%). Extent of staining was diffuse in 13 of 21 tumors. The p63 was positive in 3 of 21 (14%) CDC cases (PAX8+/p63+). UUC: The 34 UUC included 5 pT1, 4 pT2, and 25 pT3/pT4 tumors. Thirty-one of 34 (91.2%) UUC were negative for PAX8, whereas 33 of 34 (97%) were p63 positive. Staining intensity was moderate in 15 cases (44%), of which 12 were nonfocal or diffuse. The unique p63-negative UUC was a pT1 tumor that was also negative for PAX8 (PAX8-/p63-). We propose the use of the combination of PAX8 and p63 in the diagnosis of poorly differentiated renal sinus epithelial neoplasms where the differential diagnosis includes CDC versus UUC. The immunoprofile of PAX8+/p63- supports the diagnosis of CDC with a sensitivity of 85.7% and a specificity of 100%. In contrast, a (PAX8-/p63+) profile supports the diagnosis of UUC with a sensitivity of 88.2% and a specificity of 100%. The inverse PAX8/p63 expression seen in CDC and UUC supports a renal tubular rather than an urothelial differentiation in CDC given the nephric lineage restriction of PAX8.

428 IMPACT OF LYMPH NODE DISSECTION ON DISEASE FREE SURVIVAL IN PATIENTS WITH RENAL PELVIS UROTHELIAL CARCINOMA TREATED WITH RADICAL NEPHROURETERECTOMY

You have accessJournal of UrologyUrothelial Cancer: Upper Tract Tumors1 Apr 2010428 IMPACT OF LYMPH NODE DISSECTION ON DISEASE FREE SURVIVAL IN PATIENTS WITH RENAL PELVIS UROTHELIAL CARCINOMA TREATED WITH RADICAL NEPHROURETERECTOMY Yoshihisa Matsukawa, Ryohei Hattori, Yasushi Yoshino, and Momokazu Gotoh Yoshihisa MatsukawaYoshihisa Matsukawa More articles by this author , Ryohei HattoriRyohei Hattori More articles by this author , Yasushi YoshinoYasushi Yoshino More articles by this author , and Momokazu GotohMomokazu Gotoh More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.498AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Nephroureterectomy is the standard surgical procedure for upper tract urothelial carcinoma (UTUC). Recently, some papers reported that lymph node dissection (LND) at nephroureterectomy provides a survival benefit in patients with UTUC. But the impact of LND between renal pelvis tumor and ureter tumor was not reported, and the prognosis according to the range of LND was not clear. To explore these points in this study, we assessed the local recurrence after nephroureterectomy with a bladder cuff and simultaneous lymph node dissection according to the range of LND in only renal pelvis tumor. METHODS We retrospectively reviewed the database of 231 patients undergoing nephroureterectomy with a bladder cuff and lymph node dissection for UC of the renal pelvis with clinical stages of T1-3N0M0 between August 1997 and April 2008. We classified 3 categories (extended LND, limited LND, No LND) according to the range of LND. Extended LND was defined as renal hilus node dissection and para-aortic, paracaval, or interaortocaval node dissection from the hilus to the inferior mesenteric artery, and limited LND was defined only as renal hilus node dissection. Local recurrence except bladder tumor was assessed with mean follow-up periods of 85 months in the extended LND group, 45 months in the limited LND group and 47 months in the No LND group. RESULTS Extended LND/ limited LND/ no LND was 104/73/54 patients. Patients mean age was 63.6 years in the extended LND group, 66.3 years in the limited LND group and 70.7 years in the No LND group. At surgery, lymph node metastasis was pathologically positive in 9 patients (8.7%) in the extended LND group and 6 (8.2%) in the limited LND group with no statistical difference between the 2 groups. The actuarial 5-year disease free survival (DFS) rate was 91% in the extended LND group, 83% in the limited LND group and 63% in the No LND group which was statistically different. Furthermore we analyzed the influence of the LND according to pT stage. In the pTa+pT1 patients, 5-year DFS rate was 97%, 94%, 85% in the extended LND patients, the limited LND patients, in the no LND patients, which did not statistically differ between 3 groups. On the other hand, in the pT2 or higher patients, 5-year DFS rate was 89%, 67%, 23%, DFS in patients significantly depended on the extent of LND. CONCLUSIONS LND at the time of nephroureterectomy in renal pelvis tumor may provide a therapeutic advantage in patients with advanced disease (pT2 or higher). Nagoya, Japan© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e169 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yoshihisa Matsukawa More articles by this author Ryohei Hattori More articles by this author Yasushi Yoshino More articles by this author Momokazu Gotoh More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Should hilar lymph nodes be expected in radical nephrectomy specimens?

