Carcinoma Of Ureter Research Articles

Renal Autotransplantation in Lynch Syndrome: A Viable Option in a Patient With Contralateral Metachronous Ureteral Cancer

The success of human kidney allotransplantation was realized over six decades ago. First described 50 years ago, renal autotransplantation has been utilized sparingly as a salvage procedure for patients at risk of losing renal function, either from a benign or malignant condition. While classically associated with colorectal malignancies, Lynch syndrome also carries a small yet significant risk for the development of ureteral carcinoma. For these patients who develop chronic kidney disease, allotransplantation may not be an option due to the lifelong risk of several malignancies. We report the first known case of renal autotransplantation in a patient with metachronous ureteral cancer due to Lynch syndrome.

AB112. Long-term result of ileal-ureter substitution in ureteral urothelial carcinoma patients: a single-center experience

ObjectiveIn the southwest coast of Taiwan, the high prevalence rate of upper tract urothelial carcinomas (UTUCs) has been described. Renal preserving surgeries are of great importance when ureteral urothelial carcinoma (UC) happens in solitary kidney, in bilateral upper urinary tract simultaneously, or in patients with chronic kidney disease. We present the single center experience of total ureterectomy plus ileal-ureteral substitution for the ureteral UCs in the southwest of Taiwan over the last two decades.MethodsWe retrospectively reviewed patients who had undergone total ureterectomy plus ileal-ureteral substitution for ureteral UC at our center from January 1988 to December 2013. Chart review was done to obtain the information including age, sex, underlying medical diseases, oncology status before the surgery, baseline renal function, long-term renal function, duration of hospitalization, perioperative surgical complications, long-term complications, and oncological outcomes.ResultsOverall, 8 patients were treated with ileal ureteral substitution for ureteral UC, with a mean follow-up period of 66.5 months. All the resected ureters had confirmed to have UC on the final pathology reports. A total of four major complications (grade III) and 1 minor complication (grade I-II) developed according to the Clavien-Dindo complication grading system during a 30-day post-operative period. No perioperative mortality occurred in these patients. There were 3 patients (37.5%) who experienced long-term complications, including recurrent urinary tract infection and recurrent gross hematuria. At the end of follow-up, the renal function remained stable in 4 patients (50.0%), improved in 2 patients (25.0%), and deteriorated in 2 patients (25.0%). Only one of the deteriorated patient required long-term hemodialysis (12.5%). About the oncological outcome, only 1 patient (12.5%) was found to have tumor recurrence over the pelvic-ileal anastomotic site.ConclusionsIleal-ureteral substitution has been described as a reserved procedure for an extensively diseased ureter that other reconstructive procedures are not feasible. It provides good long-term outcomes for preservation of renal function, and also has acceptable safety concerns. In carefully selected patients, the procedure can also be carried out as nephro-sparing surgery for patients who have ureteral malignancy.

The expression and significance of Zinc-Alphα2 glycoprotein in serum of ureteral carcinoma patients

Objective To screen and identify the differentially expressed proteins of ureteral carcinoma by using surface-enhanced laseresorption/inionation time of flight mass spectromery (SELDI-TOF MS). Methods A total of 20 serum samples from adults with ureteral carcinoma(ureteral carcinoma group), and 20 serum samples from healthy adults(control group)were selected.SELDI-TOF MS technology was applied to detect the differentially expressed proteins.The differential spot was identified by matrix-assisted laser desorption/ionization tandem time of flight mass spectrometry(MALDITOF/TOF MS). Results Fourteen different proteins peaks were found(P< 0. 01). The highest Youden's index was obtained, selecting one differentially expressed protein with m/z of 4 222 Da. The selected expression protein in control group and ureteral carcinoma group was 12 003. 33± 3 234. 93 and 18 144. 66±2 047. 05 respectively(P< 0. 01).MALDI-TOF/TOF MS was used for identification of the peak spot, and the peak was further identified as Zinc-Alphα2 glycoprotein (ZAG). Conclusion A differentially expressed protein of ZAG of ureteral carcinoma was successfully obtained through proteomics technology.ZAG is expected to be a new marker for the early diagnosis and prognosis of ureteral carcinoma. Key words: Zinc-Alphα2 glycoprotein; Bological markers; Ureteral carcinoma; Proteomics

