Index. B Balkan endemic nephropathy (BEN), BEN. See Balkan endemic nephropathy (BEN)

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1 A AA. See Aristolochic acid (AA) ADC. See Apparent diffusion coefficient (ADC) Adjuvant chemotherapy bladder cancer, 183 cancer specific survival (CSS), 184 cisplatin, disease free survival (DFS), 184 lymphadenectomy, 170 multifocal disease, renal pelvis and the ureter, 66 paclitaxel, gemcitabine and cisplatin (PGC), 184 upper tract urothelial cancer, 184 Adjuvant intracavitary (topical) therapy, American Joint Committee on Cancer- International Union Against Cancer (AJCC/UICC), 110 Angiolymphatic invasion, 63 Apparent diffusion coefficient (ADC), 36 Aristolochic acid (AA) BEN/UTUC, 14 carcinogenic effect, 13 enzymatic nitroreduction, 14 herbaceous plants, 11 herbal medicines, 16 renal cortex and tumor tissues, 13 urothelial malignancy, 12 UTUC, 15 B Balkan endemic nephropathy (BEN), BEN. See Balkan endemic nephropathy (BEN) Benign tumors, 56, 74, 75 Biopsy grade clinical tumor grade and stage, 96 fi nal tumor stage, 38 UTUC, 39 Bladder cancer cystoscopic evaluation, 136 distal ureteral involvement, 21 lymphadenectomy, 154 lymph node density, 170 metastatic urothelial cancer, 185 mild-to-moderate dysplasia, 13 multimodal therapy, 161 neoadjuvant chemotherapy, 180 nephroureterectomy, 137 non-muscle-invasive cancer, 72 previous/synchronous, 97 radical cystectomy, 169 RNU, tumors, 13 UC, 12 upper tract recurrence, 33 urothelium, 132 UTUC, 13 Bladder cuff excision and distal ureter, 136 and distal ureterectomy, 140 and intramural ureter, 137 laparoscopic management, 136 oncological efficacy, and regional lymphadenectomy, 133 RNU, 135 transvesical resection, 136 Blood-based markers, 106 Springer Science+Business Media New York 2015 S.F. Shariat, E. Xylinas (eds.), Upper Tract Urothelial Carcinoma, DOI /

2 192 C Cancer-specific survival (CSS) clinical and pathological, 110 IncompLND, 169 LND, 135 lymphadenectomy, 155 lymphatic metastases, 155 lymph node, 110 multivariate analysis, 163 renal pelvis and proximal ureter, 66 upper tract urothelial cancer, 184 UTUC, 94 Carcinoma in situ (CIS) concomitant, IHC vs. reactive atypia, intracavitary instillation therapy in high-risk UTUC, 144 and invasive carcinoma, 51 and narrow band imaging (NBI), 37 Ta and flat noninvasive, 58 topical therapy, 124 upper tract recurrence, ureter, 139 urothelial, 54, 56, 58, 67 Chemotherapy adjuvant chemotherapy, 66, 170, in adjuvant/neoadjuvant setting, 161 cisplatin-based combination, 108 lymphadenectomy/neoadjuvant, 39 in metastatic disease, neoadjuvant chemotherapy, 108, 110, 123, perioperative intravesical, surgery and, 169 Chinese herbs nephropathy (CHN) AA exposure and urothelial malignancies, 12 BEN, herbal medicine, renal disease, 12 upper urinary tract, 2 CHN. See Chinese herbs nephropathy (CHN) CIS. See Carcinoma in situ (CIS) Cisplatin, methotrexate and vinblastine (CMV), 181, 185 Collecting duct carcinoma (CDC), 54, 55, 67, 69, 82 Complete lymphadenectomy lymph node dissection (CompLND), 162, 169, 173 Computed tomography (CT) urography cystectomy, 34 IVU, 35 MPR, 34 radiological findings, 35 upper tract recurrence, 33 upper urinary tract, 22 ureteral catheter, 36 urinary excretion, 34 UTUC, 22 Concomitant carcinoma in situ (CIS), 19 21, 70, , 124, 125, 139 Conservative management, low-risk UTUC adjuvant intracavitary (topical) therapy, clinical prognostic factors, description, 120 distal/segmental ureterectomy, 125 endoscopic management, nephroureterectomy, partial nephrectomy, prognostic patient and tumor factors, 121 urothelial carcinoma, 120 CSS. See Cancer-specific survival (CSS) D Detoxification pathways, 8 9 Diagnosis and evaluation, UTUC asymptomatic patients, bladder cancers, 32 CT urography, endoscopy, hematuria, MR, pain, 33 palpable mass, 33 predictive and prognostic statistical tools, urinary frequency, 33 urine cytology, Disease-specific survival (DSS), 44, 120, 124, 135, 143, 162, Distal/segmental ureterectomy and bladder cuff excision, 140 kidney-sparing approach, 125 LND, 99 survival after, Distal ureter management, RNU bladder cuff resection, endoscopic approach, 137 extravesical approach, 136 oncological efficacy, bladder cuff resection techniques, resection, 99 transvesical approach, 136 DSS. See Disease-specific survival (DSS)