Lymph node (LN) status is essential in staging both renal cell carcinoma (RCC) and pelvic urothelial carcinoma (PUC). The rate of regional LN involvement is influenced by pathologic tumor stage, extent of the surgical resection, and accuracy of pathologic gross examination. In this study, we assess the presence of hilar LNs in radical nephrectomies (RN) by entirely submitting the hilar fat region (HFR) for microscopic evaluation (ME). Fifty consecutive RNs from 2006 to 2008 were evaluated by a standard gross examination protocol (SGEP) which consisted of palpation and sectioning of the HFR with submission of grossly identified LNs. Subsequently, the entire HFR was re-evaluated and submitted as study's total submission protocol (TSP). The number and disease status of hilar LNs identified by the SGEP and TSP were compared. Fifty RNs (37 clear cell RCC, 6 papillary RCC, 7 PUC) were studied prospectively. Ten of the 50 RNs had LNs identified (20%) with both protocols. Four of the 50 RNs had nodal metastases (8%) with the LN sizes ranging between 1.3 and 2.5 cm (mean 1.8 cm). All nodal metastases were identified by the SGEP. In three RNs (6%), additional minute (mean 0.12 cm) negative LNs not seen by the SGEP were identified by the TSP. LNs are present in only 20% of RNs, even after complete ME of the HFR. The SGEP for identifying hilar LNs in RNs is sufficient for staging and did not lead to underreporting of LN metastases.

Renal pelvic urothelial carcinoma with divergent morphology

Compared with that of urinary bladder, urothelial carcinoma of renal pelvis is infrequent and its morphologic features and presentations have seldom been described. Fifty-nine renal pelvic urothelial carcinomas were evaluated in this study. Seventy-eight percent of these were high-grade tumors, of which 39% contained variable amount of divergent morphology. Forty-four percent of the high-grade urothelial carcinomas presented with an advanced tumor stage. Seventy-eight percent of urothelial carcinomas with divergent morphology displayed a tumor stage of pT2 and above, compared with 21% of classical urothelial carcinomas, which presented at stage pT2 and above. In summary, high-grade and unusual morphology as well as advanced tumor stage were the frequent findings in pelvicalyceal urothelial carcinomas. In addition, divergent morphology was correlated with advanced tumor stage. The clinicopathologic features of pelvicalyceal urothelial carcinomas with unusual divergent morphology were particularly emphasized in this study.

Activation of the PI3K/AKT Pathway Induces Urothelial Carcinoma of the Renal Pelvis: Identification in Human Tumors and Confirmation in Animal Models

Urothelial carcinoma of the renal pelvis is a deadly disease with an unclear tumorigenic mechanism. We conducted gene expression profiling on a set of human tumors of this type and identified a phosphatidylinositol 3-kinase (PI3K)/AKT activation expression signature in 76.9% (n = 13) of our samples. Sequence analysis found both activating mutations of PIK3CA (13.6%, n = 22) and loss of heterozygosity at the PTEN locus (25%, n = 8). In contrast, none of the other subtypes of kidney neoplasms (e.g., clear-cell renal cell carcinoma) harbored PIK3CA mutations (n = 87; P < 0.001). Immunohistochemical analysis of urothelial carcinoma samples found loss of PTEN protein expression (36.4%, n = 11) and elevation of phosphorylated mammalian target of rapamycin (mTOR; 63.6%, n = 11). To confirm the role of the PI3K/AKT pathway in urothelial carcinoma, we generated mice containing biallelic inactivation of Pten in the urogenital epithelia. These mice developed typical renal pelvic urothelial carcinomas, with an incidence of 57.1% in mice older than 1 year. Laser capture microdissection followed by PCR confirmed the deletion of Pten exons 4 and 5 in the animal tumor cells. Immunohistochemical analyses showed increased phospho-mTOR and phospho-S6K levels in the animal tumors. Renal lymph node metastases were found in 15.8% of the animals with urothelial carcinoma. In conclusion, we identified and confirmed an important role for the PI3K/AKT pathway in the development of urothelial carcinoma and suggested that inhibitors of this pathway (e.g., mTOR inhibitor) may serve as effective therapeutic agents.

The Protective Role of Renal Parenchyma as a Barrier to Local Tumor Spread of Upper Tract Transitional Cell Carcinoma and its Impact on Patient Survival

We investigated whether tumor location has independent prognostic significance in upper tract transitional cell carcinoma cases and which factor determines it. We reviewed data on 122 renal pelvis and 102 ureteral tumor cases, including the recurrence pattern. Tumor location and other clinicopathological variables were evaluated regarding cancer specific and recurrence-free survival. Stage pT3 tumors were stratified into those invading renal parenchyma or peripelvic/periureteral fat. Overall 5-year cancer specific survival and recurrence-free survival rates were 77.0% and 71.6%, respectively, at a mean followup of 60.7 months. Of the clinicopathological parameters T stage was the most significant prognosticator of the survival rate, while nodal involvement, high grade and ureteral tumor location were also significant for lower survival rates. Stratification analysis for matching pathological stage revealed that, while survival rates were similar in the renal pelvis and ureteral tumor groups at stage pT2 or less, renal pelvic tumors were associated with significantly higher survival rates than ureteral tumors for stage pT3. Specifically renal pelvic tumors invading the renal parenchyma were associated with a lower local failure rate, and higher cancer specific and recurrence-free survival rates than tumors invading peripelvic or periureteral fat, ie 77.5% vs 49.7% 5-year cancer specific survival and 75.6% vs 32.0% 5-year recurrence-free survival (p = 0.014 and 0.003, respectively). Tumor location is an independent prognostic factor for pT3 upper tract transitional cell carcinoma. The overall better prognosis of renal pelvic tumors was mainly attributable to pT3 tumor outcomes, specifically lesions invading the renal parenchyma. These findings may be due to the protective role of thick renal parenchyma against local tumor spread.