Synchronous ipsilateral renal cell carcinoma and urothelial carcinoma of kidney or ureter: Cases report and literature review

Synchronous ipsilateral renal cell carcinoma and urothelial carcinoma of kidney or ureter: Cases report and literature review

The predictive factors for concurrent renal pelvis tumor of patients with ureter carcinoma: kaohsiung chang gung memorial hospital experience

The predictive factors for concurrent renal pelvis tumor of patients with ureter carcinoma: kaohsiung chang gung memorial hospital experience

Nephron-sparing management (distal ureterectomy with reimplantation of ureter) for carcinoma of distal ureter: A single center experience

Nephron-sparing management (distal ureterectomy with reimplantation of ureter) for carcinoma of distal ureter: A single center experience

Clinical study of total transperitoneal laparoscopic nephroureterectomy in the treatment of upper urinary tract urothelial carcinoma

Objective To verify the safety and advantages of total transperitoneal laparoscopic nephroureterectomy (ttLNU) in the treatment of upper urinary tract urothelial carcinoma (UTUC). Methods From Jun. 2013 to Jun. 2014, there were 13 UTUC patients treated with ttLNU, including 7 males and 6 females. The mean age was 70.4 ± 8.3 yrs, and BMI was 23.3±4.1. Of them, 11 cases were diagnosed with renal pelvis carcinoma, 6 in the left and 5 in the right. 2 cases were diagnosed with left ureteral carcinoma. TNM stages were T1–T3N0M0. Patients were put on lateral position and the position was not changed during the operation. A ttLNU was performed, and the specimen was removed from the middle extended inferior umbilical incision. Results The mean operative time was 188±33 (150–240) min, the intraoperative blood loss was 150.5±60.1 (50–700) ml, and the time of out–of–bed activity was between 1 and 4 d. The mean postoperative drainage time was 6.8±4.6 (3–6) d. The mean postoperative bowel function recovery time was 1.5±1.0 (2–4) d and postoperative hospital stay was 12.8±7.0 (3–27) d. The ttLNU procedures were successfully performed in all cases without conversion to open surgery. Pathological results showed urothelial carcinoma in all cases, including 8 high grade and 5 low grade. All the surgical margins were negative. The followed up was from 2 to 12 mon, and there was no tumor recurrence and metastasis found. Conclusions Total transperitoneal laparoscopic nephroureterectomy in the treatment of upper urinary tract urothelial carcinoma is characterized by short operative time, low blood loss, decreased trauma and quick recovery. This is a safe and effective treatment option for the treatment of upper urinary tract urothelial carcinoma. Key words: Laparoscopic surgery; Nephroureterectomy; Renal pelvic cancer; Ureteral cancer

Primary Squamous Cell Carcinoma of the Ureter in a Patient with No Risk Factors

Upper urinary tract squamous cell carcinomas are uncommon tumors. Several risk factors have been identified with this entity. We present a case primary squamous cell carcinoma of the distal ureter in an individual with no identifiable risk factors. The patient is a 70 year-old man who presented with bilateral flank pain. Laboratory investigations showed high serum creatinine. There was left hydronephrosis on ultrasonography. Computed Tomography (CT) showed an ill-defined soft tissue mass in the left ureter. A left retrograde pyelogram revealed a mass 4 cm from the ureterovesical junction, with ureter dilation proximal to it. The patient underwent distal ureterectomy and stented ureteroneocystostomy. Pathological study of the tumor revealed a moderately differentiated stage 3 invasive squamous cell carcinoma. On serial follow up, the patient showed significant improvement of the left hydronephrosis and improvement of the renal function. Two-year follow-up was negative for recurrence.

Primary squamous cell carcinoma of kidney: a case report

Neoplasms of the kidney are most commonly adenocarcinomas. Squamous cell carcinoma of renal pelvis and ureter are very rare and account for 6-15% of all renal tumours. Very few such cases have been reported. Most are associated with calculus disease or hydronephrosis. Our case was a 44year old female having pain & lump in right flank since six months. Contrast CT abdomen showed an 8.8x8.8x6.4 cm renal upper pole mass with well-defined rounded calcification invading directly into the liver. There was no calculus or hydronephrosis. Ultrasound guided tru-cut biopsy was inconclusive, showing only dysplastic cells. On exploration, the mass was found to be arising from postero-superior pole of right kidney, with direct invasion into the liver. A nephroureterectomy with wedge resection of liver was performed. Histopathology of the specimen showed well differentiated squamous cell carcinoma of renal pelvis extending into liver.