3 193 E Eastern Cooperative Oncology Group performance status (ECOG-PS), 93, 121 Endoscopic management high-risk UTUC access, 141, 142 low-risk UTUC bladder recurrences, 124 indications, local recurrence, 124 metastatic disease by pyelovenous/ pyelolymphatic seeding, 124 renal preservation and progression, 124 treatment and limitations, 123 ureteroscopic management, 123 ureteroscopy, 122 vs. RNU, 101 Endoscopy cystoscopy, 38 flexible ureteroscopy and in situ biopsy, RUP, 37 F Fluorescence in situ hybridization (FISH), 39, 65 G Genetic markers, H Hematuria, 21, 32 33, 36, 41, 46, 80, 82 High-risk UTUC definition, 132 KSS, LND, RNU, , surgical treatment, 132 Histopathology AAN, 12 CDC, 54 dysplastic features, 54 myxoid stroma, 54 pelvicalyceal system, 54 PUNLMP, 51 renal medullary carcinoma, 54 urothelial carcinomas, 51, 52, 55 Hydronephrosis clinical tumor grade and stage, 96, 181 distal ureter, 50, 82 invasion and, 110 pyelonephritis, 33 UTUC, 94 I ICUD. See International Consultation on Urological Diseases (ICUD) Immunohistochemistry (IHC) CDC, 69 LNs, 165 MMR proteins, 7 RCC, 69 reactive atypia vs. carcinoma in situ, upper tract urothelial carcinoma, 67 urothelial carcinoma, Incomplete lymphadenectomy lymph node dissection (IncompLND), 162, 169 International Consultation on Urological Diseases (ICUD), 173 Intracavitary instillation therapy in high-risk UTUC, 144 Intravenous urography (IVU), 22, 34, 35 IVU. See Intravenous urography (IVU) K Kidney-sparing surgery (KSS) endoscopic management, intracavitary instillation therapy, 144, 145 patient selection, percutaneous nephroscopy, perioperative intravesical chemotherapy, 144, 146 treatment partial and total ureterectomy, 140 survival after distal and segmental ureterectomy, KSS. See Kidney-sparing surgery (KSS) L Laparoscopic nephroureterectomy (LNU), 98, 134 Laparoscopy and endoscopic procedures, 132 GIA tissue stapler, 136 LNU, 98, 134 management of the bladder cuff resection, 136 radical nephroureterectomy, 136 and robotic-assisted distal ureterectomy, 140 and robotic-assisted laparoscopic approaches, 126 and robotic lymphadenectomy, 172 transvesical approach, 136 LND. See Lymph node dissection (LND) LNI. See Lymph node invasion (LNI) LNs. See Lymph nodes (LNs)

4 194 LNU. See Laparoscopic nephroureterectomy (LNU) LVI. See Lymphovascular invasion (LVI) Lymphadenectomy disadvantages, ICUD and SIU, 173 laparoscopic and robotic, 172 LNs, lymphatic metastases, 154 MDCT, 171 NCCN, 173 pt stage, 171 renal cell carcinoma, 154 RLN, tumors, 171 UCUT (see Urothelial carcinoma of the upper urinary tract (UCUT)) urothelial carcinoma, 154 Lymph node dissection (LND) anatomical sites, 99 chemotheraphy, 108 CompLND, 162, 173 lymphatic distribution in retroperitoneum, 133 micro-metastatic disease, 161 and neoadjuvant chemotherapy, 108 oncological significance, RNU, Pros-CompLND and Retro-CompLND, 165 retroperitoneum, 133 RNU, 99 systemic therapy, 108 Lymph node invasion (LNI), 103, 110 Lymph nodes (LNs) AJCC, 58 bladder cancer, 166 cancer-specific survival, 170 chemotherapy, 169 density, 170 dissection technique, 166 LNU, 134 lymphadenectomy, 166 metastase, 155 micrometastases, 165 muscle-invasive bladder cancer, 169 neoadjuvant chemotherapy, 181 