Clinical analysis of 2 115 urothelial carcinoma: single-center experience

Objective To investigate the clinical features of urothelial carcinoma in a single center.Methods The clinical data of 2 115 urothelial carcinoma patients admitted to Peking Union Medical College Hospital from January 2003 to December 2012 were reviewed retrospectively.Of the 2 115 patients,1414 cases were bladder carcinoma,329 cases were ureter carcinoma and 372 cases were renal pelvic carcinoma.Statistical method was used to analyze the differences of distribution and pathological grading and staging of bladder,ureter and renal pelvic carcinoma among different ages,genders,and urban and rural patients.Results The proportion of low-grade carcinoma was 83.5％ for bladder,68.7％ for ureter and 46.5％ for renal pelvic carcinoma,and the proportion of non-muscle invasive carcinoma was 84.9％,74.8％ and 59.7％ respectively,and significant difference was found in pathological grading and staging among the three groups (P =0.000).In bladder and renal pelvic carcinoma patients,males were common,while females were more common in ureter carcinoma patients.There was significant difference in gender among the three groups (P =0.000),while there was no significant difference in pathological grading and staging between male and female patients(P＞0.05).89.7％ (1 898 cases) were concentrated in the 41-80 years old.The grading and staging of urothelial carcinoma in young,middle-aged and elderly groups showed significant difference (P＜ 0.05).The proportions of high-grade and muscle invasive urothelial carcinoma patients in rural areas were both higher than that in urban areas,the difference in pathological grading and staging between urban and rural patients was significant (P＜0.05).Of the 129 cases (6.1％) with multifocal urothelial carcinoma,there were 89 cases (70.0％) with high grade and 62 cases (48.1％) with muscle invasive carcinoma.Significant difference was found in pathological grading and staging between multifocal and single urothelial carcinoma (P=0.000).Conclusions In the uretholial carcinoma of Peking Union Medical College Hospital in the past ten years,the proportion of bladder carcinoma is the highest,while ureter and renal pelvic carcinoma have higher proportion of high grade and stage.The proportion of patients in the 41-80 years old is higher.The pathological grading and staging of urothelial carcinoma is positively correlated with age,but there is no significant correlation in gender.The patients with high grade and stage carcinoma in rural areas are more than that in urban areas.Multifocal urothelial carcinoma has higher malignancy. Key words: Urothelial carcinoma; Urinary bladder neoplasms; Ureteral neoplasms; Grading; Neoplasm staging

TERT promoter mutations are associated with distant metastases in upper tract urothelial carcinomas and serve as urinary biomarkers detected by a sensitive castPCR.

TERT promoter C228T and C250T mutations occur in various malignancies including bladder cancer (BC) and may serve as urinary tumor markers. However, the mutation association with clinical variables in upper tract urothelial carcinomas (UTUCs) is unclear. There is also a lack of sensitive tools to detect the minor mutant TERT promoter in bulk urinary DNA. Here we analyzed 220 UTUC patients [98 with renal pelvic carcinoma (RPC) and 122 with ureter carcinoma (UC)] and developed a Competitive Allele-Specific TaqMan PCR (castPCR) for urinary assay. We identified C228T or C250T mutations in 42 of 98 (43%) RPC and 23 of 122 (19%) UC tumors. Distant metastases were significantly correlated with UTUC patients harboring TERT promoter mutations (P = 0.001). C228T were detected in 6/10 and 9/10 of urine samples from patients with mutation-carrying tumors using Sanger sequencing and castPCR, respectively. When urine samples from 70 BC patients were analyzed together, the sensitivity of urinary C228T assay was 89% and 50% for castPCR and Sanger sequencing, respectively (P < 0.001). Collectively, TERT promoter mutations occur in UTUCs with a high frequency in RPCs and predict distant metastasis. castPCR assays of the mutation are a useful tool for urine-based diagnostics of urological malignancies.