patient s survival, 169 perirenal and periureteral adipose tissue, 63 recurrence-free and CSS, 166 renal parenchyma, 171 Lymphovascular invasion (LVI), 63, 103, 111, 122 Lynch syndrome (LS) adenocarcinoma, 6 colorectal cancer, 5 extra-colonic tumors, 5 HNPCC, 3, 6 immunohistochemistry, 7 microsatellite instability, 4 mutant genes, 4 MutS protein, 3 tumors, 5 UTU, 6 M Magnetic resonance (MR) urography, 35 36, 41 Malignant tumors, MDCT. See Multi-detector computed tomography (MDCT) Medical Research Council (MRC), 181 Metastatic disease, chemotherapy cisplatin and methotrexate, 185 gemcitabine and carboplatin (GCa), 183, 185 gemcitabine and cisplatin (GC), metastatic urothelial cancer, methotrexate, carboplatin and vinblastine (MCAVI), 185 nephroureterectomy, 185 paclitaxel, gemcitabine and cisplatin (PCG), 185 Methotrexate, vinblastine, doxorubicin and cisplatin (MVAC), , 185 Microsatellite instability (MSI), 4, 71, 83, Miscellaneous non-epithelial tumors, 77, 78 Mismatch repair (MMR) DNA hypermethylation, 4 DNA repair, 7 extra-colonic tumors, 5 gene mutations, 6 immunohistochemistry, 7 mammalian, 4 MSI, 71 Muir-Torre syndrome, 3 MutS protein, 3 MMR. See Mismatch repair (MMR) MRC. See Medical Research Council (MRC) MR urography. See Magnetic resonance (MR) urography MSI. See Microsatellite instability (MSI) Multi-detector computed tomography (MDCT), 171 Multifocal tumors, 96 MVAC. See Methotrexate, vinblastine, doxorubicin and cisplatin (MVAC)

5 195 N Narrow Band Imaging (NBI), 37 National Comprehensive Cancer Network (NCCN), 173 NCCN. See National Comprehensive Cancer Network (NCCN) Neoadjuvant chemotherapy carboplatin-based therapy, 184 muscle-invasive bladder cancer, 180 MVAC, pathologic down-staging effect, 181 radical cystectomy, 181 upper tract urothelial cancer, perioperative chemotherapy trials, Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser, 123 Non muscle invasive bladder cancer (NMIBC), 33, 34, 132 O Open RNU (ONU), 98 P Pain, 21, 33, 46, 80, 82, 94, 126 Papillary urothelial neoplasm of low malignant potential (PUNLMP), 51, 56, 57, 75 Papilloma, 51, 56, 74, 75 Partial nephrectomy, 51, 120, PCN. See Percutaneous nephroscopy (PCN) Percutaneous nephroscopy (PCN), Percutaneous therapy, 122, 124 Perioperative instillation, intravesical chemotherapy, 144, 146 Phenacetin. See Phenacetin and analgesic nephropathy Phenacetin and analgesic nephropathy, 11, Pluck technique, 137 Proliferative tumor-like lesions endometriosis, fibroepithelial polyp, idiopathic retroperitoneal fibrosis, 81 nephrogenic adenoma/metaplasia, R Radical nephroureterectomy (RNU) distal ureter management, intraluminal instillation regimens with BCG, 132 invasive carcinomas of urothelial origin, 51 ipsilateral bladder cuff resection, 65 kidney and ureter removal, 133 lymphadenectomy, , 170 non-muscle invasive bladder cancer, 132 oncological significance, open/laparoscopic approach, 133 prognostic factors, 132 renal function, 132 UTUC, 91, 97, 126 Reactive atypia vs. carcinoma in situ, Regional lymph nodes interaorto-caval nodes, 174 kidney, 157 left renal hilar and para-aortic nodes, 155 lymphatic metastases, 155 lymph node dissection, 157 nodal involvement, 155, 156 renal pelvis, 155 surgical specimens/radiological findings, 155 Renal cell carcinoma (RCC) IHC, 69 lymphadenectomy, 173 lymphatic metastases, 154 metastasis, 54 partial nephrectomy, 126 urothelial, 54 Renal pelvis benign tumors, 74 biopsy, 64 caliceal system, 33 functional and oncological examination, 22 interaorto-caval nodes, 155 lamina propria, 60 lymphadenectomy, 157 lymphatic drainage patterns, 133 malignant, miscellaneous non-epithelial, 77 morphologic features, 54 neoplasms and non-neoplastic tumorous lesions, noninvasive lesions, 59 palpable mass, 33 papillary/polypoid tumors, 51 proliferative tumor-like lesions, proximal ureter, 66 RCC, 69 smoking, 10 UC, 17 upper tract urothelial carcinomas, 46 upper ureteric cancers, 162 ureter, 12 ureteral biopsy, 65 ureteric cancer, 6 ureteroscopy, 122 urothelial carcinomas, 71 urothelium, 132 UTUC, 134