Evaluation of 11C-choline PET/CT for primary diagnosis and staging of urothelial carcinoma of the upper urinary tract: a pilot study

PurposeWe conducted a pilot study to prospectively evaluate the efficacy of PET/CT with 11C-choline (choline PET/CT) for primary diagnosis and staging of urothelial carcinoma of the upper urinary tract (UUT-UC).MethodsEnrolled in this study were 16 patients (9 men, 7 women; age range 51 – 83 years, mean ± SD 69 ± 10.8 years) with suspected UUT-UC. The patients were examined by choline PET/CT, and 13 underwent laparoscopic nephroureterectomy and partial cystectomy. Lymphadenectomy and chemotherapy were also performed as necessary in some of the patients. Of the 16 patients, 12 were confirmed to have UUT-UC (7 renal pelvis carcinoma and 5 ureteral carcinoma), 1 had malignant lymphoma (ureter), 1 had IgG4-related disease (ureter), and 2 had other benign diseases (ureter).ResultsOf the 16 study patients, 13 showed definite choline uptake in urothelial lesions, and of these, 11 had UUT-UC, 1 had malignant lymphoma, and 1 had IgG4-related disease. Three patients without choline uptake comprised one with UUT-UC and two with benign diseases. Of the 12 patients with UUT-UC, 3 had distant metastases, 2 had metastases only in the regional lymph nodes, and 7 had no metastases. Distant metastases and metastases in the regional lymph nodes showed definite choline uptake. The outcome in patients with UUT-UC, which was evaluated 592 – 1,530 days after surgery, corresponded to the patient classification based on the presence or absence of metastases and locoregional or distant metastases. Choline uptake determined as SUVmax 10 min after administration was significantly higher than at 20 min in metastatic tumours of UUT-UC (p < 0.05), whereas there was no statistically significant difference between the SUVmax values at 10 and those at 20 min in primary tumours of UUT-UC.ConclusionThis study suggests that choline PET/CT is a promising tool for the primary diagnosis and staging of UUT-UC.

Efficiency and outcome of Boari bladder flap plasty surgery for the treatment of middle and lower ureteral carcinoma

To study the effect and outcome of Boari bladder flap plasty surgery for the treatment of kidney-sparing strategy for patients with middle and lower ureteral carcinoma. Database at the department of urology in the Second Xiangya Hospital from 2002-2007 was screened and all cases of primary solitary lower ureteral carcinoma treated with Boari bladder flap plasty surgery or radical nephroureterectomy were collected. We performed a retrospective review of the clinical data including sex, age, smoking history, tumor site, size, stage, grade, bladder recurrence, renal function et al and evaluated survival rate. The Cox proportional hazards regression model was build to analyze the correlation between each variable and survival time. Thirty nine patients in total were enrolled, including 16 cases underwent Boari bladder flap plasty surgery and 23 cases underwent radical nephroureterectomy. The median follow-up time was 53 months (range 10-84 months). During the follow-up time, 18 patients died, including 6 patients treated with Boari bladder flap plasty surgery and 12 patients treated with radical nephroureterectomy. The estimated bladder recurrence-free survival rate and cancer-specific survival rate at 5 years were 63% vs 59% and 73.8% vs 73.5%, respectively (P>0.05). The survival rate at 5 years and the overall survival rate were 61% vs 57 % and 64.8% vs 58.1% respectively in the 2 groups (P>0.05). There was no significant difference in renal function before surgery between the two groups [creatinine clearance 57 (32-104 ) mL/ min vs 55 (30-102) mL/ min, P>0.05]. Patients underwent Boari bladder flap plasty showed better renal function than patients underwent radical nephroureterectomy [creatinine clearance 55 (35-102) mL/ min vs 43 (30-89) mL/min, P<0.05]. In multivariate Cox regression analysis, the tumor size, pT stage, tumor cell grade and the estimated glomerular filtration rate level were independent factors that affected the overall survival rate of the patients (P<0.05). The tumor size, pT stage and tumor cell grade were positively correlated to the survival time, and the estimated glomerular filtration rate was negatively correlated to the survival time. Boari bladder flap plasty surgery could be used to treat lower ureteral carcinoma. Compared with radical nephroureterectomy, Boari bladder flap plasty surgery has equal survival rate and shows superior postoperative renal function.