6 196 Renal pelvis cancer antegrade (percutaneous) ureteropyeloscopy, 122 treatment, 123 UTUC, 120 Renal preservation, 120, Retrograde ureteropyelography (RUP), 37, 41, 64 Retroperitoneum fi brotic tissue and chronic inflammation, 81 lymphatic distribution in, 133 and pelvis, 134, 172 RNU. See Radical nephroureterectomy (RNU) RUP. See Retrograde ureteropyelography (RUP) S SIU. See Société Internationale d Urologie (SIU) Smoking exposure chemotherapy, 180 upper tract urothelial carcinoma, 93, 94 Société Internationale d Urologie (SIU), 173 Spanish Oncology Group Trial, 184 Surgical treatments, 65, 123, 132 Surveillance, Epidemiology and End Results (SEER) database, 18, 120, 137, 160, 164 Survival after distal and segmental ureterectomy, cancer-specific survival (CSS), 66, 97, 104, 105, 110, 111, 126, 135, 155, 162, 170, 182, 184 disease-free survival (DFS), 126, 136, 184 grim, 120 LND, 99 lymph node density, 170 muscle-invasive bladder cancer, 180, 181 overall survival (OS), 132, 138, 170, 183, 184 patients, 66 and recurrence, 123 recurrence-free, 66, 100, 135, 138, 143, 158 RNU, 99, 132 T Tissue-based markers, 106 Topical therapy, U UC. See Urothelial carcinoma (UC) Upper tract recurrence bladder cancer, 33 CIS, tumour grade, 19 tumour stage, 19 ultrasound examination, 22 ureteral margin and frozen section analysis, 20 ureterorenoscopic treatment, 143 UTUC, Upper tract surveillance, Upper tract urothelial carcinogenesis cell carcinoma, 2 9 UC, UTUC, Upper tract urothelial carcinoma (UTUC) AA, 11 body mass index and oncologic outcomes, 94 CHN, classification, conservative management of low-risk, diagnosis and evaluation, disease related factors clinical tumor grade and stage, disease recurrence and cancer-specific mortality incidences, 95 hydronephrosis, 94 multifocal tumors, 96 previous/synchronous bladder cancer, 97 symptoms, 94 tumor location, tumor size, 96 distal ureterectomy, 99 endoscopic tools, 108 epidemiology and risk factors, 1 23 limitations, LVI, 103 lymphadenectomy, 161 molecular markers blood-based markers, 106 genetic markers, tissue-based markers, 106 novel biomarkers, 112 oncogenesis and progression pathways, 106 pan-urothelial phenomenon, 97 pathologic factors concomitant carcinoma in situ, 102 histological variants, 106

7 197 lymph node invasion, 103 lymphovascular invasion, 103 positive surgical margins, tumor architecture, tumor grade, 101 tumor necrosis, tumor stage, 99 patient related factors comorbidities ASA and ECOG, obesity, 94 patient age, patient gender, 93 patient race, 93 prognostic factors, 93 smoking status and cumulative exposure, 94 phenacetin and analgesic nephropathy, prediction tools adjuvant systemic therapy, 110 biomarkers, 110 endoscopic tools, 108 hydronephrosis, 108 imaging and ureteroscopy, 110 international UTUC collaboration nomogram study, 110 neoadjuvant chemotherapy, 108, 110 nomograms, 108, non-organ confined (NOC) UTUC, 108 T2 and higher stage UTUC, 108 prognostics factors, molecular markers and predictive tools, RNU, 92 surgery related factors delayed surgery, 8 distal ureter management, 99 lymph node dissection (LND), 99 open RNU (ONU), 98 surgical management of high-risk ( see High-risk UTUC) tumor grad, 101 ureteroscopy/cytology, 110 Upper tract urothelial cell carcinoma colorectal cancer, 7 detoxification pathways, 8 9 lynch syndrome, 3 7 MMR, 7 SNP, 9 Upper urinary tract. See Urothelial carcinoma of the upper urinary tract (UCUT) Upper Urinary Tract Urothelial Carcinoma Pathology advantage, 60 anatomic