Retroperitoneal Hodgkin's lymphoma involving right ureter misdiagnosed as right ureteral carcinoma with lymphadenopathy: a case report and review of literature

Objective To investigate the clinical and pathological features,diagnosis,differential diagnosis,treatment and prognosis of secondary Hodgkin's lymphoma of ureter.Methods We retrospectively analyzed one case with retroperitoneal Hodgkin's lymphoma involving right ureter.A 63-year-old male patient was referred to our hospital on January 22th,2013 with right hydronephrosis for 15 days,detected by abdominal color Doppler ultrasound due to constipation and difficult defecation without any urinary symptoms.Urinary CT scan revealed that there were dilation and hydrops of right pelvic and ureter in the middle and upper segment.The distal portion of ureteral wall was thick with a stenosis lumen.There was multiple larged lymph nodes surrounding the abdominal aorta.So,it was clinically diagnosed as right ureteral carcinoma with lymphadenopathy and right hydronephrosis.The patient was then performed ureteroscopic inspection under general anesthesia.There was too narrow to go through smoothly the proximal ureter when the ureteroscope ascended 15 cm.Then,the exploratory surgery of right ureter was subsequently undergone.During operation,periureteral nodular mass and thickened wall were seen in the distal segment of ureter.Then the ureter lesion was partially excised with 1 cm and fast frozen pathology was undergone during operation.The result suggested chronic inflammation of ureteral.A 6Fr double J stent was left in the ureter.Then,the ureter was closed by 3-0 monocryl suture.Results The final pathological diagnosis was retroperitoneal Hodgkin's lymphoma with the lymph node involving the right ureter.After 40 days,the patient manifested high fever,night sweat,general lymphoadenomegalies.So,the clinical stage was classified as stage Ⅱ EB and poor prognosis group.Then,the patient received regular chemotherapy according to the ABVD (pirarubicin 20 mg/m2,bleomycin 10 mg/m2,vinblastine 1.4 mg/m2,dacarbazine 375 mg/m2) regimen over 8 cycles.Finally the symptomatology and diagnostic reassessment (hemato-chemical examinations and PET/CT) showed a clinical complete recovery after the follow-up period of 3 months.The follow-up plan is ongoing.Conclusions Because secondary Hodgkin's lymphoma of ureter is rare with concealed onset feature,lacking of characteristic clinical manifestations,it is relatively difficult to achieve the diagnosis and differential diagnosis.Therefore,pathology and immunohistochemistry should be assigned to confirm the diagnosis.It is stressed that physicians should be aware of the possibility of malignant lymphoma when unexplained hydronephrosis and thickness of the ureteral wall are found clinically.Generally it has a good prognosis and combination therapy for the treatment is given priority to with chemotherapy. Key words: Ureteral cancer; Malignant lymphoma; Hodgkin's lymphoma; Diagnosis; Therapy

Marked efficacy of multimodality therapy for ureteral cancer producing granulocyte colony-stmimulating factor

A 69-year-old man was admitted with the chief complaint of macroscopic hematuria. Computerized tomography (CT) and ureteroscopy showed right ureter cancer. Right nephroureterectomy and partial cystectomy were performed. Histological examination revealed urothelial carcinoma of ureter (Grade3, pT3, INFbeta, ly1). The patient underwent two courses of adjuvant chemotherapy with gemcitabine and cisplatin. Three months later, abdominal CT showed a mass in his right obturatorius area. The patient's white blood cell count was 34,140 cells/microl. Additionally serum analysis revealed high value of granulocyte colony stimulating factor (G-CSF), 596 pg/ml with no obvious focus. After being diagnosed with recurrent ureteral cancer producing G-CSF, the patient underwent secondary chemotherapy with gemcitabine and docetaxel. After three courses of chemotherapy, CT revealed a marked decrease in tumor size, and the value of G-CSF declined at 31 pg/nl. Subsequently, radiotherapy (60 Gy) was administered. The patient has been alive for 16 months.

Age and Gender Relation in Ureterial Tumors Detected with Transurethral Resection

Bladder tumors are biologically and chemically hazardous tumors that still remains as high morbidity and mortality rates even though the improvements of diagnosis and treatment in clinical field. Ureteral tumors constitutes about 90% of all bladder tumors and their biological behaviour vary from benign lesions to agressive cancers. In our study 66 diagnosed bladder biopsy and transureteral resection material were analysed retrospectively through the database of pathology department of Iskenderun State Hospital between january 2011 and November 2013.When only the bladder tumor cases were examined, 26 (59.65%) male and 3 (10.35%) female patients were detected. The age average of these tumor cases was 63.86±14.84 and ages were varied from 28-84. The 29 patients of tumor cases were consisted of 1 (1.52%) carcinoma in situ, 2 methastathic cancers, 1 papilloma, 2 low malignity potential papillary neoplasia, 14 low grade papillary carcinoma and 9 high grade papillary carcinoma. We observed that urothelial papilloma and low malignant potential papillary carcinoma has low rates and the percentage of low grade papillary carcinoma has high rates according to smilar studies. Unlikely the other studies, we found that the high grade papillary ureteral carcinoma can seen in further ages than low grade papillary ureteral carcinoma.In the light of our study, we recommend to keep in mind that malignant tumors of ureterium can be seen in all age groups and gender.

Multimodality Therapy Including Surgical Resection and Intraoperative Electron Radiotherapy for Recurrent or Advanced Primary Carcinoma of the Urinary Bladder or Ureter

To report outcomes of multimodality therapy incorporating surgical resection and intraoperative electron radiotherapy (IOERT) for patients with locoregionally (LR) recurrent or advanced primary urothelial carcinoma. From 1983 to 2009, 17 patients, consisting of 11 with LR recurrence after cystectomy for bladder carcinoma, 4 with LR recurrence after nephroureterectomy for ureteral carcinoma, and 2 with advanced primary bladder carcinoma were treated with multimodality therapy. In 8 patients with LR recurrence, the multimodality treatment was a second salvage attempt. Sixteen patients received perioperative external beam radiotherapy (median dose, 50.4 Gy; range, 21.6 to 60 Gy). Extent of resection was R0 (n=7), R1 (n=1), and R2 (n=9). The median IOERT dose was 12.5 Gy (range, 10 to 20 Gy). Overall survival (OS) and relapse patterns were determined from the date of resection and IOERT using the Kaplan-Meier method. The median follow-up for surviving patients was 3.6 years (range, 1.1 to 10 y). OS at 1, 2, and 5 years was 53%, 31%, and 16%, respectively. Central (within the IOERT field), LR (tumor bed or regional lymph nodes), and distant relapses at 2 years were 15%, 49%, and 67%, respectively. On univariate analysis, resection of all gross disease (R0-1) was associated with improved OS (P=0.03). Mortality within 30 days was 0%. Two patients (12%) experienced NCI-CTCAE grades 4 and 5 late adverse events. In patients with recurrent or advanced urothelial carcinoma, this multimodality approach yielded a low rate of recurrence within the IOERT field with acceptable toxicity. However, LR and distant relapse were common, indicating a need for better patient selection, LR therapy, and systemic therapy.

The impact of real-time 3d imaging by ultra-high speed optical coherence tomography in urothelial carcinoma

BackgroundOptical coherence tomography (OCT) has become a promising diagnostic tool in many medical fields. In particular, noninvasive real-time optical biopsy of internal organs is one of the most attractive applications of OCT, enabling in situ diagnosis of carcinoma at an early stage. We used an ultra-high speed OCT system for real-time three-dimensional (3D) imaging of three excised specimens of advanced urothelial carcinoma (UC) and investigated the association of the images with results from histopathological examination.Case presentationsCase 1 was a 69-year-old man underwent radical cystectomy for muscle-invasive UC (pT2). Case 2 was a 53-year-old man underwent laparoscopic nephroureterectomy and partial cystectomy for left ureter carcinoma (pT2) and case 3 was a 77-year-old woman underwent radical cystectomy for advanced bladder carcinoma (pT3b). Real-time 3D OCT images of normal bladder wall and ureter showed three layers, including the urothelium, lamina propria, and muscularis layer. In contrast, normal structure was not seen in the muscle-invasive UC area or the scar tissue area.ConclusionsThis study highlighted a new diagnostic method with potential application for UC diagnosis. We will investigate more cases in the future and expect improvement in the diagnosing efficiency of carcinoma in situ or organ-confined muscle-invasive cancer by cystoscopy or ureteroscopy with ultra-high speed OCT.