distribution, epidemiology and risk factors, carcinogenesis pathway, 71 cell block, 62 conventional papillary/flat urothelial carcinoma, 49 definitive resection specimens, 63 FGFR3 and TP53 mutations, 71 histopathology, IHC, Ki-67, 72 lamina propria and smooth muscle layer, 46 lymph nodes, 63 malignant neoplasm, 46 medullary pyramids, 60 metastatic disease, 63 minor calyceal carcinomas, 60 muscle invasive cancers, 71 muscularis mucosae, neoplasms, 47, 48 nephrectomy/nephroureterectomy, 62 non-invasive lesions, 58 papillary growths, 59 partia ureterectomy, 62 primary renal cortical tumors, 51 prognostic and predictive markers, ptnm, 58, 59 pt3 tumors, 66 renal parenchymal invasion, 67 renal pelvis and ureter, renal resections, 63 stromal reaction and necrosis, 60, 61 superficial invasion, 66 upper tract lesions, 71 ureter, 62 ureteroscopic biopsy, urologic surgical oncology, 62 urothelial carcinoma, 65 urothelial neoplasms, 49, 50 vascular invasion, 63 Upper urinary tract urothelial carcinoma pathology benign neoplasms, 56 cytologic atypia, 58 invasive lesions, 58 papillary urothelial neoplasm, 56, 57 urothelial lesions, 55, 56 Upper urinary urothelial cancers urothelial cancer, urothelial carcinogenesis (see Upper tract urothelial carcinogenesis)

8 198 Ureteral cancer, muscle-invasive disease, 165 nuances unique, perforation and strictures, 123 UTUC, 120 Ureteroscopic management, 123 Ureteroscopy core biopsy fragments, 62 cystoscopy, 37 distal ureteral strictures, 143 hydronephrosis, 110 nephronsparing technique, 122 renal calyces, 142 in situ biopsies, upper urinary tract specimens, UTUC, 39 Urinary cytology, 38 39, 41 Urothelial cancer anatomic and procedural constraints, 181 chemotherapy-sensitive disease, 185 chemotherapy-sensitive malignancy, 180 cisplatin, 183 epidemiology and risk factors, 1 23 identification, 180 invasive, 183, 184 lymph node, 184 metastatic, MVAC chemotherapy, 183 papillary urothelial neoplasia, 54 retroperitoneum and pelvis, 134 traditional pathologic parameters, 72 upper tract (see Upper tract urothelial carcinoma (UTUC)) upper tract recurrence, upper tract surveillance, Urothelial cancer in the bladder (UCB) ALARA principle, 22 excretory and intravenous urography, 22 hematuria/flank pain, 21 imaging techniques and cytology, 21 radical cystectomy, 18 risk factor, 21 RNU, 21 surveillance examinations, 23 ureteral disease, 22 ureterorenoscopy, 23 urine cytology, 22 Urothelial carcinoma (UC) bladder, 154 carcinogenesis, 71 carcinogens, 8 chordoid differentiation, 54 cigarette smoking, conventional papillary, 49 detoxification and DNA repair pathways, 8 flat neoplasms, 56 gene/environmental interaction, 10 genome-wide SNP analysis, 9 hereditary cancer syndromes, 2 high-grade papillary, 58 IHC, LND, 133 LS, 3 malignant neoplasm, 46 metachronous lesions, 18 multifocality, 54 papillary necrosis, 17 radical nephroureterectomy, 65 renal pelvis, 69 upper tract, 120 UTUC, 106 Urothelial carcinoma of the upper urinary tract (UCUT) aortic bifurcation, 158 bladder cancer, 158 chemotherapy, 161 CompLND, 162 CSS, 155 DFS, 162 disadvantages, immunohistochemistry, 165 IncompLND, 162 LND, 163, 164 lymphadenectomy, 158 lymphatic metastases, 155 lymph node density, 170 lymph node map, 157 lymph node metastasis, 161 multi-institutional studies, 163 multi-modal therapy, 161 multivariate analysis, 164 muscle-invasive disease, 165 nodal involvement, 158 oncological outcome, 166 para-aorta/para-cava, 162 pathological nodal staging model, pn+ vs. pnx, 160, 161 pn0 vs. pnx, 158, 160 population-based study, 164 renal pelvic cancer stage, 165 robotic retroperitoneal lymphadenectomy, 172 template-based lymphadenectomy, 165 upper and lower urinary tract, 154 UTUC. See Upper tract urothelial carcinoma (UTUC) V Vascular invasion, 63