Upper urothelium carcinomas in Croatian endemic area

Endemic nephropathy (EN) is a chronic tubulointerstitial disease. Strong association between EN and urothelial carcinoma was noted as early as 40-50 ago. The aim of the study was to determine and compare specific mortality and morbidity of renal pelvis and ureter (upper urothelium) carcinoma (UUC) among Croatia as a whole, Brod-Posavina County, and Croatian endemic area. Data on UUC mortality and morbidity were analyzed. Indirect standardization was employed on data comparison by calculating standardized mortality ratio and morbidity ratio. Our study results showed the specific mortality rate in the endemic area to be 26.3-fold and 7.3-fold the rate recorded in Croatia and Brod-Posavina County, respectively. The mean standardized mortality ratio obtained by indirect standardization yielded an 8-fold and 32-fold risk of death from UUC in the endemic area vs. Brod-Posavina County and Croatia as a whole, respectively. These data revealed the specific morbidity in the Croatian endemic area and Brod-Posavina County to be 13.95-fold and 3.78-fold the morbidity recorded at the national level, respectively. The standardized morbidity ratio also showed the risk of developing UUC in the Croatian endemic area to be 3.75-fold the risk in Brod-Posavina County and 16.4-fold the risk in Croatia. These results showed that specific mortality and morbidity as well as standardized morbidity ratio and standardized mortality ratio were higher in Croatian endemic area than in Brod-Posavina County and Croatia.

Expression of PD-L1 in primary urothelial carcinoma (UC).

4541 Background: Engagement of programmed cell death-1 (PD-1), expressed on CD8+ T cells, with it ligand PD-L1(B7H1), expressed on tumor cells, results in T cell suppression and tumor protection. Antibodies against PD-1 or PD-L1 have reported impressive anti-tumor activities in phase I/II trials and are being tested in the phase 3 setting. Exploratory analysis indicated that expression of PD-L1 could be a predictive marker for response. Of note, urothelial carcinoma (UC) was not included in the early phase anti-PD1 or anti-PD-L1 studies. To explore anti-PD-L1 as a new treatment for this lethal disease, we assessed PD-L1 expression in UC. Methods: The relative mRNA abundance of PD-L1 mRNA in UC was studied in the Oncomine Bittner Multi-cancer dataset, which included a total of 1911 tumor samples. PD-L1 immunohistochemistry (IHC) was performed with rabbit monoclonal antibody against human PD-L1 on tissue microarrays with 83 formalin fixed paraffin embedded T1, T2 and T3 UC. IHC slides were reviewed by a genitourinary pathologist. A positive staining is defined when ≥ 5% of cancer cells had positive PD-L1 membrane and/or cytoplasmic staining. The IHC slides were scanned with the Aperio ScanScope XT and the immunopositivity of PD-L1 was quantitatively scored using commercial algorithms from the Aperio Toolbox and TissueStudio. The 1+, 2+, and 3+ score of each core was based on the dominant IHC staining intensity. Results: In the Bittner multi-cancer dataset, the log2 median mRNA intensities of PD-L1 in prostate cancer, clear cell renal cell carcinoma, colon cancer, UC of the bladder, ureter and squamous cell carcinoma of the bladder were 0.245, 0.528, 0.61, 0.81, 0.802, and 1.202 respectively. The overall PD-L1 IHC staining positivity was 45% in 83 primary UC samples. All six 3+ PD-L1 staining cores were grade 3 urothelial carcinomas and each core had more than 60% of cancer cells with 3+ PD-L1 membrane staining. Grade 3 cores also had the highest percentage of 2+ and 3+ PD-L1 positivity. No association was observed between T staging and PD-L1 staining intensity. Conclusions: PD-L1 is expressed in primary UC. We have obtained additional UC samples to correlate its expression with survival and its expression pattern with the pattern of tumor infiltrating lymphocytes.